2021/06/14 更新

写真a

エノモト タカユキ
榎本 隆之
ENOMOTO Takayuki
所属
教育研究院 医歯学系 医学系列 教授
医学部 医学科 教授
医歯学総合研究科 分子細胞医学専攻 遺伝子制御 教授
職名
教授
外部リンク

学位

  • 博士(医学) ( 1994年3月   大阪大学 )

研究キーワード

  • 婦人科腫瘍

  • gynecologic pathology

  • gynecologic oncology

  • 婦人科病理

研究分野

  • ライフサイエンス / 産婦人科学

  • ライフサイエンス / 人体病理学

経歴(researchmap)

  • :新潟大学 医歯学系 教授

    2012年 - 現在

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  • :大阪大学医学部 病院教授

    2008年 - 2012年

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  • :大阪大学医学部 助教授

    2007年 - 2008年

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  • :大阪大学医学部 講師

    2002年 - 2007年

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  • :大阪労災病院産婦人科   副部長

    1999年 - 2001年

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  • : Osaka University Medical School, Assistant Professor

    1996年 - 1999年

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  • :大阪大学医学部 助手

    1996年 - 1998年

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  • : Osaka University Medical School, Research Fellow

    1994年 - 1995年

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  • :大阪大学医学部 研究生

    1994年 - 1995年

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  • :大阪大学医学部 医員

    1991年 - 1994年

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  • : Osaka University Medical School, Staff fellow

    1991年 - 1994年

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  • : National Cancer Institute(U. S. A) Guest Researcher

    1986年 - 1991年

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  • :米国国立癌研究所 客員研究員

    1986年 - 1991年

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経歴

  • 新潟大学   医学部 医学科   教授

    2012年9月 - 現在

  • 新潟大学   医歯学総合研究科 分子細胞医学専攻 遺伝子制御   教授

    2012年9月 - 現在

学歴

  • 大阪大学   医学部   医学科

    - 1983年

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    国名: 日本国

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  • 大阪大学

    - 1983年

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所属学協会

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委員歴

  • 婦人科悪性腫瘍研究機構   理事長  

    2019年1月 - 現在   

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    団体区分:学協会

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  • 厚生労働省   患者申出療養評価会議技術専門委員  

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    団体区分:政府

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  • 日本癌治療学会   代議員  

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  • 日本産科婦人科学会   婦人科腫瘍委員会委員長  

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    団体区分:学協会

    日本婦人科腫瘍学会

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  • 日本婦人科腫瘍学会   常務理事  

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    団体区分:学協会

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  • 日本癌治療学会   機関紙編集委員、がん保険診療対策委員  

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  • 日本産科婦人科学会   常務理事(広報担当)  

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    団体区分:学協会

    日本臨床細胞診学会

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  • 日本臨床細胞学会   理事  

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    団体区分:学協会

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  • 厚生労働省   先進医療会議技術専門委員  

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    団体区分:政府

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取得資格

  • 日本産科婦人科専門医

  • 日本臨床細胞学会細胞診専門医

  • 婦人科腫瘍専門医

 

論文

  • A survey of 20-year-old Japanese women: how is their intention to undergo cervical cancer screening associated with their childhood HPV vaccination status? 査読 国際誌

    Reisa Kakubari, Tomomi Egawa-Takata, Yutaka Ueda, Yusuke Tanaka, Asami Yagi, Akiko Morimoto, Yoshito Terai, Masahide Ohmichi, Tomoyuki Ichimura, Toshiyuki Sumi, Hiromi Murata, Hidetaka Okada, Hidekatsu Nakai, Noriomi Matsumura, Kiyoshi Yoshino, Tadashi Kimura, Junko Saito, Risa Kudo, Masayuki Sekine, Takayuki Enomoto, Yorihiko Horikoshi, Tetsu Takagi, Kentaro Shimura

    Human vaccines & immunotherapeutics   1 - 9   2020年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    INTRODUCTION: In Japan, two groups of women, HPV vaccinated and unvaccinated, are approaching age 20, when they should begin cervical cancer screening. To improve Japan's current poor cervical cancer screening rate, we need to know how these women are thinking about screening. METHODS: We conducted an internet survey of 20-y-old women, exploring their understanding of HPV and cervical cancer screening. We then gave them leaflets with basic information about HPV and cervical cancer, stressing the importance of early detection by screening. We analyzed the leaflet's effects on their attitudes based on their vaccination status. RESULTS: Our study of 618 women found a significantly higher intention for engagement for cervical cancer screening in women HPV-vaccinated as teenagers (29% versus 17%). They were also more aware that: (1) HPV is transmitted by sexual intercourse (49.1% versus 39.2%); (2) the HPV vaccine prevents cervical cancer (49.0% to 34.0%); and (3) the appropriate cervical cancer screening interval is every 2 y (63.3% versus 56.2%). Women in both groups responded well to the leaflet, with significant improvements in intention to receive screening. However, 65%-67% were not swayed. DISCUSSION: HPV-vaccinated women were more knowledgeable about cervical cancer and had a greater intention to receive screening. Our educational leaflet was moderately effective in both groups for increasing intentions to screen, but the majority in both groups were still resistant to screening. CONCLUSION: Japan needs to develop more effective educational programs and tools to vigorously impart the importance of cervical cancer screening.

    DOI: 10.1080/21645515.2020.1788326

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  • Japan's Ongoing Crisis on HPV Vaccination. 査読 国際誌

    Masayuki Sekine, Risa Kudo, Manako Yamaguchi, Sharon J B Hanley, Megumi Hara, Sosuke Adachi, Yutaka Ueda, Etsuko Miyagi, Sayaka Ikeda, Asami Yagi, Takayuki Enomoto

    Vaccines8 ( 3 )   2020年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    : The Japanese government suspended proactive recommendations for the HPV vaccine in June 2013. The suspension is now in its seventh year, despite all the data pointing to the safety of the HPV vaccine. We reported a high vaccine effectiveness in the group of women vaccinated before their first intercourse (93.9%). The prevalence of cross-protected types of HPV 31/45/52 was also lower in the vaccinated group, and the vaccine effectiveness was 67.7%. Furthermore, prevalence of HPV16, 31 and 52 infection rates in the vaccinated group were obviously lower than that in the unvaccinated group, and no one had HPV18 or 45 infection in the vaccinated group. The addition of a cross-protective effect toward HPV types 31/45/52 to HPV types 16/18, which is the direct target of the bivalent HPV vaccine, may possibly prevent around 82% of invasive cervical cancer cases in Japan. With regard to the preventive effect of histological abnormalities, we also reported significant reduction in incidence of cervical intraepithelial neoplasia (CIN)3 or worse. Thus, the efficacy of the vaccine has been demonstrated for precancerous disease, and the diverse symptoms after HPV vaccination are likely functional somatic. For the future of Japanese girls, there is a need to resume the proactive recommendation of HPV vaccination and for immediate action to be taken by the Japanese government.

    DOI: 10.3390/vaccines8030362

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  • Cancers associated with extraovarian endometriosis at less common/rare sites: A nationwide survey in Japan. 査読 国際誌

    Masaki Mandai, Yutaka Osuga, Tetsuya Hirata, Takayuki Enomoto, Hidekatsu Nakai, Ritsuo Honda, Fuminori Taniguchi, Hidetaka Katabuchi

    The journal of obstetrics and gynaecology research46 ( 6 ) 917 - 923   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIM: Endometriosis mostly affects the ovary but can also be present outside of the ovary including the pelvic peritoneum, intestine, urinary tract and lung. In case of ovarian endometriotic cyst, an increased risk of ovarian cancer, especially of clear cell and endometrioid histology, has been reported. However, because of the rarity, cancer occurrence from endometriosis at less common sites/rare sites is poorly understood. METHODS: We conducted a nationwide survey on the less common/rare site endometriosis in 3539 authorized facilities in Japan. We requested to complete a case report form for each case, including information on the history of endometriosis, treatment for endometriosis, type of surgery, involved site(s) of cancer and endometriosis, histology of cancer, chemotherapy and outcome. RESULTS: Out of 1397 confirmed cases of less common/rare site endometriosis, 11 cases of rare site endometriosis-associated cancer (RSEAC) were reported: seven of them were associated with intestinal endometriosis, three were associated with urinary tract endometriosis and one was associated with umbilical endometriosis. Interestingly, the histology was endometrioid in seven (64%) cases, and serous, seromucinous borderline, clear cell and mucinous in one case each (10%), differing from the case of ovarian endometriosis-associated cancer, in which clear cell carcinoma are more common. CONCLUSION: Our nationwide survey on RSEAC has revealed that: (i) the incidence of malignant transformation may be lower than ovarian endometriosis, (ii) malignant transformation from endometriosis outside the abdominal cavity may be extremely rare and (iii) the histology of RSEAC is predominantly endometrioid type, suggesting an association of a hormonal effect.

    DOI: 10.1111/jog.14244

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  • XCL1 expression correlates with CD8-positive T cells infiltration and PD-L1 expression in squamous cell carcinoma arising from mature cystic teratoma of the ovary. 査読 国際誌

    Ryo Tamura, Kosuke Yoshihara, Hirofumi Nakaoka, Nozomi Yachida, Manako Yamaguchi, Kazuaki Suda, Tatsuya Ishiguro, Koji Nishino, Hiroshi Ichikawa, Keiichi Homma, Akira Kikuchi, Yutaka Ueda, Yuji Takei, Hiroyuki Fujiwara, Teiichi Motoyama, Shujiro Okuda, Toshifumi Wakai, Ituro Inoue, Takayuki Enomoto

    Oncogene   2020年3月

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    記述言語:英語  

    Molecular characteristics of carcinoma arising from mature cystic teratoma of the ovary (MCT) remain unclear due to its rarity. We analyzed RNA-sequencing data of 2322 pan-cancer [1378 squamous cell carcinomas (SCC), 6 adenosquamous carcinomas (ASC), and 938 adenocarcinomas (AC)] including six carcinomas arising from MCT (four SCCs, one ASC, and one AC). Hierarchical clustering and principal component analysis showed that gene expression profiles of carcinomas arising from MCT were different between each histological type and that gene expression profiles of SCCs arising MCT (MCT-SCCs) was apparently similar to those of lung SCCs. By epidermis-associated pathways activity based on gene set enrichment analysis, 1030 SCCs were divided into two groups: epidermis-signature high (head and neck, esophagus, and skin) and low (cervix, lung, and MCT). In addition to pan-SCC transcriptome analysis, cytokeratin profiling based on immunohistochemistry in the independent samples of 21 MCT-SCCs clarified that MCT-SCC dominantly expressed CK18, suggesting the origin of MCT-SCC was columnar epithelium. Subsequently, we investigated differentially expressed genes in MCT-SCCs compared with different SCCs and identified XCL1 was specifically overexpressed in MCT-SCCs. Through immunohistochemistry analysis, we identified XCL1 expression on tumor cells in 13/24 (54%) of MCT-SCCs but not in MCTs. XCL1 expression was also significantly associated with the number of tumor-infiltrating CD8-positive T cells and PD-L1 expression on tumor cells. XCL1 produced by tumor cells may induce PD1/PD-L1 interaction and dysfunction of CD8-positive T cells in tumor microenvironment. XCL1 expression may be a novel biomarker for malignant transformation of MCT into SCC and a biomarker candidate for therapeutic response to an anti-PD1/PD-L1 therapy.

    DOI: 10.1038/s41388-020-1237-0

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  • A National Survey of Umbilical Endometriosis in Japan. 査読 国際誌

    Tetsuya Hirata, Kaori Koga, Mari Kitade, Shinya Fukuda, Kazuaki Neriishi, Fuminori Taniguchi, Ritsuo Honda, Naoko Takazawa, Toshiaki Tanaka, Masatoshi Kurihara, Jun Nakajima, Shigeo Horie, Hidekatsu Nakai, Takayuki Enomoto, Masaki Mandai, Hisashi Narahara, Jo Kitawaki, Tasuku Harada, Hidetaka Katabuchi, Kotaro Yoshimura, Yutaka Osuga

    Journal of minimally invasive gynecology27 ( 1 ) 80 - 87   2020年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    STUDY OBJECTIVE: To identify the clinical presentation, diagnostic evaluation, operative or medical management, and postoperative recurrence of umbilical endometriosis. DESIGN: A retrospective national survey. SETTING: Obstetrics and Gynecology and Plastic Surgery Departments at a teaching hospital in Japan. PATIENTS: Patients with umbilical endometriosis or malignant transformation. INTERVENTIONS: A national survey was conducted to identify and evaluate cases of umbilical endometriosis or malignant transformation documented between 2006 and 2016. MEASUREMENTS AND MAIN RESULTS: The following were evaluated for each patient: age at diagnosis, body mass index, medical history, presence of extragenital endometriosis, surgical history, symptoms, imaging modalities, surgical therapy, hormonal therapy, follow-up period, postoperative recurrence, and time to recurrence. Ninety-six patients were identified with pathologically diagnosed benign umbilical endometriosis. The patients frequently had swelling (86.5%), pain (81.3%), or bleeding (44.8%) in the umbilicus. Sensitivity was 87.1% for physical examination, 76.5% for transabdominal ultrasonography, 75.6% for computed tomography, and 81.8% for magnetic resonance imaging. The cumulative recurrence rate was 1.34% at 6 months, 6.35% at 12 months, and 6.35% at 60 months after surgery. Importantly, there was no recurrence after wide resection including of the peritoneum (0 of 37 cases). The efficacy of dienogest (an oral progestin), gonadotropin-releasing hormone agonists, and oral contraceptives was 91.7%, 81.8%, and 57.1%, respectively. Finally, 2 cases of malignant transformation were identified. CONCLUSION: There was a low recurrence rate following surgery, and hormonal treatment is an option, although the current findings suggest surgical therapy as the first choice of treatment for umbilical endometriosis.

    DOI: 10.1016/j.jmig.2019.02.021

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  • Value and limitation of conization as a diagnostic procedure for cervical neoplasm. 査読

    Yamamoto R, Sekiyama K, Higuchi T, Ikeda M, Mikami M, Kobayashi Y, Nagase S, Yokoyama M, Enomoto T, Katabuchi H

    The journal of obstetrics and gynaecology research45 ( 12 ) 2419 - 2424   2019年12月

  • Germline and somatic mutations of homologous recombination-associated genes in Japanese ovarian cancer patients. 査読 国際誌

    Kentaro Sugino, Ryo Tamura, Hirofumi Nakaoka, Nozomi Yachida, Manako Yamaguchi, Yutaro Mori, Kaoru Yamawaki, Kazuaki Suda, Tatsuya Ishiguro, Sosuke Adachi, Masanori Isobe, Masayuki Yamaguchi, Katsunori Kashima, Teiichi Motoyama, Ituro Inoue, Kosuke Yoshihara, Takayuki Enomoto

    Scientific reports9 ( 1 ) 17808 - 17808   2019年11月

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    記述言語:英語  

    We explored the frequency of germline and somatic mutations in homologous recombination (HR)-associated genes in major histological types of ovarian cancer. We performed targeted sequencing to assess germline and somatic mutations of 16 HR-associated genes and 4 mismatch repair (MMR) genes among 207 ovarian cancer patients (50 high-grade serous carcinomas (HGSC), 99 clear cell carcinomas (CCC), 39 endometrioid carcinomas (EC), 13 mucinous carcinomas (MC), and 6 low-grade serous carcinomas (LGSC)). Germline or somatic mutations of HR-associated genes were detected in 44% of HGSC, 28% of CCC, 23% of EC, 16% of MC, and 17% of LGSC patients. The profile of HR-associated gene mutations was remarkably different among each histological type. Germline BRCA1/2 mutations were frequently detected in HGSC and were rarely observed in CCC, EC, and MC patients. ATM somatic mutation was more frequently detected in CCC (9%) and EC patients (18%) than in HGSC patients (4%). There was a positive correlation between MMR gene mutations and HR-associated gene mutations (p = 0.0072). Our findings might be useful in selection of ovarian cancer patients that should be treated with PARP inhibitors.

    DOI: 10.1038/s41598-019-54116-y

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  • Fertility-sparing trachelectomy for early-stage cervical cancer: A proposal of an ideal candidate. 査読

    Machida H, Iwata T, Okugawa K, Matsuo K, Saito T, Tanaka K, Morishige K, Kobayashi H, Yoshino K, Tokunaga H, Ikeda T, Shozu M, Yaegashi N, Enomoto T, Mikami M

    Gynecologic oncology   2019年11月

  • Neoadjuvant chemotherapy for epithelial ovarian cancer in Japan: a JSGO-JSOG joint study. 査読

    Machida H, Matsuo K, Enomoto T, Mikami M

    Journal of gynecologic oncology30 ( 6 ) e113   2019年11月

  • Intraoperative Capsule Rupture, Postoperative Chemotherapy, and Survival of Women With Stage I Epithelial Ovarian Cancer. 査読

    Matsuo K, Machida H, Yamagami W, Ebina Y, Kobayashi Y, Tabata T, Kaneuchi M, Nagase S, Enomoto T, Mikami M

    Obstetrics and gynecology134 ( 5 ) 1017 - 1026   2019年11月

  • The 61st Annual Meeting of the Japanese Society for Gynecologic Oncology (JSGO). 査読

    Yoshihara K, Sekine M, Nishino K, Enomoto T

    Journal of gynecologic oncology30 ( 6 ) e114   2019年11月

  • Changes in the Clinicopathological Demographics of Vulvar Cancer in Japan: Increasing Oldest-Old, Stage Shifting, and Decreasing Cohort-Level Survival <sup>†</sup>. 査読

    Nishio S, Matsuo K, Shibata T, Yamaguchi S, Kanao H, Takehara K, Kado N, Tozawa A, Tokunaga H, Matsunaga T, Kato H, Horie K, Kikuchi A, Enomoto T, Mikami M

    Journal of clinical medicine8 ( 12 )   2019年11月

  • ALDH-Dependent Glycolytic Activation Mediates Stemness and Paclitaxel Resistance in Patient-Derived Spheroid Models of Uterine Endometrial Cancer. 査読

    Mori Y, Yamawaki K, Ishiguro T, Yoshihara K, Ueda H, Sato A, Ohata H, Yoshida Y, Minamino T, Okamoto K, Enomoto T

    Stem cell reports13 ( 4 ) 730 - 746   2019年10月

  • Different mutation profiles between epithelium and stroma in endometriosis and normal endometrium. 査読

    Suda K, Nakaoka H, Yoshihara K, Ishiguro T, Adachi S, Kase H, Motoyama T, Inoue I, Enomoto T

    Human reproduction (Oxford, England)34 ( 10 ) 1899 - 1905   2019年10月

  • Biology of the vernix caseosa: A review. 査読

    Nishijima K, Yoneda M, Hirai T, Takakuwa K, Enomoto T

    The journal of obstetrics and gynaecology research   2019年9月

  • HPVワクチンの積極的勧奨一時中止継続によって増加する将来の子宮頸がんの罹患・死亡数予測(Estimated increases of cervical cancer incidence and mortality due to suspension of recommendation of HPV vaccine) 査読

    八木 麻未, 上田 豊, 中川 慧, 宮城 悦子, 榎本 隆之, 中山 富雄, 木村 正

    日本癌学会総会記事78回   P - 2210   2019年9月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • Recurrence, death, and secondary malignancy after ovarian conservation for young women with early-stage low-grade endometrial cancer. 査読

    Matsuo K, Cripe JC, Kurnit KC, Kaneda M, Garneau AS, Glaser GE, Nizam A, Schillinger RM, Kuznicki ML, Yabuno A, Yanai S, Garofalo DM, Suzuki J, St Laurent JD, Yen TT, Liu AY, Shida M, Kakuda M, Oishi T, Nishio S, Marcus JZ, Adachi S, Kurokawa T, Ross MS, Horowitz MP, Johnson MS, Kim MK, Melamed A, Machado KK, Yoshihara K, Yoshida Y, Enomoto T, Ushijima K, Satoh S, Ueda Y, Mikami M, Rimel BJ, Stone RL, Growdon WB, Okamoto A, Guntupalli SR, Hasegawa K, Shahzad MMK, Im DD, Frimer M, Gostout BS, Ueland FR, Nagao S, Soliman PT, Thaker PH, Wright JD, Roman LD

    Gynecologic oncology   2019年8月

  • Identifying the factor structure of the Mother-to-Infant Bonding Scale for post-partum women and examining its consistency during pregnancy. 査読

    Motegi T, Fukui N, Hashijiri K, Tsuboya R, Sugai T, Egawa J, Mitome S, Araki R, Haino K, Yamaguchi M, Takakuwa K, Enomoto T, Someya T

    Psychiatry and clinical neurosciences   2019年8月

  • Cervical cancer screening rate differs by HPV vaccination status: An interim analysis. 査読 国際誌

    Mariko Taniguchi, Yutaka Ueda, Asami Yagi, Sayaka Ikeda, Masayuki Endo, Takuji Tomimatsu, Tomio Nakayama, Masayuki Sekine, Takayuki Enomoto, Tadashi Kimura

    Vaccine37 ( 32 ) 4424 - 4426   2019年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The incidence of cervical cancer has been increasing, especially in younger generation, in Japan. The females born between 1994 and 1999, who achieved rates of HPV vaccination approaching 70%, have become the target of cervical cancer screening programs. Here, we have analyzed the cervical cancer screening rates among the vaccinated and unvaccinated women. METHODS: The survey data for cervical cancer screening at age 20 in FY 2015 was derived from two cities, Toyonaka and Iwaki. RESULTS: Among 2,727 females, in Toyonaka and Iwaki, who were born in FY 1995 and targeted in FY 2015 at age 20 for cervical cancer screening, their HPV vaccination rate was 64.2% (1,753/2,727). The screening rate was 6.4% (112/1,753) in the vaccinated and 3.9% (38/974) in the unvaccinated. This difference was statistically significant (p < 0.01). CONCLUSIONS: We have demonstrated that HPV-vaccinated females tended to be effectively protected from future cervical cancer than the unvaccinated.

    DOI: 10.1016/j.vaccine.2019.06.064

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  • The analysis of chromosomal abnormalities in patients with recurrent pregnancy loss, focusing on the prognosis of patients with inversion of chromosome (9). 査読

    Nonaka T, Takahashi M, Nonaka C, Enomoto T, Takakuwa K

    Reproductive medicine and biology18 ( 3 ) 296 - 301   2019年7月

  • The first Japanese nationwide multicenter study of <i>BRCA</i> mutation testing in ovarian cancer: CHARacterizing the cross-sectionaL approach to Ovarian cancer geneTic TEsting of <i>BRCA</i> (CHARLOTTE). 査読

    Enomoto T, Aoki D, Hattori K, Jinushi M, Kigawa J, Takeshima N, Tsuda H, Watanabe Y, Yoshihara K, Sugiyama T

    International journal of gynecological cancer : official journal of the International Gynecological Cancer Society29 ( 6 ) 1043 - 1049   2019年7月

  • 術前HPV診断と子宮頸部円錐切除術後診断、予後に関する検討 JSOG腫瘍委員会報告

    菊池 朗, 高橋 宏太朗, 吉田 邦彦, 横尾 朋和, 池田 仁惠, 三上 幹男, 榎本 隆之, 小林 陽一, 永瀬 智, 横山 正俊, 片渕 秀隆

    日本婦人科腫瘍学会雑誌37 ( 3 ) 436 - 436   2019年6月

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    記述言語:日本語   出版者・発行元:(公社)日本婦人科腫瘍学会  

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  • 子宮頸部円錐切除術後の追加治療例に関する検討(JSOG婦人科腫瘍委員会)

    長嶋 武雄, 寺内 文敏, 佐川 泰一, 西 洋孝, 池田 仁惠, 三上 幹男, 榎本 隆之, 小林 陽一, 永瀬 智, 横山 正俊, 片渕 秀隆

    日本婦人科腫瘍学会雑誌37 ( 3 ) 444 - 444   2019年6月

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    記述言語:日本語   出版者・発行元:(公社)日本婦人科腫瘍学会  

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  • HPVワクチンの積極的勧奨一時中止継続はどれほどの子宮頸がんの罹患者・死亡者を生むか 査読

    八木 麻未, 上田 豊, 中川 慧, 池田 さやか, 関根 正幸, 榎本 隆之, 木村 正

    日本婦人科腫瘍学会雑誌37 ( 3 ) 472 - 472   2019年6月

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    記述言語:日本語   出版者・発行元:(公社)日本婦人科腫瘍学会  

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  • HPVワクチンの接種者と非接種者で子宮頸がん検診受診率に差はあるのか 査読

    谷口 茉利子, 上田 豊, 八木 麻未, 池田 さやか, 遠藤 誠之, 冨松 拓治, 中山 富雄, 関根 正幸, 榎本 隆之, 木村 正

    日本婦人科腫瘍学会雑誌37 ( 3 ) 472 - 472   2019年6月

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    記述言語:日本語   出版者・発行元:(公社)日本婦人科腫瘍学会  

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  • わが国における子宮頸部円錐切除術の実態 日本産科婦人科学会腫瘍委員会「子宮頸部円錐切除術の実態調査に関する小委員会」報告

    池田 仁惠, 三上 幹男, 榎本 隆之, 小林 陽一, 永瀬 智, 横山 正俊, 片渕 秀隆

    日本婦人科腫瘍学会雑誌37 ( 3 ) 407 - 407   2019年6月

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    記述言語:日本語   出版者・発行元:(公社)日本婦人科腫瘍学会  

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  • 稀少部位子宮内膜症の癌化に関する全国調査

    万代 昌紀, 大須賀 穣, 平田 哲也, 谷口 文紀, 榎本 隆之, 中井 英勝, 本田 律生, 片渕 秀隆

    日本婦人科腫瘍学会雑誌37 ( 3 ) 412 - 412   2019年6月

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    記述言語:日本語   出版者・発行元:(公社)日本婦人科腫瘍学会  

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  • The prognosis of patients with recurrent or persistent ovarian clear cell carcinoma: Results from a randomized phase III study (JGOG3017/GCIG). 査読

    Kondo Eiji, Tabata Tsutomu, Suzuki Nao, Aoki Daisuke, Tokuyama Osamu, Kato Kiyoko, Hamano Tetsutaro, Kotera Yoshio, Fujiwara Keiichi, Kimura Eizo, Terauchi Fumitoshi, Sumi Toshiyuki, Okamoto Aikou, Yaegashi Nobuo, Enomoto Takayuki, Sugiyama Toru

    JOURNAL OF CLINICAL ONCOLOGY37 ( 15 )   2019年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Evaluation of future cervical cancer risk in Japan, based on birth year. 査読 国際誌

    Asami Yagi, Yutaka Ueda, Sayaka Ikeda, Masayuki Sekine, Tomio Nakayama, Etsuko Miyagi, Takayuki Enomoto

    Vaccine37 ( 22 ) 2889 - 2891   2019年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    In 2013, following the Ministry of Health, Labor and Welfare (MHLW)'s announced suspension of its vaccine recommendation due to media reports of "adverse events", HPV vaccination dropped to almost 0%. Here, we analyzed, by birth year, the cumulative vaccinations for girls up to age 16 (maximum age for public subsidies) and the results of cervical cancer screening in Matsuyama City. The incidence of CIN3 or worse was 0.09% (7/7872) for these unvaccinated generation born between 1991 and 1993, and 0.00% (0/7389) for the vaccination generation born between 1994 and 1996. This study is the first to show the significant reduction in incidence of CIN3+depending on birth year in Japan. We must keep in mind that the unacceptable high risk for cervical cancer has already begun for an entire new generation of unvaccinated girls born in or after 2000. This data encourages a resumption of MHLW's recommendation for HPV vaccination.

    DOI: 10.1016/j.vaccine.2019.04.044

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  • Current knowledge of and attitudes toward human papillomavirus-related disease prevention among Japanese: A large-scale questionnaire study. 査読 国際誌

    Yukio Suzuki, Akiko Sukegawa, Aya Nishikawa, Kazumi Kubota, Yoko Motoki, Mikiko Asai-Sato, Yutaka Ueda, Masayuki Sekine, Takayuki Enomoto, Fumiki Hirahara, Takeharu Yamanaka, Etsuko Miyagi

    The journal of obstetrics and gynaecology research45 ( 5 ) 994 - 1005   2019年5月

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    記述言語:英語  

    AIM: The human papillomavirus (HPV) vaccination rate in Japan fell to nearly 0% following widespread coverage of possible adverse events. Developing a next approach to promote the effective prevention of HPV-related diseases including cervical cancer (CC) in Japan requires comprehensive understanding of knowledge and attitudes regarding CC prevention, HPV infection and HPV vaccination among the population including laypersons and medical professions in Japan. METHODS: A questionnaire survey was administered in a wide variety of settings in Japan. The questionnaire contained items on knowledge about CC, HPV infection and HPV vaccination; awareness of the HPV vaccine's effectiveness and associated adverse events; and attitudes toward the HPV vaccination for their daughters and for men/boys. RESULTS: Of 3033 targeted people, complete survey responses were received from 1182 men and 1602 women (total: 2784). The male laypersons' group had significantly lower knowledge than did the female laypersons' group (adjusted odds ratio, aOR = 3.86, P < 0.001). Compared with the male laypersons' group, the female laypersons' group tended to have less positive attitudes toward HPV vaccination for their daughters (aOR = 0.78, P = 0.006), but the female laypersons' group showed more positive attitudes toward vaccinating men/boys (aOR = 1.93, P < 0.001). CONCLUSION: The survey results indicated that men in Japan generally lacked knowledge and awareness of HPV-related diseases and their prevention. However, women had more negative attitudes toward HPV vaccination for their daughters than did men. Increasing male involvement in HPV prevention and changing women's perceptions of the HPV vaccine are essential steps to increase the HPV vaccination rate.

    DOI: 10.1111/jog.13929

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  • Clinical background and outcomes of risk-reducing salpingo-oophorectomy for hereditary breast and ovarian cancers in Japan. 査読

    Nomura H, Sekine M, Yokoyama S, Arai M, Enomoto T, Takeshima N, Nakamura S

    International journal of clinical oncology24 ( 9 ) 1105 - 1110   2019年5月

  • HPV vaccination in Japan: what is happening in Japan? 査読 国際誌

    Sayaka Ikeda, Yutaka Ueda, Asami Yagi, Shinya Matsuzaki, Eiji Kobayashi, Tadashi Kimura, Etsuko Miyagi, Masayuki Sekine, Takayuki Enomoto, Kazuya Kudoh

    Expert review of vaccines18 ( 4 ) 323 - 325   2019年4月

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  • Asian Society of Gynecologic Oncology International Workshop 2018. 査読

    Kong TW, Ryu HS, Kim SC, Enomoto T, Li J, Kim KH, Shim SH, Wang PH, Therasakvichya S, Kobayashi Y, Lee M, Shi T, Lee SW, Mikami M, Nagase S, Lim MC, Wang J, Wilailak S, Kim SW, Hong SH, Tan DS, Mandai M, Chang SJ, Huang RYJ, Ushijima K, Lee JY, Chen X, Ochiai K, Lee TS, Yang B, Kalam F, Lv Q, Ahmad MF, Yaznil MR, Modi KB, Manopunya M, Jeong DH, Lertkhachonsuk AA, Chung HH, Watari H, Jeon S

    Journal of gynecologic oncology30 ( 2 ) e39   2019年3月

  • Treatment for patients with recurrent fetal losses positive for anti-cardiolipin beta2 glycoprotein I antibody using Sairei-to (Chai-ling-tang) and low-dose aspirin. 査読

    Nonaka T, Takahashi M, Nonaka C, Haino K, Yamaguchi M, Enomoto T, Takakuwa K

    The journal of obstetrics and gynaecology research45 ( 3 ) 549 - 555   2019年3月

  • Trends and characteristics of epithelial ovarian cancer in Japan between 2002 and 2015: A JSGO-JSOG joint study. 査読

    Machida H, Matsuo K, Yamagami W, Ebina Y, Kobayashi Y, Tabata T, Kanauchi M, Nagase S, Enomoto T, Mikami M

    Gynecologic oncology153 ( 3 ) 589 - 596   2019年3月

  • Ectopic pregnancy following oral levonorgestrel emergency contraception use. 査読 国際誌

    Yohei Kitani, Tatsuya Ishiguro, Akiko Kobayashi, Ryo Tamura, Haruka Ueda, Sosuke Adachi, Nobumichi Nishikawa, Masayuki Sekine, Takayuki Enomoto

    The journal of obstetrics and gynaecology research45 ( 2 ) 473 - 476   2019年2月

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    記述言語:英語  

    Levonorgestrel is used worldwide as an emergency oral contraceptive. There have been occasional reports of ectopic pregnancy after oral levonorgestrel use. We present a case of ectopic tubal pregnancy after the use of oral levonorgestrel as an emergency contraceptive in a 37-year-old woman with a history of treatment for Chlamydia trachomatis infection. She conceived after sexual intercourse on menstrual day 14 of the first menstrual cycle following a normal delivery. After salpingectomy for this right tubal pregnancy, her following pregnancy was an ectopic pregnancy in the contralateral tube, which was treated with laparoscopic salpingectomy. Histopathological examination revealed endometriosis. We should be aware of ectopic pregnancy even after emergency contraceptive use, especially in patients with risk factors, such as Chlamydia infection and endometriosis. Because the efficacy of levonorgestrel decreases after ovulation, we should check the stage of the cycle before prescription.

    DOI: 10.1111/jog.13815

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  • 本邦における生まれ年度ごとのCIN3罹患リスク評価とHPVワクチンの有効性 査読

    八木 麻未, 上田 豊, 榎本 隆之, 宮城 悦子, 中山 富雄, 池田 さやか

    日本産科婦人科学会雑誌71 ( 臨増 ) S - 294   2019年2月

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    記述言語:日本語   出版者・発行元:(公社)日本産科婦人科学会  

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  • Concurrent isolated retroperitoneal HGSC and STIC defined by somatic mutation analysis: a case report. 査読

    Suda K, Nakaoka H, Hata C, Yahata N, Isobe M, Kameyama H, Wakai T, Motoyama T, Inoue I, Yoshihara K, Enomoto T

    Diagnostic pathology14 ( 1 ) 17   2019年2月

  • Bivalent Human Papillomavirus Vaccine Effectiveness in a Japanese Population: High Vaccine-Type-Specific Effectiveness and Evidence of Cross-Protection. 査読 国際誌

    Risa Kudo, Manako Yamaguchi, Masayuki Sekine, Sosuke Adachi, Yutaka Ueda, Etsuko Miyagi, Megumi Hara, Sharon J B Hanley, Takayuki Enomoto

    The Journal of infectious diseases219 ( 3 ) 382 - 390   2019年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: Proactive recommendations for human papillomavirus (HPV) vaccines in Japan have been suspended for 5 years because of safety concerns. While no scientific evidence exists to substantiate these concerns, one reason given for not reinstating recommendations is the lack of reliable vaccine effectiveness (VE) data in a Japanese population. This study reports the VE of the bivalent HPV vaccine in Japanese women aged 20-22 years. Methods: During cervical screening between 2014 and 2016, women had Papanicolaou smears and HPV tests performed and provided data about their sexual history. Estimates of VE for vaccine-targeted HPV type 16 (HPV16) and 18 and cross-protection against other types were calculated. Results: Overall, 2197 women were tested, and 1814 were included in the analysis. Of these, 1355 (74.6%) were vaccinated, and 1295 (95.5%) completed the 3-dose schedule. In women sexually naive at vaccination, the pooled VEs against HPV16 and 18 and for HPV31, 45, and 52 were 95.5% (P < .01) and 71.9% (P < .01), respectively. When adjusted for number of sex partners and birth year, pooled VEs were 93.9% (P = .01) and 67.7% (P = .01) for HPV16 and 18 and HPV31, 45, and 52, respectively. Conclusions: The bivalent HPV vaccine is highly effective against HPV16 and 18. Furthermore, significant cross-protection against HPV31, 45, and 52 was demonstrated and sustained up to 6 years after vaccination. These findings should reassure politicians about the VE of bivalent HPV vaccine in a Japanese population.

    DOI: 10.1093/infdis/jiy516

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  • Association of statins, aspirin, and venous thromboembolism in women with endometrial cancer. 査読

    Matsuo K, Hom MS, Yabuno A, Shida M, Kakuda M, Adachi S, Mandelbaum RS, Ueda Y, Hasegawa K, Enomoto T, Mikami M, Roman LD

    Gynecologic oncology152 ( 3 ) 605 - 611   2019年1月

  • Japan Society of Gynecologic Oncology guidelines 2017 for the treatment of uterine cervical cancer. 査読

    Yasuhiko Ebina, Mikio Mikami, Satoru Nagase, Tsutomu Tabata, Masanori Kaneuchi, Hironori Tashiro, Masaki Mandai, Takayuki Enomoto, Yoichi Kobayashi, Hidetaka Katabuchi, Nobuo Yaegashi, Yasuhiro Udagawa, Daisuke Aoki

    International journal of clinical oncology24 ( 1 ) 1 - 19   2019年1月

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    記述言語:英語  

    The Japan Society of Gynecologic Oncology (JSGO) Guidelines 2017 for the Treatment of Uterine Cervical Cancer are for the purpose of providing standard treatment strategies for cervical cancer, indicating treatment methods currently considered appropriate for cervical cancer, minimizing variances in treatment methods among institutions, improving the safety of treatment and prognosis of diseases, reducing the economic and psychosomatic burden of patients by promoting performance of appropriate treatment, and enhancing mutual understanding between patients and healthcare professionals. The guidelines were prepared through consensus of the JSGO Guideline Committee, based on careful review of evidence gathered through the literature searches and in view of the medical health insurance system and actual clinical practice situations in Japan. The guidelines comprise eight chapters and five algorithms. The main features of the 2017 revision are as follows: (1) evidence was collected using a search formula and with cooperation of the Japan Library Association. The bibliographical search formula was placed at the end of the book; (2) regarding clinical questions (CQs) where evidence or clinical inspection in Japan was lacking, opinions of the Guidelines Committee were described as "proposals for future directions"; (3) cervical intraepithelial neoplasia (CIN) 3 and adenocarcinoma in situ (AIS) were treated as a cervical precancerous lesion; (4) the CQs of endoscopic surgery, radical trachelectomy, and sentinel node biopsy were newly added in Chapter 3, "primary treatment for stage IB-II cervical cancer"; and (5) the CQ about hormone replacement therapy after cancer treatment was newly established. Each recommendation is accompanied by a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here, we present the English version of the JSGO Guidelines 2017 for the Treatment of Uterine Cervical Cancer.

    DOI: 10.1007/s10147-018-1351-y

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  • Bcl11b controls odorant receptor class choice in mice. 査読

    Enomoto T, Nishida H, Iwata T, Fujita A, Nakayama K, Kashiwagi T, Hatanaka Y, Kondo H, Kajitani R, Itoh T, Ohmoto M, Matsumoto I, Hirota J

    Communications biology2   296   2019年

  • Erratum: Author Correction: Bcl11b controls odorant receptor class choice in mice. 査読

    Enomoto T, Nishida H, Iwata T, Fujita A, Nakayama K, Kashiwagi T, Hatanaka Y, Kondo H, Kajitani R, Itoh T, Ohmoto M, Matsumoto I, Hirota J

    Communications biology2   343   2019年

  • A Single Pheromone Receptor Gene Conserved across 400 My of Vertebrate Evolution. 査読 国際誌

    Hikoyu Suzuki, Hidefumi Nishida, Hiro Kondo, Ryota Yoda, Tetsuo Iwata, Kanako Nakayama, Takayuki Enomoto, Jiaqi Wu, Keiko Moriya-Ito, Masao Miyazaki, Yoshihiro Wakabayashi, Takushi Kishida, Masataka Okabe, Yutaka Suzuki, Takehiko Ito, Junji Hirota, Masato Nikaido

    Molecular biology and evolution35 ( 12 ) 2928 - 2939   2018年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Pheromones are crucial for eliciting social and sexual behaviors in diverse animal species. The vomeronasal receptor type-1 (V1R) genes, encoding members of a pheromone receptor family, are highly variable in number and repertoire among mammals due to extensive gene gain and loss. Here, we report a novel pheromone receptor gene belonging to the V1R family, named ancient V1R (ancV1R), which is shared among most Osteichthyes (bony vertebrates) from the basal lineage of ray-finned fishes to mammals. Phylogenetic and syntenic analyses of ancV1R using 115 vertebrate genomes revealed that it represents an orthologous gene conserved for >400 My of vertebrate evolution. Interestingly, the loss of ancV1R in some tetrapods is coincident with the degeneration of the vomeronasal organ in higher primates, cetaceans, and some reptiles including birds and crocodilians. In addition, ancV1R is expressed in most mature vomeronasal sensory neurons in contrast with canonical V1Rs, which are sparsely expressed in a manner that is consistent with the "one neuron-one receptor" rule. Our results imply that a previously undescribed V1R gene inherited from an ancient Silurian ancestor may have played an important functional role in the evolution of vertebrate vomeronasal organ.

    DOI: 10.1093/molbev/msy186

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  • Beyond resumption of the Japanese Government's recommendation of the HPV vaccine. 査読 国際誌

    Yutaka Ueda, Asami Yagi, Sayaka Ikeda, Takayuki Enomoto, Tadashi Kimura

    The Lancet. Oncology19 ( 12 ) 1563 - 1564   2018年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/S1470-2045(18)30573-4

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  • Differential misclassification between self-reported status and official HPV vaccination records in Japan: Implications for evaluating vaccine safety and effectiveness. 査読 国際誌

    Manako Yamaguchi, Masayuki Sekine, Risa Kudo, Sosuke Adachi, Yutaka Ueda, Etsuko Miyagi, Megumi Hara, Sharon J B Hanley, Takayuki Enomoto

    Papillomavirus research (Amsterdam, Netherlands)6   6 - 10   2018年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Japan has no national vaccine registry and approximately 1700 municipalities manage the immunization records independently. In June 2013, proactive recommendations for the human papillomavirus (HPV) vaccine were suspended after unconfirmed reports of adverse events following immunization in the media, despite no vaccine safety signal having been raised. Furthermore, studies assessing HPV vaccine safety and effectiveness published post suspension are predominantly based on self-reported information. Our aim was to examine the accuracy of self-reported vaccination status compared with official municipal records. Participants were women aged 20-22 yrs, who were attending for cervical screening in Niigata city. Among the 1230 eligible registrants, vaccine uptake, defined as any dose, was 75.0% and 77.2% according to a self-reported questionnaire and municipal records, respectively. The accuracy rate of self-reported information was as follows: positive predictive value (PPV) was 87.7%; negative predictive value (NPV) was 54.5%; sensitivity was 85.2%; and specificity was 59.8%. The validity of self-reported information was only moderate (Kappa statistic = 0.44, 95% confidence interval 0.37-0.50). This combined with the low NPV may lead to reduced estimation of effectiveness and safety. A more reliable method, such as a national HPV vaccine registry, needs to be established for assessing HPV immunization status in Japan.

    DOI: 10.1016/j.pvr.2018.05.002

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  • Annual report of the committee on gynecologic oncology, the Japan Society of Obstetrics and Gynecology: Annual patients report for 2015 and annual treatment report for 2010. 査読

    Nagase S, Ohta T, Takahashi F, Enomoto T, Committee on, Gynecologic Oncology of, the Japan, Society of Obstetrics, Gynecology

    The journal of obstetrics and gynaecology research45 ( 2 ) 289 - 298   2018年11月

  • Proposal for a Risk-Based Categorization of Uterine Carcinosarcoma. 査読 国際誌

    Koji Matsuo, Yutaka Takazawa, Malcolm S Ross, Esther Elishaev, Mayu Yunokawa, Todd B Sheridan, Stephen H Bush, Merieme M Klobocista, Erin A Blake, Tadao Takano, Tsukasa Baba, Shinya Satoh, Masako Shida, Yuji Ikeda, Sosuke Adachi, Takuhei Yokoyama, Munetaka Takekuma, Shiori Yanai, Satoshi Takeuchi, Masato Nishimura, Keita Iwasaki, Marian S Johnson, Masayuki Yoshida, Ardeshir Hakam, Hiroko Machida, Paulette Mhawech-Fauceglia, Yutaka Ueda, Kiyoshi Yoshino, Hiroshi Kajiwara, Kosei Hasegawa, Masanori Yasuda, Takahito M Miyake, Takuya Moriya, Yoshiaki Yuba, Terry Morgan, Tomoyuki Fukagawa, Tanja Pejovic, Tadayoshi Nagano, Takeshi Sasaki, Abby M Richmond, Miriam D Post, Mian M K Shahzad, Dwight D Im, Hiroshi Yoshida, Takayuki Enomoto, Kohei Omatsu, Frederick R Ueland, Joseph L Kelley, Rouzan G Karabakhtsian, Lynda D Roman

    Annals of surgical oncology25 ( 12 ) 3676 - 3684   2018年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PURPOSE: To propose a categorization model of uterine carcinosarcoma (UCS) based on tumor cell types (carcinoma and sarcoma) and sarcoma dominance. METHODS: This secondary analysis of a prior multicenter retrospective study examined 889 cases of UCS with available histologic evaluation. Based on survival outcome, cases were clustered into three groups: low-grade carcinoma with nondominant homologous sarcoma [type A, n = 96 (10.8%)], (1) low-grade carcinoma with heterologous sarcoma or any sarcoma dominance and (2) high-grade carcinoma with nondominant homologous sarcoma [type B, n = 412 (46.3%)], and high-grade carcinoma with heterologous sarcoma or any sarcoma dominance [type C, n = 381 (42.9%)]. Tumor characteristics and outcome were examined based on the categorization. RESULTS: Women in type C category were more likely to be older, obese, and Caucasian, whereas those in type A category were younger, less obese, Asian, and nulligravid (all P < 0.01). Type C tumors were more likely to have metastatic implants, large tumor size, lymphovascular space invasion with sarcoma cells, and higher lymph node ratio, whereas type A tumors were more likely to be early-stage disease and small (all P < 0.05). On multivariate analysis, tumor categorization was independently associated with progression-free survival (5-year rates: 70.1% for type A, 48.3% for type B, and 35.9% for type C, adjusted P < 0.01) and cause-specific survival (5-year rates: 82.8% for type A, 63.0% for type B, and 47.1% for type C, adjusted P < 0.01). CONCLUSION: Characteristic differences in clinicopathological factors and outcomes in UCS imply that different underlying etiologies and biological behaviors may be present, supporting a new classification system.

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  • Novel MXD4-NUTM1 fusion transcript identified in primary ovarian undifferentiated small round cell sarcoma. 査読 国際誌

    Ryo Tamura, Hirofumi Nakaoka, Kosuke Yoshihara, Yutaro Mori, Nozomi Yachida, Nobumichi Nishikawa, Teiichi Motoyama, Shujiro Okuda, Ituro Inoue, Takayuki Enomoto

    Genes, chromosomes & cancer57 ( 11 ) 557 - 563   2018年11月

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    記述言語:英語  

    Primary ovarian sarcomas are extremely rare tumors, and their genomic and transcriptomic alterations remain to be elucidated. We performed whole exome sequencing of primary tumor and matched normal blood samples derived from one patient with ovarian undifferentiated small round cell sarcoma. We identified 8 nonsynonymous somatic mutations, and all mutations were missense or nonsense changes. Next, we performed RNA sequencing of the tumor sample and identified two in-frame fusion transcripts: MXD4-NUTM1 and ARL6-POT1. Most NUTM1 exons were retained in the MXD4-NUTM1 fusion transcript, and we confirmed an increase in NUTM1 mRNA and protein expression in tumor tissue. Further genomic and transcriptomic analyses might lead to the development of new therapeutic strategies based on the molecular characteristics of ovarian undifferentiated small round cell sarcoma.

    DOI: 10.1002/gcc.22668

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  • Trachelectomy for stage IB1 cervical cancer with tumor size &gt;2 cm: trends and characteristics in the United States. 査読

    Matsuo K, Machida H, Mandelbaum RS, Mikami M, Enomoto T, Roman LD, Wright JD

    Journal of gynecologic oncology29 ( 6 ) e85   2018年11月

  • A Japanese survey of malignant disease in pregnancy. 査読

    Kobayashi Y, Tabata T, Omori M, Kondo E, Hirata T, Yoshida K, Sekine M, Itakura A, Enomoto T, Ikeda T

    International journal of clinical oncology24 ( 3 ) 328 - 333   2018年10月

  • OCEAN STUDY中間解析および追加解析 査読

    八木 麻未, 上田 豊, 大道 正英, 角 俊幸, 木村 正, 岡田 英孝, 松村 謙臣, 志村 研太郎, 宮城 悦子, 榎本 隆之

    日本性感染症学会誌29 ( 2 ) 256 - 256   2018年10月

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    記述言語:日本語   出版者・発行元:(一社)日本性感染症学会  

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  • Myomectomy scar ectopic pregnancy following a cryopreserved embryo transfer. 査読

    Ishiguro T, Yamawaki K, Chihara M, Nishikawa N, Enomoto T

    Reproductive medicine and biology17 ( 4 ) 509 - 513   2018年10月

  • Author Correction: Dynamic changes in Japan's prevalence of abnormal findings in cervical cytology depending on birth year. 査読 国際誌

    Yutaka Ueda, Asami Yagi, Tomio Nakayama, Kei Hirai, Sayaka Ikeda, Masayuki Sekine, Etsuko Miyagi, Takayuki Enomoto

    Scientific reports8 ( 1 ) 13384 - 13384   2018年9月

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    記述言語:英語  

    A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

    DOI: 10.1038/s41598-018-31652-7

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  • 日本における生まれ年度別の子宮頸癌検診における異常所見の頻度の変化(Dynamic change in frequency of abnormal findings in cervical cytology depending on birth year in Japan) 査読

    八木 麻未, 上田 豊, 榎本 隆之, 宮城 悦子, 中山 富雄

    日本癌学会総会記事77回   2060 - 2060   2018年9月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • Significance of Lymphovascular Space Invasion by the Sarcomatous Component in Uterine Carcinosarcoma. 査読 国際誌

    Koji Matsuo, Yutaka Takazawa, Malcolm S Ross, Esther Elishaev, Mayu Yunokawa, Todd B Sheridan, Stephen H Bush, Merieme M Klobocista, Erin A Blake, Tadao Takano, Tsukasa Baba, Shinya Satoh, Masako Shida, Yuji Ikeda, Sosuke Adachi, Takuhei Yokoyama, Munetaka Takekuma, Shiori Yanai, Satoshi Takeuchi, Masato Nishimura, Keita Iwasaki, Marian S Johnson, Masayuki Yoshida, Ardeshir Hakam, Hiroko Machida, Paulette Mhawech-Fauceglia, Yutaka Ueda, Kiyoshi Yoshino, Hiroshi Kajiwara, Kosei Hasegawa, Masanori Yasuda, Takahito M Miyake, Takuya Moriya, Yoshiaki Yuba, Terry Morgan, Tomoyuki Fukagawa, Tanja Pejovic, Tadayoshi Nagano, Takeshi Sasaki, Abby M Richmond, Miriam D Post, Mian M K Shahzad, Dwight D Im, Hiroshi Yoshida, Takayuki Enomoto, Kohei Omatsu, Frederick R Ueland, Joseph L Kelley, Rouzan G Karabakhtsian, Lynda D Roman

    Annals of surgical oncology25 ( 9 ) 2756 - 2766   2018年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: The aim of this study was to examine the significance of lymphovascular space invasion (LVSI) with a sarcomatous component on the tumor characteristics and clinical outcomes of women with uterine carcinosarcoma (UCS). METHODS: This was a secondary analysis of a prior multicenter retrospective study that examined women with stage I-IV UCS who underwent primary hysterectomy. Archived histopathology slides were reviewed and LVSI was scored as follows: LVSI with a carcinomatous component alone (LVSI-carcinoma; n = 375, 76.8%) or LVSI containing a sarcomatous component with or without a carcinomatous component (LVSI-sarcoma; n = 113, 23.2%). Qualitative metrics of LVSI were correlated to clinicopathological factors and survival outcome. RESULTS: Tumors in the LVSI-sarcoma group were more likely to have sarcoma dominance (82.1 vs. 26.4%) heterologous sarcomatous component (51.3 vs. 37.9%), low-grade carcinoma (42.5 vs. 22.4%), and large tumor size (81.0 vs. 70.2%) in the primary tumor site compared with tumors in the LVSI-carcinoma group (all p < 0.05). On multivariate analysis, LVSI-sarcoma was independently associated with decreased progression-free survival (5-year rates: 34.9 vs. 40.8%, adjusted hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.36-2.50, p < 0.001), and cause-specific survival (5-year rates: 41.8 vs. 55.9%, adjusted HR 1.95, 95% CI 1.39-2.75, p < 0.001) compared with LVSI-carcinoma. Postoperative radiotherapy for women with LVSI-sarcoma had a higher reduction rate of recurrence/progression of disease (54% reduction, p = 0.04) compared with postoperative radiotherapy for women with LVSI-carcinoma (26% reduction, p = 0.08). CONCLUSION: In UCS, the presence of a sarcomatous component in LVSI is particularly prevalent when a tumor has sarcoma dominance. Our study suggests that LVSI containing a sarcomatous component may be a predictor of decreased survival for women with UCS.

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  • Clonal Expansion and Diversification of Cancer-Associated Mutations in Endometriosis and Normal Endometrium. 査読 国際誌

    Kazuaki Suda, Hirofumi Nakaoka, Kosuke Yoshihara, Tatsuya Ishiguro, Ryo Tamura, Yutaro Mori, Kaoru Yamawaki, Sosuke Adachi, Tomoko Takahashi, Hiroaki Kase, Kenichi Tanaka, Tadashi Yamamoto, Teiichi Motoyama, Ituro Inoue, Takayuki Enomoto

    Cell reports24 ( 7 ) 1777 - 1789   2018年8月

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    記述言語:英語  

    Endometriosis is characterized by ectopic endometrial-like epithelium and stroma, of which molecular characteristics remain to be fully elucidated. We sequenced 107 ovarian endometriotic and 82 normal uterine endometrial epithelium samples isolated by laser microdissection. In both endometriotic and normal epithelium samples, numerous somatic mutations were identified within genes frequently mutated in endometriosis-associated ovarian cancers. KRAS is frequently mutated in endometriotic epithelium, with a higher mutant allele frequency (MAF) accompanied by arm-level allelic imbalances. Analyses of MAF, combined with multiregional sequencing, illuminated spatiotemporal evolution of the endometriosis and uterine endometrium genomes. We sequenced 109 single endometrial glands and found that each gland carried distinct cancer-associated mutations, demonstrating the heterogeneity of the genomic architecture of endometrial epithelium. Remarkable increases in MAF of mutations in cancer-associated genes in endometriotic epithelium suggest retrograde flow of endometrial cells already harboring cancer-associated mutations, with selective advantages at ectopic sites, leading to the development of endometriosis.

    DOI: 10.1016/j.celrep.2018.07.037

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  • Characteristics and outcomes of reproductive-aged women with early-stage cervical cancer: trachelectomy versus hysterectomy. 査読

    Machida H, Mandelbaum RS, Mikami M, Enomoto T, Sonoda Y, Grubbs BH, Paulson RJ, Roman LD, Wright JD, Matsuo K

    American journal of obstetrics and gynecology219 ( 5 ) 461.e1 - 461.e18   2018年8月

  • The use of conization to identify and treat severe lesions among prediagnosed CIN1 and 2 patients in Japan. 査読

    Mikami M, Ikeda M, Sato H, Iwase H, Enomoto T, Kobayashi Y, Katabuchi H

    Journal of gynecologic oncology29 ( 4 ) e46   2018年7月

  • Postoperative chemotherapy for node-positive cervical cancer: Results of a multicenter phase II trial (JGOG1067) 査読

    Maki Matoda, Nobuhiro Takeshima, Hirofumi Michimae, Takashi Iwata, Harushige Yokota, Yutaka Torii, Yorito Yamamoto, Kazuhiro Takehara, Shin Nishio, Hirokuni Takano, Mika Mizuno, Yoshiyuki Takahashi, Yuji Takei, Tetsuya Hasegawa, Mikio Mikami, Takayuki Enomoto, Daisuke Aoki, Toru Sugiyama

    Gynecologic Oncology149 ( 3 ) 513 - 519   2018年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Academic Press Inc.  

    Objective: This multicenter phase II Japanese Gynecologic Oncology Group study (JGOG1067) was designed to evaluate the efficacy and safety of postoperative chemotherapy in patients with node-positive cervical cancer. Methods: Patients with stage IB–IIA squamous cervical cancer who underwent radical hysterectomy and were confirmed to have pelvic lymph node metastasis were eligible for this study. The patients postoperatively received irinotecan (CPT-11
    60 mg/m2 intravenously on days 1 and 8) and nedaplatin (NDP
    80 mg/m2 intravenously on day 1). Chemotherapy administration commenced within 6 weeks after surgery and was repeated every 28 days for up to 5 cycles. The primary endpoint of this study was the 2-year recurrence-free survival (RFS) rate. The secondary endpoints were the 5-year overall survival (OS) rate, 5-year RFS rate, and adverse events such as complications of chemotherapy and lower-limb edema. Results: Sixty-two patients were analyzed according to our protocol, among whom 55 (88.7%) completed 5 cycles of scheduled treatment. The median follow-up period was 66.1 months (range, 16.8–96.6 months). The 2-year and 5-year RFS rates were 87.1% (95% confidence interval [CI]: 75.9–99.3) and 77.2% (95% CI: 64.5–85.8), respectively. Fourteen patients (22.5%) experienced recurrence during the follow-up period, 8 of whom died of the disease. The 5-year OS rate in this study was 86.5% (95% CI: 74.8–93.0). Only 9.7% of the patients experienced lymphedema in their legs. Conclusion: Postoperative chemotherapy without radiotherapy was found to be very effective in high-risk patients with node-positive cervical cancer.

    DOI: 10.1016/j.ygyno.2018.04.009

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  • Postoperative chemotherapy for node-positive cervical cancer: Results of a multicenter phase II trial (JGOG1067)

    Matoda, M, Takeshima, N, Michimae, H, Iwata, T, Yokota, H, Torii, Y, Yamamoto, Y, Takehara, K, Nishio, S, Takano, H, Mizuno, M, Takahashi, Y, Takei, Y, Hasegawa, T, Mikami, M, Enomoto, T, Aoki, D, Sugiyama, T

    Gynecol Oncol149 ( 3 ) 513 - 519   2018年6月

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    OBJECTIVE: This multicenter phase II Japanese Gynecologic Oncology Group study (JGOG1067) was designed to evaluate the efficacy and safety of postoperative chemotherapy in patients with node-positive cervical cancer. METHODS: Patients with stage IB-IIA squamous cervical cancer who underwent radical hysterectomy and were confirmed to have pelvic lymph node metastasis were eligible for this study. The patients postoperatively received irinotecan (CPT-11; 60mg/m(2) intravenously on days 1 and 8) and nedaplatin (NDP; 80mg/m(2) intravenously on day 1). Chemotherapy administration commenced within 6weeks after surgery and was repeated every 28days for up to 5cycles. The primary endpoint of this study was the 2-year recurrence-free survival (RFS) rate. The secondary endpoints were the 5-year overall survival (OS) rate, 5-year RFS rate, and adverse events such as complications of chemotherapy and lower-limb edema. RESULTS: Sixty-two patients were analyzed according to our protocol, among whom 55 (88.7%) completed 5cycles of scheduled treatment. The median follow-up period was 66.1months (range, 16.8-96.6months). The 2-year and 5-year RFS rates were 87.1% (95% confidence interval [CI]: 75.9

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  • Significance of abnormal peritoneal cytology on survival of women with stage I–II endometrioid endometrial cancer 査読

    Koji Matsuo, Akira Yabuno, Marianne S. Hom, Masako Shida, Mamoru Kakuda, Sosuke Adachi, Rachel S. Mandelbaum, Yutaka Ueda, Kosei Hasegawa, Takayuki Enomoto, Mikio Mikami, Lynda D. Roman

    Gynecologic Oncology149 ( 2 ) 301 - 309   2018年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Academic Press Inc.  

    Objective: To examine survival of women with stage I–II endometrioid endometrial cancer whose peritoneal cytology showed malignant or atypical cells (abnormal peritoneal cytology). Methods: This is a multi-center retrospective study examining 1668 women with stage I–II endometrioid endometrial cancer who underwent primary hysterectomy with available peritoneal cytology results between 2000 and 2015. Abnormal peritoneal cytology was correlated to clinico-pathological characteristics and oncological outcome. Results: Malignant and atypical cells were seen in 125 (7.5%) and 58 (3.5%) cases, respectively. On multivariate analysis, non-obesity, non-diabetes mellitus, cigarette use, and lympho-vascular space invasion were independently associated with abnormal peritoneal cytology (all, P &lt
    0.05). Abnormal peritoneal cytology was independently associated with decreased disease-free survival (hazard ratio 3.07, P &lt
    0.001) and cause-specific survival (hazard ratio 3.42, P = 0.008) on multivariate analysis. Abnormal peritoneal cytology was significantly associated with increased risks of distant-recurrence (5-year rates: 8.8% versus 3.6%, P = 0.001) but not local-recurrence (5.2% versus 3.0%, P = 0.32) compared to negative cytology. Among women with stage I disease, abnormal peritoneal cytology was significantly associated with an increased risk of distant-recurrence in the low risk group (5-year rates: 5.5% versus 1.0%, P &lt
    0.001) but not in the high-intermediate risk group (13.3% versus 10.8% P = 0.60). Among 183 women who had abnormal peritoneal cytology, postoperative chemotherapy significantly reduced the rate of peritoneal recurrence (5-year rates: 1.3% versus 9.2%, P = 0.039) whereas postoperative radiotherapy did not (7.1% versus 5.5%, P = 0.63). Conclusion: Our study suggests that abnormal peritoneal cytology may be a prognostic factor for decreased survival in women with stage I–II endometrioid endometrial cancer, particularly for low-risk group.

    DOI: 10.1016/j.ygyno.2018.02.012

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  • The Safety and Effectiveness of Abdominal Radical Trachelectomy for Early-Stage Cervical Cancer During Pregnancy 査読

    Kosuke Yoshihara, Tatsuya Ishiguro, Makoto Chihara, Eiri Shima, Sosuke Adachi, Masanori Isobe, Kazufumi Haino, Masayuki Yamaguchi, Masayuki Sekine, Katsunori Kashima, Koichi Takakuwa, Nobumichi Nishikawa, Takayuki Enomoto

    International Journal of Gynecological Cancer28 ( 4 ) 782 - 787   2018年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Lippincott Williams and Wilkins  

    Objectives: Cervical cancer is one of the most frequently diagnosed cancers in pregnancy. Our aim was to evaluate the safety and efficacy of abdominal radical trachelectomy (ART) for pregnant women with early-stage cervical cancer who strongly desire to preserve their pregnancies. Methods/Materials: A retrospective observational study was performed for stage IB1 cervical cancer patients who underwent ART or radical hysterectomy (RH) at our hospital between February 2013 and June 2017. We compared differences in perioperative findings and oncologic outcomes among ART during pregnancy (ART-DP), ART, and RH groups. Results: A total of 38 patients were included in this analysis. Six, 10, and 22 patients were assigned to the ART-DP, ART, and RH groups, respectively. There were no significant differences in the distribution of pathological TNM classifications, histology, tumor size, stromal invasion, and lymph-vascular space invasion among the 3 groups. The patients in the ART-DP group were younger than those in the RH group (P = 0.014). The ART-DP group was associated with more blood loss and prolonged surgery compared with the RH group (P = 0.017 and P = 0.014). The number of total lymph nodes in the ART-DP group was lower than that in the RH group (P = 0.036). However, there were no significant differences in age, surgical time, blood loss, or lymph node count between the ART-DP and ART groups. There were no significant differences in progression-free and overall survival times among the 3 groups, and no recurrence was observed in the ART-DP group. Conclusions: Abdominal radical trachelectomy may be a tolerable treatment option for pregnant women with early-stage cervical cancer who strongly desire a baby.

    DOI: 10.1097/IGC.0000000000001218

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  • Dynamic changes in Japan's prevalence of abnormal findings in cervical cervical cytology depending on birth year. 査読 国際誌

    Yutaka Ueda, Asami Yagi, Tomio Nakayama, Kei Hirai, Sayaka Ikeda, Masayuki Sekine, Etsuko Miyagi, Takayuki Enomoto

    Scientific reports8 ( 1 ) 5612 - 5612   2018年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Japan's governmental recommendation of HPV vaccine has now been suspended for more than 4 years. In and before 2013, the targets of 20-year-old cervical cancer screening were females born in and before 1993, i.e., those who could not have received HPV vaccination because it was not yet publicly introduced. The targets during 2014-2019 are, or will be, those born in 1994-1999, i.e., those who came of age during a period with the highest HPV immunization rate. We analyzed the statistical data for each birth year, for the cumulative HPV vaccination rates achieved as of age 16, and for the corresponding results of cervical cancer screening at age 20. The rate of abnormal findings in cervical cytology increased slightly from 3.68% in 2010 (birth year: 1990) to 4.35% in 2013 (birth year: 1993); however, it dynamically dropped to 2.99% in 2014 (birth year: 1994) and 3.03% in 2015 (birth year: 1995). In total, the rate of abnormal findings in cervical cytology was 3.96% in 2010-2013, but significantly dropped to 3.01% in 2014-2015 (p = 0.014). This is the first description of dynamic changes occurring in the abnormal rate of cervical cancer screening as a result of positive changes in national HPV vaccination rates.

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  • Microdissection testicular sperm extraction in five Japanese patients with non-mosaic Klinefelter's syndrome 査読

    Makoto Chihara, Kanna Ogi, Tatsuya Ishiguro, Kunihiko Yoshida, Chikako Godo, Koichi Takakuwa, Takayuki Enomoto

    Reproductive Medicine and Biology17 ( 2 ) 209 - 216   2018年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:John Wiley and Sons Ltd  

    Cases: Microdissection testicular sperm extraction (micro-TESE) was performed on five Japanese men with non-mosaic Klinefelter's syndrome (KS) and non-obstructive azoospermia in the authors' department. Here is reported the operative results and partner's clinical course for two cases where spermatozoa could be acquired. Also encountered was a man with non-mosaic KS with the partial deletion of azoospermia factor (AZF)b. Because this is rare, it is reported in detail in the context of the previous literature. This case series describes the first experience of micro-TESE by gynecologists in the current department. Outcome: The egg collection date was adjusted to the micro-TESE day by using the modified ultra-long method. Intracytoplasmic sperm injection (ICSI) was implemented for two men whose spermatozoa were acquired by micro-TESE, with these progressing to the blastocyst stage. Subsequently, one case conceived after the transfer of fresh embryos and a healthy baby was delivered. However, spermatozoa could not be retrieved from the man with non-mosaic KS who was harboring the partial deletion of AZFb. Conclusion: These findings suggest that ovulation induction by using the modified ultra-long method with micro-TESE and ICSI on the same day represents an effective treatment option for men with non-mosaic KS. As there are cases where AZF deletion is recognized among patients with non-mosaic KS, screening before micro-TESE is strongly recommended.

    DOI: 10.1002/rmb2.12092

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  • Genetic and clinical characteristics in Japanese hereditary breast and ovarian cancer: first report after establishment of HBOC registration system in Japan. 査読 国際誌

    Masami Arai, Shiro Yokoyama, Chie Watanabe, Reiko Yoshida, Mizuho Kita, Megumi Okawa, Akihiro Sakurai, Masayuki Sekine, Junko Yotsumoto, Hiroyuki Nomura, Yoshinori Akama, Mayuko Inuzuka, Tadashi Nomizu, Takayuki Enomoto, Seigo Nakamura

    Journal of human genetics63 ( 4 ) 447 - 457   2018年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The hereditary breast and ovarian cancer (HBOC) registration system of Japan was established by the Japanese HBOC Consortium. The first trial was registered in 2015 in four institutions to which some registration committee members belonged. We analyzed the information of 830 Japanese pedigrees, who underwent BRCA1/2 genetic testing, including mutation carriers with BRCA1 (N = 127) and BRCA2 (N = 115), and their families. The mutation-positive rate was 19.7%. Variants of uncertain significance were found in 6.5% of all individuals subjected to genetic testing for BRCA1/2. Compared to the United States, Japan had a higher mutation-positive rate in most categories, except for the groups with male breast cancer. Among the intrinsic subtypes of BRCA1-associated breast cancers, 75.8% were triple-negative. The incidence rate of contralateral breast cancer in BRCA1/2 mutation carriers was 0.99%/year. Among 240 mutation carriers, 26 and 62 patients underwent risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO), respectively; the respective frequencies of occult cancer were 7.1 and 3.2%. Metachronous breast cancer after RRM or peritoneal cancer after RRSO was not observed during the follow-up period. The nationwide registration system began last year and the system enables follow-up analysis in Japan.

    DOI: 10.1038/s10038-017-0355-1

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  • Correction: Genetic and clinical characteristics in Japanese hereditary breast and ovarian cancer: first report after establishment of HBOC registration system in Japan. 査読

    Arai M, Yokoyama S, Watanabe C, Yoshida R, Kita M, Okawa M, Sakurai A, Sekine M, Yotsumoto J, Nomura H, Akama Y, Inuzuka M, Nomizu T, Enomoto T, Nakamura S

    Journal of human genetics63 ( 4 ) 541 - 542   2018年4月

  • Motivating Mothers to Recommend Their 20-Year-Old Daughters Receive Cervical Cancer Screening: A Randomized Study. 査読

    Tomomi Egawa-Takata, Yutaka Ueda, Akiko Morimoto, Yusuke Tanaka, Asami Yagi, Yoshito Terai, Masahide Ohmichi, Tomoyuki Ichimura, Toshiyuki Sumi, Hiromi Murata, Hidetaka Okada, Hidekatsu Nakai, Masaki Mandai, Shinya Matsuzaki, Eiji Kobayashi, Kiyoshi Yoshino, Tadashi Kimura, Junko Saito, Yumiko Hori, Eiichi Morii, Tomio Nakayama, Mikiko Asai-Sato, Etsuko Miyagi, Masayuki Sekine, Takayuki Enomoto, Yorihiko Horikoshi, Tetsu Takagi, Kentaro Shimura

    Journal of epidemiology28 ( 3 ) 156 - 160   2018年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: In Japan, the rate of cervical cancer screening is remarkably low, especially among women in their twenties and thirties, when cervical cancer is now increasing dramatically. The aim of this study was to test whether a modified government reminder for 20-year-old women to engage in cervical cancer screening, acting through maternal education and by asking for a maternal recommendation to the daughter to receive the screening, could increase their participation rate. METHODS: In two Japanese cities, 20-year-old girls who had not received their first cervical cancer screening before October of fiscal year 2014 were randomized into two study arms. One group of 1,274 received only a personalized daughter-directed reminder leaflet for cervical cancer screening. In the second group of 1,274, the daughters and their mothers received a combination package containing the same reminder leaflet as did the first group, plus an additional informational leaflet for the mother, which requested that the mother recommend that her daughter undergo cervical cancer screening. The subsequent post-reminder screening rates of these two study arms were compared. RESULTS: The cervical cancer screening rate of 20-year-old women whose mothers received the information leaflet was significantly higher than that for women who received only a leaflet for themselves (11% vs 9%, P = 0.0049). CONCLUSIONS: An intervention with mothers, by sending them a cervical cancer information leaflet with a request that they recommend that their daughter receive cervical cancer screening, significantly improved their daughters' screening rate.

    DOI: 10.2188/jea.JE20160155

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  • Malignancy during pregnancy in Japan: An exceptional opportunity for early diagnosis 査読

    Masayuki Sekine, Yoshiyuki Kobayashi, Tsutomu Tabata, Tamotsu Sudo, Ryuichiro Nishimura, Koji Matsuo, Brendan H. Grubbs, Takayuki Enomoto, Tomoaki Ikeda

    BMC Pregnancy and Childbirth18 ( 1 ) 50   2018年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BioMed Central Ltd.  

    Background: Malignancy during pregnancy has become a significant cause of maternal death in developed countries, likely due to both an older pregnant population, and increases of cervical cancer in younger women. Our aim is to investigate the clinical aspects of malignancy during pregnancy in Japan and to use this information to identify opportunities for earlier detection and treatment. Methods: We provided a questionnaire to 1508 secondary or tertiary care hospitals in Japan. We reviewed the clinical characteristics of cases with malignancy during pregnancy for the period of January to December, 2008. From the 760 institutions which responded, we obtained clinical information for 227 unique cases. The questionnaire provided clinical information, including disease site, pregnancy outcome and how the disease was detected. Results: The most common type of malignancy was cervical cancer (n=162, 71.4%) followed by ovarian (n=16, 7.0%) and breast cancer (n=15, 6.6%). Leukemia (n=7, 3.1%), colon cancer (n=5, 2.2%), gastric cancer (n=5, 2.2%), malignant lymphoma (n=4, 1.8%), thyroid cancer (n=3, 1.3%), brain cancer (n=3, 1.3%), endometrial cancer (n=2, 0.9%), and head and neck cancer (n=2, 0.9%) accounted for the remaining cases. Overall, gynecological malignancies accounted for 79.3% (95% confidence interval 74.0-84.6) of pregnancy associated malignancies diagnosed in the present study. The majority of cervical cancers, 149 (92.0%) of 162, were diagnosed by a Pap (Papanicolaou) smear during early gestation. Ten (62.5%) of the ovarian cancer cases were diagnosed by ultrasonography during a prenatal checkup or at the time of initial pregnancy diagnosis. Out of 14 breast cancers, only one (7.1%) was diagnosed by screening breast exam. Conclusions: From this study, we reaffirm the clear and significant benefits of prenatal checkups starting at an early gestational age for the detection of gynecological cancers during pregnancy. Conversely, breast cancer detection during pregnancy was poor, suggesting new strategies for early identification of this disease are required.

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  • 妊娠中子宮頸部円錐切除症例の後方視的解析 子宮頸部円錐切除術の実態調査に関する小委員会(婦人科腫瘍委員会)報告

    古形祐平, 寺井義人, 田中良道, 大道正英, 池田仁惠, 三上幹男, 榎本隆之, 小林陽一, 永瀬智, 横山正俊, 片渕秀隆

    日本産科婦人科学会雑誌70 ( 2 ) 846   2018年2月

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  • 本邦における診断的円錐切除症例の検討

    山本瑠美子, 三上幹男, 関谷健太郎, 寺川耕市, 樋口壽宏, 池田仁惠, 榎本隆之, 小林陽一, 永瀬智, 横山正俊, 片渕秀隆

    日本産科婦人科学会雑誌70 ( 2 ) 656   2018年2月

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  • 本邦における子宮頸部円錐切除術14,832例の検討―円錐切除後妊娠例を中心に―「子宮頸部円錐切除術の実態調査」に関する小委員会(日本産科婦人科学会 婦人科腫瘍委員会)報告

    楢山知明, 池田仁惠, 信田政子, 柴田健雄, 三上幹男, 小林陽一, 永瀬智, 横山正俊, 榎本隆之, 片渕秀隆

    日本産科婦人科学会雑誌70 ( 2 ) 649   2018年2月

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  • 分娩後1年以内の子宮頸部円錐切除症例の後方視的解析 子宮頸部円錐切除術の実態調査に関する小委員会(婦人科腫瘍委員会)報告

    田中良道, 寺井義人, 古形祐平, 大道正英, 池田仁惠, 三上幹男, 榎本隆之, 小林陽一, 永瀬智, 横山正俊, 片渕秀隆

    日本産科婦人科学会雑誌70 ( 2 ) 846   2018年2月

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  • 本邦における稀少部位子宮内膜症の悪性化―実態調査に関する小委員会報告(日本産科婦人科学会婦人科腫瘍委員会)―

    本田律生, 大須賀穣, 平田哲也, 榎本隆之, 谷口文紀, 中井英勝, 万代昌紀, 片渕秀隆

    日本産科婦人科学会雑誌70 ( 2 ) 929   2018年2月

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  • 卵巣奇形腫を伴う抗NMDA受容体抗体脳炎に関する本邦産婦人科へのアンケート調査

    田代浩徳, 宮本新吾, 椙田賢司, 万代昌紀, 坂口勲, 榎本隆之, 片渕秀隆

    日本産科婦人科学会雑誌70 ( 2 ) 647   2018年2月

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  • Novel therapeutic strategy for cervical cancer harboring FGFR3-TACC3 fusions. 査読 国際誌

    Ryo Tamura, Kosuke Yoshihara, Tetsuya Saito, Ryosuke Ishimura, Juan Emmanuel Martínez-Ledesma, Hu Xin, Tatsuya Ishiguro, Yutaro Mori, Kaoru Yamawaki, Kazuaki Suda, Seiya Sato, Hiroaki Itamochi, Teiichi Motoyama, Yoichi Aoki, Shujiro Okuda, Cristine R Casingal, Hirofumi Nakaoka, Ituro Inoue, Roel G W Verhaak, Masaaki Komatsu, Takayuki Enomoto

    Oncogenesis7 ( 1 ) 4 - 4   2018年1月

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    記述言語:英語  

    We previously found that therapeutic targetable fusions are detected across various cancers. To identify therapeutic targetable fusion in uterine cervical cancer, for which no effective gene targeted therapy has yet been clinically applied, we analyzed RNA sequencing data from 306 cervical cancer samples. We detected 445 high confidence fusion transcripts and identified four samples that harbored FGFR3-TACC3 fusion as an attractive therapeutic target. The frequency of FGFR3-TACC3-fusion-positive cervical cancer is also 1.9% (2/103) in an independent cohort. Continuous expression of the FGFR3-TACC3 fusion transcript and protein induced anchorage-independent growth in the cervical epithelial cell line established from the ectocervix (Ect1/E6E7) but not in that from endocervix (End1/E6E7). Injection of FGFR3-TACC3 fusion-transfected-Ect1/E6E7 cells subcutaneously into NOG mice generated squamous cell carcinoma xenograft tumors, suggesting the association between FGFR3-TACC3 fusion and squamous cell carcinogenesis. Transfection of a FGFR3-TACC3 fusion transcript into four cervical cancer cell lines (SiHa, ME180, HeLa, and Ca Ski) induced activation of the MAPK pathway and enhancement of cell proliferation. Transcriptome analysis of the FGFR3-TACC3 fusion-transfected cell lines revealed that an IL8-triggered inflammatory response was increased, via activation of FGFR3-MAPK signaling. Continuous expression of FGFR3-TACC3 fusion led to activation of the PI3K-AKT pathway only in the two cell lines that harbored PIK3CA mutations. Sensitivity to the FGFR inhibitor, BGJ398, was found to depend on PIK3CA mutation status. Dual inhibition of both FGFR and AKT showed an obvious synergistic effect in cell lines that harbor mutant PIK3CA. Additionally, TACC3 inhibitor, KHS101, suppressed FGFR3-TACC3 fusion protein expression and showed antitumor effect against FGFR3-TACC3 fusion-transfected cell lines. FGFR3-TACC3 fusion-positive cancer has frequent genetic alterations of the PI3K/AKT pathway and selection of appropriate treatment based on PI3K/AKT pathway status should be required.

    DOI: 10.1038/s41389-017-0018-2

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  • LSR Antibody Therapy Inhibits Ovarian Epithelial Tumor Growth by Inhibiting Lipid Uptake. 査読 国際誌

    Kosuke Hiramatsu, Satoshi Serada, Takayuki Enomoto, Yusuke Takahashi, Satoshi Nakagawa, Satoshi Nojima, Akiko Morimoto, Shinya Matsuzaki, Takuhei Yokoyama, Tsuyoshi Takahashi, Minoru Fujimoto, Hiroshi Takemori, Yutaka Ueda, Kiyoshi Yoshino, Eiichi Morii, Tadashi Kimura, Tetsuji Naka

    Cancer research78 ( 2 ) 516 - 527   2018年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, but it still lacks effective treatment options. In this study, we utilized proteomic technology to identify lipolysis-stimulated lipoprotein receptor (LSR) as a new tumor antigen of EOC. Immunohistochemical analysis of EOC tissues in conjunction with survival analysis of EOC patients showed that high expression of LSR is associated with poor prognosis. High LSR expression also occurred in tumor metastases including to the lymph node and omentum. To evaluate the possible benefits of blocking this antigen in EOC, we raised a new monoclonal antibody (mAb) to human LSR (hLSR). In mouse xenograft models of hLSR+ EOC (cell lines or patient-derived tumors), we found that administration of anti-hLSR mAb inhibited tumor growth in a manner independent of both antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Mechanistic investigations showed that hLSR expression increased incorporation of very-low-density lipoprotein (VLDL) into EOC cells and that anti-hLSR mAb inhibited lipid uptake in vitro and in vivo Moreover, VLDL promoted cell proliferation in hLSR-positive EOC cells in vitro, and this effect was inhibited by anti-hLSR mAb. While the anti-hLSR mAb studied cross reacted with the mouse antigen, we observed no adverse effects on normal organs and lipid metabolism in murine hosts. Our findings suggest that hLSR plays a key functional role in EOC development and that this antigen can be therapeutically targeted by specific mAb to improve EOC treatment.Significance: These findings offer preclinical evidence of the therapeutic efficacy of a novel targeted antibody therapy against deadly epithelial ovarian cancers. Cancer Res; 78(2); 516-27. ©2017 AACR.

    DOI: 10.1158/0008-5472.CAN-17-0910

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  • Effectiveness of fetal cardiac screening for congenital heart disease using a combination of the four-chamber view and three-vessel view during the second trimester scan 査読

    Mina Itsukaichi, Takehiro Serikawa, Kosuke Yoshihara, Hiroshi Suzuki, Kazufumi Haino, Masayuki Yamaguchi, Takayuki Enomoto, Koichi Takakuwa, Hiroshi Aida, Masato Arakawa, Michio Ishida, Hiroaki Kase, Takaaki Sato, Naoto Sekizuka, Akira Honda, Niigata Fetal Cardiac Screening Study Group

    Journal of Obstetrics and Gynaecology Research44 ( 1 ) 49 - 53   2018年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Blackwell Publishing  

    Aim: We aimed to assess the accuracy and effectiveness of fetal cardiac screening for congenital heart disease (CHD) during the second trimester by general obstetricians in a non-selected population. Methods: In this multicenter, prospective cohort study of fetal cardiac screening, four-chamber and three-vessel views were recorded by obstetricians at 18–21 gestational weeks (GW). A total of 3005 fetuses that were scheduled for delivery at our institution were included. Results: Thirty-seven newborns were born with CHD (1.2%). On excluding 23 cases of ventricular septal defects, the prenatal detection rate of CHD was 42.8%. Although six cases (75.0%) of severe structural abnormality were diagnosed prenatally, the prenatal detection rate of valvular abnormalities was 0%. Conclusion: One-point ultrasound screening of the fetal heart using a combination of four-chamber and three-vessel views at 18–21 GW by general obstetricians in a non-selected population may be useful for detecting severe structural abnormalities but not valvular abnormalities. However, this limitation may be improved by conducting another fetal cardiac screening at approximately 30 GW along with the routine use of color Doppler.

    DOI: 10.1111/jog.13472

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  • Time-dependent changes of the intention of mothers in Japan to inoculate their daughters with the HPV vaccine after suspension of governmental recommendation. 査読 国際誌

    Asami Yagi, Yutaka Ueda, Yusuke Tanaka, Ruriko Nakae, Reisa Kakubari, Akiko Morimoto, Yoshito Terai, Masahide Ohmichi, Tomoyuki Ichimura, Toshiyuki Sumi, Hiromi Murata, Hidetaka Okada, Hidekatsu Nakai, Noriomi Matsumura, Kiyoshi Yoshino, Tadashi Kimura, Junko Saito, Sayaka Ikeda, Mikiko Asai-Sato, Etsuko Miyagi, Masayuki Sekine, Takayuki Enomoto, Kei Hirai, Yorihiko Horikoshi, Tetsu Takagi, Kentaro Shimura

    Human vaccines & immunotherapeutics14 ( 10 ) 2497 - 2502   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    In Japan, the trend for cervical cancer at younger ages has been increasing. As a countermeasure, the HPV vaccine was introduced as a routine vaccination in April 2013. However, the Ministry of Health, Labour and Welfare (MHLW) announced a "Suspension of its active inoculation recommendation for HPV vaccine" in June 2013. In 2016, 32 months after that suspension, we conducted survey via Internet and compared the results with our previous ones conducted at 9 and 23 months after suspension (in 2014 and 2015, respectively). We examined the 'time-dependent change' of the 'intention of mothers to inoculate their daughters with the HPV vaccine' in terms of efficacy of external decision-making support. 17.5% of mothers in the first survey replied that they would inoculate their daughters under the current circumstances, 12.1% in the second survey, and 6.7% in the third, showing a consistent decrease in willingness over time (p = 0.03, p < 0.01). If the government recommendation were to be reintroduced, 22.5% of mothers in the first survey replied they would inoculate their daughters, 21.0% in the second survey, which indicated no significant difference (p = 0.65) over the first interval; however, this was significantly decreased to 12.2% in the third survey (p < 0.01). Our study revealed that the intention to inoculate their daughters has been declining among Japanese mothers over time triggered by the suspension.

    DOI: 10.1080/21645515.2018.1480240

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  • 日本人若年女性におけるHPVワクチン公費接種者のHPV感染予防効果 査読

    工藤 梨沙, 山口 真奈子, 安達 聡介, 関根 正幸, 八木 麻未, 田中 佑典, 上田 豊, 宮城 悦子, 榎本 隆之

    日本癌治療学会学術集会抄録集55回   PS - 6   2017年10月

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    記述言語:日本語   出版者・発行元:(一社)日本癌治療学会  

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  • 日本人若年女性のsexual activityとHPV感染、子宮頸部細胞診異常との相関 査読

    山口 真奈子, 工藤 梨沙, 安達 聡介, 関根 正幸, 八木 麻未, 田中 佑典, 上田 豊, 宮城 悦子, 榎本 隆之

    日本癌治療学会学術集会抄録集55回   P165 - 1   2017年10月

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  • A long-range cis-regulatory element for class I odorant receptor genes 査読

    Tetsuo Iwata, Yoshihito Niimura, Chizuru Kobayashi, Daichi Shirakawa, Hikoyu Suzuki, Takayuki Enomoto, Kazushige Touhara, Yoshihiro Yoshihara, Junji Hirota

    NATURE COMMUNICATIONS8 ( 1 ) 885   2017年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Individual olfactory sensory neurons express a single odorant receptor gene from either class I genes residing in a single cluster on a single chromosome or class II genes spread over multiple clusters on multiple chromosomes. Here, we identify an enhancer element for mouse class I genes, the J element, that is conserved through mammalian species from the platypus to humans. The J element regulates most class I genes expression by exerting an effect over similar to 3 megabases within the whole cluster. Deletion of the trans J element increases the expression frequencies of class I genes from the intact J allele, indicating that the allelic exclusion of class I genes depends on the activity of the J element. Our data reveal a long-range cis-regulatory element that governs the singular class I gene expression and has been phylogenetically preserved to retain a single cluster organization of class I genes in mammals.

    DOI: 10.1038/s41467-017-00870-4

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  • Correction to Lancet Oncol 2017; 18: 1274–84 (The Lancet Oncology (2017) 18(9) (1274–1284) (S1470204517304692) (10.1016/S1470-2045(17)30469-2)) 査読

    Eric Pujade-Lauraine, the, Jonathan A Ledermann, Frédéric Selle, Val Gebski, Richard T Penson, Amit M Oza, Jacob Korach, Tomasz Huzarski, Andrés Poveda, Sandro Pignata, Michael Friedlander, Nicoletta Colombo, Philipp Harter, Keiichi Fujiwara, Isabelle Ray-Coquard, Susana Banerjee, Joyce Liu, Elizabeth S Lowe, Ralph Bloomfield, Patricia Pautier, Jacob Korach, Tomasz Huzarski, Tomasz Byrski, Patricia Pautier, Philipp Harter, Nicoletta Colombo, Sandro Pignata, Giovanni Scambia, Maria Nicoletto, Fiona Nussey, Andrew Clamp, Richard Penson, Amit Oza, Andrés Poveda Velasco, Manuel Rodrigues, Jean-Pierre Lotz, Frédéric Selle, Isabelle Ray-Coquard, Diane Provencher, Aleix Prat Aparicio, Laura Vidal Boixader, Clare Scott, Kenji Tamura, Mayu Yunokawa, Alla Lisyanskaya, Jacques Medioni, Nicolas Pécuchet, Coraline Dubot, Thibault de la Motte Rouge, Marie-Christine Kaminsky, Béatrice Weber, Alain Lortholary, Christine Parkinson, Jonathan Ledermann, Sarah Williams, Susana Banerjee, Jonathan Cosin, James Hoffman, Richard Penson, Marie Plante, Allan Covens, Gabe Sonke, Florence Joly, Anne Floquet, Susana Banerjee, Holger Hirte, Amnon Amit, Tjoung-Won Park-Simon, Koji Matsumoto, Sergei Tjulandin, Jae Hoon Kim, Laurence Gladieff, Roberto Sabbatini, David O'Malley, Patrick Timmins, Daniel Kredentser, Nuria Laínez Milagro, Maria Pilar Barretina Ginesta, Ariadna Tibau Martorell, Alfonso Gómez de Liaño Lista, Belén Ojeda González, Linda Mileshkin, Masaki Mandai, Ingrid Boere, Petronella Ottevanger, Joo-Hyun Nam, Elias Filho, Salima Hamizi, Francesco Cognetti, David Warshal, Elizabeth Dickson-Michelson, Scott Kamelle, Nathalie McKenzie, Gustavo Rodriguez, Deborah Armstrong, Eva Chalas, Paul Celano, Kian Behbakht, Susan Davidson, Stephen Welch, Limor Helpman, Ami Fishman, Ilan Bruchim, Magdalena Sikorska, Anna Słowińska, Wojciech Rogowski, Mariusz Bidziński, Beata Śpiewankiewicz, Antonio Casado Herraez, César Mendiola Fernández, Martina Gropp-Meier, Toshiaki Saito, Kazuhiro Takehara, Takayuki Enomoto, Hidemichi Watari, Chel Hun Choi, Byoung-Gie Kim, Jae Weon Kim, Roberto Hegg, Ignace Vergote

    The Lancet Oncology18 ( 9 ) 1274 - 1284   2017年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Lancet Publishing Group  

    Background Olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, has previously shown efficacy in a phase 2 study when given in capsule formulation to all-comer patients with platinum-sensitive, relapsed high-grade serous ovarian cancer. We aimed to confirm these findings in patients with a BRCA1 or BRCA2 (BRCA1/2) mutation using a tablet formulation of olaparib. Methods This international, multicentre, double-blind, randomised, placebo-controlled, phase 3 trial evaluated olaparib tablet maintenance treatment in platinum-sensitive, relapsed ovarian cancer patients with a BRCA1/2 mutation who had received at least two lines of previous chemotherapy. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status at baseline of 0–1 and histologically confirmed, relapsed, high-grade serous ovarian cancer or high-grade endometrioid cancer, including primary peritoneal or fallopian tube cancer. Patients were randomly assigned 2:1 to olaparib (300 mg in two 150 mg tablets, twice daily) or matching placebo tablets using an interactive voice and web response system. Randomisation was stratified by response to previous platinum chemotherapy (complete vs partial) and length of platinum-free interval (6–12 months vs ≥12 months) and treatment assignment was masked for patients, those giving the interventions, data collectors, and data analysers. The primary endpoint was investigator-assessed progression-free survival and we report the primary analysis from this ongoing study. The efficacy analyses were done on the intention-to-treat population
    safety analyses included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01874353, and is ongoing and no longer recruiting patients. Findings Between Sept 3, 2013, and Nov 21, 2014, we enrolled 295 eligible patients who were randomly assigned to receive olaparib (n=196) or placebo (n=99). One patient in the olaparib group was randomised in error and did not receive study treatment. Investigator-assessed median progression-free survival was significantly longer with olaparib (19·1 months [95% CI 16·3–25·7]) than with placebo (5·5 months [5·2–5·8]
    hazard ratio [HR] 0·30 [95% CI 0·22–0·41], p&lt
    0·0001). The most common adverse events of grade 3 or worse severity were anaemia (38 [19%] of 195 patients in the olaparib group vs two [2%] of 99 patients in the placebo group), fatigue or asthenia (eight [4%] vs two [2%]), and neutropenia (ten [5%] vs four [4%]). Serious adverse events were experienced by 35 (18%) patients in the olaparib group and eight (8%) patients in the placebo group. The most common in the olaparib group were anaemia (seven [4%] patients), abdominal pain (three [2%] patients), and intestinal obstruction (three [2%] patients). The most common in the placebo group were constipation (two [2%] patients) and intestinal obstruction (two [2%] patients). One (1%) patient in the olaparib group had a treatment-related adverse event (acute myeloid leukaemia) with an outcome of death. Interpretation Olaparib tablet maintenance treatment provided a significant progression-free survival improvement with no detrimental effect on quality of life in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation. Apart from anaemia, toxicities with olaparib were low grade and manageable. Funding AstraZeneca.

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  • The significance of activated PI3K/AKT pathway in FGFR3-TACC3 fusion positive cervical cancer 査読

    Tamura Ryo, Yoshihara Kosuke, Saito Tetsuya, Ishimura Ryosuke, Martinez-Ledesma Emmanuel, Mori Yutaro, Yamawaki Kaoru, Suda Kazuaki, Ishiguro Tatsuya, Aoki Yoichi, Sato Seiya, Itamochi Hiroaki, Komatsu Masaaki, Verhaak Roeland, Enomoto Takayuki

    CANCER RESEARCH77   2017年7月

  • 稀少部位子宮内膜症の悪性化―実態調査に関する小委員会報告―

    万代昌紀, 大須賀穣, 平田哲也, 榎本隆之, 谷口文紀, 本田律生, 中井英勝, 片渕秀隆

    日本婦人科腫よう学会雑誌35 ( 3 ) 372   2017年6月

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  • Anesthetic management of abdominal radical trachelectomy for uterine cervical cancer during pregnancy 査読

    Jun Terukina, Misako Takamatsu, Takayuki Enomoto, Hiroshi Baba

    JOURNAL OF ANESTHESIA31 ( 3 ) 467 - 471   2017年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER JAPAN KK  

    Abdominal radical trachelectomy has been identified as a surgical option for fertility preservation in cervical cancer patients, particularly in pregnant women who strongly desire to continue their pregnancy. Since this procedure requires operating in the uterus, the hardness of the uterus can affect the ease of surgery. Generally, sevoflurane is used for anesthesia in non-obstetric surgery for pregnant women because uterine relaxation is advantageous for uterine blood flow maintenance. However, the use of sevoflurane during radical trachelectomy has not been thoroughly evaluated. Here, we report on anesthesia use in three cases of abdominal radical trachelectomy during pregnancy. Propofol enabled maintenance of uterine tension while not significantly affecting fetal growth. It is important to consider maintenance of uterine tension and fetal circulation in anesthesia management. During the operation, we performed an ultrasound examination every 30 min to confirm fetal well-being. Although frequent fetal heart rate monitoring of the pre-viable fetus is not recommended, if fetal bradycardia is detected, sevoflurane may then be used to improve fetal circulation. Additionally, if the fetal heartbeat stops, a radical hysterectomy would then be required. Therefore, we consider that fetal heart rate monitoring during this procedure is necessary, and propofol is suitable as an anesthetic for this surgery during pregnancy.

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  • Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism 査読

    Yadav Sapkota, Valgerdur Steinthorsdottir, Andrew P. Morris, Amelie Fassbender, Nilufer Rahmioglu, Immaculata De Vivo, Julie E. Buring, Futao Zhang, Todd L. Edwards, Sarah Jones, O. Dorien, Danielle Peterse, Kathryn M. Rexrode, Paul M. Ridker, Andrew J. Schork, Stuart MacGregor, Nicholas G. Martin, Christian M. Becker, Sosuke Adachi, Kosuke Yoshihara, Takayuki Enomoto, Atsushi Takahashi, Yoichiro Kamatani, Koichi Matsuda, Michiaki Kubo, Gudmar Thorleifsson, Reynir T. Geirsson, Unnur Thorsteinsdottir, Leanne M. Wallace, Jian Yang, Digna R. Velez Edwards, Mette Nyegaard, Siew-Kee Low, Krina T. Zondervan, Stacey A. Missmer, Thomas D'Hooghe, Grant W. Montgomery, Daniel I. Chasman, Kari Stefansson, Joyce Y. Tung, Dale R. Nyholt

    NATURE COMMUNICATIONS8   15539   2017年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Endometriosis is a heritable hormone-dependent gynecological disorder, associated with severe pelvic pain and reduced fertility; however, its molecular mechanisms remain largely unknown. Here we perform a meta-analysis of 11 genome-wide association case-control data sets, totalling 17,045 endometriosis cases and 191,596 controls. In addition to replicating previously reported loci, we identify five novel loci significantly associated with endometriosis risk (P&lt;5 x 10(-8)), implicating genes involved in sex steroid hormone pathways (FN1, CCDC170, ESR1, SYNE1 and FSHB). Conditional analysis identified five secondary association signals, including two at the ESR1 locus, resulting in 19 independent single nucleotide polymorphisms (SNPs) robustly associated with endometriosis, which together explain up to 5.19% of variance in endometriosis. These results highlight novel variants in or near specific genes with important roles in sex steroid hormone signalling and function, and offer unique opportunities for more targeted functional research efforts.

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  • Recurrent ovarian undifferentiated carcinoma resembling hepatoid morphology treated with pegylated liposomal doxorubicin and bevacizumab 査読

    Tatsuya Ishiguro, Kastunori Kashima, Nozomi Yachida, Teiichi Motoyama, Takayuki Enomoto

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH43 ( 5 ) 957 - 961   2017年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Hepatoid carcinomas are undifferentiated epithelial carcinomas that are pathologically similar to hepatocellular carcinoma, but occur in a variety of organs. Hepatoid carcinomas, as strictly defined, typically produce a-fetoprotein. In addition, a standard effective chemotherapy regimen for hepatoid carcinoma has yet to be established. We present a case of advanced primary ovarian cancer that was pathologically similar to hepatoid carcinoma without staining for a-fetoprotein or hepatocyte paraffin 1. The primary ovarian, metastatic, and recurrent tumors shared similar pathological characteristics. Fourth-line chemotherapy with pegylated liposomal doxorubicin and bevacizumab was effective in treating the recurrent tumor, even though this disease had recurred three times.

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  • Sox2-dependent inhibition of p21 is associated with poor prognosis of endometrial cancer 査読

    Kaoru Yamawaki, Tatsuya Ishiguro, Yutaro Mori, Kosuke Yoshihara, Kazuaki Suda, Ryo Tamura, Masayuki Yamaguchi, Masayuki Sekine, Katsunori Kashima, Masaya Higuchi, Masahiro Fujii, Koji Okamoto, Takayuki Enomoto

    CANCER SCIENCE108 ( 4 ) 632 - 640   2017年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Sex-determining region Y-box 2 (SOX2) is an essential factor involved in the self-renewal and pluripotency of embryonic stem cells and has functions in cell survival and progression in many types of cancers. Here, we found that several endometrial cancer cell lines expressed SOX2, which was required for cell growth. Additionally, SOX2 overexpression regulated the expression of cyclin-dependent kinase inhibitor 1A (CDKN1A), and SOX2 specifically bound to p21 promoter DNA in endometrial cancer cell lines expressing SOX2. Expressions of SOX2 in endometrial cancer patients were significantly correlated with histological grade and poor prognosis. Moreover, low p21 together with high SOX2 expressions inadvanced endometrial cancer patients were associated with the most unfavorable outcomes of patients. These results indicated that simultaneous measurement of SOX2 and p21 expression in endometrial cancer patients may be a useful biomarker for patient prognosis.

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  • Sox2-dependent inhibition of p21 is associated with poor prognosis of endometrial cancer. 査読 国際誌

    Kaoru Yamawaki, Tatsuya Ishiguro, Yutaro Mori, Kosuke Yoshihara, Kazuaki Suda, Ryo Tamura, Masayuki Yamaguchi, Masayuki Sekine, Katsunori Kashima, Masaya Higuchi, Masahiro Fujii, Koji Okamoto, Takayuki Enomoto

    Cancer science108 ( 4 ) 632 - 640   2017年4月

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    記述言語:英語  

    Sex-determining region Y-box 2 (SOX2) is an essential factor involved in the self-renewal and pluripotency of embryonic stem cells and has functions in cell survival and progression in many types of cancers. Here, we found that several endometrial cancer cell lines expressed SOX2, which was required for cell growth. Additionally, SOX2 overexpression regulated the expression of cyclin-dependent kinase inhibitor 1A (CDKN1A), and SOX2 specifically bound to p21 promoter DNA in endometrial cancer cell lines expressing SOX2. Expressions of SOX2 in endometrial cancer patients were significantly correlated with histological grade and poor prognosis. Moreover, low p21 together with high SOX2 expressions in advanced endometrial cancer patients were associated with the most unfavorable outcomes of patients. These results indicated that simultaneous measurement of SOX2 and p21 expression in endometrial cancer patients may be a useful biomarker for patient prognosis.

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  • Mutations of the KLF1 gene detected in Japanese with the In(Lu) phenotype 査読

    Miho Kawai, Kumi Obara, Takayuki Onodera, Takayuki Enomoto, Kenichi Ogasawara, Hatsue Tsuneyama, Makoto Uchikawa, Shoichi Inaba

    TRANSFUSION57 ( 4 ) 1072 - 1077   2017年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    BACKGROUND: In(Lu) is characterized by a reduced expression of antigens in the Lutheran blood group system as well as other blood group antigens. Mutations of the erythroid transcription factor, KLF1, have been reported to cause the In(Lu) phenotype, and we investigated Japanese In(Lu) to estimate the prevalence of the phenotype and KLF1 polymorphism.
    STUDY DESIGN AND METHODS: Blood samples were screened by monoclonal anti-CD44 and the In(Lu) phenotype was confirmed by tube tests including adsorption and elution tests using anti-Lu-a and anti-Lu-b. KLF1, LU, and A4GALT genes were analyzed by polymerase chain reaction and sequencing.
    RESULTS: We identified 100 of 481,322 blood donors (0.02%), and the previously characterized 20 donors, who had the In(Lu) phenotype with the LUB/LUB genotype. A total of 100 of the 120 In(Lu) individuals had mutant KLF1 alleles, and we identified 13 known and 21 novel alleles. The mutant KLF1 alleles with c.947G&gt;A (p.Cys316Tyr), c.862A&gt;G (p.Lys288Glu), or c.968C&gt;G (p.Ser323Trp) were major in the In(Lu) individuals. The P1 antigen of 29 In(Lu) (two P-1/P-1, 27 P-1/P-2) showed significantly weakened expression by hemagglutination.
    CONCLUSIONS: The prevalence of the In(Lu) phenotype in the Japanese population was 0.02%, and we identified 13 known and 21 novel KLF1 alleles. The KLF1 mutations cause the reduced expression of the P1 antigen.

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  • Tumor-derived spheroids: Relevance to cancer stem cells and clinical applications 査読

    Tatsuya Ishiguro, Hirokazu Ohata, Ai Sato, Kaoru Yamawaki, Takayuki Enomoto, Koji Okamoto

    Cancer Science108 ( 3 ) 283 - 289   2017年3月

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    記述言語:英語   出版者・発行元:Blackwell Publishing Ltd  

    Recently, many types of in vitro 3-D culture systems have been developed to recapitulate the in vivo growth conditions of cancer. The cancer 3-D culture methods aim to preserve the biological characteristics of original tumors better than conventional 2-D monolayer cultures, and include tumor-derived organoids, tumor-derived spheroids, organotypic multicellular spheroids, and multicellular tumor spheroids. The 3-D culture methods differ in terms of cancer cell sources, protocols for cell handling, and the required time intervals. Tumor-derived spheroids are unique because they are purposed for the enrichment of cancer stem cells (CSCs) or cells with stem cell-related characteristics. These spheroids are grown as floating spheres and have been used as surrogate systems to evaluate the CSC-related characteristics of solid tumors in vitro. Because eradication of CSCs is likely to be of clinical importance due to their association with the malignant nature of cancer cells, such as tumorigenicity or chemoresistance, the investigation of tumor-derived spheroids may provide invaluable clues to fight against cancer. Spheroid cultures have been established from cancers including glioma, breast, colon, ovary, and prostate cancers, and their biological and biochemical characteristics have been investigated by many research groups. In addition to the investigation of CSCs, tumor-derived spheroids may prove to be instrumental for a high-throughput screening platform or for the cultivation of CSC-related tumor cells found in the circulation or body fluids.

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  • Comparison of Different Recruitment Methods for Sexual and Reproductive Health Research: Social Media-Based Versus Conventional Methods 査読

    Yoko Motoki, Etsuko Miyagi, Masataka Taguri, Mikiko Asai-Sato, Takayuki Enomoto, John Dennis Wark, Suzanne Marie Garland

    JOURNAL OF MEDICAL INTERNET RESEARCH19 ( 3 )   2017年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JMIR PUBLICATIONS, INC  

    Background
    Prior research about the sexual and reproductive health of young women has relied mostly on self-reported survey studies. Thus, participant recruitment using Web-based methods can improve sexual and reproductive health research about cervical cancer prevention. In our prior study, we reported that Facebook is a promising way to reach young women for sexual and reproductive health research. However, it remains unknown whether Web-based or other conventional recruitment methods (ie, face-to-face or flyer distribution) yield comparable survey responses from similar participants.
    Objective
    We conducted a survey to determine whether there was a difference in the sexual and reproductive health survey responses of young Japanese women based on recruitment methods: social media-based and conventional methods.
    Methods
    From July 2012 to March 2013 (9 months), we invited women of ages 16-35 years in Kanagawa, Japan, to complete a Web-based questionnaire. They were recruited through either a social media-based (social networking site, SNS, group) or by conventional methods (conventional group). All participants enrolled were required to fill out and submit their responses through a Web-based questionnaire about their sexual and reproductive health for cervical cancer prevention.
    Results
    Of the 243 participants, 52.3% (127/243) were recruited by SNS, whereas 47.7% (116/243) were recruited by conventional methods. We found no differences between recruitment methods in responses to behaviors and attitudes to sexual and reproductive health survey, although more participants from the conventional group (15%, 14/95) chose not to answer the age of first intercourse compared with those from the SNS group (5.2%, 6/116; P=.03).
    Conclusions
    No differences were found between recruitment methods in the responses of young Japanese women to a Web-based sexual and reproductive health survey.

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  • Comparison of Different Recruitment Methods for Sexual and Reproductive Health Research: Social Media-Based Versus Conventional Methods. 査読

    Motoki Y, Miyagi E, Taguri M, Asai-Sato M, Enomoto T, Wark JD, Garland SM

    Journal of medical Internet research19 ( 3 ) e73   2017年3月

  • Biochemical analysis of intraplacental choriocarcinoma and fetomaternal transfusion 査読

    Tatsuya Ishiguro, Kazuaki Suda, Takayuki Enomoto

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH43 ( 3 ) 587 - 591   2017年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Intraplacental choriocarcinoma is one of the rarest forms of gestational tumors and is believed to be one of the causes of fetomaternal transfusion (FMT). A 35-year-old woman, gravida 2, para 2, with a history of two vaginal deliveries, was incidentally diagnosed as having stage I gestational intraplacental choriocarcinoma with a FIGO/World Health Organization 2000 risk score of 2 after term delivery. This disease caused neonatal anemia but did not metastasize to either the mother or infant. Short tandem repeat analysis with laser microdissection revealed that the tumor had originated from the current pregnancy. Serological test and immunohistochemical analysis revealed that the patient and her baby suffered from FMT. She has been free from disease without any medical intervention for the last 1 year. A combination of multiple biochemical analyses might help us diagnose the precursor pregnancy of a gestational choriocarcinoma and FMT.

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  • HPVワクチン接種率の変化がもたらす出生年度ごとの子宮頸がんリスクの差異予測 査読

    八木 麻未, 上田 豊, 関根 正幸, 榎本 隆之, 佐藤 美紀子, 宮城 悦子, 大道 正英, 角 俊幸, 岡田 英孝, 万代 昌紀, 木村 正, 志村 研太郎

    日本産科婦人科学会雑誌69 ( 2 ) 675 - 675   2017年2月

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    記述言語:日本語   出版者・発行元:(公社)日本産科婦人科学会  

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  • ヒトパピローマウイルス(HPV)検査におけるハイリスクスクリーニング法とジェノタイピング法による結果不一致例の検討 査読

    工藤 梨沙, 関根 正幸, 山口 真奈子, 安達 聡介, 榎本 隆之, 上田 豊, 高田 友美, 森本 晶子, 田中 佑典, 八木 麻未

    日本産科婦人科学会雑誌69 ( 2 ) 674 - 674   2017年2月

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    記述言語:日本語   出版者・発行元:(公社)日本産科婦人科学会  

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  • Gestational choriocarcinoma: Rare spinal metastasis during a viable pregnancy 査読

    Tatsuya Ishiguro, Takehiro Serikawa, Tetsuro Yahata, Takayuki Enomoto

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH43 ( 2 ) 421 - 424   2017年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Gestational choriocarcinoma metastasizing to the bones, especially to the spine, is extremely rare. In addition, there are few reports of choriocarcinoma during a viable pregnancy. We report a case of gestational choriocarcinoma that metastasized to the lumbar spine during a viable pregnancy in a 41-year-old woman with a history of a missed abortion. A heterogeneous cervical mass was detected at gestational week 16. Subsequently, a metastatic lesion appeared during the pregnancy, and fetal demise in utero occurred. Pathological examination revealed that the cervical tumor and metastatic spinal tumor were choriocarcinoma. The patient's condition deteriorated rapidly and we were unable to save her life, despite multidrug chemotherapy. Surgical tumor resection and pregnancy might involve a substantial risk of choriocarcinoma metastasis. It is important to obtain an early diagnosis for this life-threatening disease in order to facilitate appropriate treatment, despite pregnancy.

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  • Realistic fear of cervical cancer risk in Japan depending on birth year 査読

    Asami Yagi, Yutaka Ueda, Tomomi Egawa-Takata, Yusuke Tanaka, Ruriko Nakae, Akiko Morimoto, Yoshito Terai, Masahide Ohmichi, Tomoyuki Ichimura, Toshiyuki Sumi, Hiromi Murata, Hidetaka Okada, Hidekatsu Nakai, Masaki Mandai, Shinya Matsuzaki, Eiji Kobayashi, Kiyoshi Yoshino, Tadashi Kimura, Junko Saito, Yumiko Hori, Eiichi Morii, Tomio Nakayama, Yukio Suzuki, Yoko Motoki, Akiko Sukegawa, Mikiko Asai-Sato, Etsuko Miyagi, Manako Yamaguchi, Risa Kudo, Sosuke Adachi, Masayuki Sekine, Takayuki Enomoto, Yorihiko Horikoshi, Tetsu Takagi, Kentaro Shimura

    HUMAN VACCINES & IMMUNOTHERAPEUTICS13 ( 7 ) 1700 - 1704   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS INC  

    Objective: In Japan, the possible adverse events upon HPV vaccination was widely reported in the media. MHLW announced the suspension of aggressively encouraging HPV vaccination in 2013, and inoculation rate has sharply declined. The aim of the present study was estimation of future cervical cancer risk.
    Methods: The latest data on vaccination rate at each age in Sakai City were first investigated. The rate of experiencing sexual intercourse at the age of 12, 13, 14, 15, 16, 17 and throughout lifetime is assumed to be 0%, 1%, 2%, 5%, 15%, 25%, and 85% respectively. The cervical cancer risk was regarded to be proportional to the relative risk of HPV infection over the lifetime. The risk in those born in 1993 whom HPV vaccination was not available yet for was defined to be 1.0000.
    Results: The cumulative vaccination rates were 65.8% in those born in 1994, 72.7% in 1995, 72.8% in 1996, 75.7% in 1997, 75.0% in 1998, 66.8% in 1999, 4.1% in 2000, 1.5% in 2001, 0.1% in 2002, and 0.1% in 2003. The relative cervical cancer risk in those born in 1994-1999 was reduced to 0.56-0.70, however, the rate in those born in 2000-2003 was 0.98-1.0, almost the same risk as before introduction of the vaccine.
    Discussion: The cumulative initial vaccination rates were different by the year of birth. It is confirmed that the risk of future cervical cancer differs in accordance with the year of birth. For these females, cervical cancer screening should be recommended more strongly.

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  • Project conducted in Hirakata to improve cervical cancer screening rates in 20-year-old Japanese: Influencing parents to recommend that their daughters undergo cervical cancer screening 査読

    Asami Yagi, Yutaka Ueda, Tomomi Egawa-Takata, Yusuke Tanaka, Yoshito Terai, Masahide Ohmichi, Tomoyuki Ichimura, Toshiyuki Sumi, Hiromi Murata, Hidetaka Okada, Hidekatsu Nakai, Masaki Mandai, Shinya Matsuzaki, Eiji Kobayashi, Kiyoshi Yoshino, Tadashi Kimura, Junko Saito, Yumiko Hori, Eiichi Morii, Tomio Nakayama, Yukio Suzuki, Yoko Motoki, Akiko Sukegawa, Mikiko Asai-Sato, Etsuko Miyagi, Manako Yamaguchi, Risa Kudo, Sosuke Adachi, Masayuki Sekine, Takayuki Enomoto, Yorihiko Horikoshi, Tetsu Takagi, Kentaro Shimura

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH42 ( 12 ) 1802 - 1807   2016年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Aim: In Japan, the rate of routine cervical cancer screening is quite low, and the incidence of cervical cancer has recently been increasing. Our objective was to investigate ways to effectively influence parental willingness to recommend that their 20-year-old daughters undergo cervical cancer screening.
    Methods: We targeted parents whose 20-year-old daughters were living with them. In fiscal year 2013, as usual, the daughter received a reminder postcard several months after they had received a free coupon for cervical cancer screening. In fiscal year 2014, the targeted parents received a cervical cancer information leaflet, as well as a cartoon about cervical cancer to show to their daughters, with a request that they recommend to their daughter that she undergo cervical cancer screening. The subsequent screening rates for fiscal years 2013 and 2014 were compared.
    Results: The cervical cancer screening rate of 20-year-old women whose parents received the information packet in fiscal year 2014 was significantly higher than for the women who, in fiscal year 2013, received only a simple reminder postcard (P &lt; 0.001). As a result, the total screening rate for 20-year-old women for the whole of the 2014 fiscal year was significantly increased over 2013 (P &lt; 0.001).
    Conclusion: For the first time, we have shown that the parents of 20-year-old daughters can be motivated to recommend that their daughters receive their first cervical cancer screening. This was achieved by sending a cervical cancer information leaflet and a cartoon about cervical cancer for these parents to show to their daughters. This method was significantly effective for improving cervical cancer screening rates.

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  • 出生年度によって異なるHPVワクチン接種率がもたらす、将来のHPV16/18感染リスクの格差 査読

    田中 佑典, 上田 豊, 八木 麻未, 高田 友美, 松崎 慎哉, 吉野 潔, 佐藤 美紀子, 宮城 悦子, 榎本 隆之, 中山 富雄, 森井 英一, 木村 正

    日本癌学会総会記事75回   P - 1360   2016年10月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • Mothers' attitudes in Japan regarding cervical cancer screening correlates with intention to recommend cervical cancer screening for daughters 査読

    Tomomi Egawa-Takata, Yutaka Ueda, Yusuke Tanaka, Akiko Morimoto, Satoshi Kubota, Asami Yagi, Yoshito Terai, Masahide Ohmichi, Tomoyuki Ichimura, Toshiyuki Sumi, Hiromi Murata, Hidetaka Okada, Hidekatsu Nakai, Masaki Mandai, Kiyoshi Yoshino, Tadashi Kimura, Junko Saito, Risa Kudo, Masayuki Sekine, Takayuki Enomoto, Yorihiko Horikoshi, Tetsu Takagi, Kentaro Shimura

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY21 ( 5 ) 962 - 968   2016年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER JAPAN KK  

    Cervical cancer and its precancerous lesions caused by human papilloma virus (HPV) are steadily increasing in women in Japan. In comparison with women in other resource-rich countries, young women in Japan have a dismally low screening rate for cervical cancer. Our preliminary research has shown that 20-year-old women in Japan usually ask their mothers for advice regarding their initial cervical cancer screening. The objective of our current research is to determine the social factors among mothers in Japan that are causing them to give advice to their daughters regarding the HPV vaccine and cervical cancer screening.
    The survey's targets were mothers who had 20-year-old daughters. We recruited respondents from the roster of a commercial internet survey panel. We analyzed for correlations between a mother's knowledge concerning cervical cancer, her recent cancer screening history, and the advice she gave to her daughter regarding cervical cancer screening.
    We obtained 618 valid answers to the survey. Compared with mothers who did not get screening, mothers who had cervical cancer screening had significantly more knowledge about cervical cancer and its screening (p &lt; 0.05). The daughters of mothers with recent screening had received HPV vaccination more often than those of mothers without recent screening (p = 0.018). Mothers with recent screening histories tended more often to encourage their daughters to have cervical cancer screening (p &lt; 0.05). When mothers were properly educated concerning cervical cancer and its screening, they were significantly more likely than before to recommend that their daughters have it (p &lt; 0.0001).
    In young Japanese women, given the important role their mothers have in their lives, it is probable that we could improve their cervical cancer screening rate significantly by giving their mothers better medical information, and a chance to experience cervical cancer screening for themselves.

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  • Development of an efficient strategy to improve HPV immunization coverage in Japan 査読

    Asami Yagi, Yutaka Ueda, Tomomi Egawa-Takata, Yusuke Tanaka, Akiko Morimoto, Yoshito Terai, Masahide Ohmichi, Tomoyuki Ichimura, Toshiyuki Sumi, Hiromi Murata, Hidetaka Okada, Hidekatsu Nakai, Masaki Mandai, Kiyoshi Yoshino, Tadashi Kimura, Junko Saito, Risa Kudoh, Masayuki Sekine, Takayuki Enomoto, Kei Hirai, Yorihiko Horikoshi, Tetsu Takagi, Kentaro Shimura

    BMC PUBLIC HEALTH16 ( 1 ) 1013   2016年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: In Japan, new HPV immunizations have dropped dramatically after repeated adverse media reports and a June 2013 temporary suspension of the government's recommendation for the vaccine. The aim of the present study was to develop an efficient strategy to improve HPV immunization coverage across Japan.
    Methods: We conducted an internet survey in Japan of mothers of 12-16 year-old girls who were unvaccinated as of May, 2015. The goal was to gather behavioral information from the mothers to develop a strategy for improving Japanese HPV immunization coverage.
    Results: Valid survey answers were obtained from 2060 mothers. The survey found that a hypothetical restart of a governmental recommendation for the vaccine would induce 4.1 % of all the mothers surveyed to be more likely to encourage vaccination of their daughters, without any other preconditions. This initial result would be followed by a moderate spread of vaccinations to these daughters' close friends and acquaintances, hypothetically resulting in a total vaccination rate of 21.0 % of the targeted age-eligible girls. As a second critical step for improving vaccinations, an educational information sheet integrating the concepts of behavioral economics for changing behaviors was found to be significantly effective for persuading mothers with poorer decision-making facilities, who would otherwise prefer to wait to first see the vaccination of other girls of the same age as their daughter.
    Conclusions: Following what we foresee as the inevitable restart of the Japanese government's recommendation for receiving the HPV vaccine, we expect to first see vaccinations occurring in a very small group of girls, the daughters of the most willing mothers, which will be roughly 4 % of those eligible for government paid vaccinations. This will be followed by the spread of vaccinations outward through these girls' circle of friends and acquaintances, and, finally, to the daughters of the most skeptical mothers, those who would await the return of new vaccine safety results from a large group of similarly-aged girls. As a critical step in improving HPV vaccine coverage in Japan, an educational information sheet that integrates the concepts of behavioral economics for changing behaviors can be employed to persuade mothers with poor decision-making facilities.

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  • Case with pyoderma gangrenosum abruptly emerging around the wound of cesarean section for placenta previa with placenta accrete 査読

    Taro Nonaka, Kunihiko Yoshida, Masayuki Yamaguchi, Atsuko Aizawa, Hiroshi Fujiwara, Takayuki Enomoto, Koichi Takakuwa

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH42 ( 9 ) 1190 - 1193   2016年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    A 39-year-old woman underwent emergency cesarean section (CS) due to placenta previa totalis with massive bleeding. Two major problems emerged in this patient after CS was carried out. One was partial retention of the placenta due to placenta accreta. Another major and more serious problem was pyoderma gangrenosum (PG) widely appearing at the skin of the abdomen around the CS wound. Conservative treatment was performed for the retained placenta, and it had completely disappeared by 76 days after the CS. The diagnosis of PG was promptly made in consultation with a plastic surgeon and a dermatologist when a wide ulcer emerged around the CS wound, and high-dose prednisolone was administered as treatment. At 90 days following the CS, near-complete epithelialization was achieved. This extremely rare case reflects the importance of rapid diagnosis and treatment of PG.

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  • Randomized Phase III Trial of Irinotecan Plus Cisplatin Compared With Paclitaxel Plus Carboplatin As First-Line Chemotherapy for Ovarian Clear Cell Carcinoma: JGOG3017/GCIG Trial 査読

    Toru Sugiyama, Aikou Okamoto, Takayuki Enomoto, Tetsutaro Hamano, Eriko Aotani, Yasuhisa Terao, Nao Suzuki, Mikio Mikami, Nobuo Yaegashi, Kiyoko Kato, Hiroyuki Yoshikawa, Yoshihito Yokoyama, Hiroshi Tanabe, Koji Nishino, Hiroyuki Nomura, Jae-Weon Kim, Byoung-Gie Kim, Sandro Pignata, Jerome Alexandre, John Green, Seiji Isonishi, Fumitoshi Terauchi, Keiichi Fujiwara, Daisuke Aoki

    JOURNAL OF CLINICAL ONCOLOGY34 ( 24 ) 2881 - +   2016年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

    Purpose
    Clear cell carcinoma (CCC) is a rare histologic subtype that demonstrates poor outcomes in epithelial ovarian cancer. The Japanese Gynecologic Oncology Group conducted the first randomized phase III, CCC-specific clinical trial that compared irinotecan and cisplatin (CPT-P) with paclitaxel plus carboplatin (TC) in patients with CCC.
    Patients and Methods
    Six hundred sixty-seven patients with stage I to IV CCC of the ovary were randomly assigned to receive irinotecan 60 mg/m(2) on days 1, 8, and 15 plus cisplatin 60 mg/m2 on day 1 (CPT-P group) every 4 weeks for six cycles or paclitaxel 175 mg/m2 plus carboplatin area under the curve 6.0mg/mL/min on day 1 every 3 weeks for six cycles (TC group). The primary end point was progression free survival. Secondary end points were overall survival, overall response rate, and adverse events.
    Results
    Six hundred nineteen patients were clinically and pathologically eligible for evaluation. With a median follow-up of 44.3 months, 2-year progression-free survival rates were 73.0% in the CPT-P group and 77.6% in TC group (hazard ratio, 1.17; 95% CI, 0.87 to 1.58; P = .85). Two-year overall survival rates were 85.5% with CPT-P and 87.4% with TC (hazard ratio, 1.13; 95% CI, 0.80 to 1.61; one-sided P = .76). Grade 3/4 anorexia, diarrhea, nausea, vomiting, and febrile neutropenia occurred more frequently with CPT-P, whereas grade 3/4 leukopenia, neutropenia, thrombocytopenia, peripheral sensory neuropathy, and joint pain occurred more frequently with TC.
    Conclusion
    No significant survival benefit was found for CPT- P. Both regimens were well tolerated, but the toxicity profiles differed significantly. Treatment with existing anticancer agents has limitations to improving the prognosis of CCC. (C) 2016 by American Society of Clinical Oncology

    DOI: 10.1200/JCO.2016.66.9010

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  • Bcl11b/Ctip2 is required for development of lingual papillae in mice 査読

    Yugo Nishiguchi, Makoto Ohmoto, Jun Koki, Takayuki Enomoto, Ryo Kominami, Ichiro Matsumoto, Junji Hirota

    DEVELOPMENTAL BIOLOGY416 ( 1 ) 98 - 110   2016年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Molecular mechanisms underlying the development and morphogenesis of oral epithelia, comprising the gustatory and nongustatory epithelium, remain unclear. Here, we show that Bcl11b, a zinc finger transcription factor, plays an important role in the development of lingual papillae, especially filiform papillae. In both gustatory and nongustatory epithelium, Bcl11b was expressed in keratin 14-positive epithelial basal cells, which differentiate into keratinocytes and/or taste cells. Loss of Bcl11b function resulted in abnormal morphology of the gustatory papillae: flattened fungiform papillae, shorter trench wall in the foliate and circumvallate papillae, and ectopic invagination in more than half of circumvallate papillae. However, Bcl11b loss caused no effect on differentiation of taste receptor cells. In nongustatory epithelium, the impact of Bcl11b deficiency was much more striking, resulting in a smooth surface on the tongue tip and hypoplastic filiform papillae in the dorsal lingual epithelium. Immunohistochemical analyses revealed that a keratinocyte differentiation marker, Tchh expression was severely decreased in the Bcl11b(-/-) filiform papillae. In addition, expression of Pax9, required for morphogenesis of filiform papillae and its downstream target genes, hard keratins, almost disappeared in the tongue tip and was decreased in the dorsal tongue of Bcl11b(-/-) mice. Gene expression analyses demonstrated a delayed onset of expression of epithelial differentiation complex genes, which disturbed barrier formation in the mutant tongue. These results indicate that Bcl11b regulates the differentiation of keratinocytes in the tongue and identify Bcl11b as an essential factor for the lingual papilla morphogenesis. (C) 2016 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.ydbio.2016.06.001

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  • Association of Low-Dose Aspirin and Survival of Women With Endometrial Cancer 査読

    Koji Matsuo, Sigita S. Cahoon, Kosuke Yoshihara, Masako Shida, Mamoru Kakuda, Sosuke Adachi, Aida Moeini, Hiroko Machida, Jocelyn Garcia-Sayre, Yutaka Ueda, Takayuki Enomoto, Mikio Mikami, Lynda D. Roman, Anil K. Sood

    OBSTETRICS AND GYNECOLOGY128 ( 1 ) 127 - 137   2016年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    OBJECTIVE: To examine the survival outcomes in women with endometrial cancer who were taking low-dose aspirin (81-100 mg/d).
    METHODS: A multicenter retrospective study was conducted examining patients with stage I-IV endometrial cancer who underwent hysterectomy-based surgical staging between January 2000 and December 2013 (N=1,687). Patient demographics, medical comorbidities, medication types, tumor characteristics, and treatment patterns were correlated to survival outcomes. A Cox proportional hazard regression model was used to estimate adjusted hazard ratio for disease-free and disease-specific overall survival.
    RESULTS: One hundred fifty-eight patients (9.4%, 95% confidence interval [CI] 8.8-11.9) were taking low-dose aspirin. Median follow-up time for the study cohort was 31.5 months. One hundred twenty-seven patients (7.5%) died of endometrial cancer. Low-dose aspirin use was significantly correlated with concurrent obesity, hypertension, diabetes mellitus, and hypercholesterolemia (all P&lt;.001). Low-dose aspirin users were more likely to take other antihypertensive, antiglycemic, and anticholesterol agents (all P&lt;.05). Low-dose aspirin use was not associated with histologic subtype, tumor grade, nodal metastasis, or cancer stage (all P&gt;.05). On multivariable analysis, low-dose aspirin use remained an independent prognostic factor associated with an improved 5-year disease-free survival rate (90.6% compared with 80.9%, adjusted hazard ratio 0.46, 95% CI 0.25-0.86, P=.014) and disease-specific overall survival rate (96.4% compared with 87.3%, adjusted hazard ratio 0.23, 95% CI 0.08-0.64, P=.005). The increased survival effect noted with low-dose aspirin use was greatest in patients whose age was younger than 60 years (5-year disease-free survival rates, 93.9% compared with 84.0%, P=.013), body mass index was 30 or greater (92.2% compared with 81.4%, P=.027), who had type I cancer (96.5% compared with 88.6%, P=.029), and who received postoperative whole pelvic radiotherapy (88.2% compared with 61.5%, P=.014). These four factors remained significant for disease-specific overall survival (all P&lt;.05).
    CONCLUSION: Our results suggest that low-dose aspirin use is associated with improved survival outcomes in women with endometrial cancer, especially in those who are young, obese, with low-grade disease, and who receive postoperative radiotherapy.

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  • Significance of histologic pattern of carcinoma and sarcoma components on survival outcomes of uterine carcinosarcoma. 査読

    Matsuo K, Takazawa Y, Ross MS, Elishaev E, Podzielinski I, Yunokawa M, Sheridan TB, Bush SH, Klobocista MM, Blake EA, Takano T, Matsuzaki S, Baba T, Satoh S, Shida M, Nishikawa T, Ikeda Y, Adachi S, Yokoyama T, Takekuma M, Fujiwara K, Hazama Y, Kadogami D, Moffitt MN, Takeuchi S, Nishimura M, Iwasaki K, Ushioda N, Johnson MS, Yoshida M, Hakam A, Li SW, Richmond AM, Machida H, Mhawech-Fauceglia P, Ueda Y, Yoshino K, Yamaguchi K, Oishi T, Kajiwara H, Hasegawa K, Yasuda M, Kawana K, Suda K, Miyake TM, Moriya T, Yuba Y, Morgan T, Fukagawa T, Wakatsuki A, Sugiyama T, Pejovic T, Nagano T, Shimoya K, Andoh M, Shiki Y, Enomoto T, Sasaki T, Fujiwara K, Mikami M, Shimada M, Konishi I, Kimura T, Post MD, Shahzad MM, Im DD, Yoshida H, Omatsu K, Ueland FR, Kelley JL, Karabakhtsian RG, Roman LD

    Annals of oncology : official journal of the European Society for Medical Oncology27 ( 7 ) 1257 - 1266   2016年7月

  • Single-dose intra-arterial neoadjuvant chemotherapy while waiting for radical hysterectomy for stage IB-IIB cervical cancer. 査読

    Yoshino K, Hosoi A, Osuga K, Enomoto T, Ueda Y, Sawada K, Mabuchi S, Kobayashi E, Matsuo K, Kimura T

    Molecular and clinical oncology4 ( 6 ) 1068 - 1072   2016年6月

  • 20-21歳女性におけるHPVワクチン接種とHPV感染率、および性活動性との相関 査読

    関根 正幸, 山口 真奈子, 工藤 梨沙, 安達 聡介, 田中 佑典, 森本 晶子, 高田 友美, 八木 麻未, 上田 豊, 榎本 隆之

    日本婦人科腫瘍学会雑誌34 ( 3 ) 411 - 411   2016年6月

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    記述言語:日本語   出版者・発行元:(公社)日本婦人科腫瘍学会  

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  • Japanese crisis of HPV vaccination 査読

    Masayuki Sekine, Risa Kudo, Sosuke Adachi, Manako Yamaguchi, Yutaka Ueda, Tomomi Takata, Akiko Morimoto, Yusuke Tanaka, Asami Yagi, Etsuko Miyagi, Takayuki Enomoto

    Int J Pathol Clin Res2 ( 039s )   2016年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Establishment of a Novel Histopathological Classification of High-Grade Serous Ovarian Carcinoma Correlated with Prognostically Distinct Gene Expression Subtypes 査読

    Ryusuke Murakami, Noriomi Matsumura, Masaki Mandai, Kosuke Yoshihara, Hiroshi Tanabe, Hidekatsu Nakai, Koji Yamanoi, Kaoru Abiko, Yumiko Yoshioka, Junzo Hamanishi, Ken Yamaguchi, Tsukasa Baba, Masafumi Koshiyama, Takayuki Enomoto, Aikou Okamoto, Susan K. Murphy, Seiichi Mori, Yoshiki Mikami, Sachiko Minamiguchi, Ikuo Konishi

    AMERICAN JOURNAL OF PATHOLOGY186 ( 5 ) 1103 - 1113   2016年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Recently, The Cancer Genome Atlas data revealed four molecular subtypes of high-grade serous ovarian carcinoma (HGSOC) exhibiting distinct prognoses. We developed four novel HGSOC histopathological subtypes by focusing on tumor microenvironment: mesenchymal transition, defined by a remarkable desmoplastic reaction; immune reactive by lymphocytes infiltrating the tumor; solid and proliferative by a solid growth pattern; and papilloglandular by a papillary architecture. Unsupervised hierarchical clustering revealed four clusters correlated with histopathological subtypes in both Kyoto and Niigata HGSOC transcriptome data sets (P &lt; 0.001). Gene set enrichment analysis revealed pathways enriched in our histopathological classification significantly overlapped with the four molecular subtypes: mesenchymal, immunoreactive, proliferative, and differentiated (P &lt; 0.0001, respectively). In 132 HGSOC cases, progression-free survival and overall survival were best in the immune reactive, whereas overall survival was worst in the mesenchymal transition (P &lt; 0.001, respectively), findings reproduced in 89 validation cases (P &lt; 0.05, respectively). The CLOVAR_MES_UP single-sample gene set enrichment analysis scores representing the mesenchymal molecular subtype were higher in paclitaxel responders than nonresponders (P = 0.002) in the GSE15622 data set. Taxane-containing regimens improved survival of cases with high MES_UP scores compared with nontaxane regimens (P &lt; 0.001) in the GSE9891 data set. Our novel histopathological classification of HGSOC correlates with distinct prognostic transcriptome subtypes. The mesenchymal transition subtype might be particularly sensitive to taxane.

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  • A phase II study of postoperative concurrent carboplatin and paclitaxel combined with intensity-modulated pelvic radiotherapy followed by consolidation chemotherapy in surgically treated cervical cancer patients with positive pelvic lymph nodes 査読

    Seiji Mabuchi, Fumiaki Isohashi, Takeshi Yokoi, Masahiko Takemura, Kiyoshi Yoshino, Yasuhiko Shiki, Kimihiko Ito, Takayuki Enomoto, Kazuhiko Ogawa, Tadashi Kimura

    GYNECOLOGIC ONCOLOGY141 ( 2 ) 240 - 246   2016年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Objectives. A phase II study was conducted to evaluate the efficacy and toxicity of carboplatin plus paclitaxel (TC)-based postoperative concurrent chemoradiotherapy (CCRT) followed by TC-based consolidation chemotherapy in surgically-treated early-stage cervical cancer patients.
    Methods. Women with surgically-treated early-stage cervical cancer with positive pelvic lymph nodes were eligible for this study. The patients were postoperatively treated with pelvic intensity modulated radiotherapy (50.4 Gy) and concurrent weekly carboplatin (AUC: 2) and paclitaxel (35 mg/m(2)) (TC-based CCRT). Three cycles of consolidation chemotherapy involving carboplatin (AUC: 5) and paclitaxel (175 mg/m2) were administered after TC-based CCRT.
    Results. Thirty-one patients were enrolled and treated. Overall, the treatment was well tolerated, and 26 patients (83.9%) completed the planned TC-based CCRT. The most frequently observed acute grade 3/4 hematological toxicities were leukopenia and neutropenia, and diarrhea was the most common acute grade 3/4 non hematological toxicity. After a median follow-up period of 36.5 months,. 2 patients (6.5%) had developed recurrent disease. The patients' estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 88.5% and 93.8%, respectively. In comparisons with historical control groups, TC-based CCRT followed by TC-based consolidation chemotherapy was found to be significantly superior to CCRT involving a single platinum agent in terms of PFS (p = 0.026) and significantly superior to extended-field radiotherapy in terms of both PFS (p = 0.0004) and OS (p = 0.034).
    Conclusions. In women with surgically treated early-stage cervical cancer, pelvic TC-based CCRT followed by TC-based consolidation chemotherapy is feasible and highly effective. Future randomized trials are needed to verify the efficacy of this regimen. (C) 2016 Elsevier Inc. All rights reserved.

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  • Allelic Imbalance in Regulation of ANRIL through Chromatin Interaction at 9p21 Endometriosis Risk Locus. 査読 国際誌

    Hirofumi Nakaoka, Aishwarya Gurumurthy, Takahide Hayano, Somayeh Ahmadloo, Waleed H Omer, Kosuke Yoshihara, Akihito Yamamoto, Keisuke Kurose, Takayuki Enomoto, Shigeo Akira, Kazuyoshi Hosomichi, Ituro Inoue

    PLoS genetics12 ( 4 ) e1005893   2016年4月

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    記述言語:英語  

    Genome-wide association studies (GWASs) have discovered numerous single nucleotide polymorphisms (SNPs) associated with human complex disorders. However, functional characterization of the disease-associated SNPs remains a formidable challenge. Here we explored regulatory mechanism of a SNP on chromosome 9p21 associated with endometriosis by leveraging "allele-specific" functional genomic approaches. By re-sequencing 1.29 Mb of 9p21 region and scrutinizing DNase-seq data from the ENCODE project, we prioritized rs17761446 as a candidate functional variant that was in perfect linkage disequilibrium with the original GWAS SNP (rs10965235) and located on DNase I hypersensitive site. Chromosome conformation capture followed by high-throughput sequencing revealed that the protective G allele of rs17761446 exerted stronger chromatin interaction with ANRIL promoter. We demonstrated that the protective allele exhibited preferential binding affinities to TCF7L2 and EP300 by bioinformatics and chromatin immunoprecipitation (ChIP) analyses. ChIP assays for histone H3 lysine 27 acetylation and RNA polymerase II reinforced the enhancer activity of the SNP site. The allele specific expression analysis for eutopic endometrial tissues and endometrial carcinoma cell lines showed that rs17761446 was a cis-regulatory variant where G allele was associated with increased ANRIL expression. Our work illuminates the allelic imbalances in a series of transcriptional regulation from factor binding to gene expression mediated by chromatin interaction underlie the molecular mechanism of 9p21 endometriosis risk locus. Functional genomics on common disease will unlock functional aspect of genotype-phenotype correlations in the post-GWAS stage.

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  • Allelic Imbalance in Regulation of ANRIL through Chromatin Interaction at 9p21 Endometriosis Risk Locus 査読

    Hirofumi Nakaoka, Aishwarya Gurumurthy, Takahide Hayano, Somayeh Ahmadloo, Waleed H. Omer, Kosuke Yoshihara, Akihito Yamamoto, Keisuke Kurose, Takayuki Enomoto, Shigeo Akira, Kazuyoshi Hosomichi, Ituro Inoue

    PLOS GENETICS12 ( 4 )   2016年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Genome-wide association studies (GWASs) have discovered numerous single nucleotide polymorphisms (SNPs) associated with human complex disorders. However, functional characterization of the disease-associated SNPs remains a formidable challenge. Here we explored regulatory mechanism of a SNP on chromosome 9p21 associated with endometriosis by leveraging "allele-specific" functional genomic approaches. By re-sequencing 1.29 Mb of 9p21 region and scrutinizing DNase-seq data from the ENCODE project, we prioritized rs17761446 as a candidate functional variant that was in perfect linkage disequilibrium with the original GWAS SNP (rs10965235) and located on DNase I hypersensitive site. Chromosome conformation capture followed by high-throughput sequencing revealed that the protective G allele of rs17761446 exerted stronger chromatin interaction with ANRIL promoter. We demonstrated that the protective allele exhibited preferential binding affinities to TCF7L2 and EP300 by bioinformatics and chromatin immunoprecipitation (ChIP) analyses. ChIP assays for histone H3 lysine 27 acetylation and RNA polymerase II reinforced the enhancer activity of the SNP site. The allele specific expression analysis for eutopic endometrial tissues and endometrial carcinoma cell lines showed that rs17761446 was a cis-regulatory variant where G allele was associated with increased ANRIL expression. Our work illuminates the allelic imbalances in a series of transcriptional regulation from factor binding to gene expression mediated by chromatin interaction underlie the molecular mechanism of 9p21 endometriosis risk locus. Functional genomics on common disease will unlock functional aspect of genotype-phenotype correlations in the post-GWAS stage.

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  • The utility of anatomic diagnosis for identifying femoral nerve palsy following gynecologic surgery 査読

    Tatsunori Watanabe, Masayuki Sekine, Takayuki Enomoto, Hiroshi Baba

    JOURNAL OF ANESTHESIA30 ( 2 ) 317 - 319   2016年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER JAPAN KK  

    We describe a case in which an anatomic diagnosis was useful for diagnosing and estimating the cause of femoral nerve palsy following gynecologic surgery. A 49-year-old female received general and epidural anesthesia for radical ovarian cancer surgery. Although injection pain was noted in the left medial shin with 1 % mepivacaine administered as a test dose, the catheter was left indwelling because it improved her symptoms. The surgery, which lasted 195 min, was performed in the lithotomy position, and a self-retained retractor was used to gain a good surgical field. Postoperatively, the patient complained of difficulty in stretching her knee joint and left lower limb paresthesia that did not improve after stopping continuous epidural administration. A spinal cord injury related to epidural anesthesia was suspected because the sites of sensory impairment and epidural injection pain were the same; however, the patient had greater weakness of the quadriceps muscle than the iliopsoas, and no other muscle weakness was observed. These findings and previous reports suggest that her femoral nerve palsy was caused by compression of the inguinal ligament from the self-retaining retractor and lithotomy position. Twenty months after surgery, her muscle strength had fully recovered.

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  • Similar protein expression profiles of ovarian and endometrial high-grade serous carcinomas 査読

    Kosuke Hiramatsu, Kiyoshi Yoshino, Satoshi Serada, Kosuke Yoshihara, Yumiko Hori, Minoru Fujimoto, Shinya Matsuzaki, Tomomi Egawa-Takata, Eiji Kobayashi, Yutaka Ueda, Eiichi Morii, Takayuki Enomoto, Tetsuji Naka, Tadashi Kimura

    BRITISH JOURNAL OF CANCER114 ( 5 ) 554 - 561   2016年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Background: Ovarian and endometrial high-grade serous carcinomas (HGSCs) have similar clinical and pathological characteristics; however, exhaustive protein expression profiling of these cancers has yet to be reported.
    Methods: We performed protein expression profiling on 14 cases of HGSCs (7 ovarian and 7 endometrial) and 18 endometrioid carcinomas (9 ovarian and 9 endometrial) using iTRAQ-based exhaustive and quantitative protein analysis.
    Results: We identified 828 tumour-expressed proteins and evaluated the statistical similarity of protein expression profiles between ovarian and endometrial HGSCs using unsupervised hierarchical cluster analysis (P&lt;0.01). Using 45 statistically highly expressed proteins in HGSCs, protein ontology analysis detected two enriched terms and proteins composing each term: IMP2 and MCM2. Immunohistochemical analyses confirmed the higher expression of IMP2 and MCM2 in ovarian and endometrial HGSCs as well as in tubal and peritoneal HGSCs than in endometrioid carcinomas (P&lt;0.01). The knockdown of either IMP2 or MCM2 by siRNA interference significantly decreased the proliferation rate of ovarian HGSC cell line (P&lt;0.01).
    Conclusions: We demonstrated the statistical similarity of the protein expression profiles of ovarian and endometrial HGSC beyond the organs. We suggest that increased IMP2 and MCM2 expression may underlie some of the rapid HGSC growth observed clinically.

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  • インターネット調査による子宮頸癌検診に対する意識調査と有効な勧奨手法 査読

    安達 聡介, 山口 真奈子, 工藤 梨沙, 関根 正幸, 榎本 隆之, 上田 豊, 高田 友美, 森本 晶子, 田中 佑典, 八木 麻未

    日本産科婦人科学会雑誌68 ( 2 ) 825 - 825   2016年2月

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    記述言語:日本語   出版者・発行元:(公社)日本産科婦人科学会  

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  • 若年女性を対象としたHPVワクチンに対するインターネット意識調査と有効な勧奨手法 査読

    山口 真奈子, 関根 正幸, 工藤 梨沙, 安達 聡介, 榎本 隆之, 上田 豊, 高田 友美, 森本 晶子, 田中 佑典, 八木 麻未

    日本産科婦人科学会雑誌68 ( 2 ) 823 - 823   2016年2月

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    記述言語:日本語   出版者・発行元:(公社)日本産科婦人科学会  

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  • Human papillomavirus vaccination of the daughters of obstetricians and gynecologists in Japan 査読

    Tomomi Egawa-Takata, Yutaka Ueda, Akiko Morimoto, Yusuke Tanaka, Shinya Matsuzaki, Eiji Kobayashi, Kiyoshi Yoshino, Masayuki Sekine, Takayuki Enomoto, Tadashi Kimura

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY21 ( 1 ) 53 - 58   2016年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER JAPAN KK  

    Most adolescents in Japan have recently been refraining from receiving the human papillomavirus (HPV) vaccine, following media reports of adverse medical events surrounding the vaccination and suspension of the Japanese governmental recommendation. We have previously reported that HPV vaccination of young girls is heavily influenced by guidance from their physicians concerning the vaccine and by the knowledge and attitude of the girls' mothers towards cervical cancer. However, it has been unclear as to how the obstetricians and gynecologists were themselves affected by the negative media reports.
    A questionnaire, including questions about their working status, attitudes toward HPV vaccination and about cervical cancer, and the HPV vaccination status of their daughters, was posted to obstetricians and gynecologists.
    None of the daughters of the responding obstetrician and gynecologists received the HPV vaccination after the announced suspension of the governmental recommendation for the vaccine. The number who received the HPV vaccine in the 6th to 9th grade in 2014 was significantly lower than those in 2012 (p = 0.012). However, 64.7 % of the responders whose daughters were eligible and in the 6th to 12th grade still intended to vaccinate their daughters in the future. Of the responders, 65 % also intended to recommend vaccination to their teenage patients.
    Our study revealed that obstetricians and gynecologists, like the general population, were negatively influenced by media reports of the adverse effect of the HPV vaccine and the suspension of the governmental recommendation. However, their intention to vaccinate their daughters was much higher than that of the general population. Restart of the governmental recommendation for HPV vaccines and better education about the HPV vaccine, including its adverse effects, and about cervical cancer and cervical cancer screening, are strongly recommended, for both the general public and for doctors, for improved prevention of cervical cancer.

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  • 20-21歳女性におけるHPVワクチン接種とHPV感染率および性活動性との相関 査読

    関根 正幸, 山口 真奈子, 工藤 梨沙, 安達 聡介, 榎本 隆之, 上田 豊, 高田 友美, 森本 晶子, 田中 佑典, 八木 麻未

    日本産科婦人科学会雑誌68 ( 2 ) 825 - 825   2016年2月

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    記述言語:日本語   出版者・発行元:(公社)日本産科婦人科学会  

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  • 若年者子宮がん検診受診率向上プロジェクト 母親を介した20歳女性に対する子宮がん検診受診勧奨 査読

    八木 麻未, 上田 豊, 高田 友美, 田中 佑典, 関根 正幸, 榎本 隆之, 大道 正英, 角 俊幸, 岡田 英孝, 万代 昌紀, 木村 正, 志村 研太郎

    日本産科婦人科学会雑誌68 ( 2 ) 824 - 824   2016年2月

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    記述言語:日本語   出版者・発行元:(公社)日本産科婦人科学会  

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  • Early metabolic change in F-18-FDG-PET by measuring the single largest lesion predicts chemotherapeutic effects and patients' survival: PEACH study 査読

    Yusuke Tanaka, Yutaka Ueda, Tomomi Egawa-Takata, Shinya Matsuzaki, Eiji Kobayashi, Kiyoshi Yoshino, Takayuki Enomoto, Mitsuaki Tatsumi, Tadashi Kimura

    CANCER CHEMOTHERAPY AND PHARMACOLOGY77 ( 1 ) 121 - 126   2016年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    The objective of this study was to investigate the predictive value of F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) for early assessment of tumor response to chemotherapy and for patient survival in gynecologic malignancies.
    We performed CT and FDG-PET scans before initiation of chemotherapy to determine baseline conditions. PET scan was repeated after the first cycle of chemotherapy. The tumor response was later evaluated by CT scans after three cycles of chemotherapy, using RECIST. The PET response was analyzed in terms of the difference in SUVmax for FDG of the patient's largest lesion between the baseline scan and after the first cycle of chemotherapy. The metabolic response for the tumor was defined as a 30 % reduction in its SUVmax.
    Eleven patients received platinum-based regimens, and 20 patients received non-platinum-based regimens. The mean progression-free survival (PFS) for the patients with a metabolic response was 13 months (range 5-29). In contrast, the mean PFS of the patients with no metabolic response was only 4.3 months (range 1-18). There was a statistically significant difference between the metabolic response and PFS (p = 0.002, Mann-Whitney U test). There was a strong correlation between the metabolic response and RECIST, regardless of the chemotherapy regimens used (platinum-based group, p = 0.006; non-platinum group, p = 0.046, Fisher's exact test). The metabolic change in SUVmax was clearly predictive of tumor response in 93.5 % of patients.
    Early FDG-PET assessment by measuring the single largest lesion is a very promising tool for rapidly predicting tumor responses and patient survival, regardless of the chemotherapy regimen.

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  • Association of NR3C1/Glucocorticoid Receptor gene SNP with azoospermia in Japanese men 査読

    Makoto Chihara, Kosuke Yoshihara, Tatsuya Ishiguro, Sosuke Adachi, Hiroyuki Okada, Katsunori Kashima, Takaaki Sato, Atsushi Tanaka, Kenichi Tanaka, Takayuki Enomoto

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH42 ( 1 ) 59 - 66   2016年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    AimThe molecular pathogenesis of non-obstructive azoospermia (NOA) is unclear. Our aim was to identify the genetic susceptibility for NOA in Japanese men by using a combination of transcriptome network analysis and SNP genotyping.
    Material and MethodsWe searched for candidate genes using RNA transcriptome network analysis of 2611 NOA-related genes that we had previously reported. We analyzed candidate genes for disease linkage with single nucleotide polymorphisms (SNP) in the genomes of 335 Japanese men with NOA and 410 healthy controls using SNP-specific real-time polymerase chain reaction TaqMan assays.
    ResultsThree candidate genes (NR3C1, YBX2, and BCL2) were identified by the transcriptome network analysis, each with three SNP. Allele frequency analysis of the nine SNP indicated a significantly higher frequency of the NR3C1 rs852977 G allele in NOA cases compared with controls (corrected P = 5.7e-15; odds ratio = 3.20; 95% confidence interval, 2.40-4.26). The other eight candidate polymorphisms showed no significant association.
    ConclusionThe NR3C1 rs852977 polymorphism is a potential marker for genetic susceptibility to NOA in Japanese men. Further studies are necessary to clarify the association between the NR3C1 polymorphism and alterations of glucocorticoid signaling pathway leading to male infertility.

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  • Establishment and Characterization of an In Vitro Model of Ovarian Cancer Stem-like Cells with an Enhanced Proliferative Capacity 査読

    Tatsuya Ishiguro, Ai Sato, Hirokazu Ohata, Yoshinori Ikarashi, Ryou-u Takahashi, Takahiro Ochiya, Masayuki Yoshida, Hitoshi Tsuda, Takashi Onda, Tomoyasu Kato, Takahiro Kasamatsu, Takayuki Enomoto, Kenichi Tanaka, Hitoshi Nakagama, Koji Okamoto

    CANCER RESEARCH76 ( 1 ) 150 - 160   2016年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    The establishment of cancer stem-like cell (CSC) culture systems may be instrumental in devising strategies to fight refractory cancers. Inhibition of the Rho kinase ROCK has been shown to favorably affect CSC spheroid cultures. In this study, we show how ROCK inhibition in human serous ovarian cancer (SOC) cells can help establish a CSC system, which illuminates cancer pathophysiology and its treatment in this setting. In the presence of a ROCK kinase inhibitor, spheroid cultures of SOC cells expressed characteristic CSC markers including ALDH1A1, CD133, and SOX2, along with differentiation and tumorigenic capabilities in mouse xenograft models of human SOC. High expression levels of ALDH, but not CD133, correlated with spheroid formation CSC marker expression and tumor forming capability. In clinical specimens of SOC, high levels of ALDH1A1 correlated with advanced stage and poor prognosis. Pharmacologic or genetic blockade of ALDH blocked cell proliferation and reduced expression of SOX2, the genetic ablation of which abolished spheroid formation, whereas SOX2 overexpression inhibited ALDH1A1 expression and blocked spheroid proliferation. Taken together, our findings illustrated a new method to culture human ovarian CSC, and they defined a reciprocal regulatory relationship between ALDH1A1 and SOX2, which impacts ovarian CSC proliferation and malignant progression. (C)2015 AACR.

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  • Novel kinase fusion transcripts found in endometrial cancer 査読

    Ryo Tamura, Kosuke Yoshihara, Kaoru Yamawaki, Kazuaki Suda, Tatsuya Ishiguro, Sosuke Adachi, Shujiro Okuda, Ituro Inoue, Roel G. W. Verhaak, Takayuki Enomoto

    SCIENTIFIC REPORTS5   18657   2015年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Recent advances in RNA-sequencing technology have enabled the discovery of gene fusion transcripts in the transcriptome of cancer cells. However, it remains difficult to differentiate the therapeutically targetable fusions from passenger events. We have analyzed RNA-sequencing data and DNA copy number data from 25 endometrial cancer cell lines to identify potential therapeutically targetable fusion transcripts, and have identified 124 high-confidence fusion transcripts, of which 69% are associated with gene amplifications. As targetable fusion candidates, we focused on three in-frame kinase fusion transcripts that retain a kinase domain (CPQ-PRKDC, CAPZA2-MET, and VGLL4-PRKG1). We detected only CPQ-PRKDC fusion transcript in three of 122 primary endometrial cancer tissues. Cell proliferation of the fusion-positive cell line was inhibited by knocking down the expression of wild-type PRKDC but not by blocking the CPQ-PRKDC fusion transcript expression. Quantitative real-time RT-PCR demonstrated that the expression of the CPQ-PRKDC fusion transcript was significantly lower than that of wild-type PRKDC, corresponding to a low transcript allele fraction of this fusion, based on RNA-sequencing read counts. In endometrial cancers, the CPQ-PRKDC fusion transcript may be a passenger aberration related to gene amplification. Our findings suggest that transcript allele fraction is a useful predictor to find bona-fide therapeutic-targetable fusion transcripts.

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  • Survey of Japanese mothers of daughters eligible for human papillomavirus vaccination on attitudes about media reports of adverse events and the suspension of governmental recommendation for vaccination 査読

    Tomomi Egawa-Takata, Yutaka Ueda, Akiko Morimoto, Kiyoshi Yoshino, Tadashi Kimura, Nobumichi Nishikawa, Masayuki Sekine, Yorihiko Horikoshi, Tetsu Takagi, Takayuki Enomoto

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH41 ( 12 ) 1965 - 1971   2015年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Aim: Following media reports of adverse medical events surrounding human papillomavirus (HPV) vaccination and the suspension of Japanese governmental recommendation, most adolescents have refrained from receiving the vaccine. This represents a national critical event, because the incidence of cervical cancer in Japan continues to increase.
    Methods: We conducted an Internet survey to investigate why Japanese adolescent girls decline, continue or discontinue their HPV vaccination, how their mothers influence their decision, and the mothers' feelings about future HPV vaccination for their daughters. One thousand mothers with daughters 10-18 years of age were recruited for our questionnaire.
    Results: Our results suggest that acceptance of the HPV vaccine was determined predominantly by the mother's perceptions of risk versus benefits, rather than the daughter's wishes. The mothers' knowledge of the benefits of the prophylactic HPV vaccine and their attitude toward cervical cancer screening influenced their decision whether to allow their daughter to receive future vaccinations. The tenor of survey responses of those mothers who were anti-vaccine changed significantly to the positive in response to a proposed scenario where the governmental recommendation for the HPV vaccine was reinstated, whereas a hypothetical educational intervention sheet did not significantly change their attitude.
    Conclusions: Promotion of the HPV vaccine through comprehensive education for both mothers and daughters, not only on the vaccine itself, but also about cervical cancer and screening, is required for any successful program to prevent cervical cancer.

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  • [Mesorectal Lymph Node Metastasis Arising from Rectal Invasion by an Ovarian Cancer--A Case Report]. 査読

    Mizuki T, Shimada Y, Yagi Y, Tajima Y, Nakano M, Nakano M, Tatsuda K, Ishikawa T, Sakata J, Kameyama H, Kobayashi T, Kosugi S, Koyama Y, Wakai T, Enomoto T

    Gan to kagaku ryoho. Cancer & chemotherapy42 ( 12 ) 2300 - 2302   2015年11月

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  • CpG oligodeoxynucleotides potentiate the antitumor activity of anti-BST2 antibody 査読

    Kosuke Hiramatsu, Satoshi Serada, Kouji Kobiyama, Satoshi Nakagawa, Akiko Morimoto, Shinya Matsuzaki, Yutaka Ueda, Minoru Fujimoto, Kiyoshi Yoshino, Ken J. Ishii, Takayuki Enomoto, Tadashi Kimura, Tetsuji Naka

    CANCER SCIENCE106 ( 10 ) 1474 - 1478   2015年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Numerous monoclonal antibodies (mAb) targeting tumor antigens have recently been developed. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) via effector cells such as tumor-infiltrating natural killer (NK) cells and macrophages are often involved in mediating the antitumor activity of mAb. CpG oligodeoxynucleotides (ODN) have a potent antitumor activity and are considered to increase tumor infiltration of NK cells and macrophages. Our group previously reported significant antitumor activity of anti-bone marrow stromal antigen 2 (BST2) mAb against BST2-positive endometrial cancer cells through ADCC. In this study, we evaluated the synergistic antitumor activity of combination therapy with anti-BST-2 mAb and CpG ODN using SCID mice and elucidated the mechanisms underlying this activity. Anti-BST2 mAb and CpG ODN monotherapy had a significant dose-dependent antitumor activity (P=0.0135 and P=0.0196, respectively). Combination therapy with anti-BST2 mAb and CpG ODN had a significant antitumor activity in SCID mice (P&lt;0.01), but not in NOG mice. FACS analysis revealed significantly increased numbers of NK cells and macrophages in tumors treated with a combination of anti-BST2 mAb and CpG ODN and with CpG ODN alone in SCID mice (P&lt;0.05 and P&lt;0.01, respectively). These results suggested that the combination therapy with anti-BST2 mAb and CpG ODN has a significant antitumor activity and induces tumor infiltration of NK cells and macrophages. Combination therapy with CpG ODN and anti-BST2 mAb or other antitumor mAb depending on ADCC may represent a new treatment option for cancer.

    DOI: 10.1111/cas.12738

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  • Venous thromboembolism, interleukin-6 and survival outcomes in patients with advanced ovarian clear cell carcinoma 査読

    Koji Matsuo, Kosei Hasegawa, Kiyoshi Yoshino, Ryusuke Murakami, Takeshi Hisamatsu, Rebecca L. Stone, Rebecca A. Previs, Jean M. Hansen, Yuji Ikeda, Akiko Miyara, Kosuke Hiramatsu, Takayuki Enomoto, Keiichi Fujiwara, Noriomi Matsumura, Ikuo Konishi, Lynda D. Roman, Hani Gabra, Christina Fotopoulou, Anil K. Sood

    EUROPEAN JOURNAL OF CANCER51 ( 14 ) 1978 - 1988   2015年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI LTD  

    Background: We compared survival outcomes and risk of venous thromboembolism (VTE) among patients with advanced and early-stage ovarian clear cell carcinoma (OCCC) and serous ovarian carcinoma (SOC), as well as potential links with interleukin-6 (IL-6) levels.
    Methods: A multicenter case-control study was conducted in 370 patients with OCCC and 938 with SOC. In a subset of 200 cases, pretreatment plasma IL-6 levels were examined.
    Findings: Patients with advanced OCCC had the highest 2-year cumulative VTE rates (advanced OCCC 43.1%, advanced SOC 16.2%, early-stage OCCC 11.9% and early-stage SOC 6.4%, P &lt; 0.0001) and the highest median levels of IL-6 (advanced OCCC 17.8 pg/mL, advanced SOC 9.0 pg/mL, early-stage OCCC 4.2 pg/mL and early-stage SOC 5.0 pg/mL, P = 0.006). Advanced OCCC (hazard ratio [HR] 3.38, P &lt; 0.0001), thrombocytosis (HR 1.42, P = 0.032) and elevated IL-6 (HR 8.90, P = 0.046) were independent predictors of VTE. In multivariate analysis, patients with advanced OCCC had significantly poorer 5-year progression-free and overall survival rates than those with advanced SOC (P &lt; 0.01), and thrombocytosis was an independent predictor of decreased survival outcomes (P &lt; 0.01). Elevated IL-6 levels led to poorer 2-year progression-free survival rates in patients with OCCC (50% versus 87.5%, HR 4.89, P = 0.016) than in those with SOC (24.9% versus 40.8%, HR 1.40, P = 0.07).
    Interpretation: Advanced OCCC is associated with an increased incidence of VTE and decreased survival outcomes, which has major implications for clinical management of OCCC. (C) 2015 Elsevier Ltd. All rights reserved.

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  • Differential diagnosis of uterine smooth muscle tumors using diffusion-weighted imaging: correlations with the apparent diffusion coefficient and cell density 査読

    Akiko Tasaki, Mina O. Asatani, Hajime Umezu, Katsunori Kashima, Takayuki Enomoto, Norihiko Yoshimura, Hidefumi Aoyama

    ABDOMINAL IMAGING40 ( 6 ) 1742 - 1752   2015年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    The purpose of this study is to investigate the utility of the apparent diffusion coefficient (ADC) in differentiating benign and malignant uterine smooth muscle tumors classified by signal intensity (SI) on T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI), and to determine the correlation between ADC and tumor cell density. This retrospective study reviewed 168 lesions in 134 cases with pathologically confirmed uterine smooth muscle tumors, including 6 leiomyosarcomas and 3 smooth muscle tumors of uncertain malignant potential, and preoperative magnetic resonance imaging examinations performed between October 2009 and November 2012. T2WI and DWI were also performed for each subject. Tumors were then classified according to SI on T2WI and DWI relative to myometrial SI. The correlation between ADC and tumor cell density was also determined. In Group 1 (high on both T2WI/DWI), mean ADC was significantly lower for leiomyosarcoma (0.91 x 10(-3) mm(2)/s) than for leiomyoma (1.30 x 10(-3) mm(2)/s; p &lt; 0.05) and mean cell density significantly higher for leiomyosarcoma (42.9%) than for leiomyoma (22.4%; p &lt; 0.05). A strong negative correlation was seen between ADC and tumor cell density in Group 1 (Spearman, R = -0.72; p &lt; 0.05). ADC may help to differentiate benign from malignant uterine smooth muscle tumors, particularly tumors with high SI on T2WI and DWI.

    DOI: 10.1007/s00261-014-0324-5

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  • 20歳の女性の母親に対するインターネット調査 若年者の子宮がん検診受診率向上を目指して 査読

    八木 麻未, 上田 豊, 高田 友美, 森本 晶子, 田中 佑典, 吉野 潔, 工藤 梨沙, 関根 正幸, 榎本 隆之, 木村 正

    日本がん検診・診断学会誌23 ( 1 ) 53 - 53   2015年8月

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    記述言語:日本語   出版者・発行元:(NPO)日本がん検診・診断学会  

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  • Effect on HPV vaccination in Japan resulting from news report of adverse events and suspension of governmental recommendation for HPV vaccination 査読

    Akiko Morimoto, Yutaka Ueda, Tomomi Egawa-Takata, Asami Yagi, Yoshito Terai, Masahide Ohmichi, Tomoyuki Ichimura, Toshiyuki Sumi, Hiromi Murata, Hideharu Kanzaki, Hidekatsu Nakai, Masaki Mandai, Kiyoshi Yoshino, Masami Fujita, Tadashi Kimura, Junko Saito, Tomotaka Sobue, Nobumichi Nishikawa, Masayuki Sekine, Takayuki Enomoto, Yorihiko Horikoshi, Tetsu Takagi

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY20 ( 3 ) 549 - 555   2015年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER JAPAN KK  

    Administration of the human papillomavirus (HPV) vaccine decreased dramatically in Japan after extensive news of adverse vaccine events and suspension of the governmental recommendation for the vaccine. In this study, we investigated the knowledge and acceptance of vaccinated adolescents concerning cervical cancer, cancer screening and the HPV vaccine. Furthermore, we analyzed whether and by how much the news affected acceptance of the vaccination.
    This study was conducted as a part of Osaka Clinical resEArch of HPV vacciNe (OCEAN) study. A questionnaire was distributed to 2,777 study registrants.
    The response rate was 38 %. The recognition rate of the news of the vaccine's adverse events was 80 %; it was 68 % for awareness of the government's announcement of the suspension of its recommendation for the vaccine. Among those who had a chance to hear or see the negative news during their vaccination period, 46 (60 %) continued vaccination while knowing of the news, 22 (29 %) discontinued vaccination, and 9 (11 %) continued vaccination without an awareness of the news. Reports of the vaccine's adverse events were the main reason for not continuing the vaccination series. Those who consulted doctors after hearing the adverse news were significantly more likely to continue their vaccinations than those who did not.
    Our results should help in understanding the need for a strong promotion of vaccine usage and cancer screening after future retraction of the recommendation suspension. This may apply to other countries with an unsatisfactory rate of HPV vaccination due to fears of adverse vaccine events.

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  • Susceptibility to male infertility: replication study in Japanese men looking for an association with four GWAS-derived loci identified in European men 査読

    Makoto Chihara, Kosuke Yoshihara, Tatsuya Ishiguro, Yuki Yokota, Sosuke Adachi, Hiroyuki Okada, Katsunori Kashima, Takaaki Sato, Atsushi Tanaka, Kenichi Tanaka, Takayuki Enomoto

    JOURNAL OF ASSISTED REPRODUCTION AND GENETICS32 ( 6 ) 903 - 908   2015年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER/PLENUM PUBLISHERS  

    A previous genome-wide association study in European men identified four single nucleotide polymorphism (SNP) loci associated with male infertility. Our aim was to replicate, if possible, the association of these SNPs with Japanese male infertility.
    We genotyped four SNPs (rs5911500, rs10246939, rs2059807, and rs11204546) in 517 Japanese patients with male infertility and 369 fertile controls using SNP-specific real-time polymerase chain reaction TaqMan assays. Subsequently, we divided patients with male infertility into azoospermia (n = 417) and oligospermia subgroups (n = 70).
    The four SNPs previously identified in European men showed no significant association with collective male infertility in our Japanese cohort. However, allele frequency analysis did indicate a significantly higher frequency of the rs11204546 C allele of the OR2W3 gene in the oligospermia subset of infertility patients compared with controls (p = 0.0037; odds ratio = 1.74; 95 % confidence interval, 1.21-2.53).
    Although this study was somewhat limited by overall sample size, the OR2W3 gene polymorphism rs11204546 was significantly associated with oligospermia in Japanese men, suggesting that OR2W3 might be involved in genetic susceptibility to Japanese male infertility as well as in European males.

    DOI: 10.1007/s10815-015-0468-4

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  • Japan's failure to vaccinate girls against human papillomavirus 査読

    Yutaka Ueda, Takayuki Enomoto, Masayuki Sekine, Tomomi Egawa-Takata, Akiko Morimoto, Tadashi Kimura

    AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY212 ( 3 ) 405 - 406   2015年3月

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    記述言語:英語   出版者・発行元:MOSBY-ELSEVIER  

    OBJECTIVE: Human papillomavirus (HPV) vaccination has proven to be effective for prevention of HPV infection and HPV-associated precancerous cervical lesions.(1) However, HPV vaccination rates have remained flat, and whether or not to vaccinate has become a social issue. In the United States in 2013, HPV vaccine coverage for girls ages 13-17 years was only 57%.(2) A notable inhibitory factor to getting vaccinated has been reports of possible adverse effects. Safety concerns among US parents have increased (4.5% in 2008 to 16.4% in 2010), as have intentions not to vaccinate their daughters against HPV (39.8% in 2008 to 43.9% in 2010; odds ratio for trend, 1.08; 95% confidence interval, 1.04-1.13).(3)
    STUDY DESIGN: In Japan, financial support of the government was initiated from 2011, and recommendation was initiated in April 2013. However, Japan has failed to capitalize on the HPV vaccine's potential for cervical cancer prevention. Japanese media reports in May and June 2013 concerning the vaccine's potential for adverse effects including complex regional pain syndrome and suspension of the government's recommendation for the vaccination on June 14, 2013, have led to public distrust and a dramatic decrease in HPV vaccination rates.(4) To demonstrate the depth of the problem, we analyzed the HPV vaccine coverage for 7th-grade girls in Sakai, Japan. We looked at those who had initiated their 3-dosage series either before or after the negative media reports ran. Girls from 7-11th grade were vaccination targets, with vaccinations at the 7th-grade level being the most desirable.
    RESULTS: The first trimester of the Japanese school year runs from April 1 through late July; the summer break is about 6 weeks. The adverse Japanese media reports and the Ministry of Health, Labor, and Welfare suspension announcement occurred about 40 days prior to summer vacation, during which the girls in Sakai were expected to go to a clinic for HPV vaccination. During the summer vacation period of 2012, nearly half of the 7th-grade girls got an inoculation. However, in 2013, the number of girls vaccinated in May began to decrease following the news reports, and by late June it was almost 0 (Figure, A). The vaccination rates of the 7-10th graders who had an opportunity for vaccination prior to the media reports were between 57.8-74.8% (2012). However, following the adverse reports, the rate plunged from 65.4% (2012) to 3.9% (2013) (incidence rate ratio, 0.060; 95% confidence interval, 0.051-0.071) (Figure, B). The girls received HPV vaccination mostly in the 7th grade. The rate of the number of those vaccinated in 7th grade was 70.4% (7th grade: 2632; and 8-10th grade: 1105) in 2012. In 2013, not only the number of those vaccinated in 7th grade but also those in 8-10th grades decreased significantly (7th grade: 158; and 8-10th grade: 90).
    CONCLUSION: Improved education around the critical importance of HPV vaccine and screening for cervical cancer prevention is needed worldwide.

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  • Somatic Copy Number Alterations Associated with Japanese or Endometriosis in Ovarian Clear Cell Adenocarcinoma 査読

    Aikou Okamoto, Jalid Sehouli, Nozomu Yanaihara, Yukihiro Hirata, Ioana Braicu, Byoung-Gie Kim, Satoshi Takakura, Misato Saito, Satoshi Yanagida, Masataka Takenaka, Noriko Yamaguchi, Asuka Morikawa, Hiroshi Tanabe, Kyosuke Yamada, Kosuke Yoshihara, Takayuki Enomoto, Hiroaki Itamochi, Junzo Kigawa, Noriomi Matsumura, Ikuo Konishi, Satoshi Aida, Yuko Aoki, Nobuya Ishii, Kazunori Ochiai, Tetsu Akiyama, Mitsuyoshi Urashima

    PLOS ONE10 ( 2 ) e0116977   2015年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    When compared with other epithelial ovarian cancers, the clinical characteristics of ovarian clear cell adenocarcinoma (CCC) include 1) a higher incidence among Japanese, 2) an association with endometriosis, 3) poor prognosis in advanced stages, and 4) a higher incidence of thrombosis as a complication. We used high resolution comparative genomic hybridization (CGH) to identify somatic copy number alterations (SCNAs) associated with each of these clinical characteristics of CCC. The Human Genome CGH 244A Oligo Microarray was used to examine 144 samples obtained from 120 Japanese, 15 Korean, and nine German patients with CCC. The entire 8q chromosome (minimum corrected p-value: q = 0.0001) and chromosome 20q13.2 including the ZNF217 locus (q = 0.0078) were amplified significantly more in Japanese than in Korean or German samples. This copy number amplification of the ZNF217 gene was confirmed by quantitative real-time polymerase chain reaction (Q-PCR). ZNF217 RNA levels were also higher in Japanese tumor samples than in non-Japanese samples (P = 0.027). Moreover, endometriosis was associated with amplification of EGFR gene (q = 0.047), which was again confirmed by Q-PCR and correlated with EGFR RNA expression. However, no SCNAs were significantly associated with prognosis or thrombosis. These results indicated that there may be an association between CCC and ZNF217 amplification among Japanese patients as well as between endometriosis and EGFR gene amplifications.

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  • Survival outcome of stage I ovarian clear cell carcinoma with lympho-vascular space invasion 査読

    Koji Matsuo, Kiyoshi Yoshino, Kosei Hasegawa, Ryusuke Murakami, Yuji Ikeda, Sosuke Adachi, Kosuke Hiramatsu, Takuhei Yokoyama, Masato Nishimura, Todd B. Sheridan, Takayuki Enomoto, Keiichi Fujiwara, Noriomi Matsumura, Ikuo Konishi, Christina Fotopoulou, Lynda D. Roman, Anil K. Sood

    GYNECOLOGIC ONCOLOGY136 ( 2 ) 198 - 204   2015年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Background. The clinical impact of lympho-vascular space invasion (LVSI) in early-stage ovarian clear cell carcinoma (OCCC) is not well understood. Given the distinct tumor biology and survival patterns of OCCC, the significance of LVSI on survival outcome and treatment response was examined in OCCC.
    Methods. A multicenter study was conducted to examine stage IA-IC3 OCCC cases that underwent primary surgical staging including lymphadenectomy. LVSI status was determined from archived histopathology slides, correlated with clinico-pathological results, chemotherapy patterns, and survival outcomes.
    Results. LVSI was observed in 47 (20.3%) among 232 cases. In univariate analysis, LVSI was associated with older age (p = 0.042), large tumor size (p = 0.048), and stage IC (p = 0.035). In survival analysis, LVSI was associated with decreased disease-free survival (DFS, 5-year rate, 70.6% versus 92.1%, p = 0.0004) and overall survival (OS, 78.8% versus 93.3%, p = 0.008) on univariate analysis. After controlling for age, tumor size, stage, and chemotherapy use, LVSI remained an,independent prognostic factor for decreased survival outcomes (DFS, hazard ratio [HR] 4.35, 95% confidence interval [CI] 1.73-10.9, p = 0.002; and OS, HR 4.73, 95%CI 1.60-14.0, p = 0.015). Among 210 cases who received postoperative chemotherapy, while regimen type did not impact survival outcome regardless of LVSI status (DFS, p = 0.63), the number of administered cycles showed a survival benefit towards cycles for patients with LVSI-positive tumors (DFS, p = 0.009; and OS, p = 0.016).
    Conclusion. LVSI is an important marker to predict survival outcome of stage I OCCC. Regardless of chemotherapy type, patients with stage I OCCC showing LVSI may benefit from receiving postoperative chemotherapy. (C) 2014 Elsevier Inc. All rights reserved.

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  • Evaluation of a Free-Coupon Program for Cervical Cancer Screening Among the Young: A Nationally Funded Program Conducted by a Local Government in Japan 査読

    Yutaka Ueda, Tomotaka Sobue, Akiko Morimoto, Tomomi Egawa-Takata, Chie Hashizume, Hisayo Kishida, Satomi Okamoto, Kiyoshi Yoshino, Masami Fujita, Takayuki Enomoto, Yoshimi Tomine, Jun Fukuyoshi, Tadashi Kimura

    JOURNAL OF EPIDEMIOLOGY25 ( 1 ) 50 - 56   2015年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPAN EPIDEMIOLOGICAL ASSOC  

    Background: Finding ways to improve the cervical cancer screening rates among young women has been seen as a critical national health problem in many countries, including Japan. The aim of the present study was to evaluate the effects of a free-coupon program for cervical cancer screening conducted by a local government under financial support from the Japanese national government.
    Methods: The personal cervical cancer screening information was analyzed for all female residents of Toyonaka City, including any past screening history and clinical results since the year 2009, when a free-coupon program for screening was started. These results were compared to results from 2008, prior to implementation of the free-coupon screening program.
    Results: The screening rates of women eligible for the free-coupon peaked dramatically compared to women of similar age who paid for their screening; however, the rates for the ineligible-age population also increased significantly in parallel to those in the free-coupon program, possibly by indirect peer and publicity effects. In women aged 20 to 25 years, the consecutive screening rate after a free-coupon screening was significantly lower than for those women who received a regular residential screening. After a free-coupon screening, the rate for participating in consecutive screenings depended significantly on the institution where the participant received her first screening test.
    Conclusions: These results suggest that, for a generation of young women 20-25 years of age, a free-coupon program for cervical cancer screening was effective in increasing the first-time participation rate for screening; however, the increase in first-time participation did not lead to the expected increase in consecutive screenings.

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  • Complex chromosomal rearrangements in couples affected by recurrent spontaneous abortion 査読

    Taro Nonaka, Izumi Ooki, Takayuki Enomoto, Koichi Takakuwa

    INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS128 ( 1 ) 36 - 39   2015年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    Objective: To determine the proportion of couples affected by recurrent spontaneous abortion in which one partner carries balanced translocations among three chromosomes. Methods: In a retrospective study, G-banded chromosome complements were analyzed for couples affected by recurrent spontaneous abortion who were referred to Niigata University Hospital, Japan, between January 1, 1990, and December 31, 2011. The frequency of couples in whom one of the partners carried balanced translocations among three chromosomes was determined, and the clinical outcomes for affected couples who subsequently achieved term pregnancies were reviewed. Results: Of 1415 couples with recurrent spontaneous abortion during the study period, there were two (0.1%) in which one of the partners (the woman in both cases) carried balanced translocations among three chromosomes. Both couples achieved a subsequent pregnancy that continued successfully and resulted in a phenotypically normal neonate. Conclusion: The frequency of balanced translocations among three chromosomes was estimated to be approximately 0.1% in a population affected by recurrent spontaneous abortion. With appropriate treatment based on careful examinations, affected couples can go on to achieve a successful pregnancy outcome. (C) 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

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  • Identification of novel exonic mobile element insertions in epithelial ovarian cancers. 査読 国際誌

    Takahide Hayano, Shiro Yamada, Kazuyoshi Hosomichi, Hirofumi Nakaoka, Kosuke Yoshihara, Sosuke Adachi, Katsunori Kashima, Kenichi Tanaka, Takayuki Enomoto, Ituro Inoue

    Human genome variation2   15030 - 15030   2015年

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    記述言語:英語  

    Mobile elements comprise about half of the human genome. Three active mobile element families (L1, Alu, and SVA) possibly cause diseases such as cancer. We conducted mobile element insertion (MEI) profiling of 44 epithelial ovarian cancers using exome-sequencing data. We identified a total of 106 MEIs using the Mobster program, 8 of which were novel exonic MEIs.

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  • Prenatal molecular diagnosis of X-linked hydrocephalus via a silent C924T mutation in the L1CAM gene 査読

    Takehiro Serikawa, Kenichi Nishiyama, Jun Tohyama, Ryushi Tazawa, Kiyoe Goto, Yoko Kuriyama, Kazufumi Haino, Yonehiro Kanemura, Mami Yamasaki, Koh Nakata, Koichi Takakuwa, Takayuki Enomoto

    CONGENITAL ANOMALIES54 ( 4 ) 243 - 245   2014年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    The Majewski syndrome or short rib-polydactyly syndrome (SRPS) type II is a lethal skeletal dysplasia characterized by severe IUGR (intrauterine growth restriction) and dysmorphic face, polydactyly, relatively proportionate head size at birth with later progression to microcephaly. A case of second trimester ultrasound diagnosis of SRPS type II is reported with review of the medical record of previous observed cases. Postmortem examination and radiogram confirmed the clinical diagnosis. Histological examination of the femoral epypheseal chondral plate showed an expanded and irregular hypertrophic zone. Moreover, characteristic cortico-medullary cysts of both kidneys and portal fibrosis were also demonstrated; findings consistent with the broad phenotypic spectrum of this rare skeletal disease.

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  • Outcomes and Prognostic Factors for Adenocarcinoma/Adenosquamous Carcinomas Treated with Radical Hysterectomy and Adjuvant Therapy 査読

    Masayuki Yamaguchi, Yoko Yamagishi, Nobumichi Nishikawa, Masayuki Sekine, Takehiro Serikawa, Katsunori Kashima, Takayuki Enomoto

    Open Journal of Obstetrics and Gynecology4 ( 14 ) 909 - 915   2014年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • 常染色体劣性多発性嚢胞腎が疑われた出生前診断症例に関する検討 査読

    生野 寿史, 山口 雅幸, 芹川 武大, 和田 雅樹, 榎本 隆之, 高桑 好一

    日本遺伝カウンセリング学会誌35 ( 3 ) 117 - 120   2014年10月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Annexin A4 induces platinum resistance in a chloride-and calcium-dependent manner 査読

    Akiko Morimoto, Satoshi Serada, Takayuki Enomoto, Ayako Kim, Shinya Matsuzaki, Tsuyoshi Takahashi, Yutaka Ueda, Kiyoshi Yoshino, Masami Fujita, Minoru Fujimoto, Tadashi Kimura, Tetsuji Naka

    ONCOTARGET5 ( 17 ) 7776 - 7787   2014年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:IMPACT JOURNALS LLC  

    Platinum resistance has long been a major issue in the treatment of various cancers. We previously reported that enhanced annexin A4 (ANXA4) expression, a Ca2+-regulated phospholipid-binding protein, induces chemoresistance to platinum-based drugs. In this study, we investigated the role of annexin repeats, a conserved structure of all the annexin family, responsible for platinum-resistance as well as the effect of knockdown of ANXA4. ANXA4 knockdown increased sensitivity to platinum-based drugs both in vitro and in vivo. To identify the domain responsible for chemoresistance, ANXA4 deletion mutants were constructed by deleting annexin repeats one by one from the C terminus. Platinum resistance was induced both in vitro and in vivo in cells expressing either full-length ANXA4 or the deletion mutants, containing at least one intact annexin repeat. However, cells expressing the mutant without any calcium-binding sites in the annexin repeated sequence, which is essential for ANXA4 translocation from the cytosol to plasma membrane, failed to acquire platinum resistance. After cisplatin treatment, the intracellular chloride ion concentration, whose channel is partly regulated by ANXA4, significantly increased in the platinum-resistant cells. These findings indicate that the calcium-binding site in the annexin repeat induces chemoresistance to the platinum-based drug by elevating the intracellular chloride concentration.

    DOI: 10.18632/oncotarget.2306

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  • Successful management of severe intrahepatic cholestasis of pregnancy: report of a first Japanese case 査読

    Kenya Kamimura, Hiroyuki Abe, Naomi Kamimura, Masayuki Yamaguchi, Maiko Mamizu, Kanna Ogi, Yoshifumi Takahashi, Ken-ichi Mizuno, Hiroteru Kamimura, Yuji Kobayashi, Manabu Takeuchi, Kunihiko Yoshida, Kyoko Yamada, Takayuki Enomoto, Koichi Takakuwa, Minoru Nomoto, Miki Obata, Yoshinori Katsuragi, Yukio Mishima, Ryo Kominami, Tomoteru Kamimura, Yutaka Aoyagi

    BMC GASTROENTEROLOGY14   160   2014年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: Intrahepatic cholestasis of pregnancy (ICP) is a cholestasis condition caused by elevated levels of serum bile acids that mainly occurs in the third trimester of pregnancy. Maternal symptoms include pruritus; elevation of transaminases, biliary enzymes, and bilirubin levels; and abnormal liver function tests. Fetal symptoms include spontaneous preterm labor, fetal distress, and intrauterine death. It is more prevalent in the Caucasians and is rarely found in Asian countries, including Japan. The etiology of ICP has been reported as involving various factors such as, environmental factors, hormone balance, and genetic components. The genetic factors include single-nucleotide polymorphisms (SNPs) in the genes of canalicular transporters, including ABCB4 and ABCB11. It has also been reported that the combination of these SNPs induces severe cholestasis and liver dysfunction.
    Case presentation: Here, we report for the first time a 24-year Japanese case of severe ICP diagnosed by typical symptoms, serum biochemical analysis, and treated with the administration of ursodeoxycholic acid which improved cholestasis and liver injury and prevented fetal death. The sequence analysis showed SNPs reported their association with ICP in the ABCB11 (rs2287622, V444A) and ABCB4 (rs1202283, N168N) loci.
    Conclusion: The risk of ICP has been reported to be population-specific, and it is rare in the Japanese population. Our case was successfully treated with ursodeoxycholic acid and the genetic sequence analysis has supported the diagnosis. Because genetic variation in ABCB4 and ABCB11 has also been reported in the Japanese population, we need to be aware of potential ICP cases in pregnant Japanese women although further studies are necessary.

    DOI: 10.1186/1471-230X-14-160

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  • 妊娠26週未満破水症例の後方視的検討 招待 査読

    鈴木 美保, 山口 雅幸, 島 英里, 冨永 麻理恵, 松本 賢典, 田村 亮, 佐藤 ひとみ, 能仲 太郎, 榎本 隆之, 生野 寿史, 高桑 好一

    新潟産科婦人科学会会誌109 ( 2 ) 79 - 84   2014年9月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • 重篤な疾患を合併する妊産婦の管理 泌尿器系 腎不全、透析中の妊娠 招待 査読

    高桑 好一, 能仲 太郎, 佐藤 ひとみ, 生野 寿史, 山口 雅幸, 榎本 隆之

    周産期医学44 ( 9 ) 1177 - 1179   2014年9月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Two cases of recurrent abortion in which isodicentric chromosome 15 was observed in the husbands 査読

    Taro Nonaka, Izumi Ooki, Takayuki Enomoto, Koichi Takakuwa

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH40 ( 6 ) 1795 - 1798   2014年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    We report two cases of women positive for anticardiolipin antibodies who experienced recurrent abortion whose husbands had isodicentric chromosome 15 aberrations who eventually had successful pregnancies. Two women were referred to our hospital due to their medical history of recurrent abortion. Both were diagnosed as being positive for anticardiolipin antibodies and their husbands with isodicentric chromosome 15. After both patients were treated with a Japanese herbal medicine (Sairei-to) and low-dose aspirin for the positive anticardiolipin antibodies, they delivered appropriate-for-date infants at term gestation. Although both husbands were revealed to have isodicentric chromosome 15, and coincidentally both wives were positive for anticardiolipin antibodies, their next pregnancies continued uneventfully as a result of the treatment.

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  • Preoperative Ultrasound-Guided Needle Biopsy of 63 Uterine Tumors Having High Signal Intensity Upon T2-Weighted Magnetic Resonance Imaging 査読

    Ryo Tamura, Katsunori Kashima, Mina Asatani, Koji Nishino, Nobumichi Nishikawa, Masayuki Sekine, Takehiro Serikawa, Takayuki Enomoto

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER24 ( 6 ) 1042 - 1047   2014年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Objective The differential diagnosis between uterine sarcoma and benign leiomyoma is difficult when made only by magnetic resonance imaging (MRI); it usually requires an additional preoperative diagnostic procedure. We report our results using ultrasound-guided needle biopsy for these types of uterine tumors.
    Methods Ultrasound-guided needle biopsy was performed on 63 patients with uterine smooth muscle tumors suspected of malignancy by MRI. We compared the results of presurgical biopsy against the postsurgical pathology of the tumor.
    Results Among 63 patients with a high signal intensity of the uterine tumor on T2-weighted MRI (1 case was undetermined), 12 cases (19.3%) were diagnosed by the needle biopsy as malignant, and 51 cases (80.6%) were benign. Among the 12 diagnosed as malignant tumors, 11 had surgery performed, and one was treated with chemotherapy. Among the 51 patients diagnosed with a benign tumor, 27 had surgery performed, and 24 were put on a wait-and-see clinical follow-up schedule. One of the 27 surgical patients with a benign tumor had a postsurgical diagnosis of a low-grade endometrial stromal sarcoma. In the 38 cases where surgery was performed, we found the sensitivity, specificity, and the positive and negative predictive values of the needle biopsy were 91.7%, 100%, 100%, and 96.2%, respectively.
    Conclusions Ultrasound-guided needle biopsy may be a reliable preoperative diagnostic procedure for uterine tumors with suspected malignancy.

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  • Novel alleles of Lan- in Japanese populations. 査読

    Tanaka M, Yamamuro Y, Takahashi J, Ogasawara K, Osabe T, Tsuneyama H, Enomoto T, Watanabe S, Uchikawa M, Tadokoro K, Tani Y

    Transfusion54 ( 5 ) 1438 - 1439   2014年5月

  • Effect of Lymphovascular Space Invasion on Survival of Stage I Epithelial Ovarian Cancer 査読

    Koji Matsuo, Kiyoshi Yoshino, Kosuke Hiramatsu, Chiaki Banzai, Kosei Hasegawa, Masanori Yasuda, Masato Nishimura, Todd B. Sheridan, Yuji Ikeda, Yasuhiko Shiki, Seiji Mabuchi, Takayuki Enomoto, Tadashi Kimura, Keiichi Fujiwara, Lynda D. Roman, Anil K. Sood

    OBSTETRICS AND GYNECOLOGY123 ( 5 ) 957 - 965   2014年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    OBJECTIVE: To evaluate the effect of lymphovascular space invasion on survival of patients with early-stage epithelial ovarian cancer.
    METHODS: A multicenter retrospective study was conducted for patients with stage IA-C epithelial ovarian cancer who underwent primary comprehensive surgery including lymphadenectomy. Histopathology slides for ovarian tumors were examined by gynecologic pathologists for the presence or absence of lymphovascular space invasion. Survival analysis was performed examining tumoral factors.
    RESULTS: A total of 434 patients were included in the analysis. Lymphovascular space invasion was detected in 76 (17.5%) patients associated with histology (P=.042) and stage (P=.044). Lymphovascular space invasion was significantly associated with decreased survival outcomes (disease-free survival, 5-year rate 78.4% compared with 90.7%, P=.024 and overall survival, 84.9% compared with 93.2%, P=.031) in univariate analysis. In multivariate analysis, lymphovascular space invasion did not remain a significant variable for disease-free survival (hazard ratio [HR] 1.98, 95% confidence interval [CI] 0.97-3.97, P=059) or overall survival (HR 2.41, 95% CI 0.99-5.85, P=052). Lymphovascular space invasion was associated with increased risk of hematogenous and lymphatic metastasis (HR 4.79, 95% CI 1.75-13.2, P=002) but not peritoneal metastasis (P=.33) in multivariate analysis. Among lymphovascular space invasion-expressing tumors, patients who received fewer than six cycles of postoperative chemotherapy had significantly poorer disease-free survival than those who received six or more cycles (HR 4.59, 95% CI 1.20-17.5, P=.015).
    CONCLUSION: Lymphovascular space invasion is an important histologic feature to identify a subgroup of patients with increased risk of recurrence in stage I epithelial ovarian cancer.

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  • Annexin A4-conferred platinum resistance is mediated by the copper transporter ATP7A 査読

    Shinya Matsuzaki, Takayuki Enomoto, Satoshi Serada, Kiyoshi Yoshino, Shushi Nagamori, Akiko Morimoto, Takuhei Yokoyama, Ayako Kim, Toshihiro Kimura, Yutaka Ueda, Masami Fujita, Minoru Fujimoto, Yoshikatsu Kanai, Tadashi Kimura, Tetsuji Naka

    INTERNATIONAL JOURNAL OF CANCER134 ( 8 ) 1796 - 1809   2014年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Although platinum drugs are often used for the chemotherapy of human cancers, platinum resistance is a major issue and may preclude their use in some cases. We recently reported that enhanced expression of Annexin A4 (Anx A4) increases chemoresistance to carboplatin through increased extracellular efflux of the drug. However, the precise mechanisms underlying that chemoresistance and the relationship of Anx A4 to platinum resistance in vivo remain unclear. In this report, the in vitro mechanism of platinum resistance induced by Anx A4 was investigated in endometrial carcinoma cells (HEC1 cells) with low expression of Anx A4. Forced expression of Anx A4 in HEC1 cells resulted in chemoresistance to platinum drugs. In addition, HEC1 control cells were compared with Anx A4-overexpressing HEC1 cells in xenografted mice. Significantly greater chemoresistance to cisplatin was observed in vivo in Anx A4-overexpressing xenografted mice. Immunofluorescence analysis revealed that exposure to platinum drugs induced relocation of Anx A4 from the cytoplasm to the cellular membrane, where it became colocalized with ATP7A, a copper transporter also well known as a mechanism of platinum efflux. ATP7A expression suppressed by small interfering RNA had no effect on HEC1 control cells in terms of chemosensitivity to platinum drugs. However, suppression of ATP7A in Anx A4-overexpressing platinum-resistant cells improved chemosensitivity to platinum drugs (but not to 5-fluorouracil) to a level comparable to that of control cells. These results indicate that enhanced expression of Anx A4 confers platinum resistance by promoting efflux of platinum drugs via ATP7A.

    DOI: 10.1002/ijc.28526

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  • 産婦人科医必携 現代漢方の基礎知識 不育症・習慣流産 招待 査読

    高桑 好一, 能仲 太郎, 高橋 真紀子, 山岸 葉子, 吉田 邦彦, 生野 寿史, 山口 雅幸, 榎本 隆之

    産婦人科の実際63 ( 3 ) 363 - 371   2014年3月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Endometrial Adenocarcinoma Arising in a Turner's Syndrome Patient with Spontaneous Menstruation A Case Report 査読

    Naoko Sasamoto, Yutaka Ueda, Kyoka Amemiya, Takayuki Enomoto, Eiichi Morii, Kazushige Adachi

    JOURNAL OF REPRODUCTIVE MEDICINE59 ( 3-4 ) 177 - 180   2014年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SCI PRINTERS & PUBL INC  

    BACKGROUND: Women with Turner's syndrome exhibit anovulation, and the majority do not sponta-syndrome detected spontaneous menstruation in only neously menstruate. We present an unusual case of endometrial adenocarcinoma developing in a Turner's syndrome patient who was exhibiting spontaneous menstruation while not receiving regular hormone therapy.
    CASE: The patient's karyotype from blood lymphocytes was a mosaic of 45,XO/46,XX. Menarche and sexual development were normal. Her menstrual cycle had been regular for one year, but then became noticeably irregular. At age 26 she was referred to our hospital after bleeding for almost 1 year. An endometrial adenocarcinoma was detected during performance of diagnostic endometrial curettage. A total abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy was conducted. The final histological diagnosis was endometrial adenocarcinoma, Grade 1, pT1a NO MO. Fluorescence in situ hybridization analysis of the right and left ovaries revealed a mosaic karyotype of 45,XO/46,XX/47,XXX.
    CONCLUSION: Previous reports regarding Turner's syndrome detected spontaneous menstruation in only 16% of patients; however, spontaneous menstruation was observed in 8 of 10 (80%) Turner's syndrome cases that developed endometrial carcinoma without receiving regular hormone therapy (p &lt; 0.0001). Hormone therapy may be indicated for an irregular menstrual cycle in Turner's syndrome patients.

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  • Molecular characterization of an intact p53 pathway subtype in high-grade serous ovarian cancer. 査読 国際誌

    Takahide Hayano, Yuki Yokota, Kazuyoshi Hosomichi, Hirofumi Nakaoka, Kosuke Yoshihara, Sosuke Adachi, Katsunori Kashima, Hitoshi Tsuda, Takuya Moriya, Kenichi Tanaka, Takayuki Enomoto, Ituro Inoue

    PloS one9 ( 12 ) e114491   2014年

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    記述言語:英語  

    High-grade serous ovarian cancer (HGSOC) is the most aggressive histological type of epithelial ovarian cancer, which is characterized by a high frequency of somatic TP53 mutations. We performed exome analyses of tumors and matched normal tissues of 34 Japanese patients with HGSOC and observed a substantial number of patients without TP53 mutation (24%, 8/34). Combined with the results of copy number variation analyses, we subdivided the 34 patients with HGSOC into subtypes designated ST1 and ST2. ST1 showed intact p53 pathway and was characterized by fewer somatic mutations and copy number alterations. In contrast, the p53 pathway was impaired in ST2, which is characterized by abundant somatic mutations and copy number alterations. Gene expression profiles combined with analyses using the Gene Ontology resource indicate the involvement of specific biological processes (mitosis and DNA helicase) that are relevant to genomic stability and cancer etiology. In particular we demonstrate the presence of a novel subtype of patients with HGSOC that is characterized by an intact p53 pathway, with limited genomic alterations and specific gene expression profiles.

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  • Placenta previa and percreta with massive genital bleeding in the first trimester of pregnancy: A case report 査読

    Masayuki Yamaguchi, Kunihiko Yoshida, Toru Takano, Takayuki Enomoto, Koichi Takakuwa

    Open Journal of Obstetrics and Gynecology3 ( 9 ) 690 - 693   2013年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • 初期子宮体癌に対する腹腔鏡下根治手術 複数術者によるfeasibilityと予後の検討 査読

    安達聡介, 八幡哲郎, 工藤梨沙, 山岸葉子, 山脇芳, 須田一暁, 田村亮, 茅原誠, 南川高廣, 萬歳千秋, 西野幸治, 西川伸道, 加嶋克則, 榎本隆之

    日本産科婦人科内視鏡学会雑誌   2013年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.5180/jsgoe.29.313

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  • Authors' response. 査読 国際誌

    Kosuke Hiramatsu, Yutaka Ueda, Kiyoshi Yoshino, Masami Fujita, Eiichi Morii, Takayuki Enomoto, Tadashi Kimura

    European journal of obstetrics, gynecology, and reproductive biology170 ( 1 ) 297 - 297   2013年9月

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  • A phase II study of combination chemotherapy using docetaxel and irinotecan for TC-refractory or TC-resistant ovarian carcinomas (GOGO-OV2 study) and for primary clear or mucinous ovarian carcinomas (GOGO-OV3 Study) 査読

    Yutaka Ueda, Takashi Miyatake, Masaaki Nagamatsu, Masato Yamasaki, Yukihiro Nishio, Kiyoshi Yoshino, Masami Fujita, Tateki Tsutsui, Takayuki Enomoto, Tadashi Kimura

    EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY170 ( 1 ) 259 - 263   2013年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Objective: To analyze the efficacy and safety of combination chemotherapy of docetaxel and irinotecan for paclitaxel and carboplatin (TC) -refractory or -resistant ovarian carcinomas and for first treatment of primary clear cell and mucinous ovarian carcinomas.
    Study design: Between 2002 and 2009, we conducted a prospective Phase II study of the efficacy and safety of combination chemotherapy using docetaxel and irinotecan in 62 patients with TC-refractory or -resistant ovarian carcinoma cases (GOGO-OV2) and 15 patients with primary clear cell and mucinous ovarian carcinoma cases (GOGO-OV3). The dose of docetaxel and irinotecan was determined during our previous Phase I study.
    Results: A docetaxel plus irinotecan regimen provided a 53% response rate, 6 months progression-free survival (PFS), and 12 months overall survival (OS) for primary clear cell and mucinous ovarian carcinomas (similar to TC therapy). The differences of anti-tumor and survival effects between refractory and resistant cases were not statistically significant. The regimen also provided a 15% response rate, 5 months PFS, and 15 months OS for TC-refractory or TC-resistant cases, when used as a second-line chemotherapy. These data are similar to previous reports, however, our study provides the first data exclusively for the cases refractory or resistant to a gold standard TC therapy as a second-line chemotherapy. The regimen was demonstrated to be well tolerable.
    Conclusion: Combination chemotherapy of docetaxel and irinotecan may be a useful option to treat TC-refractory/resistant cases and primary clear cell and mucinous adenocarcinoma cases of ovarian carcinoma. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

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  • Endometrial cancer: preoperative staging using three-dimensional T2-weighted turbo spin-echo and diffusion-weighted MR imaging at 3.0 T: a prospective comparative study 査読

    Masatoshi Hori, Tonsok Kim, Hiromitsu Onishi, Izumi Imaoka, Yuki Kagawa, Takamichi Murakami, Atsushi Nakamoto, Takashi Ueguchi, Mitsuaki Tatsumi, Takayuki Enomoto, Tadashi Kimura, Noriyuki Tomiyama

    EUROPEAN RADIOLOGY23 ( 8 ) 2296 - 2305   2013年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    To prospectively assess the efficacy of 3-T magnetic resonance (MR) imaging using the three-dimensional turbo spin-echo T2-weighted and diffusion-weighted technique (3D-TSE/DW) compared with that of conventional imaging using the two-dimensional turbo spin-echo T2-weighted and dynamic contrast-enhanced technique (2D-TSE/DCE) for the preoperative staging of endometrial cancer, with pathological analysis as the reference standard.
    Seventy-one women with endometrial cancer underwent MR imaging using 3D-TSE/DW (b = 1,000 s/mm(2)) and 2D-TSE/DCE. Two radiologists independently assessed the two imaging sets. Accuracy, sensitivity, and specificity for staging were analysed with the McNemar test; the areas under the receiver operating characteristic curve (Az) were compared with a univariate z-score test.
    The results for assessing deep myometrial invasion, accuracy, sensitivity, specificity and Az, respectively, were as follows: 3D-TSE/DW-observer 1, 87 %, 95 %, 85 % and 0.96; observer 2, 92 %, 84 %, 94 % and 0.95; 2D-TSE/DCE-observer 1, 80 %, 79 %, 81 % and 0.89; observer 2, 86 %, 84 %, 87 % and 0.86. Most of the values were higher with 3D-TSE/DW without significant differences (P &gt; 0.12). For assessing cervical stromal invasion, there were no significant differences in those values for both observers (P &gt; 0.6).
    Accuracy of 3D-TSE/DW was at least equivalent to that of the conventional technique for the preoperative assessment of endometrial cancer.

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  • Taxane-sensitivity of ovarian carcinomas previously treated with paclitaxel and carboplatin 査読

    Yutaka Ueda, Takayuki Enomoto, Shinya Matsuzaki, Eiji Kobayashi, Toshihiro Kimura, Kiyoshi Yoshino, Masami Fujita, Tateki Tsutsui, Tadashi Kimura

    CANCER CHEMOTHERAPY AND PHARMACOLOGY71 ( 6 ) 1411 - 1416   2013年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    The aim of the present study was to investigate, in ovarian carcinoma cases, the predictive association between the treatment-free interval (TFI) after an initial paclitaxel plus carboplatin (TC) therapy and the subsequent effectiveness of a second-line taxane-containing chemotherapy.
    Patients with a TFI &lt; 6 months from the first-line TC therapy were treated with a combination chemotherapy using docetaxel and irinotecan; patients with a TFI a parts per thousand yen 6 months were retreated with the same regimen as the initial TC therapy. The clinical data of these patients were retrospectively analyzed for this study.
    The response rate of those with a TFI equal to 6-12 months was greater than that of those with a TFI &lt; 6 months (p = 0.014) and less than that of those with a TFI &gt; 12 months (p = 0.012). The progression-free survival of the cases with TFI equal to 6-12 months was longer than that of those with TFI &lt; 6 months (p = 0.012) and shorter than that of those with TFI &gt; 12 months (p = 0.0011). Overall survival of cases with a TFI equal to 6-12 months was longer than that of those with TFI &lt; 6 months (p = 0.012) and shorter than that of those with TFI &gt; 12 months (p = 0.0005).
    The effectiveness of using a second-line taxane-containing chemotherapy was shown to be predictable by the TFI after the first-line taxane-containing chemotherapy, implying that the theory of 'taxane-sensitivity' may be applied for second-line chemotherapy in the same way as that of 'platinum-sensitivity'.

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  • Conization using the Shimodaira-Taniguchi procedure for adenocarcinoma in situ of the uterine cervix. 査読 国際誌

    Kosuke Hiramatsu, Yutaka Ueda, Kiyoshi Yoshino, Masami Fujita, Eiichi Morii, Takayuki Enomoto, Tadashi Kimura

    European journal of obstetrics, gynecology, and reproductive biology168 ( 2 ) 218 - 21   2013年6月

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    記述言語:英語  

    OBJECTIVE: The Shimodaira-Taniguchi conization procedure addresses the disadvantages of the loop electrosurgical excision procedure (LEEP) by using a high frequency current and a triangular probe with a linear excision electrode to extract the tissue as a single informative specimen, without incurring accompanying thermal trauma. The aim of the present study was to analyze the surgical efficacy of the Shimodaira-Taniguchi conization procedure for adenocarcinoma in situ (AIS) of the uterine cervix. STUDY DESIGN: At the Osaka University Hospital, conization using the Shimodaira-Taniguchi procedure has long been routinely performed for AIS. Medical records of patients during the period from 2005 to 2011, whose post-conization diagnosis was AIS, were retrospectively analyzed. A literature review was conducted of the PubMed database to clarify the surgical outcome efficacy of the Shimodaira-Taniguchi procedure compared to other procedures. RESULTS: During the study period, a post-conization diagnosis of AIS was made in 10 patients. A positive resection margin was detected in 4 of the 10 cases (40%), and residual disease was observed in 3 cases (30%). A review of the relevant literature indicates that the rate of positive margin and residual disease by the Shimodaira-Taniguchi procedure, including our cases, was not significantly different from the cold knife, LEEP or laser procedures (p=0.32, 0.99, and 0.40, respectively, for positive margin, and p=0.76, 0.94, and 0.063, respectively, for residual disease). CONCLUSION: AIS was demonstrated to be efficaciously treated, with a low risk of residual disease, by the Shimodaira-Taniguchi conization procedure. Further study is still needed to establish a standard of conservative treatment for AIS.

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  • Bacillus subtilis genome vector-based complete manipulation and reconstruction of genomic DNA for mouse transgenesis 査読

    Tetsuo Iwata, Shinya Kaneko, Yuh Shiwa, Takayuki Enomoto, Hirofumi Yoshikawa, Junji Hirota

    BMC GENOMICS14   300   2013年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: The Bacillus subtilis genome (BGM) vector is a novel cloning system for large DNA fragments, in which the entire 4.2 Mb genome of B. subtilis functions as a vector. The BGM vector system has several attractive properties, such as a large cloning capacity of over 3 Mb, stable propagation of cloned DNA and various modification strategies using RecA-mediated homologous recombination. However, genetic modifications using the BGM vector system have not been fully established, and this system has not been applied to transgenesis. In this study, we developed important additions to the genetic modification methods of the BGM vector system. To explore the potential of the BGM vector, we focused on the fish-like odorant receptor (class I OR) gene family, which consists of 158 genes and forms a single gene cluster. Although a cis-acting locus control region is expected to regulate transcription, this has not yet been determined experimentally.
    Results: Using two contiguous bacterial artificial chromosome clones containing several class I OR genes, we constructed two transgenes in the BGM vector by inserting a reporter gene cassette into one class I OR gene. Because they were oriented in opposite directions, we performed an inversion modification to align their orientation and then fused them to enlarge the genomic structure. DNA sequencing revealed that no mutations occurred during gene manipulations with the BGM vector. We further demonstrated that the modified, reconstructed genomic DNA fragments could be used to generate transgenic mice. Transgenic mice carrying the enlarged transgene recapitulated the expression and axonal projection patterns of the target class I OR gene in the main olfactory system.
    Conclusion: We offer a complete genetic modification method for the BGM vector system, including insertion, deletion, inversion and fusion, to engineer genomic DNA fragments without any trace of modifications. In addition, we demonstrate that this system can be used for mouse transgenesis. Thus, the BGM vector system can be an alternative platform for engineering large DNA fragments in addition to conventional systems such as bacterial and yeast artificial chromosomes. Using this system, we provide the first experimental evidence of a cis-acting element for a class I OR gene.

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  • WT1 peptide immunotherapy for gynecologic malignancies resistant to conventional therapies: a phase II trial 査読

    Takashi Miyatake, Yutaka Ueda, Akiko Morimoto, Takayuki Enomoto, Sumiyuki Nishida, Toshiaki Shirakata, Yoshihiro Oka, Akihiro Tsuboi, Yusuke Oji, Naoki Hosen, Shin-ichi Nakatsuka, Satoshi Morita, Junichi Sakamoto, Haruo Sugiyama, Tadashi Kimura

    JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY139 ( 3 ) 457 - 463   2013年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    The aim of the present study was to analyze the long-term survival effects of WT1 peptide vaccine, in addition to its anti-tumor effects and toxicity.
    A phase II clinical trial was conducted during the period of 2004-2010 at Osaka University Hospital, Osaka, Japan. The patients who had gynecologic malignancies progressing against previous treatments received WT1 peptide vaccine intradermally at 1-week intervals for 12 weeks. The vaccination was allowed to further continue, unless the patient's condition became significantly worse due to the disease progression.
    Forty out of 42 patients, who met all the inclusion criteria, underwent WT1 peptide vaccine. Among these 40 patients, stable disease was observed in 16 cases (40 %). Skin toxicity of a grade 1, 2 and 3 occurred in 25 cases (63 %), 9 cases (23 %) and a single case (3 %), respectively, and liver toxicity of grade 1 in a single case (3 %). The overall survival period was significantly longer in cases positive for the WT1 peptide-specific delayed-type hypersensitivity (DTH) reaction after the vaccination, compared to those negative for the DTH reaction (p = 0.023). Multivariate Cox proportional hazards analysis demonstrated that the adjusted hazard ratio for the negative DTH reaction was 2.73 (95 % CI 1.04-7.19, p = 0.043).
    WT1 peptide vaccine may be a potential treatment, with limited toxicity, for gynecologic malignancies that have become resistant to conventional therapies. Larger scale of clinical studies is required to establish the efficacy of the WT1 peptide vaccine for gynecologic malignancies.

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  • 本態性血小板血症合併妊娠の2症例 査読

    小木 幹奈, 山口 雅幸, 上村 直美, 吉田 邦彦, 山田 京子, 芹川 武大, 榎本 隆之, 高桑 好一

    新潟産科婦人科学会会誌108 ( 1 ) 24 - 27   2013年3月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Salvage chemotherapy for recurrent or persistent clear cell carcinoma of the ovary: a single-institution experience for a series of 20 patients 査読

    Kiyoshi Yoshino, Takayuki Enomoto, Masami Fujita, Yutaka Ueda, Toshihiro Kimura, Eiji Kobayashi, Tateki Tsutsui, Tadashi Kimura

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY18 ( 1 ) 148 - 153   2013年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER JAPAN KK  

    Recurrent or persistent clear cell carcinoma (CCC) of the ovary is particularly chemotherapy resistant. The purpose of this study was to review our extensive institutional experiences with recurrent or persistent CCC with the aim of finding a more effective chemotherapy regimen.
    The medical records of 67 patients treated for CCC of the ovary were retrospectively reviewed to select patients subsequently treated for recurrence or persistence of the disease.
    The review identified 20 patients treated for recurrent or persistent CCC. For these 20 patients, 9 chemotherapeutic regimens, with 125 cycles, were administered. Gemcitabine monotherapy showed the best response rate [1 partial response (20%) and 2 stable diseases out of 5 patients so treated]. A partial response was observed with a combination of docetaxel plus irinotecan in 1 of 11 patients (9%). Stable disease was observed in 1 of 9 cases on a paclitaxel/carboplatin doublet and in 1 case on a docetaxel/carboplatin doublet. The median overall survival time was 8 months (range, 2-52). One group of patients who received gemcitabine therapy showed significantly better survival (n = 5, median 18 months) compared with a group who did not (n = 15, median 7 months) (P = 0.0108, by univariate analysis). In addition, multivariate Cox proportional hazards analysis revealed that gemcitabine administration was a significant factor for survival (hazard ratio: 13.0, 95% CI: 1.4727-115.2255, P = 0.02).
    Although most chemotherapeutic regimens for recurrent or persistent CCC have little or no effect, gemcitabine showed modest activity and is the most effective agent we have tested to date.

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  • Plasma membrane proteomics identifies bone marrow stromal antigen 2 as a potential therapeutic target in endometrial cancer 査読

    Takuhei Yokoyama, Takayuki Enomoto, Satoshi Serada, Akiko Morimoto, Shinya Matsuzaki, Yutaka Ueda, Kiyoshi Yoshino, Masami Fujita, Satoru Kyo, Kota Iwahori, Minoru Fujimoto, Tadashi Kimura, Tetsuji Naka

    International Journal of Cancer132 ( 2 ) 472 - 484   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    This report utilizes a novel proteomic method for discovering potential therapeutic targets in endometrial cancer. We used a biotinylation-based approach for cell-surface protein enrichment combined with isobaric tags for relative and absolute quantitation (iTRAQ) technology using nano liquid chromatography-tandem mass spectrometry analysis to identify specifically overexpressed proteins in endometrial cancer cells compared with normal endometrial cells. We identified a total of 272 proteins, including 11 plasma membrane proteins, whose expression increased more than twofold in at least four of seven endometrial cancer cell lines compared with a normal endometrial cell line. Overexpression of bone marrow stromal antigen 2 (BST2) was detected and the observation was supported by immunohistochemical analysis using clinical samples. The expression of BST2 was more characteristic of 118 endometrial cancer tissues compared with 59 normal endometrial tissues (p &lt
    0.0001). The therapeutic effect of an anti-BST2 antibody was studied both in vitro and in vivo. An anti-BST2 monoclonal antibody showed in vitro cytotoxicity in BST2-positive endometrial cancer cells via antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. In an in vivo xenograft model, anti-BST2 antibody treatment significantly inhibited tumor growth of BST2-positive endometrial cancer cells in an NK cell-dependent manner. The anti-BST2 antibody had a potent antitumor effect against endometrial cancer both in vitro and in vivo, indicating a strong potential for clinical use of anti-BST2 antibody for endometrial cancer treatment. The combination of biotinylation-based enrichment of cell-surface proteins and iTRAQ analysis should be a useful screening method for future discovery of potential therapeutic targets. What's new? In this study, we have used a biotinylation-based approach for cell-surface protein enrichment combined with iTRAQ technology to identify and quantify membrane proteins which might represent potential therapeutic targets of endometrial cancer. A monoclonal antibody targeting BST2, one of the proteins identified in the iTRAQ analysis, have a potent antitumor effect against endometrial cancer both in vitro and in vivo, indicating a strong potential for clinical use of anti-BST2 antibody for endometrial cancer treatment. Copyright © 2012 UICC.

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  • Biomarkers for Screening, Diagnosis, and Monitoring of Ovarian Cancer 査読

    Eiji Kobayashi, Yutaka Ueda, Shinya Matsuzaki, Takuhei Yokoyama, Toshihiro Kimura, Kiyoshi Yoshino, Masami Fujita, Tadashi Kimura, Takayuki Enomoto

    CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION21 ( 11 ) 1902 - 1912   2012年11月

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    記述言語:英語   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    Serum tumor markers have a major role in the screening, diagnosis, and monitoring of most of the gynecologic cancers. Ovarian cancer is one of the deadliest of the group because it is so frequently asymptomatic until it has advanced to an untreatable stage. Even serum cancer antigen-125 (CA-125), clinically one of the most reliable serum markers for ovarian cancer, is elevated in only half of early-stage still-treatable tumors. Because of the very low prevalence of ovarian cancer in the general population, at present, there is no cost-effective imaging or simple microscopic screening test for ovarian cancer as there is for breast and cervical cancers. However, recent proteomics and nucleic acid based analyses have shown great promise for the discovery of new and more useful serum biomarkers, which cumulatively might provide such a screening tool. In this review, we will discuss both the currently used serum tumor markers for screening, diagnosis, monitoring of ovarian cancer, and the novel biomarkers that are now under investigation and validation. Cancer Epidemiol Biomarkers Prev; 21(11); 1902-12. (C)2012 AACR.

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  • Significance of lymphovascular space invasion in epithelial ovarian cancer 査読

    Koji Matsuo, Todd B. Sheridan, Kiyoshi Yoshino, Takahito Miyake, Karina E. Hew, Dwight D. Im, Neil B. Rosenshein, Seiji Mabuchi, Takayuki Enomoto, Tadashi Kimura, Anil K. Sood, Lynda D. Roman

    CANCER MEDICINE1 ( 2 ) 156 - 164   2012年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    While the prognostic significance of lymphovascular space invasion (LVSI) is well established in endometrial and cervical cancer, its role in ovarian cancer is not fully understood. First, a training cohort was conducted to explore whether the presence and quantity of LVSI within the ovarian tumor correlated with nodal metastasis and survival (n = 127). Next, the results of the training cohort were applied to a different study population (validation cohort, n = 93). In both cohorts, histopathology slides of epithelial ovarian cancer cases that underwent primary cytoreductive surgery including pelvic and/or aortic lymphadenectomy were examined. In a post hoc analysis, the significance of LVSI was evaluated in apparent stage I cases (n = 53). In the training cohort, the majority of patients had advanced-stage disease (82.7%). LVSI was observed in 79.5% of cases, and nodal metastasis was the strongest variable associated with the presence of LVSI (odds ratio [OR]: 7.99, 95% confidence interval [CI]: 1.98-32.1, P = 0.003) in multivariate analysis. The presence of LVSI correlated with a worsened progression-free survival on multivariate analysis (hazard ratio [HR]: 2.06, 95% CI: 1.01-4.24, P = 0.048). The significance of the presence of LVSI was reproduced in the validation cohort (majority, early stage 61.3%). In apparent stage I cases, the presence of LVSI was associated with a high negative predictive value for nodal metastasis (100%, likelihood ratio, P = 0.034) and with worsened progression-free survival (HR: 5.16, 95% CI: 1.00-26.6, P = 0.028). The presence of LVSI is an independent predictive indicator of nodal metastasis and is associated with worse clinical outcome of patients with epithelial ovarian cancer.

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  • Cervical non-squamous carcinoma: an effective combination chemotherapy of taxane, anthracycline and platinum for advanced or recurrent cases 査読

    Toshihiro Kimura, Takashi Miyatake, Yutaka Ueda, Yukinobu Ohta, Takayuki Enomoto, Tadashi Kimura, Shoji Kamiura

    EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY164 ( 2 ) 200 - 204   2012年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Objective: An effective salvage chemotherapy for advanced and recurrent non-squamous carcinoma of the uterine cervix has not yet been established. The aim of the present study was to analyze the safety and efficacy of a combination chemotherapy for this disease using taxane, anthracycline, and platinum.
    Study design: This was a retrospective analysis of advanced and recurrent non-squamous cervical cancers treated at the Osaka University Hospital and the Osaka Medical Center for Cancer and Cardiovascular Diseases during a 10 year study period from 2000 to 2009. Single agent chemotherapies and combination chemotherapies for advanced and recurrent cervical cancer cases of non-squamous histology which were reported in the English literature were also reviewed.
    Results: Salvage chemotherapy, using taxane, anthracycline and platinum, was performed for 5 advanced and 14 recurrent cases. Prior to the salvage chemotherapy, 15 (79%) of the 19 patients had already received either radiation or chemotherapy. A complete or partial tumor response was achieved in 8 (42%) of the 19 cases. The response rate for recurrent disease in a previously irradiated field was 40%. The median progression-free survival (PFS) and overall survival (OS) were 8 months (1-108) and 13 months (5-108), respectively. Grade 4 and febrile grade 3 neutropenia was observed in 6 cases (32%), but there was no case in which salvage chemotherapy had to be cancelled due to toxicity. According to previous reports, the cumulative response rate of combination chemotherapy (35%) was significantly higher than that of single agent chemotherapy (17%) (p &lt; 0.001). OS tended to be longer in the combination chemotherapy cases (8.7 months to 18 months) than that of single agent chemotherapy cases (7.3+ months to 9.1+ months).
    Conclusion: Combination chemotherapy of taxane, anthracycline, and platinum was found to have a survival benefit for advanced and recurrent cervical cancer patients of non-squamous carcinoma histology, with a tolerable toxicity. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

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  • Impact of histological subtype on survival of patients with surgically-treated stage IA2-IIB cervical cancer: Adenocarcinoma versus squamous cell carcinoma 査読

    Seiji Mabuchi, Mika Okazawa, Koji Matsuo, Mahiru Kawano, Osamu Suzuki, Takashi Miyatake, Takayuki Enomoto, Shoji Kamiura, Kazuhiko Ogawa, Tadashi Kimura

    GYNECOLOGIC ONCOLOGY127 ( 1 ) 114 - 120   2012年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Objectives. To evaluate the significance of adenocarcinoma (AC) compared with squamous cell carcinoma (SCC) with regard to the survival of surgically-treated early stage cervical cancer patients.
    Methods. We retrospectively reviewed the medical records of 520 patients with FIGO stage IA2-IIB cervical cancer who were treated with radical hysterectomy with or without adjuvant radiotherapy between January 1998 and December 2008. The patients were classified according to (i) pathological risk factors (low-, intermediate-, or high-risk group) and (ii) adjuvant radiotherapy (concurrent chemoradiotherapy [CCRT group] or radiotherapy alone [RT group]). Survival outcomes were examined by Kaplan-Meier method and compared with Log-rank test Multivariate analysis for disease-specific survival (DSS) was performed using Cox proportional hazards regression model to investigate the prognostic significance of histological subtype.
    Results: AC histology was associated with significantly decreased DSS compared with SCC histology in the intermediate- and high-risk groups (hazard ratio: 3.06 and 2.88, respectively, both P&lt;0.05) while there was no survival difference in the low-risk group (P=0.1). Among patients who received any types of adjuvant radiotherapy, DSS of AC histology patients were significantly poorer than SCC histology. Multivariate analysis demonstrated AC histology to be an independent predictor of decreased DSS in both CCRT and RT groups. Moreover, pelvic nodal metastasis significantly predicted the poor survival of patients with AC histology who received CCRT in multivariate analysis.
    Conclusions. Adenocarcinoma is an independent prognostic indicator of poor survival in early stage cervical cancer patients with intermediate- and high-risk factors, regardless of the type of adjuvant radiotherapy after radical hysterectomy. (C) 2012 Elsevier Inc. All rights reserved.

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  • Salvage Chemotherapy Using Gemcitabine for Taxane/Platinum-resistant Recurrent Ovarian Cancer: A Single Institutional Experience 査読

    Kiyoshi Yoshino, Kosuke Hiramatsu, Takayuki Enomoto, Masami Fujita, Yutaka Ueda, Toshihiro Kimura, Eiji Kobayashi, Yumiko Kiyohara, Tateki Tsutsui, Tadashi Kimura

    ANTICANCER RESEARCH32 ( 9 ) 4029 - 4033   2012年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:INT INST ANTICANCER RESEARCH  

    Background: The purpose of this study was to report on the safety and efficacy of gemcitabine used as salvage chemotherapy for ovarian cancer. Patients and Methods: From January 2002 to October 2011, 27 patients were treated with gemcitabine for platinum-resistant recurrent ovarian cancer. Gemcitabine (800 mg/m(2)) was given on days 1, 8, and 15 of every 28 days. The patients' medical records were retrospectively reviewed. Results: All 27 patients had previously received paclitaxel/carboplatin doublet and their disease had become platinum-resistant. The median number of previous chemotherapy regimens was 2 (range 1-7). A total of 114 cycles of single-agent gemcitabine were administered, with a median of 3 (range 1-10). No complete responses were observed. Partial response (PR) was observed in five patients (18.5%). Eight patients demonstrated stable disease (SD). The median duration of response for 5 responders was 4 months (range 2-6 months). The median survival time was 15 months. Patients with PR or SD (n=13) had significantly better survival compared with the group with progressive disease (n=14) (p=0.03, by univariate analysis). In addition, multivariate Cox proportional hazards analysis revealed that responses to gemcitabine were a significant factor for survival (hazard ratio=0.08, 95% confidence interval=0.0138 to 0.5614, p=0.01). Cases with hematological toxicity included 10 patients (37.0%) with grade 314 neutropenia, 3 patients (11.1%) with grade 3 thrombocytopenia, and 3 patients (11.1%) with grade 3 anemia. Non-hematological toxicity was well-tolerated. Conclusion: Gemcitabine (800 mg/m(2)) used for recurrent ovarian cancer possesses a modest activity and a well-tolerated toxicity.

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  • Primary retroperitoneal mucinous cystadenocarcinoma with mural nodules: a case report and literature review 査読

    Tomoko Kanayama, Kiyoshi Yoshino, Takayuki Enomoto, Hiroshi Ohashi, Masami Fujita, Yutaka Ueda, Toshihiro Kimura, Eiji Kobayashi, Eiichi Morii, Tadashi Kimura

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY17 ( 4 ) 407 - 411   2012年8月

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    記述言語:英語   出版者・発行元:SPRINGER JAPAN KK  

    A primary retroperitoneal mucinous cystadenocarcinoma (PRMC) is an extremely rare lesion. To date, only 49 cases have been reported. The presence of mural nodules in a PRMC may indicate a worse prognosis. We report the case of a 40-year-old Japanese woman with a PRMC with mural nodules. Microscopic examination revealed that the stromal cells of the nodules were spindle-shaped and varied in size. The nodules were immunoreactive for vimentin but negative for cytokeratin and EMA, and the nuclei of the stromal cells were pleomorphic and strongly Ki-67 immunoreactive. The nodules were diagnosed as true sarcoma. To the best of our knowledge, this is 11th published case report of a PRMC with mural nodules.

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  • [Analysis of clonality and HPV infection in benign, premalignant and malignant lesions of the uterine cervix]. 査読

    Ueda Y, Yoshino K, Fujita M, Enomoto T

    Nihon rinsho. Japanese journal of clinical medicine70 Suppl 4   95 - 99   2012年6月

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  • [Genetic diagnosis of the endometrial cancer]. 査読

    Kimura T, Fujita M, Kobayashi E, Ueda Y, Yoshino K, Enomoto T

    Nihon rinsho. Japanese journal of clinical medicine70 Suppl 4   367 - 371   2012年6月

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  • A retrospective analysis of endometrial carcinoma cases surgically treated with or without para-aortic lymph node dissection followed by adjuvant chemotherapy 査読

    Okazawa M, Ueda Y, Enomoto T, Yoshino K, Kono K, Mabuchi S, Kimura T, Nagamatsu M

    European journal of gynaecological oncology33 ( 6 ) 620 - 624   2012年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • [Genetic abnormalities in the pathogenesis of ovarian cancer]. 査読

    Yoshino K, Ueda Y, Kimura T, Kobayashi E, Fujita M, Enomoto T

    Nihon rinsho. Japanese journal of clinical medicine70 Suppl 4   480 - 487   2012年6月

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  • Prediction of Progression-Free Survival and Response to Paclitaxel Plus Carboplatin in Patients With Recurrent or Advanced Cervical Cancer 査読

    Takeshi Hisamatsu, Seiji Mabuchi, Kiyoshi Yoshino, Masami Fujita, Takayuki Enomoto, Toshimitsu Hamasaki, Tadashi Kimura

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER22 ( 4 ) 623 - 629   2012年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Objective: The aim of this study was to identify predictors of the response to paclitaxel-carboplatin chemotherapy (TC) in recurrent or patients with advanced cervical cancer.
    Methods: The records of 61 consecutive women with recurrent or advanced cervical cancer who were treated with TC were retrospectively reviewed. Data regarding their primary disease, follow-up, recurrence, and the activity and toxicity of TC were collected. Multivariate analysis was performed using the Cox proportional hazards regression model to identify predictors of the response to TC. Survival was calculated using the Kaplan-Meier method and compared using the log-rank test.
    Results: Overall, TC was well tolerated and displayed a response rate of 60.7% (19 complete response and 18 partial response). The median progression-free survival was 14 months for all patients and 20 months for the responders. Grade 3 to grade 4 toxicities were observed in 51 patients (83.6%). Multivariate analysis revealed that performance status, symptom status, and prior chemotherapy were independent prognostic predictors of a poor response. Patient survival was inversely correlated with the number of these prognostic factors. When the patients were divided into 2 prognostic groups (low risk: patients with no or one poor prognostic factor; and high-risk: patients with 2 or more poor prognostic factors), the patients in the high-risk group had a significantly shorter progression-free survival than those in the low-risk group (4 vs 16 months, log-rank; P &lt; 0.0001).
    Conclusions: The combination of paclitaxel and carboplatin is effective in patients with recurrent or advanced cervical cancer. Our prognostic model composed of 3 clinical variables might enable physicians to identify patients who would not derive clinical benefit from TC and offer them the opportunity to receive other types of treatment.

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  • Investigating the relative efficacies of combination chemotherapy of paclitaxel/carboplatin, with or without anthracycline, for endometrial carcinoma 査読

    Kazuko Fujiwara, Tomomi Egawa-Takata, Yutaka Ueda, Toshihiro Kimura, Kiyoshi Yoshino, Masami Fujita, Takashi Miyatake, Yukinobu Ohta, Shoji Kamiura, Takayuki Enomoto, Tadashi Kimura

    ARCHIVES OF GYNECOLOGY AND OBSTETRICS285 ( 5 ) 1447 - 1453   2012年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER HEIDELBERG  

    Recently a combination of paclitaxel and carboplatin (TC) (without an anthracycline) has begun to be used as an adjuvant or remission induction therapy, without any critical supportive evidence of its efficacy relative to a combination chemotherapy of taxane, platinum and anthracycline such as TEC (paclitaxel, epirubicin and carboplatin). The aim of our present study was to conduct the required clinical evaluations of the relative effectiveness of TC compared to TEC.
    A retrospective comparison between the efficacy of TEC and TC regimens used for endometrial carcinoma at the Osaka University Hospital and the Osaka Medical Center for Cancer and Cardiovascular Diseases in Osaka, Japan, respectively, from 1999 to 2009 was performed. The clinical characteristics of the patients who received either TEC or TC were not significantly different, and TEC and TC therapies were initiated based on similar indications for chemotherapy. TEC regimen was paclitaxel (150 mg/m(2)), epirubicin (50 mg/m(2)) and carboplatin (AUC 4). TC regimen consisted of paclitaxel (175 mg/m(2)) and carboplatin (AUC 5).
    TEC was demonstrated to provide significantly better survival than TC as an adjuvant therapy for resected Stage III/IV diseases (p = 0.017 for progression-free survival and p = 0.014 for overall survival, by the log-rank test). However, in recurrent or more advanced cases, TC and TEC demonstrated similar effects on survival (p = 0.55 for progression-free survival and p = 0.63 for overall survival).
    TEC should be offered as an adjuvant therapy to Stage III/IV patients. TC may be considered for recurrent or unresectable cases as a remission induction therapy.

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  • Prediction, based on resection margins, of long-term outcome of cervical intraepithelial neoplasia 3 treated by Shimodaira-Taniguchi conization 査読

    Yukari Miyoshi, Takashi Miyatake, Yutaka Ueda, Akiko Morimoto, Takuhei Yokoyama, Shinya Matsuzaki, Toshihiro Kimura, Kiyoshi Yoshino, Masami Fujita, Hiroshi Ohashi, Eiichi Morii, Takayuki Enomoto, Tadashi Kimura

    ARCHIVES OF GYNECOLOGY AND OBSTETRICS285 ( 5 ) 1427 - 1432   2012年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER HEIDELBERG  

    The aim of the present study was to analyze the long-term outcome of cervical intraepithelial neoplasia 3 (CIN 3) after treatment with the Shimodaira-Taniguchi conization procedure, based on the status of the resection margins.
    In the Osaka University Hospital, conization using the Shimodaira-Taniguchi procedure has been routinely performed for CIN 3. Medical records of patients during the period from 2001 to 2008, whose post-conization diagnosis was CIN 3, were retrospectively analyzed for outcome versus margin status.
    During the median follow-up period of 565 days (range 34-3,013), CIN disease was again detected in 14 of 243 patients; it was found in 7 patients among 198 margin-negative cases, and in 7 patients among 45 margin-positive cases. There was a significant difference in the reappearance rate demonstrated between the cases with positive and negative margins (p = 0.0018). Among the patients whose first follow-up post-conization cytology was normal, recurrence-free probability was significantly higher in margin-negative cases than in margin-positive ones (hazard ratio, 5.19; 95% CI, 1.175-22.994; p = 0.0041).
    For the first time, we demonstrate that after treatment of CIN 3 lesions by Shimodaira-Taniguchi conization the status of the resection margin was a significant predictor for long-term outcome.

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  • HB-EGF and PDGF mediate reciprocal interactions of carcinoma cells with cancer-associated fibroblasts to support progression of uterine cervical cancers 査読

    Takuya Murata, Takayuki Enomoto, Yutaka Ueda, Kiyoshi Yoshino, Shigeo Yagi, Robert M. Hoffman, Hiroto Mizushima, Tadashi Kimura, Eisuke Mekada

    CANCER RESEARCH72   2012年4月

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    記述言語:英語   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2012-1516

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  • High-Risk Ovarian Cancer Based on 126-Gene Expression Signature Is Uniquely Characterized by Downregulation of Antigen Presentation Pathway 査読

    Kosuke Yoshihara, Tatsuhiko Tsunoda, Daichi Shigemizu, Hiroyuki Fujiwara, Masayuki Hatae, Hisaya Fujiwara, Hideaki Masuzaki, Hidetaka Katabuchi, Yosuke Kawakami, Aikou Okamoto, Takayoshi Nogawa, Noriomi Matsumura, Yasuhiro Udagawa, Tsuyoshi Saito, Hiroaki Itamochi, Masashi Takano, Etsuko Miyagi, Tamotsu Sudo, Kimio Ushijima, Haruko Iwase, Hiroyuki Seki, Yasuhisa Terao, Takayuki Enomoto, Mikio Mikami, Kohei Akazawa, Hitoshi Tsuda, Takuya Moriya, Atsushi Tajima, Ituro Inoue, Kenichi Tanaka

    CLINICAL CANCER RESEARCH18 ( 5 ) 1374 - 1385   2012年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    Purpose: High-grade serous ovarian cancers are heterogeneous not only in terms of clinical outcome but also at the molecular level. Our aim was to establish a novel risk classification system based on a gene expression signature for predicting overall survival, leading to suggesting novel therapeutic strategies for high-risk patients.
    Experimental Design: In this large-scale cross-platform study of six microarray data sets consisting of 1,054 ovarian cancer patients, we developed a gene expression signature for predicting overall survival by applying elastic net and 10-fold cross-validation to a Japanese data set A (n = 260) and evaluated the signature in five other data sets. Subsequently, we investigated differences in the biological characteristics between high-and low-risk ovarian cancer groups.
    Results: An elastic net analysis identified a 126-gene expression signature for predicting overall survival in patients with ovarian cancer using the Japanese data set A (multivariate analysis, P = 4 x 10(-20)). We validated its predictive ability with five other data sets using multivariate analysis (Tothill's data set, P = 1 x 10(-5); Bonome's data set, P = 0.0033; Dressman's data set, P = 0.0016; TCGA data set, P = 0.0027; Japanese data set B, P = 0.021). Through gene ontology and pathway analyses, we identified a significant reduction in expression of immune-response-related genes, especially on the antigen presentation pathway, in high-risk ovarian cancer patients.
    Conclusions: This risk classification based on the 126-gene expression signature is an accurate predictor of clinical outcome in patients with advanced stage high-grade serous ovarian cancer and has the potential to develop new therapeutic strategies for high-grade serous ovarian cancer patients. Clin Cancer Res; 18(5); 1374-85. (C)2012 AACR.

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  • The Prognostic Significance of Multiple Pelvic Node Metastases in Cervical Cancer Patients Treated With Radical Hysterectomy Plus Adjuvant Chemoradiotherapy 査読

    Mika Okazawa, Seiji Mabuchi, Fumiaki Isohashi, Osamu Suzuki, Yukinobu Ohta, Masami Fujita, Kiyoshi Yoshino, Takayuki Enomoto, Shoji Kamiura, Tadashi Kimura

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER22 ( 3 ) 490 - 497   2012年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Objective: We investigated the prognostic significance of multiple pelvic node metastases in cervical cancer patients who were treated with radical hysterectomy plus adjuvant chemoradiotherapy.
    Methods: We retrospectively reviewed the medical records of 311 patients with International Federation of Gynecology and Obstetrics stage IB1-IIB cervical cancer who had been treated with radical hysterectomy plus adjuvant radiotherapy (RT) between January 1998 and December 2008. Of these, 119 received adjuvant RT and 192 received adjuvant concurrent chemoradiotherapy (CCRT) postoperatively. Multivariate analysis for progressionfree survival (PFS) was performed using the Cox proportional hazards regression model to investigate the prognostic significance of pelvic node metastases in the 2 treatment groups. Survival was calculated using the Kaplan-Meier method and compared using the log-rank test.
    Results: Multivariate analysis demonstrated pelvic node metastasis to be an independent prognostic factor for shorter PFS in both treatment groups. When the node-positive patients were analyzed according to the number of positive pelvic nodes, we found that the patients with multiple pelvic node metastases (&gt;= 3) displayed significantly shorter PFS than those with 1 or 2 pelvic node metastases in the RT group. In contrast, in the CCRT group, the PFS of the patients with multiple pelvic node metastases (&gt;= 3) was similar to that observed of the patients with 1 or 2 pelvic node metastases.
    Conclusions: The presence of multiple pelvic node metastases was not an independent predictor of shorter PFS in the CCRT group.

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  • Biased usage of T cell receptor β-chain variable region genes of Wilms' tumor gene (WT1)-specific CD8+ T cells in patients with solid tumors and healthy donors. 査読

    Soyoko Morimoto, Yoshihiro Oka, Akihiro Tsuboi, Yukie Tanaka, Fumihiro Fujiki, Hiroko Nakajima, Naoki Hosen, Sumiyuki Nishida, Jun Nakata, Yoshiki Nakae, Motohiko Maruno, Akira Myoui, Takayuki Enomoto, Shuichi Izumoto, Mitsugu Sekimoto, Naoki Kagawa, Naoya Hashimoto, Toshiki Yoshimine, Yusuke Oji, Atsushi Kumanogoh, Haruo Sugiyama

    Cancer Sci.103 ( 3 ) 408 - 414   2012年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Wilms&#039; tumor gene 1 (WT1) protein is a promising tumor-associated antigen. In patients with WT1-expressing malignancies, WT1-specific CTLs are spontaneously induced as a result of an immune response to the WT1 protein. In the present study, we performed single cell-level comparative analysis of T cell receptor β-chain variable region (TCR-BV) gene families of a total of 750 spontaneously induced WT1(126) peptide (amino acids 126-134, WT1(126))-specific CTLs in both HLA-A*0201(+) patients with solid tumors and healthy donors (HDs). This is the first report of direct usage analysis of 24 kinds of TCR-BV gene families of WT1(126)-specific CTLs at the single cell level. Usage analysis with single-cell RT-PCR of TCR-BV gene families of individual FACS-sorted WT1(126) tetramer(+) CD8(+) T cells showed, for the first time, that: (i) BVs 3, 6, 7, 20, 27, and 28 were commonly biased in patients and HDs; (ii) BVs 2, 11, and 15 were biased only in patients; and (iii) BVs 4, 5, 9, and 19 were biased only in HDs. However, statistical analysis of similarity of individual usage frequencies of 24 kinds of TCR-BV gene families between patients and HDs indicated that the usage frequencies of TCR-BV

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  • Biased usage of T cell receptor β-chain variable region genes of Wilms' tumor gene (WT1)-specific CD8+ T cells in patients with solid tumors and healthy donors. 査読 国際誌

    Morimoto S, Oka Y, Tsuboi A, Tanaka Y, Fujiki F, Nakajima H, Hosen N, Nishida S, Nakata J, Nakae Y, Maruno M, Myoui A, Enomoto T, Izumoto S, Sekimoto M, Kagawa N, Hashimoto N, Yoshimine T, Oji Y, Kumanogoh A, Sugiyama H

    Cancer science103 ( 3 ) 408 - 14   2012年3月

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  • Therapeutic strategies in epithelial ovarian cancer. 査読

    Kim A, Ueda Y, Naka T, Enomoto T

    Journal of experimental & clinical cancer research : CR31   14   2012年2月

  • Prognostic significance of elongator protein 3 expression in endometrioid adenocarcinoma 査読

    Yi Wang, Jun-Ichiro Ikeda, Nur Rahadiani, Suhana Mamat, Yutaka Ueda, Tian Tian, Takayuki Enomoto, Tadashi Kimura, Katsuyuki Aozasa, Eiichi Morii

    ONCOLOGY LETTERS3 ( 1 ) 25 - 29   2012年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Elongator protein 3 (ELP3), the catalytic subunit of the elongator complex of RNA polymerase II, is involved in various functions, including transcriptional elongation, chromatin modification and cytoskeletal regulation. In this study, ELP3 expression was immunohistochemically examined in normal uterus tissue and uterine endometrioid adenocarcinoma tissue. ELP3 was abundantly expressed in both the proliferative and secretory phases of the endometrial cycle. However, ELP3 expression levels varied among cases of endometrioid adenocarcinoma. In patients with endometrioid adenocarcinoma, a low ELP3 expression was correlated to a high T-factor (p=0.036), tumor stage (p=0.001), lymph node metastasis (p&lt;0.001), resistance to chemotherapy (p=0.045), recurrence (p=0.004) and poor prognosis (p=0.003). Univariate and multivariate analyses revealed that a low ELP3 expression was an independent factor for poor prognosis. In conclusion, this is the first study to examine the clinical implications of ELP3 expression in cancer.

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  • Enormous Cystic Tumor of Peritoneal Psammocarcinoma Exhibiting Complete Response to Cisplatin and Cyclophosphamide after Suboptimal Cytoreduction: Case Report and Review of the Literature 査読

    Ryoko Takahashi, Yutaka Ueda, Mitsunori Shioji, Shiro Adachi, Hiroshi Ohashi, Eiichi Morii, Katsuyuki Aozasa, Kiyoshi Yoshino, Masami Fujita, Takayuki Enomoto, Tadashi Kimura, Atsushi Tokuhira

    GYNECOLOGIC AND OBSTETRIC INVESTIGATION74 ( 2 ) 165 - 170   2012年

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    記述言語:英語   出版者・発行元:KARGER  

    Psammocarcinoma is a serous peritoneal tumor arising from the ovary or the peritoneum and characterized by low-grade nuclear features, extensive psammoma bodies, and invasiveness. Only 62 cases have ever been documented, 30 primary peritoneal and 32 primary ovarian, most of which presented as small tumors. Adjuvant therapies, including chemotherapy and radiation, were performed in 12 of the primary peritoneal cases, without any clear evidence of benefit. We present a case of an unusually large primary peritoneal psammocarcinoma with unexpected outcome. The patient was a 38-year-old woman with a tumor of the peritoneum which adhered densely to the uterus and rectum and developed into the intra-abdominal cavity and retroperitoneal space. After adhesiolysis of the tumor and rectum, suboptimal surgical reduction left a 4 cm x 2 cm tumor segment. Postoperative chemotherapy, consisting of paclitaxel and carboplatin (TC) for 1 course, and cyclophosphamide and cisplatin (CP) for 5 courses, was conducted. The residual tumor responded completely to the chemotherapy and the patient is alive today, with no evidence of disease 15 months after the surgery. Our case implies that CP therapy is a potential regimen of postoperative remission-induction therapy for suboptimally resected primary peritoneal psammocarcinoma. Copyright (C) 2012 S. Karger AG, Basel

    DOI: 10.1159/000336793

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  • Salvage Chemotherapy for Ovarian Carcinoma Recurring During or After Consolidation Chemotherapy with Paclitaxel 査読

    Yukari Miyoshi, Yutaka Ueda, Akiko Morimoto, Takuhei Yokoyama, Shinya Matsuzaki, Eiji Kobayashi, Toshihiro Kimura, Kiyoshi Yoshino, Masami Fujita, Takayuki Enomoto, Tadashi Kimura

    ANTICANCER RESEARCH31 ( 12 ) 4613 - 4617   2011年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:INT INST ANTICANCER RESEARCH  

    Background: The aim of the study was to analyze the effectiveness of salvage chemotherapy for recurring ovarian carcinoma during or after consolidation chemotherapy. Patients and Methods: During the study period, 12 patients received salvage chemotherapy for recurrence during or after consolidation chemotherapy. These cases were retrospectively reviewed. Results: The response rate for salvage chemotherapy was 67% and was significantly associated with treatment-free interval (TFI) after consolidation (p=0.038). Progression-free survival was also significantly related to TFI (p=0.032). Combination chemotherapy of cisplatin plus irinotecan was effective in all five cases with TFI &gt;= 6 months and in three out of seven cases with TFI&lt;6 months. Conclusion: Our study provides, for the first time, evidence that effectiveness of salvage chemotherapy for recurrent ovarian carcinoma occurring during or after consolidation chemotherapy can be predicted by TFI, and that combination chemotherapy of cisplatin plus irinotecan is potentially useful for these cases.

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  • Usefulness of computed tomography in predicting cytoreductive surgical outcomes for ovarian cancer 査読

    Kazuko Fujwara, Kiyoshi Yoshino, Takayuki Enomoto, Masami Fujita, Yutaka Ueda, Takashi Miyatake, Toshihiro Kimura, Miho Muraji, Haruyasu Fujita, Tadashi Kimura, Masatoshi Hori

    ARCHIVES OF GYNECOLOGY AND OBSTETRICS284 ( 6 ) 1501 - 1507   2011年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER HEIDELBERG  

    Purpose The objective of this study was to identify features of preoperative computed tomography (CT) scans that can best predict outcomes of primary cytoreductive surgery in ovarian cancer patients.
    Methods Preoperative CT scans of 98 patients were evaluated retrospectively. Multiple logistic regression analysis was used to develop two models.
    Results Although optimal surgical reduction was attempted in 98 patients, 12 had suboptimal results. Having tumor implants on the small or large bowel mesenteries (any size) or at other sites (cutoff index: a parts per thousand yen1 cm) was found to be significant (p &lt; 0.001) for predicting a suboptimal cytoreduction outcome. Two predictive models were created using multiple logistic regression analysis; both consider diffuse peritoneal thickening (DPT), infrarenal para-aortic or pelvic lymph node involvement, a bowel encasement tumor (a parts per thousand yen2 cm), and any tumor implants in the cul-de-sac as significant. Model 1 adds consideration to any tumors in the pelvic or retroperitoneum and has an accuracy of 90.8% for predicting a suboptimal surgery. Model 2 (accuracy of 93.9%) adds to the core of predictors the presence of tumor implants on the bowel mesenteries (a parts per thousand yen2 cm), omental caking (a parts per thousand yen2 cm), and ascites fluid.
    Conclusion Using specific CT findings from patients with ovarian cancer, we have devised two predictive models that have an accuracy of greater than 90% for predicting whether cytoreductive surgery will completely remove all tumor tissue, which should greatly aid in the differential decision-making as to whether to attempt cytoreductive surgery first, or to advance directly to neoadjuvant chemotherapy.

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  • Dissection of Unsuspicious Para-aortic Lymph Nodes Does Not Improve Prognosis of Advanced Endometrial Carcinoma with Intra- or Extra-abdominal Metastasis 査読

    Yutaka Ueda, Mika Okazawa, Takayuki Enomoto, Tomomi Egawa-Takata, Toshihiro Kimura, Kiyoshi Yoshino, Masami Fujita, Yukinobu Ohta, Shoji Kamiura, Tadashi Kimura

    ANTICANCER RESEARCH31 ( 12 ) 4513 - 4517   2011年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:INT INST ANTICANCER RESEARCH  

    Background: The aim of this study was to analyze the significance of dissection of unsuspicious para-aortic lymph nodes (PAN) in patients with advanced endometrial carcinomas with intra- or extra-abdominal metastasis. Patients and Methods: We conducted a retrospective comparison of the results of PAN dissection versus non-dissection for endometrial carcinomas with macroscopic metastatic lesions beyond the uterus (without significant swelling of the regional lymph nodes, including PAN), whose lesions were completely resected. Results: Disease-free survival and overall survival did not exhibit a significant difference between the two groups. Multivariate Cox proportional hazards analysis demonstrated that PAN dissection was not an independent prognostic factor for survival. The frequency of PAN involvement at the first recurrence did not differ between the two groups. Conclusion: For advanced endometrial carcinomas with macroscopic metastatic lesions beyond the uterus, without significant swelling of regional lymph nodes, PAN dissection may be omitted without a significant adverse effect on prognosis and survival.

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  • Chemotherapy for endometrial carcinoma (GOGO-EM1 study): TEC (paclitaxel, epirubicin, and carboplatin) is an effective remission-induction and adjuvant therapy 査読

    Tomomi Egawa-Takata, Yutaka Ueda, Chie Kuragaki, Takahito Miyake, Takashi Miyatake, Masami Fujita, Kiyoshi Yoshino, Ryuichi Nakashima, Mika Okazawa, Tateki Tsutsui, Ken-Ichirou Morishige, Tadashi Kimura, Masato Yamasaki, Takamichi Nishizaki, Masaaki Nagamatsu, Kimihiko Ito, Masahiro Asada, Kazuhide Ogita, Akinori Wakimoto, Toshiya Yamamoto, Yukihiro Nishio, Takayuki Enomoto

    CANCER CHEMOTHERAPY AND PHARMACOLOGY68 ( 6 ) 1603 - 1610   2011年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Background TAP chemotherapy (paclitaxel, doxorubicin, and cisplatin) is effective for advanced and recurrent endometrial carcinoma, but has occasional severe toxicity. TEC chemotherapy (paclitaxel, epirubicin, and carboplatin) has been suggested to have less toxicity; however, the optimal dosage has yet to be determined.
    Patients and methods Phase I/II prospective study for TEC therapy was performed. A retrospective comparison of the prognosis between adjuvant TEC therapy and radiation for completely resected cases with risk factors was also performed.
    Results The recommended dose of TEC therapy was determined to be paclitaxel 150 mg/m(2), epirubicin 50 mg/m(2), and carboplatin AUC 4. A TEC regimen at this dose level was shown to be tolerable. The response rate and median overall survival were 74% and 37 months for those with advanced primary disease (Group B) and 50% and 26 months for recurrent tumors (Group C), respectively. A retrospective comparison showed that adjuvant TEC therapy for completely resected stage III cases improved their prognosis when compared to an adjuvant radiation therapy.
    Conclusion TEC therapy was demonstrated to be a tolerable and effective treatment, not only as a remission-induction therapy for advanced and recurrent endometrial carcinomas but also as the adjuvant therapy.

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  • Radical hysterectomy with adjuvant radiotherapy versus definitive radiotherapy alone for FIGO stage IIB cervical cancer 査読

    Seiji Mabuchi, Mika Okazawa, Fumiaki Isohashi, Koji Matsuo, Yukinobu Ohta, Osamu Suzuki, Yasuo Yoshioka, Takayuki Enomoto, Shoji Kamiura, Tadashi Kimura

    GYNECOLOGIC ONCOLOGY123 ( 2 ) 241 - 247   2011年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Objectives. The aim of this study was to compare the treatment outcomes and adverse effects of radical hysterectomy followed by adjuvant radiotherapy with definitive radiotherapy alone in patients with FIGO stage BB cervical cancer.
    Methods. We retrospectively reviewed the medical records of FIGO stage IIB cervical cancer patients who were treated between April 1996 and December 2009. During the study period, 95 patients were treated with radical hysterectomy, all of which received adjuvant radiotherapy (surgery-based group). In addition, 94 patients received definitive radiotherapy alone (RT-based group). The recurrence rate, progression-free survival (PFS), overall survival (OS), and treatment-related complications were compared between the two groups.
    Results. Radical hysterectomy followed by adjuvant radiotherapy resulted in comparable recurrence (44.2% versus 41.5%, p = 0.77), PFS (log-rank, p = 0.57), and OS rates (log-rank, p = 0.41) to definitive radiotherapy alone. The frequencies of acute grade 3-4 toxicities were similar between the two groups (24.2% versus 24.5%, p = 1.0), whereas the frequencies of grade 3-4 late toxicities were significantly higher in the surgery-based group than in the RT-based group (24.1% versus 10.6%, p = 0.048). Cox multivariate analyses demonstrated that treatment with surgery followed by adjuvant radiotherapy was associated with an increased risk of grade 3-4 late toxicities, although the statistical significance of the difference was marginal (odds ratio 2.41, 95%CI 0.97-5.99, p = 0.059).
    Conclusions. Definitive radiotherapy was found to be a safer approach than radical hysterectomy followed by postoperative radiotherapy with less treatment-related complications and comparable survival outcomes in patients with FIGO stage IIB cervical cancer. (C) 2011 Elsevier Inc. All rights reserved.

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  • HB-EGF and PDGF Mediate Reciprocal Interactions of Carcinoma Cells with Cancer-Associated Fibroblasts to Support Progression of Uterine Cervical Cancers 査読

    Takuya Murata, Hiroto Mizushima, Ichino Chinen, Hiroki Moribe, Shigeo Yagi, Robert M. Hoffman, Tadashi Kimura, Kiyoshi Yoshino, Yutaka Ueda, Takayuki Enomoto, Eisuke Mekada

    CANCER RESEARCH71 ( 21 ) 6633 - 6642   2011年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    Tumor stroma drives the growth and progression of cancers. A heparin-binding epidermal growth factor-like growth factor, HB-EGF, is an EGF receptor ligand that stimulates cell growth in an autocrine or paracrine fashion. While elevated expression of HB-EGF in cancer cells and its contribution to tumor progression are well documented, the effects of HB-EGF expression in the tumor stroma have not been clarified. Here, we show that HB-EGF is expressed in stromal fibroblasts where it promotes cancer cell proliferation. In uterine cervical cancers, HB-EGF was detected immunohistochemically in the stroma proximal to the cancer epithelium. Proliferation of cervical cancer cells in vitro was enhanced by coculture with fibroblasts isolated from tumor tissues of patients with cervical cancer. Inhibition of HB-EGF function or treatment with platelet-derived growth factor (PDGF) inhibitors abrogated cancer cell growth enhanced by cervical cancer-associated fibroblast (CCF) coculture. Furthermore, tumor formation in a mouse xenograft model was enhanced by cotransplantation of CCF or mouse embryonic fibroblasts, but not with embryonic fibroblasts from HB-EGF-deficient mice. Conversely, conditioned medium from cancer cells induced HB-EGF expression in CCF. Mechanistic investigations established that PDGF was the primary factor responsible. Together, our findings indicate that HB-EGF and PDGF reciprocally mediate the interaction of cancer cells with cancer-associated fibroblasts, promoting cancer cell proliferation in a paracrine manner that has implications for novel combinatorial cancer therapies. Cancer Res; 71(21); 6633-42. (C)2011 AACR.

    DOI: 10.1158/0008-5472.CAN-11-0034

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  • A successful case of abdominal radical trachelectomy for cervical cancer during pregnancy 査読

    Takayuki Enomoto, Kiyoshi Yoshino, Masami Fujita, Yukari Miyoshi, Yutaka Ueda, Shinsuke Koyama, Toshihiro Kimura, Takuji Tomimatsu, Tadashi Kimura

    EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY158 ( 2 ) 365 - 366   2011年10月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    DOI: 10.1016/j.ejogrb.2011.04.048

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  • Intraoperative Frozen Section Assessment of Myometrial Invasion and Histology of Endometrial Cancer Using the Revised FIGO Staging System 査読

    Hiromi Ugaki, Toshihiro Kimura, Takashi Miyatake, Yutaka Ueda, Kiyoshi Yoshino, Shinya Matsuzaki, Masami Fujita, Tadashi Kimura, Eiichi Morii, Takayuki Enomoto

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER21 ( 7 ) 1180 - 1184   2011年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Objectives: The objective of this study was to assess the value of intraoperative frozen section (IFS) diagnosis for myometrial invasion and histology of endometrial cancer using the revised International Federation of Gynecology and Obstetrics (FIGO) staging system.
    Methods: The medical records of 303 patients with endometrial cancer who underwent surgery with intraoperative diagnosis at the Osaka University Hospital between January 1999 and December 2008 were reviewed. Intraoperative frozen section diagnosis was retrospectively analyzed for the accuracy rates of myometrial invasion and histology compared with the final diagnosis and with preoperative prediction by magnetic resonance imaging (MRI) and endometrial curettage.
    Results: When using the previous FIGO staging system, the accuracy rate of IFS for the diagnosis of myometrial invasion was 77%, whereas the accuracy rate of preoperative prediction by MRI was 54%. However, using the newly revised FIGO staging system for myometrial invasion, the accuracy rate of IFS was 87% and the preoperative prediction by MRI was 82%. The accuracy rate of IFS for the diagnosis of histology was 71%, whereas the accuracy rate of preoperative prediction by endometrial curettage was 68%.
    Conclusion: Although under the previous FIGO staging system IFS diagnosis was significantly more accurate than preoperative prediction by MRI, when using the newly revised FIGO staging system, there are no significant differences between the values of preoperative and intraoperative diagnoses. The accuracy of IFS, however, trends to be slightly better than the preoperative procedures of MRI and endometrial surface biopsy. Thus, IFS diagnosis is still useful for directing primary operative management.

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  • Targeting Src in Mucinous Ovarian Carcinoma 査読

    Koji Matsuo, Masato Nishimura, Justin N. Bottsford-Miller, Jie Huang, Kakajan Komurov, Guillermo N. Armaiz-Pena, Mian M. K. Shahzad, Rebecca L. Stone, Ju Won Roh, Angela M. Sanguino, Chunhua Lu, Dwight D. Im, Neil B. Rosenshien, Atsuko Sakakibara, Tadayoshi Nagano, Masato Yamasaki, Takayuki Enomoto, Tadashi Kimura, Prahlad T. Ram, Kathleen M. Schmeler, Gary E. Gallick, Kwong K. Wong, Michael Frumovitz, Anil K. Sood

    CLINICAL CANCER RESEARCH17 ( 16 ) 5367 - 5378   2011年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    Purpose: Mucinous ovarian carcinomas have a distinct clinical pattern compared with other subtypes of ovarian carcinoma. Here, we evaluated (i) stage-specific clinical significance of mucinous ovarian carcinomas in a large cohort and (ii) the functional role of Src kinase in preclinical models of mucinous ovarian carcinoma.
    Experimental Design: A total of 1,302 ovarian cancer patients including 122 (9.4%) cases of mucinous carcinoma were evaluated for survival analyses. Biological effects of Src kinase inhibition were tested using dasatinib-based therapy in a novel orthotopic mucinous ovarian cancer model (RMUG-S-ip2).
    Results: Patients with advanced-stage mucinous ovarian cancer had significantly worse survival than those with serous histology: median overall survival, 1.67 versus 3.41 years, P = 0.002; median survival time after recurrence of 0.53 versus 1.66 years, P &lt; 0.0001. Among multiple ovarian cancer cell lines, RMUG-S-ip2 mucinous ovarian cancer cells showed the highest Src kinase activity. Moreover, oxaliplatin treatment induced phosphorylation of Src kinase. This induced activity by oxaliplatin therapy was inhibited by concurrent administration of dasatinib. Targeting Src with dasatinib in vivo showed significant antitumor effects in the RMUG-S-ip2 model but not in the serous ovarian carcinoma (SKOV3-TR) model. Combination therapy of oxaliplatin with dasatinib further showed significant effects on reducing cell viability, increasing apoptosis, and in vivo antitumor effects in the RMUG-S-ip2 model.
    Conclusions: Our results suggest that poor survival of women with mucinous ovarian carcinoma is associated with resistance to cytotoxic therapy. Targeting Src kinase with a combination of dasatinib and oxaliplatin may be an attractive approach for this disease. Clin Cancer Res; 17(16); 5367-78. (C)2011 AACR.

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  • Bcl11b/Ctip2 Controls the Differentiation of Vomeronasal Sensory Neurons in Mice 査読

    Takayuki Enomoto, Makoto Ohmoto, Tetsuo Iwata, Ayako Uno, Masato Saitou, Tatsuya Yamaguchi, Ryo Kominami, Ichiro Matsumoto, Junji Hirota

    JOURNAL OF NEUROSCIENCE31 ( 28 ) 10159 - 10173   2011年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SOC NEUROSCIENCE  

    The transcription factor Bcl11b/Ctip2 plays critical roles in the development of several systems and organs, including the immune system, CNS, skin, and teeth. Here, we show that Bcl11b/Ctip2 is highly expressed in the developing vomeronasal system in mice and is required for its proper development. Bcl11b/Ctip2 is expressed in postmitotic vomeronasal sensory neurons (VSNs) in the vomeronasal epithelium (VNE) as well as projection neurons and GABAergic interneurons in the accessory olfactory bulb (AOB). In the absence of Bcl11b, these neurons are born in the correct number, but VSNs selectively die by apoptosis. The critical role of Bcl11b in vomeronasal system development is demonstrated by the abnormal phenotypes of Bcl11b-deficient mice: disorganization of layer formation of the AOB, impaired axonal projections of VSNs, a significant reduction in the expression of vomeronasal receptor genes, and defective mature differentiation of VSNs. VSNs can be classified into two major types of neurons, vomeronasal 1 receptor (V1r)/G alpha(i2)-positive and vomeronasal 2 receptor (V2r)/G alpha(o)-positive VSNs. We found that all G alpha(i2)-positive cells coexpressed G alpha(o) during embryogenesis. This coexpression is also observed in newly differentiated neurons in the adult VNE. Interestingly, loss of Bcl11b function resulted in an increased number of V1r/G alpha(i2)-type VSNs and a decreased number of V2r/G alpha(o)-type VSNs, suggesting that Bcl11b regulates the fate choice between these two VSN types. These results indicate that Bcl11b/Ctip2 is an essential regulator of the differentiation and dichotomy of VSNs.

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  • Recurrent endometrial carcinoma: prognosis for patients with recurrence within 6 to 12 months is worse relative to those relapsing at 12 months or later 査読

    Takahito Miyake, Yutaka Ueda, Tomomi Egawa-Takata, Shinya Matsuzaki, Takuhei Yokoyama, Yukari Miyoshi, Toshihiro Kimura, Kiyoshi Yoshino, Masami Fujita, Masato Yamasaki, Takayuki Enomoto, Tadashi Kimura

    AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY204 ( 6 ) 535.e1 - 5   2011年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MOSBY-ELSEVIER  

    OBJECTIVE: We evaluated association of prognosis of endometrial carcinoma patients and treatment-free intervals (TFIs).
    STUDY DESIGN: We compared the effectiveness of second-line chemotherapy performed for patients with TFIs of 6-12 months and 12 or more months following a first-line chemotherapy based on taxane (paclitaxel) and carboplatin, with or without the anthracycline (TC).
    RESULTS: Progression-free and overall survivals were significantly shorter in patients with TFIs of 6-12 months than those with TFIs of 12 or more months. Among the patients who received similar second-line chemotherapy, response rates of 15 patients with TFIs of 12 or more months and 7 patients with TFIs of 6-12 months were 67% and 43%, respectively. Progression-free survival was significantly worse in those with TFIs of 6-12 months (median, 7 months) than those with TFIs of 12 or more months (median, 12 months).
    CONCLUSION: Our small retrospective analysis suggests that recurrent endometrial carcinomas with TFIs of 6-12 months can be regarded as being partially sensitive to TC-based chemotherapy.

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  • 子宮頸癌及び体癌PET/CTにおけるFDG集積の腫瘍内均一性と辺縁不整度の評価 査読

    巽 光朗, 礒橋 佳也子, 井上 敦夫, 中城 和也, 加藤 弘樹, 榎本 隆之, 木村 正, 下瀬川 恵久, 畑澤 順

        2011年5月

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    記述言語:日本語  

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  • Questionnaire survey of the current status of radical trachelectomy in Japan 査読

    Shinya Sato, Daisuke Aoki, Hiroaki Kobayashi, Tsuyoshi Saito, Ryuichiro Nishimura, Tadayoshi Nagano, Nobuo Yaegashi, Takayuki Enomoto, Junzo Kigawa

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY16 ( 2 ) 141 - 144   2011年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER TOKYO  

    The number of young patients with cervical cancer has been increasing recently in Japan. Radical trachelectomy is a potential option for patients who wish to preserve their fertility, but its status is not clear. The present survey was conducted to clarify the status of radical trachelectomy in Japan.
    Questionnaires were mailed to 164 selected institutions based on tumor registration with the Japanese Obstetrics Gynecology Society. The subjects were patients undergoing radical trachelectomy between 2000 and 2008.
    The response rate to the questionnaire was 88.4% (145/164). Radical trachelectomy was performed on 269 patients in 26 institutions (17.9%) . Most cases (74.7%, 201/269) underwent an abdominal approach. Three institutions had performed more than 21 cases (max. 61 cases), whereas 8 institutions had performed only one case. Twenty pregnancies and 13 deliveries were achieved and the frequency of delivery later than the 29th gestational week was 62% (8/13). "Tumor size a parts per thousand currency sign2 cm (81%)" and "stage a parts per thousand currency signIb1 (96%)" were commonly regarded as indications for radical trachelectomy. On the other hand, 46% of the centers did not consider the histological type as an indication.
    This survey is the first report on the current status of radical trachelectomy in Japan. It reveals a difference in the criteria for surgery applied in each institution.

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  • CRABP1-reduced expression is associated with poorer prognosis in serous and clear cell ovarian adenocarcinoma 査読

    Takahito Miyake, Yutaka Ueda, Shinya Matsuzaki, Takashi Miyatake, Kiyoshi Yoshino, Masami Fujita, Taisei Nomura, Takayuki Enomoto, Tadashi Kimura

    JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY137 ( 4 ) 715 - 722   2011年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    CRABP1 is a modulator of retinoic acid function. The aim of the present study was to investigate CRABP1 expression and its clinical significance in ovarian carcinoma.
    Expression of CRABP1 protein was investigated by immunohistochemical analysis in 100 ovarian carcinomas of various histological sub-types, including serous and clear cell adenocarcinomas. Relationship of CRABP1 expression to clinical features, including prognosis, was analyzed.
    Reduced expression of CRABP1 protein was detected especially frequently in the serous and clear cell adenocarcinomas sub-types, 50% (20 of 40) and 38% (10 of 26) of cases, respectively. We found that in both serous and clear cell adenocarcinomas overall survival was significantly poorer in the cases with reduced CRABP1 expression compared to similar cases where expression was maintained, irrespective of the disease stage (P = 0.0073 and 0.049, respectively). Disease-free survival of the serous and clear cell adenocarcinoma cases with reduced CRABP1 expression was significantly poorer, compared to the cases whose CRABP1 expression was maintained (P = 0.024). Multivariate analysis showed that reduced expression of CRABP1 was a significantly important prognostic factor (adjusted hazard ratio: 8.189 (95% CI, 2.186-30.672, P = 0.0019)).
    The present study is the first to demonstrate that the reduced expression of CRABP1 has a potential as a prognostic marker for serous adenocarcinoma which is the most frequent histological ovarian tumor type and also for clear cell carcinoma that often exhibits chemo-resistance. Further study is necessary to clarify how CRABP1 protein expression was altered and how CRABP1 affects ovarian carcinoma cells.

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  • Second-line chemotherapy for advanced or recurrent endometrial carcinoma previously treated with paclitaxel and carboplatin, with or without epirubicin 査読

    Yutaka Ueda, Takahito Miyake, Tomomi Egawa-Takata, Takashi Miyatake, Shinya Matsuzaki, Takuhei Yokoyama, Kiyoshi Yoshino, Masami Fujita, Takayuki Enomoto, Tadashi Kimura

    CANCER CHEMOTHERAPY AND PHARMACOLOGY67 ( 4 ) 829 - 835   2011年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    A combined chemotherapy of taxane and platinum, with or without anthracycline, has been used as a standard first-line regimen. The purpose of this study was to investigate the effectiveness of second-line chemotherapy for treatment of advanced or recurrent endometrial carcinoma previously treated with a combined chemotherapy of taxane and platinum, with or without anthracycline.
    During the 2000-2008 study period, 723 patients were diagnosed with endometrial cancer at the Departments of Obstetrics and Gynecology of the Osaka University and the Osaka Rosai Hospitals, Osaka, Japan. The subset of these cases that eventually required treatment by second-line chemotherapy was retrospectively analyzed.
    Response rate to second-line chemotherapy was 25%. Treatment-free interval (TFI) of a parts per thousand yen or &lt; 6 months was demonstrated to be significantly associated with the response to second-line chemotherapy (P = 0.0026), progression-free survival (P = 0.0003) and overall survival (P = 0.025). The second-line chemotherapy similar to the first-line regimen was ineffective in all the 7 cases (100%) whose TFI was shorter than 6 months. Multivariate analysis showed that TFI was the most significantly important factor predicting the effectiveness of second-line chemotherapy (the adjusted hazard ratio of TFI on PFS and OS: 3.482, 95% CI, 1.641-7.388, P = 0.0012, and 2.341, 95% CI, 1.034-5.301, P = 0.042, respectively).
    Our present study provides, for the first time, evidence that the majority of refractory or recurrent diseases, if they occur within 6 months of a first-line chemotherapy using taxane and platinum with or without anthracycline, are non-responsive to the current regimens of second-line chemotherapy.

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  • Expression of aldehyde dehydrogenase 1 (ALDH1) in endometrioid adenocarcinoma and its clinical implications 査読

    Nur Rahadiani, Jun-ichiro Ikeda, Suhana Mamat, Shinya Matsuzaki, Yutaka Ueda, Reina Umehara, Tian Tian, Yi Wang, Takayuki Enomoto, Tadashi Kimura, Katsuyuki Aozasa, Eiichi Morii

    CANCER SCIENCE102 ( 4 ) 903 - 908   2011年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Aldehyde dehydrogenase 1 (ALDH1) is expressed in stem/progenitor cells, including cancer-initiating cells (CIC) of various organs. In the present study, ALDH1 expression was immunohistochemically examined in uterine endometrioid adenocarcinoma. The ALDH1 was expressed in a small portion of tumor cells, and these ALDH1-expressing cells were less mature than ALDH1-non-expressing cells. The ALDH1-expressing (ALDH1-hi) cells were more tumorigenic, resistant to anti-cancer agents and more invasive than ALDH1-lo cells. Culture of the sorted ALDH1-hi cells yielded both ALDH1-hi and ALDH1-lo cells, whereas ALDH1-lo cells yielded ALDH-lo cells alone. Clinically, a high-level of ALDH1 expression in tumor cells was correlated with T category, lymphatic invasion, recurrence and prognosis of patients. Patients with high ALDH1 expression showed poorer prognoses than those with low expression (P = 0.015 for disease-free survival [DFS] and P = 0.010 for overall survival [OS]), and high ALDH1 expression was an independent factor for poor prognosis. Aldehyde dehydrogenase 1 is a candidate for CIC marker for uterine endometrioid adenocarcinoma. (Cancer Sci 2011; 102: 903-908)

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  • Impaired Delivery Outcomes in Pregnancies Following Myomectomy Compared to Myoma-Complicated Pregnancies 査読

    Yukiko Kinugasa-Taniguchi, Yutaka Ueda, Chifumi Hara-Ohyagi, Takayuki Enomoto, Takeshi Kanagawa, Tadashi Kimura

    JOURNAL OF REPRODUCTIVE MEDICINE56 ( 3-4 ) 142 - 148   2011年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SCI PRINTERS & PUBL INC  

    OBJECTIVE: To compare obstetric and delivery outcomes between myoma-complicated pregnancies and pregnancies that follow myomectomy.
    STUDY DESIGN: Among the 7,589 deliveries performed in the Department of Obstetrics and Gynecology of the Osaka University Hospital, Osaka, Japan, from 1994 to 2007, women with a past history of myomectomy and those with myoma during their pregnancy were enrolled in this study. Their clinical records were reviewed retrospectively.
    RESULTS: The frequency of myomas detected during pregnancy significantly increased by 1.8-fold during the first 7-year period as compared with the latter 7-year period of the study (p &lt; 0.001). The obstetric and delivery outcomes, including the rate of cesarean section, the rate of preterm delivery and the amount of blood loss at delivery, were better in pregnancies complicated with current myoma than those in pregnancies which had undergone previous myomectomy (p &lt; 0.001, p = 0.002 and p = 0.005, respectively), with the exception of an increased need for analgesic medication.
    CONCLUSION: Myomectomy of large asymptomatic myomas does not improve future obstetric and delivery outcomes, indicating that most asymptomatic myomas should be managed conservatively in women still considering childbearing. (J Reprod Med 2011;56:142 148)

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  • Postoperative whole pelvic radiotherapy plus concurrent chemotherapy versus extended-field irradiation for early-stage cervical cancer patients with multiple pelvic lymph node metastases 査読

    Seiji Mabuchi, Mika Okazawa, Fumiaki Isohashi, Yukinobu Ohta, Shintaroh Maruoka, Yasuo Yoshioka, Takayuki Enomoto, Kenichirou Morishige, Shoji Kamiura, Tadashi Kimura

    GYNECOLOGIC ONCOLOGY120 ( 1 ) 94 - 100   2011年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Objectives. The aim of this study was to compare the efficacy of postoperative pelvic radiotherapy plus concurrent chemotherapy with that of extended-field irradiation (EFRT) in patients with FIGO Stage IA2-IIb cervical cancer with multiple pelvic lymph node metastases.
    Methods. We retrospectively reviewed the medical records of patients with FIGO Stage IA2-IIb cervical cancer who had undergone radical surgery between April 1997 and March 2008. Of these, 55 patients who demonstrated multiple pelvic lymph node metastases were treated postoperatively with pelvic radiotherapy plus concurrent chemotherapy (n = 29) or EFRT (n = 26). Thirty-six patients with single pelvic node metastasis were also treated postoperatively with pelvic radiotherapy plus concurrent chemotherapy. The recurrence rate, progression free survival (PFS), and overall survival (OS) were compared between the treatment groups.
    Results. Pelvic radiotherapy plus concurrent chemotherapy was significantly superior to EFRT with regard to recurrence rate (37.9% vs 69.2%, p = 0.0306), PFS (log-rank, p = 0.0236), and OS (log-rank, p = 0.0279). When the patients were treated with pelvic radiotherapy plus concurrent chemotherapy, there was no significant difference in PFS or OS between the patients with multiple lymph node metastases and those with single node metastases. With regards to grade 3-4 acute or late toxicities, no statistically significant difference was observed between the two treatment groups.
    Conclusions. Postoperative pelvic radiotherapy plus concurrent chemotherapy is superior to EFRT for treating patients with FIGO Stage IA2-IIb cervical cancer displaying multiple pelvic lymph node metastases. (C) 2010 Elsevier Inc. All rights reserved.

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  • Metastatic Mucinous Adenocarcinoma of the Ovary Is Characterized by Advanced Patient Age, Small Tumor Size, and Elevated Serum CA125 査読

    Makiko Maeda-Taniguchi, Yutaka Ueda, Takahito Miyake, Takashi Miyatake, Toshihiro Kimura, Kiyoshi Yoshino, Masami Fujita, Tomoko Wakasa, Hiroshi Ohashi, Eiichi Morii, Takayuki Enomoto, Tadashi Kimura

    GYNECOLOGIC AND OBSTETRIC INVESTIGATION72 ( 3 ) 196 - 202   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KARGER  

    Background/Aims: An intraoperative diagnosis in cases with primary and metastatic ovarian carcinomas is important for adequate treatment. The aim of the present study was to find a reliable method to discriminate primary from metastatic mucinous adenocarcinomas (MACs) of the ovary intraoperatively. Methods: Clinical features of all primary and metastatic mucinous ovarian carcinomas diagnosed from 1994 to 2008 at the Osaka University and Osaka Rosai Hospitals, Osaka, Japan, were reviewed retrospectively. Results: Among the 73 MACs, 51 (70%) and 22 cases (30%) were diagnosed as primary and metastatic ovarian carcinomas, respectively. The distributions of tumor size, patient age, and serum CA125 level were significantly different between primary and metastatic cases. Our algorithm that categorizes patients 6 50 years whose tumor size was &lt; 10 cm into metastatic cases, and patients &lt; 50 years, or the ones whose tumor size was 6 10 cm, into primary tumors, provided an 84% accuracy in our population. Conclusions: A more reliable method to discriminate primary from metastatic MACs of the ovary by patient age and serum tumor markers was derived from our study population. Copyright (C) 2011 S. Karger AG, Basel

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  • Two distinct pathways to development of squamous cell carcinoma of the vulva. 査読

    Ueda Y, Enomoto T, Kimura T, Yoshino K, Fujita M, Kimura T

    Journal of skin cancer2011   951250   2011年

  • Disease-free Interval after Primary Treatment Predicts Prognosis of Recurrent Endometrial Carcinoma 査読

    Yutaka Ueda, Yuki Matsumura, Tomomi Egawa-Takata, Takahito Miyake, Takashi Miyatake, Kiyoshi Yoshino, Masami Fujita, Shinya Matsuzaki, Takuhei Yokoyama, Yukari Miyoshi, Masato Yamasaki, Takayuki Enomoto, Tadashi Kimura

    ANTICANCER RESEARCH30 ( 10 ) 4347 - 4352   2010年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:INT INST ANTICANCER RESEARCH  

    Aim: The aim of this study was to determine if the disease-free interval after initial surgical resection has any useful prognostic value for recurrent endometrial carcinoma patients. Patients and Methods: Between 1998 and 2007, complete resection of endometrial carcinoma was achieved in 536 cases at the Departments of Obstetrics and Gynecology of the Osaka University and Osaka Rosai Hospitals of Osaka, Japan. Clinical characteristics of these cases were retrospectively reviewed. Results: Recurrence was subsequently detected in 54 cases. Overall survival after recurrence in 27 patients with recurrences earlier than 12 months who received no postoperative therapy, radiation, and chemotherapy as an adjuvant therapy were significantly shorter than that of those with recurrences later than 12 months with similar treatments. Multivariate analysis demonstrated that the disease-free interval was an independent factor for prognosis. Conclusion: We demonstrate a significantly worse prognosis in cases with early versus late recurrence of resected endometrial carcinomas, irrespective of the type of adjuvant therapy.

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  • Early reduction of glucose uptake after cisplatin treatment is a marker of cisplatin sensitivity in ovarian cancer 査読

    Tomomi Egawa-Takata, Hiroko Endo, Masami Fujita, Yutaka Ueda, Takashi Miyatake, Hiroaki Okuyama, Kiyoshi Yoshino, Shoji Kamiura, Takayuki Enomoto, Tadashi Kimura, Masahiro Inoue

    CANCER SCIENCE101 ( 10 ) 2171 - 2178   2010年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Cisplatin is an effective chemotherapeutic agent for ovarian cancer, but the sensitivity of cancers differs in individual cases. Because cisplatin is reported to suppress glucose uptake, we investigated the correlation between glucose uptake and sensitivity to the drug. A fluorescent derivative of D-glucose, 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-yl) amino]-2-deoxyglucose), was used to evaluate glucose uptake. Two ovarian cancer cell lines, SKOV-3 as a relatively resistant line and OVCAR-3 as a relatively sensitive line, were analyzed. Both cell lines had a decreased number of cells accompanied by cell death 24 h after cisplatin treatment, but not at 3 h. In contrast, glucose uptake was decreased 3 h after high-dose cisplatin treatment, which correlated with the sensitivity to the drug at 24 h. The protein levels of glucose transporter 1 (GLUT1) did not change with cisplatin treatment. In contrast, the membrane localization of GLUT1 disappeared after cisplatin treatment. Other cisplatin-resistant cell lines did not show an early decrease in glucose uptake after cisplatin treatment. The early decrease in glucose uptake and later cell death also correlated in cultured cancer cells from ovarian cancer patients. Thus, the decrease in glucose uptake at an early time point after high dose cisplatin treatment reflected cisplatin chemosensitivity in ovarian cancer cells. Measuring glucose uptake might be useful as a rapid evaluation of cisplatin chemosensitivity in ovarian cancer patients. (Cancer Sci 2010).

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  • Targeting annexin A4 to counteract chemoresistance in clear cell carcinoma of the ovary 査読

    Ayako Kim, Satoshi Serada, Takayuki Enomoto, Tetsuji Naka

    EXPERT OPINION ON THERAPEUTIC TARGETS14 ( 9 ) 963 - 971   2010年9月

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    記述言語:英語   出版者・発行元:INFORMA HEALTHCARE  

    Importance of the field: Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancies in Western countries. Among the four major histological subtypes of EOC, clear cell carcinoma (CCC) of the ovary is highly resistant to platinum-based chemotherapy and is consequently associated with poor patient prognosis in advanced stages.
    Areas covered in this review: An overview of the clinical characteristics of ovarian CCC; the role of annexin family proteins in tumor development and progression; the role of annexin A4 in enhancing cellular drug resistance; recent studies linking annexin A4 overexpression to chemoresistance in tumors of ovarian CCC.
    What the reader will gain: Insight into the emerging role for annexin A4 in enhancing chemoresistance in ovarian CCC.
    Take home message: Annexin A4 enhances cancer cell chemoresistance and is overexpressed in tumors of patients with ovarian CCC. Targeting of annexin A4 may represent a future strategy to counteract resistance to chemotherapy in ovarian CCC.

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  • Endometrial carcinoma: better prognosis for asymptomatic recurrences than for symptomatic cases found by routine follow-up 査読

    Yutaka Ueda, Takayuki Enomoto, Tomomi Egawa-Takata, Takashi Miyatake, Kiyoshi Yoshino, Masami Fujita, Shinya Matsuzaki, Takuhei Yokoyama, Yukari Miyoshi, Tadashi Kimura

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY15 ( 4 ) 406 - 412   2010年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER TOKYO  

    The aim of this study was to determine if there is a prognostic value for the presence of symptoms at the time of recurrence detection in surgically resected endometrial carcinoma patients.
    During the study period of 2000-2006, complete surgical removal of endometrial carcinoma was achieved in 271 stage I-IV endometrial cancer cases at the Department of Obstetrics and Gynecology of Osaka University Hospital, Osaka, Japan. A subsequent recurrence was detected in 29 (11%) of these cases. Patient characteristics and clinicopathological features were retrospectively reviewed utilizing their clinical records.
    Among the 29 cases with a recurrence, 13 (45%) had symptoms, whereas in the other 16 cases (55%) the recurrent disease was found only during routine follow-up procedures. Although the time to detection of recurrence was similar for both asymptomatic and symptomatic cases, progression-free survival after detection in the 16 asymptomatic patients was significantly longer than for the 13 symptomatic patients (P = 0.017); this was found to be especially true in those who underwent chemotherapy as their adjuvant therapy (P = 0.023).
    A better prognosis after recurrence was demonstrated in cases that were asymptomatic at the time of recurrence detection than in those in which the tumor was symptomatic. This finding implies that, after the initial surgical resection, intensive follow-up intervention looking for asymptomatic recurrences may significantly improve the prognosis of endometrial carcinoma patients. A further in-depth prospective study is required to establish a standard strategy of follow-up care for endometrial cancer patients.

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  • Prognostic Factors for Survival in Patients With Recurrent Cervical Cancer Previously Treated With Radiotherapy 査読

    Seiji Mabuchi, Fumiaki Isohashi, Yasuo Yoshioka, Kumiko Temma, Takashi Takeda, Toshiya Yamamoto, Takayuki Enomoto, Kenichirou Morishige, Takehiro Inoue, Tadashi Kimura

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER20 ( 5 ) 834 - 840   2010年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Introduction: The aim of this study was to identify the prognostic factors and to establish a model for the prediction of life expectancy in patients with recurrent cervical cancer that had previously been treated with radiotherapy.
    Methods: The records of consecutive women with recurrent cervical cancer after radiotherapy were retrospectively reviewed. Primary disease, follow-up, and recurrence data were collected. Univariate and multivariate analyses of prognostic factors of survival were performed.
    Results: A total of 162 patients were included in our database. The median survival after recurrence was 15 months. Multivariate analysis revealed that symptom status, the site of relapse, prior chemoradiotherapy, and treatment modality were significant prognostic factors in terms of survival after recurrence. Patient survival was inversely correlated with the number of these prognostic factors. When the patients were divided into 3 prognostic groups, (low risk: patients with no poor prognostic factors; intermediate: patients with one poor prognostic factor; and high-risk: patients with more than 2 poor prognostic factors), the patients in the high-risk group had a significantly shorter survival (median, 10 months) than those with one risk factor (median, 20 months) or no risk factors (median, 36 months).
    Conclusions: Symptom status, the site of relapse, prior chemoradiotherapy, and treatment modality are significant prognostic factors in patients with recurrent cervical cancer that had previously been treated with radiotherapy. Our prognostic model, composed of 4 clinical variables, may enable physicians to predict survival more accurately.

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  • Serum biomarkers for early detection of gynecologic cancers 査読

    Yutaka Ueda, Takayuki Enomoto, Toshihiro Kimura, Takashi Miyatake, Kiyoshi Yoshino, Masami Fujita, Tadashi Kimura

    Cancers2 ( 2 ) 1312 - 1327   2010年6月

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    記述言語:英語  

    Ovarian, endometrial, and cervical cancers are three of the most common malignancies of the female reproductive organs. CA 125, historically the most reliable serum marker for ovarian cancer, is elevated in 50% of early-stage ovarian tumors. For endometrial cancers, there are no established serum markers. SCC, which is the best studied serum marker for squamous cell carcinomas, has been unreliable
    SCC is elevated in cervical squamous cell carcinomas ranging from 28-85% of the time. Recent proteomics-based analyses show great promise for the discovery of new and more useful biomarkers. In this review, we will discuss the currently utilized serum tumor markers for gynecologic cancers and the novel biomarkers that are now under investigation. © 2010 by the authors
    licensee MDPI, Basel, Switzerland.

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  • A retrospective analysis of ovarian endometriosis during pregnancy 査読

    Yutaka Ueda, Takayuki Enomoto, Takashi Miyatake, Masami Fujita, Ryo Yamamoto, Takeshi Kanagawa, Hiromu Shimizu, Tadashi Kimura

    FERTILITY AND STERILITY94 ( 1 ) 78 - 84   2010年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Objective: To clarify the frequency of pregnancy complicated by ovarian endometriosis and to investigate the size change and outcome of ovarian endometriosis during pregnancy.
    Design: Retrospective study.
    Setting: Departments of obstetrics and gynecology of the Osaka University and Izumiotsu Municipal Hospitals of Osaka, Japan.
    Patient(s): Women who delivered between 1996 and 2007.
    Intervention(s): None.
    Main Outcome Measure(s): The frequency of pregnancies complicated by ovarian endometriosis and the size change of the lesions during pregnancy.
    Result(s): The frequency of ovarian endometriosis-complicated pregnancy has almost quadrupled over the last 12 years, to become the most common adnexal mass detected during pregnancy; it was 0.14% (five cases among 3558 deliveries) during the 6-year period from 1996 to 2001, but has increased to 0.52% (19 cases among 3599 deliveries) during the 6-year period from 2002 to 2007, a statistically significant increase of 3.8-fold. Among 25 ovarian endometriotic lesions observed during pregnancy in 24 women (one case had two lesions), the size of the cyst decreased in 13 lesions (52%), went unchanged in 7 (28%), and increased in 5 (20%), that demonstrated decidualization, abscess and rupture.
    Conclusion(s): Ovarian endometriosis during pregnancy can be safely observed conservatively; however, further investigation is required to predict the occurrence of abscess formation or rupture of ovarian endometriosis, and to distinguish the enlargements due to malignant transformation from those related to decidualization. (Fertil Steril (R) 2010; 94: 78-84. (C) 2010 by American Society for Reproductive Medicine.)

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  • Carboplatin and paclitaxel as an initial treatment in patients with stage IVb cervical cancer: a report of 7 cases and a review of the literature 査読

    Seiji Mabuchi, Kenichirou Morishige, Takayuki Enomoto, Tadashi Kimura

    JOURNAL OF GYNECOLOGIC ONCOLOGY21 ( 2 ) 93 - 96   2010年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KOREAN SOC GYNECOLOGY ONCOLOGY & COLPOSCOPY  

    Objective: The aim of this study is to evaluate the efficacy of carboplatin-paclitaxel (TC) as an initial treatment in patients with the International Federation of Gynecology and Obstetrics (FIGO) stage IVb cervical cancer.
    Methods: We retrospectively reviewed seven patients with stage IVb cervical cancer who have been primarily treated with TC. The activity and the toxicity were evaluated. Response rate was the main endpoint.
    Results: Overall, the treatment of TC was well tolerated. The overall response rate was 71.4% (2 complete response, 3 partial response). Although grade 3-4 hematologic toxicities were observed in 3 out of 7 patients (42.8%), no patients experienced grade 3-4 non-hematologic toxicities. When we combined our present results with the previous reports, the overall response rate of TC is 63.6%.
    Conclusion: TC is active and well tolerated in patients FIGO stage IVb cervical cancer. This combination may be considered as an initial treatment regimen in this patient population.

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  • Prognostic significance of CUB domain containing protein expression in endometrioid adenocarcinoma 査読

    Suhana Mamat, Jun-Ichiro Ikeda, Takayuke Enomoto, Yutaka Ueda, Nur Rahadiani, Tian Tian, Yi Wang, Ying Qiu, Tadashi Kimura, Katsuyuki Aozasa, Eiichi Morii

    ONCOLOGY REPORTS23 ( 5 ) 1221 - 1227   2010年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    CDCP1, a transmembrane protein with intracellular tyrosine residues which are phosphorylated upon activation, is supposed to be engaged in proliferative activities and resistance to apoptosis of cancer cells. High level of CDCP1 expression proved to be a poor prognosticator for lung adenocarcinoma. Here, expression level of CDCP1 was immunohistochemically examined in 110 cases (median age of 54.7 years) of endometrioid adenocarcinoma, and its clinical implications were evaluated. Tumor stage was stage I in 71 cases (64.5%). II in 5 (4.5%), III in 28 (25.5%), and IV in 6 (5.5%). Staining intensity of tumor cells was divided into two categories; tumor cells with no to weak and moderate to strong membrane staining. The intensity of CDCP1 expression in each case was defined by the staining of major population of cells as follows; cases with tumor cells showing no to weak and moderate to high membrane staining were categorized as CDCP1-low and CDCP1-high, respectively. Eighty-seven of 110 cases were categorized as CDCP1-high. and the remaining as CDCP1-low. Significant positive correlation was observed between low CDCP1 expression and stage (p=0.0091), relapse rate (p=0.0017), and poor prognosis (p=0.0009). Multivariate analysis revealed that low CDCP1 and advanced stage were independent poor prognostic factors for both OS and DES. As compared to cancer cells, normal endometrium continuously expressed CDCP1. These suggested that the attitude of CDCP1 in cancers of lung and endometrium was different. Different role of CDCP1 by tissues and cancers is discussed.

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  • High frequencies of less differentiated and more proliferative WT1-specific CD8+ T cells in bone marrow in tumor-bearing patients: An important role of bone marrow as a secondary lymphoid organ 査読

    Ayako Murao, Yoshihiro Oka, Akihiro Tsuboi, Olga A. Elisseeva, Yukie Tanaka-Harada, Fumihiro Fujiki, Hiroko Nakajima, Sumiyuki Nishida, Naoki Hosen, Toshiaki Shirakata, Nobuyuki Hashimoto, Akira Myoui, Takafumi Ueda, Yoshito Takeda, Tadashi Osaki, Takayuki Enomoto, Hideki Yoshikawa, Tadashi Kimura, Yusuke Oji, Ichiro Kawase, Haruo Sugiyama

    Cancer Science101 ( 4 ) 848 - 854   2010年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    In tumor-bearing patients, tumor-associated antigen (TAA)-specific CTLs are spontaneously induced as a result of immune response to TAAs and play an important role in anti-tumor immunity. Wilms' tumor gene 1 (WT1) is overexpressed in various types of tumor and WT1 protein is a promising pan-TAA because of its high immunogenicity. In this study, to clarify the immune response to the WT1 antigen, WT1-specific CD8+ T cells that were spontaneously induced in patients with solid tumor were comparatively analyzed in both bone marrow (BM) and peripheral blood (PB). WT1-specific CD8+ T cells more frequently existed in BM than in PB, whereas frequencies of naïve (CCR7+ CD45RA+), central memory (CCR7+ CD45RA-), effector-memory (CCR7- CD45RA-), and effector (CCR7- CD45RA+) subsets were not significantly different between BM and PB. However, analysis of these subsets for the expression of CD57 and CD28, which were associated with differentiation, revealed that effector-memory and effector subsets of the WT1-specific CD8+ T cells in BM had less differentiated phenotypes and more proliferative potential than those in PB. Furthermore, CD107a/b functional assay for WT1 peptide-specific cytotoxic potential and carboxyfluorescein diacetate succinimidyl ester dilution assay for WT1 peptide-specific proliferation also showed that WT1-specific CD8+ T cells in BM were less cytotoxic and more proliferative in response to WT1 peptide than those in PB. These results implied that BM played an important role as a secondary lymphoid organ in tumor-bearing patients. Preferential residence of WT1-specific CD8+ T cells in BM could be, at least in part, explained by higher expression of chemokine receptor CCR5, whose ligand was expressed on BM fibroblasts on the WT1-specific CD8+ T cells in BM, compared to those in PB. These results should provide us with an insight into WT1-specific immune response in tumor-bearing patients and give us an idea of enhancement of clinical response in WT1 protein-targeted immunotherapy. © 2010 Japanese Cancer Association.

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  • Endometrial Carcinoma with Extra-abdominal Metastasis: Improved Prognosis Following Cytoreductive Surgery 査読

    Yutaka Ueda, Takayuki Enomoto, Takashi Miyatake, Tomomi Egawa-Takata, Hiromi Ugaki, Kiyoshi Yoshino, Masami Fujita, Tadashi Kimura

    ANNALS OF SURGICAL ONCOLOGY17 ( 4 ) 1111 - 1117   2010年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Incidence of endometrial carcinoma, the most common malignancy of the female pelvis, has been steadily increasing during the last three decades. The prognosis for stage IVb cases with extra-abdominal metastases is extremely poor, with no current consensus regarding treatment. The aim of the present study was to examine the benefits of cytoreductive surgery for such cases.
    Clinicopathological features of 33 stage IVb cases of endometrial carcinoma diagnosed during the 1991-2008 study period were retrospectively reviewed utilizing clinical records. Cytoreduction was conducted in 30 cases.
    The median progression-free survival (PFS) and overall survival (OS) of those patients with optimal cytoreduction of their disease (with residual masses a parts per thousand currency sign 2 cm), were significantly better than those with suboptimal reduction (with residual masses &gt; 2 cm), not only among the 15 stage IVb patients with only intra-abdominal metastasis (group I) (P = 0.0003 and 0.0007) but also among the 15 cases with extra-abdominal metastasis (group E) (P = 0.013 and 0.016). Multivariate Cox proportional-hazards analysis demonstrated that the adjusted hazard ratio (HR) for the maximum size of residual disease (&gt; 2 vs. a parts per thousand currency sign2 cm) was 10.4 [95% confidence interval (CI), 1.27-84.70, P = 0.030] in group I and 16.92 (95% CI, 1.41-203.09, P = 0.026) in group E.
    This is the first demonstration that aggressive cytoreductive surgery for stage IVb endometrial carcinoma with extra-abdominal metastasis has a beneficial role. However, further investigation is still required to establish better standard therapy for stage IVb endometrial cancer.

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  • High frequencies of less differentiated and more proliferative WT1-specific CD8+ T cells in bone marrow in tumor-bearing patients: an important role of bone marrow as a secondary lymphoid organ. 査読

    Ayako Murao, Yoshihiro Oka, Akihiro Tsuboi, Olga A Elisseeva, Yukie Tanaka-Harada, Fumihiro Fujiki, Hiroko Nakajima, Sumiyuki Nishida, Naoki Hosen, Toshiaki Shirakata, Nobuyuki Hashimoto, Akira Myoui, Takafumi Ueda, Yoshito Takeda, Tadashi Osaki, Takayuki Enomoto, Hideki Yoshikawa, Tadashi Kimura, Yusuke Oji, Ichiro Kawase, Haruo Sugiyama

    Cancer Sci.101 ( 4 ) 848 - 854   2010年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    In tumor-bearing patients, tumor-associated antigen (TAA)-specific CTLs are spontaneously induced as a result of immune response to TAAs and play an important role in anti-tumor immunity. Wilms&#039; tumor gene 1 (WT1) is overexpressed in various types of tumor and WT1 protein is a promising pan-TAA because of its high immunogenicity. In this study, to clarify the immune response to the WT1 antigen, WT1-specific CD8(+) T cells that were spontaneously induced in patients with solid tumor were comparatively analyzed in both bone marrow (BM) and peripheral blood (PB). WT1-specific CD8(+) T cells more frequently existed in BM than in PB, whereas frequencies of naïve (CCR7(+) CD45RA(+)), central memory (CCR7(+) CD45RA-), effector-memory (CCR7- CD45RA(-)), and effector (CCR7- CD45RA(+)) subsets were not significantly different between BM and PB. However, analysis of these subsets for the expression of CD57 and CD28, which were associated with differentiation, revealed that effector-memory and effector subsets of the WT1-specific CD8(+) T cells in BM had less differentiated phenotypes and more proliferative potential than those in PB. Furthermore, CD107a/b functional assay for WT1 peptide-spe

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  • Amputation of uterine corpus as the intraoperative modification during cesarean radical hysterectomy for invasive cervical cancer during pregnancy 査読

    Koji Matsuo, Takayuki Enomoto, Masato Yamasaki

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY15 ( 1 ) 77 - 81   2010年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER TOKYO  

    Cesarean radical hysterectomy (CRH) for invasive cervical cancer during pregnancy is characterized by heavy blood loss. Any surgical modifications made in an attempt to reduce the blood loss are valuable. Our study was designed to evaluate the efficacy of amputating the uterine corpus during CRH.
    All cases of radical hysterectomy (RH) were evaluated. Cases were divided into: (a) cesarean section immediately followed by RH for invasive cervical cancer complicating pregnancy (CRH group); and (b) RH for nonpregnant subjects (RH group). The information abstracted included estimated blood loss (EBL), operative time, intraoperative transfusion, and use of amputation of uterine corpus during CRH. Nonparametric tests were used for the statistical analysis.
    There were five CRH cases (3 for CRH with amputation, 2 for CRH without amputation) and 209 RH cases were evaluated for statistics during the study period. The difference in mean operative time between the CRH group and the RH group was not statistically significant: 276.6 min (range 160-425) versus 297.3 min (range 147-645), p = 0.66. The mean EBL for the CRH group was significantly larger than that for the RH group: 2106.6 ml (range 730-4150) versus 858.8 ml (range 150-4770), p &lt; 0.001. Mean operative time and mean EBL for CRH with amputation of uterine corpus were significantly less than those for CRH without amputation of uterine corpus: operative time, 186.0 min (range 160-228) versus 412.5 min (range 400-425), p = 0.043; EBL, 1034.3 ml (range 730-1540) versus 3715.0 ml (range 3280-4150), p = 0.043. No intraoperative tumor exposures were observed in the amputated cases.
    Amputation of uterine corpus during CRH for invasive cervical cancer during pregnancy significantly improves the intraoperative performance, although it should be used with care.

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  • Diagnostic performance of fluorodeoxyglucose positron emission tomography/magnetic resonance imaging fusion images of gynecological malignant tumors: comparison with positron emission tomography/computed tomography. 査読

    Kazuya Nakajo, Mitsuaki Tatsumi, Atsuo Inoue, Kayako Isohashi, Ichiro Higuchi, Hiroki Kato, Masao Imaizumi, Takayuki Enomoto, Eku Shimosegawa, Tadashi Kimura, Jun Hatazawa

    Japanese journal of radiology28 ( 2 ) 95 - 100   2010年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PURPOSE: We compared the diagnostic accuracy of fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and PET/magnetic resonance imaging (MRI) fusion images for gynecological malignancies. MATERIALS AND METHODS: A total of 31 patients with gynecological malignancies were enrolled. FDG-PET images were fused to CT, T1- and T2-weighted images (T1WI, T2WI). PET-MRI fusion was performed semiautomatically. We performed three types of evaluation to demonstrate the usefulness of PET/MRI fusion images in comparison with that of inline PET/CT as follows: depiction of the uterus and the ovarian lesions on CT or MRI mapping images (first evaluation); additional information for lesion localization with PET and mapping images (second evaluation); and the image quality of fusion on interpretation (third evaluation). RESULTS: For the first evaluation, the score for T2WI (4.68 +/- 0.65) was significantly higher than that for CT (3.54 +/- 1.02) or T1WI (3.71 +/- 0.97) (P < 0.01). For the second evaluation, the scores for the localization of FDG accumulation showing that T2WI (2.74 +/- 0.57) provided significantly more additional information for the identification of anatomical sites of FDG accumulation than did CT (2.06 +/- 0.68) or T1WI (2.23 +/- 0.61) (P < 0.01). For the third evaluation, the three-point rating scale for the patient group as a whole demonstrated that PET/T2WI (2.72 +/- 0.54) localized the lesion significantly more convincingly than PET/CT (2.23 +/- 0.50) or PET/T1WI (2.29 +/- 0.53) (P < 0.01). CONCLUSION: PET/T2WI fusion images are superior for the detection and localization of gynecological malignancies.

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  • The incidence, treatment and prognosis of cervical carcinoma in young women: A retrospective analysis of 4,975 cases in Japan 査読

    K. Kokawa, S. Takekida, S. Kamiura, M. Kita, T. Enomoto, R. Kawaguchi, J. Saito, A. Horie, N. Umesaki

    European Journal of Gynaecological Oncology31 ( 1 ) 37 - 43   2010年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Objective: To determine the clinical characteristics of patients (young women) with cervical carcinoma aged less than 35 years. Methods: Data from patients who were treated for cervical carcinomas from 1990 to 2000 in the Kinki District were retrospectively investigated for clinical stage, histologic type, treatment procedure and prognosis. Results: Of a total of 4,975 cases, 441 patients were aged less than 35 years old. The incidence of cervical carcinoma in these women was 7.9% from 1990 to 1995, 9.1% from 1996 to 2000, and 9.5% from 2001 to 2005. FIGO Stage I included 374 cases, followed by, 49 in Stage II, 11 in Stage III, and seven in Stage IV. Squamous cell carcinoma incidence was 80.7% and non-squamous cell carcinoma incidence was 19.3%. Several types of surgery were performed in patients with Stage I and II, while patients with Stage III and IV were treated with radiotherapy and/or chemotherapy without any type of surgery. In patients who underwent lymphadenectomy, 21.1% cases had nodal involvement. The 5-year survival rate was 95% for Stage I disease, 73% for Stage II, 68% for Stage III, and 19% for Stage IV. Conclusion: The incidence of cervical carcinoma in young women slightly increased from 1990 to 2005. The prognosis of cervical carcinoma tends to be better in young women than in older patients, especially in Stage III disease.

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  • Concurrent Weekly Nedaplatin, External Beam Radiotherapy and High-Dose-Rate Brachytherapy in Patients with FIGO Stage IIIb Cervical Cancer: A Comparison with a Cohort Treated by Radiotherapy Alone 査読

    Seiji Mabuchi, Hiromi Ugaki, Fumiaki Isohashi, Yasuo Yoshioka, Kumiko Temma, Namiko Yada-Hashimoto, Takashi Takeda, Toshiya Yamamoto, Kiyoshi Yoshino, Ryuichi Nakajima, Chie Kuragaki, Kenichirou Morishige, Takayuki Enomoto, Takehiro Inoue, Tadashi Kimura

    GYNECOLOGIC AND OBSTETRIC INVESTIGATION69 ( 4 ) 224 - 232   2010年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KARGER  

    Objectives: The aim of this study was to evaluate whether nedaplatin-based concurrent chemoradiotherapy (CCRT) using high-dose-rate intracavitary brachytherapy (HDR-ICBT) is superior to radiotherapy (RT) alone in patients with FIGO stage IIIb cervical cancer. Methods: The records of 41 consecutive women treated either with nedaplatin-based CCRT using HDR-ICBT (n = 20) or RT alone (nonrandomized control group, n = 21) for stage IIIb cervical cancer were retrospectively reviewed. The activity and toxicity were compared between the two treatment groups. Progression-free survival (PFS) and overall survival (OS) were the main endpoints. Results: The 5-year overall survival rates in the CCRT and RT groups were 65 and 33.3%, respectively. The median OS of the CCRT and RT groups were 60 and 29 months, respectively. CCRT was significantly superior to RT alone with regard to PFS (p = 0.0015) and OS (p = 0.0364). The frequency of acute grade 3-4 toxicity was significantly higher in the CCRT group than in the RT group. However, no statistically significant difference was observed with regard to severe late toxicity. Conclusions: Nedaplatin-based concurrent chemoradiotherapy was safely performed and significantly improved the prognosis of patients with FIGO stage IIIb cervical cancer. This treatment can be considered as an alternative to cisplatin-based chemoradiotherapy in this patient population. Copyright (C) 2010 S. Karger AG, Basel

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  • Postoperative concurrent nedaplatin-based chemoradiotherapy improves survival in early-stage cervical cancer patients with adverse risk factors 査読

    Seiji Mabuchi, Ken-ichirou Morishige, Fumiaki Isohashi, Yasuo Yoshioka, Takashi Takeda, Toshiya Yamamoto, Kiyoshi Yoshino, Takayuki Enomoto, Takehiro Inoue, Tadashi Kimura

    GYNECOLOGIC ONCOLOGY115 ( 3 ) 482 - 487   2009年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Objectives. The aim Of this Study was to evaluate the efficacy of postoperative nedaplatin-based concurrent chemoradiotherapy (CCRT) in patients with FIGO stage IA2-IIB cervical cancer with adverse risk factors.
    Methods. We retrospectively reviewed the medical records of 183 patients with early-stage cervical cancer who had undergone radical Surgery between April 1997 and March 2006. Of these, 68 patients displayed high-risk prognostic factors Such as positive pelvic lymph nodes, parametrial involvement, or a positive surgical margin. Fifty-seven patients demonstrated intermediate-risk prognostic factors including deep stromal invasion, capillary lymphatic space involvement, or large tumor diameter. These patients were treated postoperatively with CCRT or radiotherapy alone (RT). Fifty-eight patients showed no risk factors and, therefore, received no adjuvant therapy after Surgery. The 3-year recurrence rate, progression free survival (PFS), and overall Survival (OS) were compared between the treatment groups.
    Results. CCRT was significantly superior to RT alone with regard to recurrence rate, PFS, and OS in patients that displayed high-risk and intermediate-risk prognostic factors. The frequencies Of acute grade 3-4 toxicities were significantly higher in patients treated with CCRT than in those treated with RT alone. However, no statistically significant difference was observed with regard to severe late toxicities.
    Conclusions. Postoperative nedaplatin-based CCRT was safely performed and improved the prognosis of FIGO stage IA2-IIB cervical cancer patients displaying high-risk or intermediate-risk prognostic factors. This treatment can be considered as an alternative to cisplatin-based chemoradiotherapy in this patient population. (C) 2009 Elsevier Inc. All rights reserved.

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  • Wilms&apos; Tumor 1 (WT1) Peptide Immunotherapy for Gynecological Malignancy 査読

    Satoshi Ohno, Satoru Kyo, Subaru Myojo, Satoshi Dohi, Junko Ishizaki, Ken-Ichi Miyamoto, Satoshi Morita, Jun-Ichi Sakamoto, Takayuki Enomoto, Tadashi Kimura, Yoshihiro Oka, Akihiro Tsuboi, Haruo Sugiyama, Masaki Inoue

    ANTICANCER RESEARCH29 ( 11 ) 4779 - 4784   2009年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:INT INST ANTICANCER RESEARCH  

    Background: The object of this study was to investigate the safety and clinical response of immunotherapy targeting the WT1 (Wilms&apos; tumor 1) gene product in patients with gynecological cancer. Patients and Methods: Twelve patients with WT1/human leukocyte antigen (HLA)-A*2402-positive gynecological cancer were included in a Phase II clinical trial of WT1 vaccine therapy. In all the patients, the tumors were resistant to standard therapy. The patients received intradermal injections of a HLA-A*2402-restricted, modified 9-mer WTI peptide every week for 12 weeks. Tumor size, which was measured by computed tomography (CT), was determined ever), 4 weeks. The responses were analyzed according to Response Evaluation Criteria in Solid Tumors (RECIST). Results: The protocol was well tolerated; only local erythema occurred at the WTI vaccine injection site. The clinical responses were as follows: stable disease (SD) in 3 patients and progressive disease (PD) in 9 patients. No patients had a complete (CR) or partial response (PR). The disease control rate was 25.0%. Conclusion: Although a small, uncontrolled, nonrandomized trial, this study showed that WT1 vaccine therapy for patients with gynecological cancer was safe and produced a clinical response.

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  • Enhanced expression of Annexin A4 in clear cell carcinoma of the ovary and its association with chemoresistance to carboplatin 査読

    Ayako Kim, Takayuki Enomoto, Satoshi Serada, Yutaka Ueda, Tsuyoshi Takahashi, Barry Ripley, Takashi Miyatake, Masami Fujita, Chun Man Lee, Koji Morimoto, Minoru Fujimoto, Tadashi Kimura, Tetsuji Naka

    INTERNATIONAL JOURNAL OF CANCER125 ( 10 ) 2316 - 2322   2009年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-LISS  

    Clear cell carcinoma (CCC) of the ovary is known to he highly resistant to platinum-based chemotherapy. The purpose of our study was to identify a candidate protein that is associated with chemoresistance of CCC and to investigate the specific mechanism of chemoresistance conferred by the identified protein. Enhanced expression of Annexin A4 (Anx A4.) was identified in ovarian CCC cells using 2-D differential gel electrophoresis (2D-DIGE) and mass spectrometry. Anx A4 levels were elevated in CCC cells compared with non-CCC cells as determined by real-time RT-PCR and Western blot analysis. Immunohistochemical analysis of Anx A4 was performed in 126 epithelial ovarian cancer tissue samples and demonstrated significantly elevated levels of Anx A4 protein levels in ovarian CCC tumors compared with ovarian serous and endometrioid tumors (p &lt; 0.01). Anx A4-transfected ovarian non-CCC cells were more resistant to carboplatin (IC50 = 42 mu M) compared with control cells (IC50 = 23 mu M) as determined by modified MTT assay. Intracellular platinum levels were significantly lower in Anx A4-transfected cells compared with control cells after carboplatin treatment (p = 0.0020) and after an additional 360 min (if carboplatin-free incubation (p = 0.0004). as measured by atonmic absorption spectrophotometry. Expression of Anx A4 is elevated in ovarian UCC tumors and is associated with chemoresistance in cultured ovarian cancer cells. These results demonstrate that Anx A4 confers chemoresistance in ovarian cancer cells in part by enhancing drug efflux. Thus, Anx A4 may represent a novel therapeutic target of chemoresistance in patients with ovarian CCC. (C) 2009 UICC

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  • Postpartum Outcome of Cervical Intraepithelial Neoplasia in Pregnant Women Determined by Route of Delivery 査読

    Yutaka Ueda, Takayuki Enomoto, Takashi Miyatake, Kiyoshi Yoshino, Masami Fujita, Takahito Miyake, Kazuko Fujiwara, Miho Muraji, Takeshi Kanagawa, Tadashi Kimura

    REPRODUCTIVE SCIENCES16 ( 11 ) 1034 - 1039   2009年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SAGE PUBLICATIONS INC  

    Cervical intraepithelial neoplasia (CIN) has its highest incidence during women&apos;s reproductive years. During 2 sequential 7-year periods, 1994 to 2000 and 2001 to 2007, 3695 and 3894 deliveries were performed, respectively, at Osaka University Hospital. CIN was detected in 21 cases (0.57%) during 1994-2000 and in 43 cases (1.1%) during 2001-2007. By comparison, cervical intraepithelial neoplasia-complicated pregnancies increased significantly in the latter period (P = .015 by Fisher exact test, Odds ratio = 1.95; 95% CI: 1.16-3.30). We observed CIN regression in 34 (76%) of 45 cases of vaginal delivery and in 6 (50%) of 12 cases of cesarean delivery, indicating that the outcome of an initially diagnosed CIN and the delivery routes appeared not to be significantly related. However, a different result was obtained when only those patients whose CIN lesions persisted until the delivery were analyzed. Among the 35 such cases in the vaginal delivery group, 24 cases (69%) regressed after the delivery; in 8 such cases from the cesarean delivery group, only 2 cases (25%) regressed afterward. Our study clearly shows that pregnancy complicated with CIN is increasing rapidly in Japan. We also find that there is a significantly more frequent postpartum regression of biopsy-proven CIN lesions following a vaginal delivery compared to cesarean section (P = .042 by Fisher exact test, Odds ratio = 6.55; 95% CI: 1.13-37.8).

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  • Luteoma-induced fetal virilization 査読

    Hiromi Ugaki, Takayuki Enomoto, Yoshihiro Tokugawa, Tadashi Kimura

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH35 ( 5 ) 991 - 993   2009年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    A pregnancy luteoma represents an unusual response of ovarian stromal cells to the altered hormonal levels of pregnancy. It is a distinctive non-neoplastic lesion characterized by solid proliferations of luteinized cells resulting in a tumor-like ovarian enlargement. Most patients are asymptomatic; the ovarian enlargement is usually discovered incidentally at cesarean section or during postpartum tubal ligation. We report a typical case that we found at cesarean section to be associated with a virilized infant who manifested clitoromegaly and labial fusion. We detected an increased level of testosterone in the maternal patient. We concluded that the ovarian luteoma induced the fetal virilization.

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  • MR Imaging of Endometrial Carcinoma for Preoperative Staging at 3.0 T: Comparison With Imaging at 1.5 T 査読

    Masatoshi Hori, Tonsok Kim, Takamichi Murakami, Izumi Imaoka, Hiromitsu Onishi, Atsushi Nakamoto, Yasuhiro Nakaya, Kaname Tomoda, Tateki Tsutsui, Takayuki Enomoto, Tadashi Kimura, Hironobu Nakamura

    JOURNAL OF MAGNETIC RESONANCE IMAGING30 ( 3 ) 621 - 630   2009年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOHN WILEY & SONS INC  

    Purpose: To prospectively compare magnetic resonance imaging (MRI) at 3.0 T and 1.5 T in the same patients for preoperative evaluation of endometrial carcinoma.
    Materials and Methods: Thirty consecutive patients with endometrial carcinoma underwent MRI at both 3.0 T and 1.5 T as well as surgery. Quantitative and qualitative analyses were performed. Two radiologists independently evaluated images. MR findings were compared with surgicopathologic findings.
    Results: Image homogeneity of T2-weighted images at 3.0 T was significantly inferior to that at 1.5 T (P = 0.007). The scores of image homogeneity and susceptibility artifacts were not significantly different between 3.0 T gadolinium-enhanced imaging and 1.5 T imaging (P = 0.09 and 0.36). Kappa statistics showed good interobserver agreement between the two radiologists for local-regional staging on T2-weighted images (kappa&gt;0.6). The area under the receiver operating characteristic curve (Az) values for T2-weighted imaging in terms of myometrial invasion, cervical invasion, and lymph node metastases were 0.88 (3.0 T) versus 0.91 (1.5 T), 0.84 versus 0.83, and 0.94 versus 0.95 for reader 1, respectively. There were no significant differences between imaging at 3.0 T and at 1.5 T in Az values for either reader (P &gt; 0.35).
    Conclusion: 3.0 T MRI is an equivalent imaging modality to 1.5 T imaging for presurgical evaluation of endometrial carcinoma, although not significantly superior to 1.5 T imaging.

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  • The activity of carboplatin and paclitaxel for recurrent cervical cancer after definitive radiotherapy 査読

    Seiji Mabuchi, Kenichirou Morishige, Masami Fujita, Tateki Tsutsui, Masahiro Sakata, Takayuki Enomoto, Tadashi Kimura

    GYNECOLOGIC ONCOLOGY113 ( 2 ) 200 - 204   2009年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Objectives. The aim of this study was to evaluate the efficacy of paclitaxel-carboplatin (TC) for recurrent cervical cancer after definitive radiotherapy and to compare the results with non-taxane containing platinum-based chemotherapies (NTP).
    Methods. The records of 59 consecutive women who had undergone salvage chemotherapy with TC (n = 28) or NTP (historical control, n = 31) for recurrence after definitive radiotherapy were retrospectively reviewed. Primary disease and recurrence data was collected. The activity and toxicity of TC were compared with those of NTP. The response rate and progress ion-free survival (PFS) after recurrence were the main endpoints. Multivariate analysis of prognostic factors for response was performed using the Cox proportional hazards regression model. Survival was calculated using the Kaplan-Meier methods and compared by the log-rank test.
    Results. Overall, TC was well tolerated with a response rate of 67.9% (5 CR and 14 PR). The median PFS was 7 months for all patients and 10 months for responders. Myelosuppression was the most common toxicity (grade 3 in 16 patients, grade 4 in 5 patients). On the contrary, NTP showed a response rate of 22.6% with median and mean PFS of 0 month and 2 months, respectively. When compared, TC was significantly superior to NTP with regard to its response rate (p = 0.001) and PFS (p&lt;0.0001). Moreover, TC showed significantly higher activity in patients with adenocarcinoma histology.
    Conclusions. Carboplatin-paclitaxel is active and well tolerated in patients with recurrent cervical cancer after definitive radiotherapy. This combination should be considered as an alternative regimen to cisplatin-paclitaxel in this patient population. (C) 2009 Elsevier Inc. All rights reserved.

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  • High-dose-rate interstitial brachytherapy for previously untreated cervical carcinoma 査読

    Fumiaki Isohashi, Yasuo Yoshioka, Masahiko Koizumi, Koji Konishi, Iori Sumida, Yutaka Takahashi, Toshiyuki Ogata, Ken-ichirou Morishige, Takayuki Enomoto, Yoshifumi Kawaguchi, Tadayuki Kotsuma, Kana Adachi, Shoichi Fukuda, Yuichi Akino, Takehiro Inoue

    BRACHYTHERAPY8 ( 2 ) 234 - 239   2009年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    PURPOSE: The aim of the study was to evaluate the results of high-dose-rate interstitial brachytherapy (HDR-ISBT) for patients with advanced cervical carcinoma in which intracavitary radiation therapy may result in a suboptimal dose distribution.
    METHODS AND MATERIALS: Between 1995 and 2005, 25 patients of median age 64 years were treated with external beam radiation therapy and HDR-ISBT. The International Federation of Gynecology and Obstetrics stages of the patients were I (4%), II (16%), III (68%), and IVA (12%). Whole pelvic irradiation of 30 Gy/15 fractions was followed by HDR-ISBT of 30 Gy/5 fractions/3 days. Subsequently, additional pelvic external beam radiation therapy of 20 Gy/10 fractions was delivered with a midline block. The median followup period was 55 months.
    RESULTS: The actuarial 5-year progression-free survival and overall survival rates for all cases were 42% and 54%, respectively. For the 17 patients with a Stage III tumor, the 5-year local control and overall survival rates were 73% and 51%, respectively. Two patients (8%) developed late toxicities of Grade 3.
    CONCLUSIONS: A high rate of pelvic control and survival with acceptable level of late toxicities were obtained for patients with advanced cervical carcinoma treated with HDR-ISBT. (C) 2009 Published by Elsevier Inc on behalf of American Brachytherapy Society.

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  • Uterine Cervical Carcinoma: Preoperative Staging with 3.0-T MR Imaging-Comparison with 1.5-T MR Imaging 査読

    Masatoshi Hori, Tonsok Kim, Takamichi Murakami, Izumi Imaoka, Hiromitsu Onishi, Kaname Tomoda, Tateki Tsutsui, Takayuki Enomoto, Tadashi Kimura, Hironobu Nakamura

    RADIOLOGY251 ( 1 ) 96 - 104   2009年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:RADIOLOGICAL SOC NORTH AMERICA  

    Purpose: To prospectively evaluate the efficacy of 3.0-T magnetic resonance (MR) imaging in the preoperative staging of cervical carcinoma compared with that at 1.5-T imaging, with surgery and pathologic analysis as the reference standards.
    Materials and Methods: Institutional review board approval and informed consent were obtained. Thirty-one consecutive patients (age range, 27-71 years; mean age, 51.1 years) underwent 3.0-and 1.5-T MR imaging. Quantitative and qualitative analyses were performed. Two radiologists independently evaluated images in terms of local-regional staging. MR findings were compared with surgicopathologic findings.
    Results: Mean tumor signal-to-noise ratios, mean cervical stroma signal-to-noise ratios, and mean tumor-to-cervical stroma contrast-to-noise ratios at 3.0-T imaging were significantly higher than those at 1.5-T imaging (P = 9.1 x 10(-6), P = 1.8 x 10(-6), and P = .008, respectively). Image homogeneity at 3.0-T imaging was significantly inferior to that at 1.5-T imaging (P = .005). There were no significant differences in terms of the degree of susceptibility artifacts. Interobserver agreement between the two radiologists for local-regional staging was good or excellent (kappa = 0.65-0.89). Sensitivity, specificity, and area under the receiver operating characteristic curve for radiologist 1 in the evaluation of parametrial invasion were (a) 75% for both 3.0-and 1.5-T imaging, (b) 70% for both 3.0-and 1.5-T imaging, and (c) 0.82 for 3.0-T imaging and 0.85 for 1.5-T imaging, respectively. Corresponding values for vaginal invasion were (a) 67% for both 3.0-and 1.5-T imaging, (b) 68% for 3.0-T imaging and 72% for 1.5-T imaging, and (c) 0.62 for 3.0-T imaging and 0.67 for 1.5-T imaging, respectively. Corresponding values for lymph node metastases were (a) 57% for both 3.0-and 1.5-T imaging, (b) 83% for 3.0-T imaging and 88% for 1.5-T imaging, and (c) 0.72 for 3.0-T imaging and 0.78 for 1.5-T imaging, respectively. Neither radiologist noted significant differences between values obtained with 3.0-T imaging and those obtained with 1.5-T imaging (P &gt; .5 for all comparison pairs).
    Conclusion: In this study, 3.0-T MR imaging was characterized by high diagnostic accuracy in the presurgical evaluation of patients with cervical carcinoma, although 3.0-T imaging was not significantly superior to 1.5-T imaging. (c) RSNA, 2009

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  • A Case of Disseminated Peritoneal Leiomyomatosis Developing after Laparoscope-Assisted Myomectomy 査読

    Takahito Miyake, Takayuki Enomoto, Yutaka Ueda, Kenichiro Ikuma, Eiichi Morii, Shinya Matsuzaki, Yuji Murata

    GYNECOLOGIC AND OBSTETRIC INVESTIGATION67 ( 2 ) 96 - 102   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KARGER  

    A 36-year-old nulliparous woman developed multiple extrauterine fibroids in the pelvic cavity years after laparoscopic myomectomy. Molecular genetic analysis by methylation-specific polymerase chain reaction (MSPCR) of the human X-linked androgen receptor gene and loss of heterozygosity (LOH) analysis at 5 microsatellite loci was performed on the tumors. All tumors showed an identical non-random X-chromosome inactivation pattern by MSPCR and an identical pattern of LOH was found in all the tumors by LOH analysis. This demonstrated that 3 fibroids resected 2 years later and 14 fibroids resected 6 years later were all metastatic tumors originating from the uterine leiomyoma found during the initial surgery, suggesting that morcellation before removal of the leiomyoma nodule during laparoscopic myomectomy may have been associated with the pathogenesis of this case. Copyright (C) 2008 S. Karger AG, Basel

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  • Safety and efficacy of lower-dose unfractionated heparin for prophylaxis of deep vein thrombosis and pulmonary embolism in an Asian population 査読

    Hiromi Ugaki, Takayuki Enomoto, Kazuko Fujiwara, Tadashi Kimura, Tomio Kawasaki

    BLOOD COAGULATION & FIBRINOLYSIS19 ( 6 ) 585 - 589   2008年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    The objective of this study is to analyze the tolerance and efficacy of the subcutaneous administration of a reduced 2500-unit low-dose unfractionated heparin given for an efficacious, yet Asian population-sensitive, prophylaxis for deep vein thrombosis and fatal pulmonary embolism. Eighty-seven Japanese patients were operated on either for abdominal or pelvic complications or both, as well as for gynecologic conditions including ovarian, cervical, and corpus cancers. Thirty-two of the patients were administered the experimental low dose of unfractionated calcium heparin for prophylaxis. The 2500 units of low-dose unfractionated heparin were given subcutaneously 2 h preoperatively and again 12 h postoperatively. Other standard methods of mechanical prophylaxis, including graduated compression stockings and intermittent pneumatic compression, were performed. Fifty-five of the patients were not administered heparin, but did receive the same standard mechanical graduated compression stockings and intermittent pneumatic compression prophylaxis. We compared the surgical and postsurgical complications noted for low-dose unfractionated heparin patients with the results of those who received no heparin prophylaxis and analyzed this data using the Mann-Whitney U-test. There was no significant difference in the mean of the blood loss volumes. There were also no significant differences found in the perioperative bleeding complications between the two groups. However, three (3/55; 6%) of the patients in the no-heparin group suffered a symptomatic pulmonary embolism, although none were fatal. There were no pulmonary embolism onsets in the heparin prophylaxis group. We feel that we have provided evidence that several serious complications, such as perisurgical hemorrhage, deep vein thrombosis, fatal pulmonary embolism, and increased postoperative recovery times, can be prevented by prophylaxis with 2500-unit low-dose unfractionated heparin.

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  • Frequent inactivation of RUNX3 in endometrial carcinoma 査読

    Tatsuo Yoshizaki, Takayuki Enomoto, Masami Fujita, Yutaka Ueda, Takashi Miyatake, Kazuko Fujiwara, Takahito Miyake, Toshihiro Kimura, Kiyoshi Yoshino, Tadashi Kimura

    GYNECOLOGIC ONCOLOGY110 ( 3 ) 439 - 444   2008年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Objective. Our objective was to determine whether RUNX3 tumor suppressor is inactivated in endometrial carcinoma.
    Methods. We have investigated 24 endometrial carcinomas, 3 endometrial carcinoma cell lines, and 9 normal endometria for genetic and epigenetic alterations of RUNX3. Reverse-transcription PCR (RT-PCR), methylation-specific PCR (MS-PCR) analysis, and loss of heterozygosity (LOH) analysis were performed. We also tested RUNX3 protein expression by immunohistochemistry.
    Results. Using RT-PCR technique, we observed a significant loss of RUNX3 mRNA expression in nine of 24 endometrial carcinomas (38%) and in all 3-cell lines (100%). In contrast, all nine of the normal endometria showed an abundant expression of RUNX3 mRNA. Methylation-specific PCR (MS-PCR) analysis of the CpG islands of RUNX3 showed the promoter region to be hypermethylated in 18 of 21 analyzed carcinomas (86%), whereas only two of nine normal endometria (22%) were methylated (p&lt;0.01). By using two polymorphic microsatellite markers, DIS199 and D1S1676, we detected 1p36 LOH in 7 of 21 carcinomas (33%). We observed a significant relationship between the loss of RUNX3 mRNA expression and this regional LOH (p&lt;0.01). Immunohistochemical staining showed that RUNX3 protein expression was lost in 12 of 21 endometrial carcinomas (57%). We observed a significantly snore frequent loss of RUNX3 protein expression in the histologically higher-grade tumors (Grade 3) than in Grade 1 or 2 tumors (p&lt;0.01).
    Conclusion. These findings indicate that RUNX3 inactivation may play an important role in carcinogenesis of the endometrium, especially in high-grade endometrial carcinoma. (C) 2008 Elsevier Inc. All rights reserved.

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  • Clonality and HPV infection analysis of concurrent glandular and squamous lesions and adenosquamous carcinomas of the uterine cervix 査読

    Yutaka Ueda, Takashi Miyatake, Mika Okazawa, Toshihiro Kimura, Takahito Miyake, Kazuko Fujiwara, Kiyoshi Yoshino, Ryuichi Nakashima, Masami Fujita, Takayuki Enomoto

    AMERICAN JOURNAL OF CLINICAL PATHOLOGY130 ( 3 ) 389 - 400   2008年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS INC  

    We analyzed the clonality and human papillomavirus (HPV) infection status of concurrent glandular and sqamous lesions and adenosquamous carcinomas of the uterine cervix to clarify their histogenesis. The glandular and squamous components were clonally different from each other in 7 informative concurrent lesions. HPV was episomal in 2 polyclonal glandular dysplasias (GDs). HPV was in a mixed integrated-episomal form in a monoclonal GD, an adenocarcinoma in situ, and an adenocarcinoma. Both tumor components were monoclonal in origin in 6 adenosquamous carinomas, with identical patterns of X-chromosomal inactivation and types and physical status of HPV. These results imply that the concurrent glandular and squamous lesions are formed separately, whereas adenosquamous carcinoma is more likely to be a combination tumor of monoclonal origin, and that integration of HPV has an important role in the progression from polyclonal GD through monoclonal expansion to adenocarcinoma in situ and adenocarcinoma.

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  • Alterations of the K-ras and p53 genes in Tamoxifen-associated endometrial carcinoma 査読

    Kazuko Fujiwara, Takayuki Enomoto, Masami Fujita, Takayoshi Kanda, Shingo Fujii, Kimihiko Ito, Kenichi Wakasa, Osamu Ishiko, Masatsugu Ueda, Satoshi Yamaguchi, Tadashi Kimura, Naohiko Umesaki

    ONCOLOGY REPORTS19 ( 5 ) 1293 - 1298   2008年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PROFESSOR D A SPANDIDOS  

    To better understand the molecular mechanisms of carcinogenesis induced in uterine endometrium by therapeutic anti-estrogenic Tamoxifen (TAM) exposure, 27 uterine tumors (4 benign endometrial polyps and 23 carcinomas) associated with TAM exposure were analyzed for the presence and spectrum of p53 and K-ras mutations. Although there was no significant difference between TAM-associated endometrial carcinomas and sporadic endometrial tumors in the frequency of these mutations, the spectrum of p53 mutations was characteristically unique to the TAM-associated tumors. The median duration of TAM exposure was significantly longer in patients with p53 mutations than those without p53 mutations (62 vs. 30 months, p=0.028). Our observation suggests that prolonged TAM exposure may directly inactivate the p53 gene by acting as a mutagen in a significant fraction of TAM-associated endometrial carcinomas.

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  • PIK3CA gene mutations and amplifications in uterine cancers, identified by methods that avoid confounding by PIK3CA pseudogene sequences 査読

    Takahito Miyake, Kiyoshi Yoshino, Takayuki Enomoto, Tomomi Takata, Hiromi Ugaki, Ayako Kim, Kazuko Fujiwara, Takashi Miyatake, Masami Fujita, Tadashi Kimura

    CANCER LETTERS261 ( 1 ) 120 - 126   2008年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    PIK3CA codes for a Class TA p110-alpha catalytic subunit of the P13Ks (phosphatidylinositol 3-kinases) that regulate various signaling pathways important for neoplasia, including cell proliferation, motility, adhesion, and survival. Pro-oncogenic mutations in exons 9 and 20 of the PIK3CA gene have been frequently observed in numerous types of human malignancies. Amplification of the PIK3CA gene has been reported in uterine cervical cancers. In this study, we have done in depth analysis of uterine cervical and endometrial cancers for PIK3CA gene mutations and amplifications. In uterine cervical cancers, PIK3CA mutations were found in 3 of 22 cases (14%), all of them in exon 9. In endometrial cancers, a similar incidence of mutations was found, in 3 of 29 cases (10%), however they were all within exon 20. Amplification of the PIK3CA gene was also detected in 2 out of 22 (9%) cervical cancers and 3 out of 29 (10%) endometrial cancers. In this study, we were unable to find a clear association between PIK3CA mutations and gene amplifications, nor with tumor histological subtypes or staging.
    Mutations and amplifications of the PIK3CA gene are relatively infrequent in human cervical and endometrial cancers; however, PIK3CA gene alteration may still play a role in some subset of uterine cancers. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

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  • B7-H4 (DD-O110) is overexpressed in high risk uterine endometrioid adenocarcinomas and inversely correlated with tumor T-cell infiltration 査読

    Takashi Miyatake, Barbara Tringler, Wenhui Liu, Shu-Hui Liu, Jackie Papkoff, Takayuki Enomoto, Kathleen C. Torkko, Donna L. Dehn, Ashanta Swisher, Kenneth R. Shroyer

    GYNECOLOGIC ONCOLOGY106 ( 1 ) 119 - 127   2007年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Objectivc and inelhods. B7-H4 (DD-O110), a member of the 137 family, negatively regulates T cell-inediated immune response. Previous Studies have shown that B7-H4 is highly expressed in endoinctrioid ovarian cancers with relatively low levels of expression in normal ovary which was confirmed by Western blot. The present Study was designed to localize B7-H4 expression by inuilunohistochemistry (IHC) in normal endometrium, endorrietrial hyperplasia and uterine endometrioid adenocarcinoma. The pattern of B7-H4 localization was compared with the IHC detection of CD3 and CD8-positive T lymphocytes and CD14 positive macrophages to investigate the role of B7-H4 in the regulation of tumor immune Surveillance. B7-H4 expression was evaluated in apoptotic tumor cells.
    Results. The proportion and intensity of B7-H4 staining were increased in the progression from normal, hyperplastic and malignant endometrial glandular mucosa. B7-H4 showed a predominantly apical membranous staining (pattern 1) in normal and hyperplastic endonietrial epithelium but showed intense circumferential membranous and cytoplasmic staining (pattern 2) in a majority of endometrioid carcinoma cases (p=0.018). The proportion of B7-H4 positive tumor cells and staining intensity was also higher in high risk rumors than in low risk tumors (p=0.001 and p=0.032, respectively). The proportion of 137-1-14 positive tumor cells was inversely related to the number of CD3-positive and CD8-positive turnor-associated lymphocytes (TALs). There was a positive correlation between 137-H4 pattern 2 staining and both CD3-positive and CD8-positive tutnor-infiltrating lymphocytes (TILs) (p=0.039 and p=0.031, respectively).
    Conclusions. B7-H4 is overexpressed in hyperplastic and malignant endometrial epithelium and is correlated with the numberTcells associated with the unnor. These results suggest that B7-H4 overexpression may reflect a more aggressive biologic potential and may play a role in tumor immune surveillance mechanisms. (c) 2007 Elsevier Inc. All rights reserved.

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  • Down-regulation of insulin-like growth factor binding protein-5 (IGFBP-5): Novel marker for cervical carcinogenesis 査読

    Takashi Miyatake, Yutaka Ueda, Ryuichi Nakashima, Kiyoshi Yoshino, Toshihiro Kimura, Takuya Murata, Taisei Nomura, Masami Fujita, Gregory S. Buzard, Takayuki Enomoto

    INTERNATIONAL JOURNAL OF CANCER120 ( 10 ) 2068 - 2077   2007年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-LISS  

    To better understand the underlying pathways of cervical carcinogenesis, cDNA microarray analysis was performed on 2 sets of squamous cell carcinomas (SCCs) and their adjacent normal squamous epitheliums. Consistently altered expression was detected for 32 genes. Real-time RT-PCR analysis was conducted on a selected subset of these genes (S100A2, GPC4, p72, IGFBP-5, TRIM2 and NAB2) for 14 additional SCCs and 10 normal epithelia. This found that, of the 6 candidate genes, only the insulin-like growth factor binding protein-5 (IGFBP-5) mRNA was generally and significantly under-expressed in SCCs (p &lt; 0.001). All normal cervical epithelia (30 of 30) stained positively for IGFBP-5 protein, with 70% showing strong staining, whereas 65% (17/26) of SCC had complete loss of IGFBP-5, and only 8% (2/26) SCC retained strong expression (p &lt; 0.001). Immunohistochemistry of premalignant cervical intraepithelial neoplasia (CIN) lesions shows a significantly weaker or negative staining in advanced CIN3 lesions compared with normal squamous epithelia (p = 0.001). This is the first study to show that down-regulation of IGFBP-5 protein correlates with cervical carcinogenesis and does so at a preneoplastic stage. (c) 2007 Wiley-Liss, Inc.

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  • Clonality analysis and human papillomavirus infection in squamous metaplasia and atypical immature metaplasia of uterine cervix: Is atypical immature metaplasia a precursor to cervical intraepithelial neoplasia 3? 査読

    Takashi Miyatake, Yutaka Ueda, Kiyoshi Yoshino, Kenneth R. Shroyer, Hiroyuki Kanao, Hongbo Sun, Ryuichi Nakashima, Toshihiro Kimura, Tomoko Wakasa, Takayuki Enomoto

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY26 ( 2 ) 180 - 187   2007年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Atypical immature squamous metaplasia (ISM) of the uterine cervix often has histological features that overlap with the histological characteristics of high-grade cervical intraepithelial neoplasia. To identify the cellular basis and clinical significance of atypical immature metaplasia (AIM), 10 cases of AIM were analyzed for the clonal status, and the presence of human papillomavirus (HPV) infection. The physical status of HPV was also evaluated in HPV type 16 (HPV-16)-positive cases. Squamous metaplasias with no nuclear atypia (29 mature squamous metaplasias [SMs]) and a single case of ISM were analyzed as a control. Nine AIMs, 20 SMs, and a single case of ISM were informative for clonal analysis. Monoclonal composition of the lesion was demonstrated in 8 (89%) of 9 AIMs, but only in 2 (10%) of 21 cases of SM without atypia (AIM vs SM + ISM, 8/9 vs 2/21; P &lt; 0.0001). High-risk HPV was detected in 6 (60%) of 10 AlMs, all were HPV-16, but only in 3 (13%) of 24 SMs with no atypia (2/23 SM and 1/1 ISM). The frequency of high-risk HPV infection was also significant between AlMs and SM with no atypia (6/10 vs 3/24; P &lt; 0.001). Among the cases, which were informative for clonal analysis, all 5 AlMs positive for high-risk HPV were monoclonal in composition. Physical status of HPV was examined in HPV-16-positive cases. Human papillomavirus type 16 was present as a mixture of episomal form and integrated form in 4 of 6 AlMs. These observations imply that unlike SMs with no atypia, which arises as a result of reactive or inflammatory process, lesions with the histological characteristics of AIM may be indeed true precursors of cervical carcinoma.

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  • Prognostic significance of p53 mutation in suboptimally resected advanced ovarian carcinoma treated with the combination chemotherapy of paclitaxel and carboplatin 査読

    Yuko Ueno, Takayuki Enomoto, Yoshiro Otsuki, Nagatoshi Sugita, Ryuichi Nakashima, Kiyoshi Yoshino, Chie Kuragaki, Yutaka Ueda, Tadaatsu Aki, Hiromasa Ikegami, Masato Yamazaki, Kimihiko Ito, Masaaki Nagamatsu, Takamichi Nishizaki, Masahiro Asada, Takashi Kameda, Akinori Wakimoto, Takahiro Mizutani, Takako Yamada, Yuji Murata

    CANCER LETTERS241 ( 2 ) 289 - 300   2006年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    The prognostic significance of p53 mutation, microsattelite instability and DNA mismatch protein hMLH1 expression in suboptimally resected advanced ovarian carcinoma treated with the combination chemotherapy of paclitaxel and carboplatin was evaluated. The overall combination chemotherapy response rate and the complete remission rate were significantly higher among patients with mutant p53 tumors than those with wild-type p53 tumors (35/42 (83%) vs. 32/58 (55%); P=0.003 and 18/42 (43%) vs. 16/58 (28%); P=0.03, respectively). This tendency apparently existed in non-serous carcinoma, but not in serous carcinoma. Univariate analysis showed that the risk of death due to disease and risk of progression was significantly lower among patients with p53 mutation (P=0.0357 and 0.0281, respectively). However, the presence of microsattelite instability or loss of hMLH1 expression was not associated with either the clinical response or prognosis. Determining p53 mutational status can be useful in predicting therapeutic response to drugs in ovarian carcinoma, especially in non-serous tumors. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

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  • Clinical outcomes of uterine sarcomas: Results from 14 years worth of experience in the Kinki district in Japan (1990-2003) 査読

    K. Kokawa, K. Nishiyama, M. Ikeuchi, Y. Ihara, N. Akamatsu, T. Enomoto, O. Ishiko, S. Motoyama, S. Fujii, N. Umesaki

    International Journal of Gynecological Cancer16 ( 3 ) 1358 - 1363   2006年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    To review clinical outcomes and therapeutic varieties, we were invited to submit data from the patients who were treated for uterine sarcomas in Japan from 1990 to 2003. Uterine sarcomas were defined as leiomyosarcoma (LMS), endometrial stromal sarcoma (ESS), and carcinosarcoma (CS). Of a total of 97 patients, 36 (37.1%) were diagnosed with LMS of the uterine corpus, 15 (15.5%) with ESS, 46 (47.4%) with CS. Median age at diagnosis was 59 (21-85) years. Clinical stages based on FIGO were 41 (42.3%) with stage I disease, 6 (6.2%) with staged II, 34 (35.1%) with stage III, and 16 (16.5%) with stage IV. The median follow-up period for all patients was 13 (1-108) months and median disease-free period was 9 (0-96) months. The 1-year survival rate and disease-free survival (DFS) rate were calculated in patients with all sarcomas (overall survival [OAS], 61.3%
    DFS, 46.6%). Statistical analysis showed that younger age (less than 50 years), early stage (stages I and II), and surgical procedure (extended hysterectomy [EH] and radical hysterectomy [RH]) were associated with significantly better OAS. Histologic types did not affect the survival period. In conclusion, aggressive surgery including EH or RH at the time of initial operation offers the possibility of prolonged survival. © 2006, Copyright the Authors.

    DOI: 10.1111/j.1525-1438.2006.00536.x

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  • Mutational analysis of TP53 and p21 in familial and sporadic ovarian cancer in Japan 査読

    T Amikura, M Sekine, Y Hirai, S Fujimoto, M Hatae, Kobayashi, I, T Fujii, Nagata, I, K Ushijima, K Obata, M Suzuki, M Yoshinaga, N Umesaki, S Satoh, T Enomoto, S Motoyama, K Nishino, K Haino, K Tanaka

    GYNECOLOGIC ONCOLOGY100 ( 2 ) 365 - 371   2006年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Objective. To investigate whether somatic mutations in cell cycle checkpoint genes, TP53 and p21, are involved in the development of ovarian cancer with or without BRCA1 germline mutation.
    Methods. We analyzed somatic genetic alterations of TP53 and p21 in 46 ovarian cancer patients with BRCA1 germline mutations and 93 sporadic patients, using direct sequencing for the entire coding sequences in TP53 and p21.
    Results. TP53 somatic mutations were detected in 25 of the 46 BRCA1 cases and 40 of the 93 sporadic cases (54.3% vs. 43.0%). In contrast, p21 somatic mutations were detected in I of the 46 BRCA1 cases and 2 of the 93 sporadic cases (2.2% vs. 2.2%). TP53 mutations in sporadic cases more frequently occurred in exons 6-11 than those in cases with germline BRCA1 mutations (84.4% vs. 56.3%: P = 0.013). The proportion of sporadic cases with TP53 mutations in non-serous tumors (e.g. endometrioid, clear cell, or mucinous) was significantly lower than that in serous tumors (18.5% vs. 53.0%: P = 0.0038). However, there was no significant difference between the proportion of BRCA1 cases with TP53 mutation in non-serous and in serous tumors (37.5% vs. 57.9%).
    Conclusions. Our results suggest that somatic mutation of TP53 plays less of a role in the carcinogenesis of sporadic non-serous tumors than in that of sporadic serous tumors or BRCA1-related tumors. Furthermore, p21 somatic mutation appears to be less involved in the development of ovarian cancer than TP53 somatic mutation. (c) 2005 Elsevier Inc. All rights reserved.

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  • B7-H4 overexpression in ovarian tumors 査読

    B Tringler, WH Liu, L Corral, KC Torkko, T Enomoto, S Davidson, MS Lucia, DE Heinz, J Papkoff, KR Shroyer

    GYNECOLOGIC ONCOLOGY100 ( 1 ) 44 - 52   2006年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Objectives. Despite great advances in therapeutic management, the mortality rate for ovarian cancer has remained relatively stable over the past 50 years. This study was designed to evaluate the expression of B7-H4 protein, recently identified as a potential molecular marker of breast and ovarian cancer by quantitative PCR analysis, in benign tumors, tumors of low malignant potential and malignant tumors of the ovary.
    Methods. Archival formalin-fixed tissue blocks from serous, mucinous, endometrioid and clear cell ovarian tumors were evaluated by immunohistochemistry for the distribution of B7-H4 expression, and staining intensity was measured by automated image analysis. Univariate analyses were used to test for statistically significant relationships.
    Results. B7-H4 cytoplasmic and membranous expression was detected in all primary serous (n = 32), endometrioid (it 12). and clear cell carcinomas (it = 15), and in all metastatic serous (it = 23) and endometrioid (it = 7) ovarian carcinomas. By contrast, focal B7-H4 expression was detected in only 1/11 mucinous carcinomas. The proportion of positive cells and median staining intensity was greater in serous carcinomas than in serous cystadenomas or serous tumors of low malignant potential, and the differences were statistically significant (P &lt; 0.0001 and P = 0.034, respectively). The median staining intensity was also significantly greater in endometrioid carcinomas than in endometriosis (P = 0.005).
    Conclusions. The consistent overexpression of B7-H4 in serous, endometrioid and clear cell ovarian carcinomas and the relative absence of expression in most normal somatic tissues indicates that B7-H4 should be further investigated as a potential diagnostic marker or therapeutic target for ovarian cancer. (c) 2005 Elsevier Inc. All rights reserved.

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  • Overexpression of LAMP3/TSC403/DC-LAMP promotes metastasis in uterine cervical cancer 査読

    H Kanao, T Enomoto, T Kimura, M Fujita, R Nakashima, Y Ueda, Y Ueno, T Miyatake, T Yoshizaki, GS Buzard, A Tanigami, K Yoshino, Y Murata

    CANCER RESEARCH65 ( 19 ) 8640 - 8645   2005年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    LAMP3 (DC-LAMP, TSC403, CD208) was originally isolated as a gene specifically expressed in lung tissues. LAMP3 is located on a chromosome 3q segment that is frequently amplified in some human cancers, including uterine cervical cancer. Because two other members of the LAMP family of lysosomal membrane glycoproteins, LAMP1 and LAMP2, were previously implicated in potentially modulating the interaction of vascular endothelial and cancer cells, we hypothesized that LAMP3 might also play an important part in metastasis. To clarify the metastatic potential of LAMP3 in cervical cancers, we transfected a LAMP3 expression vector into a human uterine cervical cancer cell line, TCS. In an in vitro invasion assay, the migration of LAMP3-overexpressing TCS cells was significantly higher than in control TCS cells. In an in vivo metastasis assay, distant metastasis was detected in 9 of 11 LAMP3-overexpressing TCS cell-injected mice and in only 1 of 11 control mice. Histologic study showed that LAMP3-overexpressing cells readily invaded into the lymph-vascular space. In clinical samples, quantitative real-time reverse transcription-PCR (RT-PCR) analyses showed that LAMP3 mRNA was significantly up-regulated in 47 of 47 (100%) cervical cancers and in 2 of 15 (13%) cervical intraepithelial neoplasias, compared with a low level of LAMP3 mRNA expressed in normal uterine cervixes. Interestingly, high LAMP3 expression was significantly correlated with the overall survival of patients with stage I/II cervical cancers. These findings indicate that LAMP3 overexpression is associated with an enhanced metastatic potential and may be a prognostic factor for cervical cancer.

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  • Altered protein expression in endometrial carcinogenesis 査読

    T Yoshizaki, T Enomoto, R Nakashima, Y Ueda, H Kanao, K Yoshino, M Fukumoto, Y Yoneda, GS Buzard, Y Murata

    CANCER LETTERS226 ( 2 ) 101 - 106   2005年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    We have discovered several protein biomarkers that are altered during carcinogenesis of the human uterine endometrium. Proteins prepared from 19 endometrial carcinomas (Group A), and 20 normal endometria obtained from benign gynecological conditions (Group B), were investigated by Surface Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS). Two proteins, EC1 and EC2, were consistently expressed differentially. EC1 had an increased level of expression in carcinomas (P &lt; 0.001), while EC2 was expressed at a lower level (P = 0.004). The isoelectric points of EC1 and EC2 were approximately pH 5.0 and 7.0, respectively. These proteins are thus potential biomarkers for detection of endometrial carcinoma. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

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  • Mutational analysis of the estrogen receptor-alpha gene in familial ovarian cancer 査読

    HJ Wu, M Sekine, K Kashima, Y Hirai, M Hatae, Kobayashi, I, K Obata, T Enomoto, N Umesaki, K Ushijima, K Tanaka

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH31 ( 5 ) 375 - 383   2005年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING  

    Aim: The genetic region of 6q25 containing the estrogen receptor-alpha (ER-alpha) gene is lost in a significant number of ovarian tumors. The aim of this study was to identify how inherited variation in the ER-alpha gene contributes to susceptibility to familial ovarian cancer.
    Methods: DNA obtained from 18 cases of familial ovarian cancer without mutation of the BRCA1 and BRCA2 genes, 20 cases with BRCA1 mutation, 20 cases of sporadic ovarian cancer, and 19 controls were screened for mutations in the coding region of the ER-alpha gene using direct sequencing.
    Results: Two germline missense variants at codons 307 [GCC(Ala)-&gt; TCC(Ser)] and 347 [ACC(Thr)-&gt; TCC(Ser)] were detected in two unrelated cases with BRCA1 mutation, but not in all other cases tested. Three polymorphisms in codon 10 [TCT -&gt; TCC(Ser)], codon 325 [CCC -&gt; CCG(Pro)], and codon 594 [ACA -&gt; ACG(Thr)] were identified in this series, and a higher frequency of the allele TCC at codon 10 and a lower frequency of the allele CCG at codon 325 were observed in familial cases without BRCA1 mutation, compared with those in familial cases with BRCA1 mutation, in both the sporadic cases and in the controls.
    Conclusions: We could not detect pathogenic mutations of the ER-alpha gene in ovarian cancer cases without BRCA1 mutation. However, association analyses of two polymorphisms suggest that the ER-alpha gene or a gene located close to the ER-alpha locus might be related to susceptibility of familial ovarian cancer without BRCA1 mutation.

    DOI: 10.1111/j.1447-0756.2005.00305.x

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  • [Activity of paclitaxel, epirubicin and carboplatin in patients with advanced or recurrent endometrial cancer]. 査読

    Nakashima R, Enomoto T, Murata Y, Fujita M

    Nihon rinsho. Japanese journal of clinical medicine62 Suppl 10   360 - 364   2004年10月

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  • [Molecular carcinogenesis of the uterine cervix]. 査読

    Enomoto T

    Nihon rinsho. Japanese journal of clinical medicine62 Suppl 10   61 - 65   2004年10月

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  • Cisplatin enhances the p53-independent apoptosis induced by a topoisomerase I inhibitor (CPT-11) in the lens epithelial tumors in transgenic mice 査読

    T Nakamura, Y Nakajima, T Enomoto, S Hori, T Hidaka, Y Murata, S Saito

    ONCOLOGY REPORTS12 ( 2 ) 253 - 258   2004年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PROFESSOR D A SPANDIDOS  

    We reported that CPT-11 could induce apoptosis in mouse lens epithelial tumors when it was administered to pregnant alphaT3 mice which developed epithelial cell carcinoma in situ in the lens in the perinatal period. p53-deficient alphaT3 mice were generated to analyze the influence of p53 status on tumor cells under combined chemotherapy. On the 16-18th gestational day, alphaT3 received a single i.p. administration of both CPT-11 and Cisplatin, and fetal lens epithelial tumors were examined two days later. Apoptosis in the p53-wild-type alphaT3 tumors was observed in a Cisplatin dose-dependent manner. In addition, it was found that Cisplatin augmented CPT-11-induced p53-independent apoptosis in p53-deficient alphaT3 mice.

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  • Mutations in the STKK11 gene characterize minimal deviation adenocarcinoma of the uterine cervix 査読

    C Kuragaki, T Enomoto, Y Ueno, HB Sun, M Fujita, R Nakashima, Y Ueda, H Wada, Y Murata, T Toki, Konishi, I, S Fujii

    LABORATORY INVESTIGATION83 ( 1 ) 35 - 45   2003年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Minimal deviation adenocarcinoma (MDA) is a well-differentiated variant of mucinous adenocarcinoma of the uterine cervix and is found relatively infrequently in the general population. However, MDA is strongly associated with Peutz-Jeghers syndrome (PJS), a rare hereditary autosomal disorder characterized by benign hamartomatous polyposis in the gastrointestinal tract and mucocutaneous pigmentation. A serine threonine kinase gene, STK11, has been identified as the tumor suppressor gene responsible for the PJS. In this study we investigated the possible direct role of STK11 in the development of MDA of the uterine cervix. Eleven rare cases of mucinous MDA, not known to be associated with PJS, were screened for the presence of mutations in the STK11 gene by single-strand conformation polymorphism analysis of PCR-amplified DNA fragments. Subsequently our findings were confirmed with cloning and sequencing. As a control, 24 cases of endocervical adenocarcinomas of other histologic subtypes, with no family history of PJS (19 mucinous adenocarcinomas, 4 endometrioid adenocarcinomas, and 1 clear cell adenocarcinoma), 15 cases of squamous cell carcinomas of the uterine cervix, 5 cases of endocervical glands with pyloric gland metaplasia, and 2 deeply situated nabothian cysts were investigated. Somatic mutations of the STK11 gene were confirmed in 6 (55%) of the 11 mucinous MDAs and 1 (5%) of the 19 mucinous adenocarcinomas, but not in the 5 nonmucinous adenocarcinomas, the 15 squamous cell carcinomas, nor the 5 endocervical glands with gastric metaplasia. MDAs with the STK11 mutation had a significantly poorer prognosis than MDAs without the STK11 mutation (p = 0.039). A germline mutation of STK11 was detected in one PJS patient with mucinous adenocarcinoma of the uterine cervix. These results suggest that mutations in the STK11 gene may play an important role in the etiology of MDA of the uterine cervix and may distinguish this rare tumor from other common types of adenocarcinoma of the uterine cervix.

    DOI: 10.1097/01.LAB.0000049821.16698.D0

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  • Loss of one allele of the p53 gene in the lens epithelial tumor in transgenic mice suppresses apoptosis induced by a topoisomerase I inhibitor (CPT-11) 査読

    Y Nakajima, T Nakamura, T Enomoto, Y Murata

    CANCER LETTERS179 ( 2 ) 165 - 173   2002年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    To examine whether CPT-11 can induce apoptosis in the mouse lens tumor, it was administered to pregnant alphaT3 mice, which developed epithelial tumors in the lens during the perinatal stage. Three different p53 genotypes were generated to analyze the influence of p53 status on tumor cells under chemotherapy. On day 16-17 of gestation, alphaT3 mice received an i.p. injection of CPT-11, and fetal lens tumors were examined 2 clays later. Apoptosis in the tumors was observed in both a CPT-11 dose- and p53 gene copy-dependent manner. In addition, it was found that CPT-11 could also induce apoptosis via a p53-independent pathway. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

    DOI: 10.1016/S0304-3835(02)00008-3

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  • Paclitaxel, epirubicin and carboplatin in advanced and recurrent endometrial carcinoma 査読

    R Nakashima, M Fujita, T Enomoto, Y Ueda, H Kanao, T Miyatake, T Yoshizaki, T Kimura, T Murata, Y Murata

    9TH BIENNIAL MEETING OF THE INTERNATIONL GYNECOLOGIC CANCER SOCIETY   205 - 208   2002年

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)   出版者・発行元:MEDIMOND S R L  

    The purpose of this study was to evaluate the combination of paclitaxel, epirubicin, and carboplatin in patients with endometrial cancer known to be resistant to standard therapy. The combination of carboplatin (AUC 4), epirubicin (50 mg/m(2)), and paclitaxel (150 mg/m(2) over 3 hours) was given intravenously every 4 weeks for a maximum of six courses. Twenty-six patients have participated to date, including eight considered evaluable for response. Of patients with measurable disease, one of eight was a complete responder, and six of eight has had partial response. Twenty-three patients had grade 3 or 4 hematologic toxicity, but were controlled conservatively. In this preliminary report, this combination is active against tumors of the endometrium, with acceptable levels of toxicity.

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  • Impaired FHIT expression characterizes serous ovarian carcinoma 査読

    Ozaki K, Enomoto T, Yoshino K, Fujita M, Buzard GS, Kawano K, Yamasaki M, Murata Y

    British journal of cancer85 ( 2 ) 247 - 254   2001年7月

  • Localization of a novel susceptibility gene for familial ovarian cancer to chromosome 3p22-p25 査読

    M Sekine, H Nagata, S Tsuji, Y Hirai, S Fujimoto, M Hatae, Kobayashi, I, T Fujii, Nagata, I, K Ushijima, K Obata, M Suzuki, M Yoshinaga, N Umesaki, S Satoh, T Enomoto, S Motoyama, K Tanaka

    HUMAN MOLECULAR GENETICS10 ( 13 ) 1421 - 1429   2001年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    We performed genome-wide linkage analysis in 58 patients and nine unaffected members among 28 families with no mutation in BRCA1 or BRCA2, employing a set of 410 microsatellite markers. We initially screened the whole genome, including the X chromosome, by a non-parametric method using the GENEHUNTER program. As a result, chromosome 3p22-p25 showed a suggestive score for linkage [LOD = 3.49 and non-parametric LOD (NPL)= 2.77 at D3S3611] based on a multipoint analysis. Additionally, based on a two-point analysis using dense markers, this 3p22-p25 region showed a P-value &lt; 0.05 at 10 markers and there is suggestive evidence for linkage at two markers within &lt;similar to&gt;19 cM (NPL = 2.60 and 2.49 at D3S1597 and D3S3611, respectively). To explore whether the candidate gene in this 3p22-p25 region contributed to carcinogenesis of familial ovarian cancer in a similar fashion to the tumor suppressor gene, we performed loss of heterozygosity (LOH) analysis. It was observed that the frequency of LOH at four markers in this region was &gt;50% only in tumor tissues from patients with no mutation in BRCA1 or BRCA2, not in those with a BRCA1 mutation.

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  • MR imaging of mesenteric hemangioma: A case report 査読

    M. Takamura, T. Murakami, H. Kurachi, T. Kim, T. Enomoto, Y. Narumi, H. Nakamura

    Radiation Medicine - Medical Imaging and Radiation Oncology18 ( 1 ) 67 - 69   2000年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A 62-year-old woman presented with a mobile abdominal palpable mass. She underwent MR examination twice. Because of the mobility of the mass, it was out of the field of view on the first MR examination. The second MR examination detected the mass, which showed heterogeneous signal intensity including low and high intensity on T2-weighted spin echo images. The mass, which was cavernous hemangioma with old hemorrhage, was difficult to differentiate from fibroma or thecoma of the ovary or subserosal leiomyoma of the uterus.

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  • Activation of neu by missense point mutation in the transmembrane domain in schwannomas induced in C3H/HeNCr mice by transplacental exposure to N-nitrosoethylurea 査読

    GS Buzard, T Enomoto, LM Anderson, AO Perantoni, DE Devor, JM Rice

    JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY125 ( 12 ) 653 - 659   1999年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER VERLAG  

    Transplacentally initiated schwannomas in mice and rats arise preferentially in the Gasserian ganglion of the trigeminal nerve and spinal root ganglia, while those of the Syrian golden hamster most commonly occur subcutaneously. Rat and hamster schwannomas almost invariably contain a mutationally activated neu oncogene. In rat schwannomas, the mutant allele predominates, while the relative abundance of mutant alleles is very low in hamster nerve tumors. We investigated whether neu is mutated in mouse schwannomas and whether the pattern and allelic ratio of the mutation resemble those for the hamster or the rat, Pregnant C3H/HeNCr mice received 0.4 mu mol N-nitrosoethylurea/g body weight on day 19 of gestation. Ten trigeminal and one peripheral nerve schwannomas developed in II of the 201 offspring. Missense T --&gt; A transversion mutations were detected in the neu transmembrane domain in eight of ten schwannomas analyzed, as determined by MnlI digestion of polymerase chain reaction products. The mutant allele was pre dominantly detected in two tumors and was abundant in six others. Transfection of eight out of ten mouse tumor DNAs into hamster cells yielded transformed foci; seven out of eight contained mutant mouse neu. Mouse schwannomas closely resembled those of rats both in the preferred anatomical site and in the mutant/wild-type neu allele ratios.

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  • K‐ras activation and ras p21 expression in latent prostatic carcinoma in Japanese men 査読

    Noboru Konishi, Takayuki Enomoto, Gregory Buzard, Masato Ohshima, Jerrold M. Ward, Jerry M. Rice

    Cancer69 ( 9 ) 2293 - 2299   1992年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Twenty‐three clinically silent prostatic carcinomas discovered in Japanese men at autopsy were surveyed for ras proto‐oncogene mutations by mutation‐specific oligonucleotide probe hybridization after polymerase chain reaction (PCR) amplification from a section of formalin‐fixed, paraffin‐embedded tissue. Six of the 22 that were satisfactorily amplified contained activating point mutations in codon 12 of K‐ras, a significantly higher frequency than has been reported in patients with clinically advanced disease in the United States. Of the six cases with activating point mutations in codon 12 of K‐ras, one had a GGT → GAT transition, four had GGT → GTT trans‐versions, and one had both GGT → GAT and GGT → GTT mutations. Sections from the same tissues were immunohistochemically stained with an anti‐ras p21 antibody. Carcinoma cells stained for ras p21 to some degree in 13 cases. Immunohistochemically detectable expression of p21 was always focal and was not necessarily associated with K‐ras mutation. K‐ras oncogene activation in prostatic carcinoma appears to merit additional study as a significant event in the pathogenesis of this neoplasm. Copyright © 1992 American Cancer Society

    DOI: 10.1002/1097-0142(19920501)69:9<2293::AID-CNCR2820690915>3.0.CO;2-O

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MISC

  • 進行卵巣癌に対するWT1を標的とした癌ワクチンに関する臨床研究(Clinical Study of the Cancer Vaccine targeting WT1 for Advanced Ovarian Cancer)

    西田 純幸, 白方 俊章, 森本 創世子, 榎本 隆之, 吉野 潔, 冨松 拓治, 藤木 文博, 尾路 祐介, 上田 豊, 坪井 昭博, 森田 智視, 岡 芳弘, 熊ノ郷 淳, 木村 正, 杉山 治夫

    日本がん免疫学会総会プログラム・抄録集23回   159 - 159   2019年7月

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    記述言語:英語   出版者・発行元:日本がん免疫学会  

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  • 卵巣奇形腫を伴う抗NMDA受容体抗体脳炎における卵巣奇形腫の手術時期および術式と脳炎の短期的転帰との関連をみる調査 日本産科婦人科学会婦人科腫瘍委員会、抗NMDA受容体抗体脳炎に関する小委員会(多施設共同研究)

    田代 浩徳, 宮本 新吾, 椙田 賢司, 万代 昌紀, 坂口 勲, 片渕 秀隆, 八重樫 伸生, 榎本 隆之

    日本婦人科腫瘍学会雑誌37 ( 3 ) 410 - 410   2019年6月

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    記述言語:日本語   出版者・発行元:(公社)日本婦人科腫瘍学会  

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  • 妊産婦の発達特性が子へのボンディングに与える影響について

    坪谷 隆介, 茂木 崇治, 福井 直樹, 橋尻 洸陽, 須貝 拓朗, 江川 純, 三留 節子, 荒木 理恵, 池 睦美, 生野 寿史, 山口 雅幸, 高桑 好一, 榎本 隆之, 染矢 俊幸

    精神神経学雑誌 ( 2019特別号 ) S641 - S641   2019年6月

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    記述言語:日本語   出版者・発行元:(公社)日本精神神経学会  

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  • 低侵襲広汎子宮全摘術の課題と展望 日本の広汎子宮全摘出術は本当に優れているのか?

    永瀬 智, 太田 剛, 八重樫 伸生, 榎本 隆之

    日本婦人科腫瘍学会雑誌37 ( 3 ) 356 - 356   2019年6月

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    記述言語:日本語   出版者・発行元:(公社)日本婦人科腫瘍学会  

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  • 分娩歴と完全母乳栄養が妊産婦の不安・抑うつに与える影響について

    福井 直樹, 茂木 崇治, 橋尻 洸陽, 坪谷 隆介, 須貝 拓朗, 江川 純, 三留 節子, 荒木 理恵, 池 睦美, 生野 寿史, 山口 雅幸, 高桑 好一, 榎本 隆之, 染矢 俊幸

    精神神経学雑誌 ( 2019特別号 ) S771 - S771   2019年6月

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    記述言語:日本語   出版者・発行元:(公社)日本精神神経学会  

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  • 胞状奇胎の掻爬回数と続発症頻度に関する多施設調査研究

    兼城 英輔, 碓井 宏和, 山本 英子, 田代 浩徳, 宮本 新吾, 井箟 一彦, 八重樫 伸生, 榎本 隆之

    日本婦人科腫瘍学会雑誌37 ( 3 ) 413 - 413   2019年6月

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    記述言語:日本語   出版者・発行元:(公社)日本婦人科腫瘍学会  

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  • 【卵巣がん征圧へのマイルストーン】JGOG-ToMMoバイオバンキング事業

    島田 宗昭, 峯岸 直子, 八重樫 伸生, 山本 雅之, 榎本 隆之, 杉山 徹

    産婦人科の実際68 ( 3 ) 267 - 271   2019年3月

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    記述言語:日本語   出版者・発行元:金原出版(株)  

    <文献概要>婦人科悪性腫瘍研究機構(JGOG)は,Gynecologic Cancer Intergroup(GCIG)やGynecologic Oncology Group(GOG)へ加入し,データ管理,臨床試験のコーディネートなどのインフラ整備を進め,国際共同第III相試験も主導し,国際的評価に耐えうる臨床研究の成果を報告してきた。近年の医療を取り巻く環境の変化に伴い,JGOGは東北メディカル・メガバンク機構(ToMMo)および臨床研究情報センター(TRI)との連携を進め,公的資金の獲得,Translational Research(TR)の推進,がんゲノム医療の実装化を目指す体制を強化した。JGOG-ToMMoバイオバンキング事業はJGOGの主たる事業であり,新設されたJGOG TR委員会主導のもと,より精密な個別化医療の実装を目指す臨床研究の遂行を可能にするとともに,GCIGなどとの国際連携も強化し,わが国から婦人科悪性腫瘍に対する新たな治療戦略の発信を目指す。

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  • 女性の家族性がん 新潟県におけるHBOC診療体制の確立に向けての取り組み

    西野 幸治, 須田 一暁, 安達 聡介, 吉原 弘祐, 関根 正幸, 榎本 隆之, 五十嵐 真由子, 土田 純子, 中島 真人, 永橋 昌幸, 田澤 立之, 栗山 洋子, 藤田 沙織里, 小山 諭, 菊池 朗, 佐藤 信昭, 金子 耕司, 田村 恵美子, 三富 亜希, 後藤 清恵

    人間ドック33 ( 2 ) 232 - 232   2018年8月

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    記述言語:日本語   出版者・発行元:(公社)日本人間ドック学会  

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  • 腹腔鏡による迅速な診断が可能であった悪性リンパ腫の一例

    西野 幸治, 安達 聡介, 明石 英彦, 工藤 梨沙, 茅原 誠, 石黒 竜也, 吉原 弘祐, 磯部 真倫, 小林 暁子, 西川 伸道, 関根 正幸, 榎本 隆之

    日本産科婦人科内視鏡学会雑誌34 ( Suppl.I ) 202 - 202   2018年8月

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    記述言語:日本語   出版者・発行元:(一社)日本産科婦人科内視鏡学会  

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  • 機能性子宮体部を持つ先天性腟・頸管欠損症に対する腹腔鏡下広汎頸部摘出術を応用した腹腔鏡下形成手術

    小林 暁子, 磯部 真倫, 上田 遥香, 工藤 梨沙, 石黒 竜也, 安達 聡介, 吉原 弘祐, 西野 幸治, 西川 伸道, 関根 正幸, 榎本 隆之

    日本産科婦人科内視鏡学会雑誌34 ( Suppl.I ) 399 - 399   2018年8月

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    記述言語:日本語   出版者・発行元:(一社)日本産科婦人科内視鏡学会  

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  • 機能性単角子宮を伴う先天性腟閉鎖に対する腹腔鏡下頸管形成造腟術を施行した1例

    小林 暁子, 磯部 真倫, 上田 遥香, 工藤 梨沙, 石黒 竜也, 安達 聡介, 吉原 弘祐, 西野 幸治, 西川 伸道, 関根 正幸, 榎本 隆之

    産婦人科手術 ( 29 ) 165 - 165   2018年6月

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    記述言語:日本語   出版者・発行元:(株)メジカルビュー社  

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  • 妊産婦の不安・抑うつと子との間のアタッチメントとの関連について

    福井 直樹, 茂木 崇治, 須貝 拓朗, 江川 純, 橋尻 洸陽, 生野 寿史, 山口 雅幸, 高桑 好一, 榎本 隆之, 染矢 俊幸

    精神神経学雑誌 ( 2018特別号 ) S670 - S670   2018年6月

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    記述言語:日本語   出版者・発行元:(公社)日本精神神経学会  

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  • 妊産婦の発達特性と子との間のアタッチメントとの関連について

    茂木 崇治, 福井 直樹, 須貝 拓朗, 江川 純, 橋尻 洸陽, 生野 寿史, 山口 雅幸, 高桑 好一, 榎本 隆之, 染矢 俊幸

    精神神経学雑誌 ( 2018特別号 ) S669 - S669   2018年6月

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    記述言語:日本語   出版者・発行元:(公社)日本精神神経学会  

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  • 妊産婦における発達特性と不安・抑うつとの関連について

    茂木 崇治, 福井 直樹, 須貝 拓朗, 江川 純, 橋尻 洸陽, 生野 寿史, 山口 雅幸, 高桑 好一, 榎本 隆之, 染矢 俊幸

    精神神経学雑誌 ( 2018特別号 ) S669 - S669   2018年6月

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    記述言語:日本語   出版者・発行元:(公社)日本精神神経学会  

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  • 消化器合併切除 (特集 卵巣癌の手術up to date)

    西川 伸道, 島田 能史, 若井 俊文, 吉野 潔, 榎本 隆之

    産婦人科の実際 = Obstetrical and gynecological practice67 ( 5 ) 503 - 508   2018年5月

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    記述言語:日本語   出版者・発行元:金原出版  

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  • 【婦人科がん(第2版)-最新の研究動向-】 卵巣がん 卵巣癌の治療 PARP阻害薬

    関根 正幸, 榎本 隆之

    日本臨床76 ( 増刊2 婦人科がん ) 640 - 645   2018年3月

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    記述言語:日本語   出版者・発行元:(株)日本臨床社  

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  • 新潟県におけるHBOC診療の取り組み

    西野 幸治, 須田 一暁, 安達 聡介, 吉原 弘祐, 関根 正幸, 榎本 隆之, 菊池 朗

    日本産科婦人科学会雑誌70 ( 2 ) 685 - 685   2018年2月

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    記述言語:日本語   出版者・発行元:(公社)日本産科婦人科学会  

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  • 2歳女児の腟内異物の一症例

    上田 遥香, 茅原 誠, 磯部 真倫, 山口 真奈子, 小木 幹奈, 工藤 梨沙, 石黒 竜也, 安達 聡介, 吉原 弘祐, 小林 暁子, 西野 幸治, 西川 伸道, 関根 正幸, 榎本 隆之

    新潟産科婦人科学会会誌112 ( 2 ) 99 - 99   2017年12月

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    記述言語:日本語   出版者・発行元:新潟産科婦人科学会  

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  • 母親の不安・抑うつと母子間のアタッチメントに関する周産期メンタルヘルス研究

    福井 直樹, 茂木 崇治, 橋尻 洸陽, 須貝 拓朗, 江川 純, 三留 節子, 池 睦美, 生野 寿史, 山口 雅幸, 高桑 好一, 榎本 隆之, 染矢 俊幸

    新潟医学会雑誌131 ( 12 ) 720 - 720   2017年12月

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    記述言語:日本語   出版者・発行元:新潟医学会  

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  • SOX2は子宮体がんの細胞増殖と細胞周期制御において重要である

    山脇 芳, 石黒 竜也, 森 裕太郎, 吉原 弘祐, 樋口 雅也, 藤井 雅寛, 岡本 康司, 榎本 隆之

    日本癌学会総会記事76回   J - 1100   2017年9月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • 新潟県若手周産期・内視鏡縫合セミナー 若手がつくる新しいリクルートメントの形

    磯部 真倫, 吉原 弘祐, 生野 寿史, 西野 幸治, 西川 伸道, 関根 正幸, 榎本 隆之

    北日本産科婦人科学会総会・学術講演会プログラム・抄録集65回   78 - 78   2017年9月

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    記述言語:日本語   出版者・発行元:東北連合産科婦人科学会・北日本産科婦人科学会  

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  • 癌性腹膜炎との鑑別に腹腔鏡下生検が有用であった結核性腹膜炎の2例

    上田 遥香, 工藤 梨沙, 茅原 誠, 石黒 竜也, 安達 聡介, 郷戸 千賀子, 吉原 弘祐, 磯部 真倫, 小林 暁子, 西野 幸治, 西川 伸道, 関根 正幸, 榎本 隆之

    日本産科婦人科内視鏡学会雑誌33 ( Suppl.I ) 1460 - 1460   2017年8月

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    記述言語:日本語   出版者・発行元:(一社)日本産科婦人科内視鏡学会  

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  • 当院における前回帝王切開症例の膀胱挙上、癒着に対する剥離の工夫

    小林 暁子, 磯部 真倫, 茅原 誠, 石黒 竜也, 安達 聡介, 吉原 弘祐, 西野 幸治, 西川 伸道, 関根 正幸, 榎本 隆之

    日本産科婦人科内視鏡学会雑誌33 ( Suppl.I ) 1501 - 1501   2017年8月

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    記述言語:日本語   出版者・発行元:(一社)日本産科婦人科内視鏡学会  

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  • 研修医セミナー改め新潟県若手周産期セミナーのご報告 これからのリクルートメントのかたち

    磯部 真倫, 吉原 弘祐, 生野 寿史, 西川 伸道, 関根 正幸, 榎本 隆之

    新潟産科婦人科学会会誌112 ( 1 ) 35 - 35   2017年8月

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    記述言語:日本語   出版者・発行元:新潟産科婦人科学会  

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  • 当科で経験した腹腔鏡手術中における器具破損・紛失症例について

    安達 聡介, 磯部 真倫, 上田 遥香, 工藤 梨沙, 茅原 誠, 石黒 竜也, 吉原 弘祐, 小林 暁子, 西野 幸治, 西川 伸道, 関根 正幸, 榎本 隆之

    日本産科婦人科内視鏡学会雑誌33 ( Suppl.I ) 1153 - 1153   2017年8月

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    記述言語:日本語   出版者・発行元:(一社)日本産科婦人科内視鏡学会  

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  • 深化 TLHこんな時どうする 教育、普及する側から見たTLH難症例への対応

    磯部 真倫, 安達 聡介, 吉原 弘祐, 西野 幸治, 西川 伸道, 関根 正幸, 榎本 隆之

    日本産科婦人科内視鏡学会雑誌33 ( Suppl.I ) 358 - 358   2017年8月

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    記述言語:日本語   出版者・発行元:(一社)日本産科婦人科内視鏡学会  

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  • 先進医療「腹腔鏡下広汎子宮全摘術」施設認定の報告

    磯部 真倫, 上田 遥香, 工藤 梨沙, 茅原 誠, 石黒 竜也, 安達 聡介, 吉原 弘祐, 小林 暁子, 西野 幸治, 西川 伸道, 関根 正幸, 榎本 隆之

    新潟産科婦人科学会会誌112 ( 1 ) 43 - 43   2017年8月

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    記述言語:日本語   出版者・発行元:新潟産科婦人科学会  

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  • 当科で経験した腹腔鏡手術中における器具破損・紛失症例について

    安達 聡介, 磯部 真倫, 上田 遥香, 茅原 誠, 石黒 竜也, 郷戸 千賀子, 吉原 弘祐, 西野 幸治, 西川 伸道, 関根 正幸, 榎本 隆之

    新潟産科婦人科学会会誌112 ( 1 ) 48 - 48   2017年8月

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    記述言語:日本語   出版者・発行元:新潟産科婦人科学会  

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  • 卵巣癌に対するベバシズマブ投与後の手術は安全に施行可能か?

    西野 幸治, 上田 遥香, 茅原 誠, 石黒 竜也, 安達 聡介, 郷戸 千賀子, 吉原 弘祐, 磯部 真倫, 小林 暁子, 西川 伸道, 関根 正幸, 榎本 隆之

    日本婦人科腫瘍学会雑誌35 ( 3 ) 634 - 634   2017年6月

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    記述言語:日本語   出版者・発行元:(公社)日本婦人科腫瘍学会  

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  • 進行卵巣癌に対する腹腔鏡生検の意義

    谷地田 希, 西野 幸治, 安達 聡介, 上田 遥香, 工藤 梨沙, 茅原 誠, 石黒 竜也, 郷戸 千賀子, 吉原 弘祐, 小林 暁子, 西川 伸道, 関根 正幸, 榎本 隆之

    日本婦人科腫瘍学会雑誌35 ( 3 ) 553 - 553   2017年6月

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    記述言語:日本語   出版者・発行元:(公社)日本婦人科腫瘍学会  

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  • 癌性腹膜炎が疑われた結核性腹膜炎の2症例

    安達 聡介, 上田 遥香, 工藤 梨沙, 茅原 誠, 石黒 竜也, 郷戸 千賀子, 吉原 弘祐, 磯部 真倫, 小林 暁子, 西野 幸治, 西川 伸道, 関根 正幸, 榎本 隆之

    日本婦人科腫瘍学会雑誌35 ( 3 ) 614 - 614   2017年6月

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    記述言語:日本語   出版者・発行元:(公社)日本婦人科腫瘍学会  

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  • 腹腔鏡下付属器手術後に境界悪性あるいは悪性卵巣腫瘍と診断された9例の検討

    小林 暁子, 茅原 誠, 石黒 竜也, 安達 聡介, 郷戸 千賀子, 吉原 弘祐, 磯部 真倫, 西野 幸治, 西川 伸道, 関根 正幸, 榎本 隆之

    日本婦人科腫瘍学会雑誌35 ( 3 ) 596 - 596   2017年6月

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    記述言語:日本語   出版者・発行元:(公社)日本婦人科腫瘍学会  

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  • Tumor-derived spheroids: Relevance to cancer stem cells and clinical applications

    Tatsuya Ishiguro, Hirokazu Ohata, Ai Sato, Kaoru Yamawaki, Takayuki Enomoto, Koji Okamoto

    CANCER SCIENCE108 ( 3 ) 283 - 289   2017年3月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:WILEY  

    Recently, many types of in vitro 3-D culture systems have been developed to recapitulate the in vivo growth conditions of cancer. The cancer 3-D culture methods aim to preserve the biological characteristics of original tumors better than conventional 2-D monolayer cultures, and include tumor-derived organoids, tumor-derived spheroids, organotypic multicellular spheroids, and multicellular tumor spheroids. The 3-D culture methods differ in terms of cancer cell sources, protocols for cell handling, and the required time intervals. Tumor-derived spheroids are unique because they are purposed for the enrichment of cancer stem cells (CSCs) or cells with stem cell-related characteristics. These spheroids are grown as floating spheres and have been used as surrogate systems to evaluate the CSC-related characteristics of solid tumors in vitro. Because eradication of CSCs is likely to be of clinical importance due to their association with the malignant nature of cancer cells, such as tumorigenicity or chemoresistance, the investigation of tumor-derived spheroids may provide invaluable clues to fight against cancer. Spheroid cultures have been established from cancers including glioma, breast, colon, ovary, and prostate cancers, and their biological and biochemical characteristics have been investigated by many research groups. In addition to the investigation of CSCs, tumor-derived spheroids may prove to be instrumental for a high-throughput screening platform or for the cultivation of CSC-related tumor cells found in the circulation or body fluids.

    DOI: 10.1111/cas.13155

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  • Identification of therapeutically targetable FGFR‐fusion genes in cervical cancer through RNA sequencing

    TAMURA Ryo, YOSHIHARA Kosuke, MORI Yutaro, YAMAWAKI Kaoru, SUDA Kazuaki, ISHIGURO Tatsuya, AOKI Yoichi, SATO Seiya, ITAMOCHI Hiroaki, ENOMOTO Takayuki

    日本産科婦人科学会雑誌69 ( 2 ) 518   2017年2月

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    記述言語:英語  

    J-GLOBAL

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  • 非常に稀なPrimary Retroperitoneal Serous Adenocarcinomaの一例

    八幡 夏美, 吉原 弘祐, 磯部 真倫, 西野 幸治, 西川 伸道, 関根 正幸, 榎本 隆之

    日本産科婦人科学会雑誌69 ( 2 ) 828 - 828   2017年2月

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    記述言語:日本語   出版者・発行元:(公社)日本産科婦人科学会  

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  • 完全型アンドロゲン不応症に対し腹腔鏡下性腺摘出術を施行した症例の検討

    茅原 誠, 安達 聡介, 谷地田 希, 田村 亮, 石黒 竜也, 吉田 邦彦, 吉原 弘祐, 磯部 真倫, 西野 幸治, 西川 伸道, 関根 正幸, 榎本 隆之

    新潟産科婦人科学会会誌111 ( 2 ) 84 - 88   2016年12月

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    記述言語:日本語   出版者・発行元:新潟産科婦人科学会  

    完全型アンドロゲン不応症(AIS)に対し腹腔鏡下性腺摘出術を施行した4例について検討した。年齢は16歳が2例、19歳が2例であった。性腺が鼠径管内に存在した1例も含めて、全例で腹腔鏡下に性腺摘出が可能であった。全例、術後経過は良好で、外来通院にてエストロゲン補充療法中である。今回の検討から、術前画像診断(特にMRI所見)により性腺の存在位置を予測し、鼠径管内に存在が疑われる場合には開腹手術への移行に備えることで、腹腔鏡下手術をAISに対する予防的性腺摘出術に適応することが可能であると考えられた。

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  • Analysis of pregnant women with inflammatory bowel disease in our hospital

    Kunihiko Yoshida, Taeko Hyuga, Kentaro Sugino, Manako Yamaguchi, Tomoko Tamura, Taro Nonaka, Kazufumi Haino, Masayuki Yamaguchi, Koichi Takakuwa, Takayuki Enomoto

    JOURNAL OF REPRODUCTIVE IMMUNOLOGY118   122 - 122   2016年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.jri.2016.10.040

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  • Expression analysis of Bcl11b in Xenopus tropicalis olfactory epithelium 査読

    Nakayama Kanako, Suzuki Hikoyu, Nikaido Masato, Enomoto Takayuki, Hirota Junji

    CHEMICAL SENSES41 ( 9 ) E201 - E202   2016年11月

  • A case-control study of risk factors for placenta previa accreta

    Masayuki Yamaguchi, Taeko Hyuga, Kunihiko Yoshida, Mina Itsukaichi, Taro Nonaka, Kazufumi Haino, Takayuki Enomoto, Koichi Takakuwa

    JOURNAL OF REPRODUCTIVE IMMUNOLOGY118   122 - 123   2016年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.jri.2016.10.041

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  • 卵巣 卵巣がんに対する抗がん剤治療 卵巣癌に対するベバシズマブの投与状況 著効例の提示と今後の課題

    西野 幸治, 工藤 梨沙, 茅原 誠, 石黒 竜也, 安達 聡介, 郷戸 千賀子, 吉原 弘祐, 磯部 真倫, 西川 伸道, 関根 正幸, 榎本 隆之

    日本癌治療学会学術集会抄録集54回   WS55 - 5   2016年10月

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    記述言語:日本語   出版者・発行元:(一社)日本癌治療学会  

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  • COMPARISON OF RESPONSES BETWEEN DIFFERENT RECRUITMENT METHODS FOR SEXUAL AND REPRODUCTIVE HEALTH RESEACH ABOUT CERVICAL CANCER PREVENTION: WEB-BASED METHOD AND THE OTHERS

    Y. Motoki, E. Miyagi, M. Taguri, M. Asai-Sato, T. Enomoto, J. D. Wark, S. M. Garland

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER26   410 - 410   2016年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

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  • Anti-cancer antibody against lipolysis-stimulated lipoprotein receptor inhibits tumor growth of ovarian cancer via inhibition of lipid catabolism

    K. Hiramatsu, K. Yoshino, S. Serada, S. Nakagawa, A. Morimoto, T. Yokoyama, K. Amemiya, M. Fujimoto, Y. Ueda, T. Enomoto, T. Naka, T. Kimura

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER26   714 - 714   2016年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Web of Science

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  • 子宮頸癌と結腸癌の重複傍大動脈リンパ節転移を呈した1例

    杉野 健太郎, 関根 正幸, 工藤 梨沙, 島 英里, 石黒 竜也, 安達 聡介, 吉原 弘祐, 磯部 真倫, 西野 幸治, 西川 伸道, 榎本 隆之

    日本癌治療学会学術集会抄録集54回   P17 - 4   2016年10月

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    記述言語:日本語   出版者・発行元:(一社)日本癌治療学会  

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  • 医師の人材育成における「メンター制度」の有効性 新潟県における腹腔鏡手術の教育から得たもの

    磯部 真倫, 茅原 誠, 石黒 竜也, 安達 聡介, 吉原 弘祐, 西野 幸治, 西川 伸道, 関根 正幸, 榎本 隆之

    北日本産科婦人科学会総会・学術講演会プログラム・抄録集64回   147 - 147   2016年9月

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    記述言語:日本語   出版者・発行元:東北連合産科婦人科学会・北日本産科婦人科学会  

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  • 当科における胞状奇胎症例の後方視的検討

    森 裕太郎, 工藤 梨沙, 茅原 誠, 石黒 竜也, 安達 聡介, 吉原 弘祐, 磯部 真倫, 西野 幸治, 西川 伸道, 関根 正幸, 榎本 隆之

    北日本産科婦人科学会総会・学術講演会プログラム・抄録集64回   158 - 158   2016年9月

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    記述言語:日本語   出版者・発行元:東北連合産科婦人科学会・北日本産科婦人科学会  

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  • 腹腔鏡下卵巣腫瘍摘出術術後血腫感染に対して腹腔鏡下ドレナージを施行した1例

    杉野 健太郎, 磯部 真倫, 工藤 梨沙, 島 英里, 石黒 竜也, 安達 聡介, 吉原 弘祐, 西野 幸治, 西川 伸道, 関根 正幸, 榎本 隆之

    日本産科婦人科内視鏡学会雑誌32 ( Suppl.I ) 216 - 216   2016年8月

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    記述言語:日本語   出版者・発行元:(一社)日本産科婦人科内視鏡学会  

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  • 腹腔鏡下リンパ節生検が診断に有用であった原発不明癌の一例

    吉原 弘祐, 磯部 真倫, 工藤 梨沙, 茅原 誠, 石黒 竜也, 安達 聡介, 西野 幸治, 西川 伸道, 関根 正幸, 榎本 隆之

    日本産科婦人科内視鏡学会雑誌32 ( Suppl.I ) 304 - 304   2016年8月

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    記述言語:日本語   出版者・発行元:(一社)日本産科婦人科内視鏡学会  

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  • BMI40以上の高度肥満3症例に対する腹腔鏡手術の経験

    西野 幸治, 磯部 真倫, 工藤 梨沙, 島 英里, 茅原 誠, 石黒 竜也, 安達 聡介, 郷戸 千賀子, 吉原 弘祐, 西川 伸道, 関根 正幸, 榎本 隆之

    日本産科婦人科内視鏡学会雑誌32 ( Suppl.I ) 241 - 241   2016年8月

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    記述言語:日本語   出版者・発行元:(一社)日本産科婦人科内視鏡学会  

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  • 腹腔鏡下に腫大リンパ節を摘出後、迅速診断でリンパ節転移陽性と診断し、開腹による根治術を施行したMPA療法後子宮体癌の一例

    茅原 誠, 西野 幸治, 磯部 真倫, 島 英里, 石黒 竜也, 安達 聡介, 吉原 弘祐, 西川 伸道, 関根 正幸, 榎本 隆之

    日本産科婦人科内視鏡学会雑誌32 ( Suppl.I ) 206 - 206   2016年8月

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    記述言語:日本語   出版者・発行元:(一社)日本産科婦人科内視鏡学会  

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  • 骨盤腹腔鏡手術の若手教育 地方における腹腔鏡手術の教育、普及をいかに行うか? 腹腔鏡に関連した地域全体での「メンター制度」の有効性

    磯部 真倫, 石黒 竜也, 安達 聡介, 吉原 弘祐, 西野 幸治, 西川 伸道, 関根 正幸, 榎本 隆之

    日本産科婦人科内視鏡学会雑誌32 ( Suppl.I ) 118 - 118   2016年8月

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    記述言語:日本語   出版者・発行元:(一社)日本産科婦人科内視鏡学会  

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  • 腹腔鏡下卵巣腫瘍摘出術 術後血腫感染に対して腹腔鏡下ドレナージを施行した1例

    杉野 健太郎, 磯部 真倫, 工藤 梨沙, 島 英里, 石黒 竜也, 安達 聡介, 吉原 弘祐, 西野 幸治, 西川 伸道, 関根 正幸, 榎本 隆之

    新潟産科婦人科学会会誌111 ( 1 ) 48 - 48   2016年7月

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    記述言語:日本語   出版者・発行元:新潟産科婦人科学会  

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  • Identification of novel kinase fusion transcripts in endometrial cancer

    Ryo Tamura, Kosuke Yoshihara, Kazuaki Suda, Kaoru Yamawaki, Tatsuya Ishiguro, Sosuke Adachi, Takayuki Enomoto

    CANCER RESEARCH76   2016年7月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2016-1504

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  • Ovarian cancer specific therapeutic vulnerability

    Kosuke Yoshihara, Ryo Tamura, Kazuaki Suda, Tatsuya Ishiguro, Takayuki Enomoto

    CANCER RESEARCH76   2016年7月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2016-99

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  • 新潟大学と関連病院における腹腔鏡手術教育の現況(その2) 関連病院全体での安全な手術の普及を目指して

    磯部 真倫, 杉野 健太郎, 山口 真奈子, 島 英里, 石黒 竜也, 安達 聡介, 吉原 弘祐, 西野 幸治, 西川 伸道, 関根 正幸, 榎本 隆之

    新潟産科婦人科学会会誌111 ( 1 ) 37 - 37   2016年7月

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    記述言語:日本語   出版者・発行元:新潟産科婦人科学会  

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  • 婦人科悪性腫瘍手術の周術期予防的抗菌薬投与について

    西川 伸道, 工藤 梨沙, 茅原 誠, 石黒 竜也, 安達 聡介, 吉原 弘祐, 磯部 真倫, 西野 幸治, 関根 正幸, 榎本 隆之

    新潟産科婦人科学会会誌111 ( 1 ) 26 - 28   2016年7月

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    記述言語:日本語   出版者・発行元:新潟産科婦人科学会  

    婦人科悪性腫瘍手術の周術期予防的抗菌薬投与について検討した。開腹による悪性腫瘍根治術を施行し、術後の抗生剤を使用せず周術期のみセファゾリン(CEZ)を使用した140例を対象とした。手術部位感染(SSI)を発症した感染例6例、非感染例134例であった。6例でSSIを認めたが、6時間以上の手術20例では3例でSSIを発症した。術後1日目のCRP値は、感染群で高値の傾向があった。発症率は、腸管切除施行83%、施行していない32%であったが、有意差を認めなかった。抗菌剤投与が適正に行われていた60例中1例、適正投与されなかった44例中3例でSSIを発症していたが、有意差は認めなかった。腸管切除を施行した12例のうち8例に3時間毎の適正な抗菌剤投与が施行された。

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  • 当科における腹腔鏡下準広汎子宮全摘術の工夫

    磯部 真倫, 安達 聡介, 吉原 弘祐, 西野 幸治, 西川 伸道, 関根 正幸, 榎本 隆之

    新潟産科婦人科学会会誌111 ( 1 ) 51 - 51   2016年7月

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    記述言語:日本語   出版者・発行元:新潟産科婦人科学会  

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  • 当科の過去9年間で治療した子宮頸癌I・II期の治療成績について

    西川 伸道, 吉原 弘祐, 島 英里, 工藤 梨沙, 茅原 誠, 石黒 竜也, 安達 聡介, 磯部 真倫, 西野 幸治, 関根 正幸, 榎本 隆之

    日本婦人科腫瘍学会雑誌34 ( 3 ) 435 - 435   2016年6月

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    記述言語:日本語   出版者・発行元:(公社)日本婦人科腫瘍学会  

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  • 腹腔鏡下に摘出した卵巣Sertoli-Leydig cell tumorの2症例

    磯部 真倫, 山口 真奈子, 茅原 誠, 石黒 竜也, 安達 聡介, 吉原 弘祐, 西野 幸治, 西川 伸道, 関根 正幸, 榎本 隆之

    日本婦人科腫瘍学会雑誌34 ( 3 ) 517 - 517   2016年6月

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    記述言語:日本語   出版者・発行元:(公社)日本婦人科腫瘍学会  

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  • 卵巣成熟奇形腫内の呼吸上皮の腸上皮化生から発生した粘液性癌の一例

    工藤 梨沙, 吉原 弘祐, 西野 幸治, 谷地田 希, 島 英里, 茅原 誠, 石黒 竜也, 安達 聡介, 磯部 真倫, 西川 伸道, 関根 正幸, 榎本 隆之

    日本婦人科腫瘍学会雑誌34 ( 3 ) 526 - 526   2016年6月

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    記述言語:日本語   出版者・発行元:(公社)日本婦人科腫瘍学会  

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  • 肝細胞癌あるいは肝様癌との鑑別に苦慮した再発を繰り返す卵巣未分化癌の一例

    市川 希, 石黒 竜也, 西野 幸治, 工藤 梨沙, 島 英里, 茅原 誠, 安達 聡介, 吉原 弘祐, 磯部 真倫, 西川 伸道, 関根 正幸, 榎本 隆之

    日本婦人科腫瘍学会雑誌34 ( 3 ) 525 - 525   2016年6月

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    記述言語:日本語   出版者・発行元:(公社)日本婦人科腫瘍学会  

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  • 当院における卵巣癌に対するベバシズマブの使用状況 著効例の提示と今後の課題を踏まえて

    西野 幸治, 谷地田 希, 工藤 梨沙, 茅原 誠, 石黒 竜也, 安達 聡介, 吉原 弘祐, 磯部 真倫, 西川 伸道, 関根 正幸, 榎本 隆之

    日本婦人科腫瘍学会雑誌34 ( 3 ) 441 - 441   2016年6月

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    記述言語:日本語   出版者・発行元:(公社)日本婦人科腫瘍学会  

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  • 新潟大学における腹腔鏡手術教育の現況(その2) 関連病院全体での安全な腹腔鏡手術の普及を目指して

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  • SOCS-1 inhibits proliferation of ovarian cancer cell lines by regulating JAK/STAT3 pathway and p53

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  • 当院における腹腔鏡下子宮体癌手術の成績 開腹手術との比較検討

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  • Effect of Adverse Media Reports and Abeyance of Governmental Recommendation of Human Papillomavirus Vaccine in Japan

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  • 卵巣がん high-grade漿液性腺癌/HBOC 卵巣および子宮体部のhigh-grade serous carcinomaの類似性の証明

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  • NW-3-3 卵巣明細胞腺癌に対する術後初回化学療法としてのパクリタキセル・カルボプラチン(TC)療法とイリノテカン・シスプラチン(CPT-P)療法のランダム化第III相比較試験 : GCIG/JGOG2017試験(ミニワークショップ3 卵巣がん3 明細胞腺癌,一般演題,公益社団法人日本産科婦人科学会第67回学術講演会)

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  • ABDOMINAL RADICAL TRACHELECTOMY DURING PREGNANCY FOR EARLY STAGE CERVICAL CANCER

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  • A PROTEOMIC ANALYSIS DEMONSTRATES SIMILAR EXPRESSION PATTERN BETWEEN OVARIAN AND ENDOMETRIAL HIGH-GRADE SEROUS CARCINOMA BEYOND AN ORGAN

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  • 【産婦人科における漢方の理論と実践】 不妊症・不育症に対する漢方

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  • Human ovarian cancer stem cells: In vitro cultivation and characterization

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  • 卵巣がんの早期発見が可能であったBRCA1キャリアの一例

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  • Randomized phase III trial of paclitaxel/carboplatin (PC) versus cisplatin/irinotecan (CPT-P) as first-line chemotherapy in patients with clear cell carcinoma (CCC) of the ovary: A Japanese Gynecologic Oncology Group (JGOG)/GCIG study.

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  • Mesenchymal stem or stromal cells: a review of clinical applications and manufacturing practices

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Mesenchymal stem cells (MSCs) have recently generated great interest in the fields of regenerative medicine and immunotherapy due to their unique biologic properties. In this review we attempt to provide an overview of the current clinical status of MSC therapy, primarily focusing on immunomodulatory and regenerative or tissue repair applications of MSCs. In addition, current manufacturing is reviewed with attention to variation in practices (e.g., starting material, approach to culture and product testing). There is considerable variation among the 218 clinical trials assessed here; variations include proposed mechanisms of action, optimal dosing strategy, and route of administration. To ensure the greatest likelihood of success in clinical trials as the field progresses, attention must be given to the optimization of MSC culture.

    DOI: 10.1111/trf.12421

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  • A CASE REPORT OF PLACENTA PREVIA PERCRETA WITH MASSIVE HEMORRHAGE IN EARLY PREGNANCY

    Masayuki Yamaguchi, Kunihiko Yoshida, Kazufumi Haino, Koichi Takakuwa, Takayuki Enomoto

    PLACENTA34 ( 10 ) A14 - A14   2013年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO LTD  

    DOI: 10.1016/j.placenta.2013.07.053

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  • Conization using the Shimodaira-Taniguchi procedure for adenocarcinoma in situ of the uterine cervix Response

    KosukeHiramatsu, Yutaka Ueda, Kiyoshi Yoshino, Masami Fujita, Eiichi Morii, Takayuki Enomoto, Tadashi Kimura

    EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY170 ( 1 ) 297 - 297   2013年9月

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    記述言語:英語   掲載種別:速報,短報,研究ノート等(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    DOI: 10.1016/j.ejogrb.2013.07.001

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  • X連鎖性遺伝性水頭症の出生前診断

    芹川 武大, 遠山 潤, 田澤 立之, 西山 健一, 後藤 清恵, 栗山 洋子, 生野 寿史, 金村 米博, 山崎 麻美, 中田 光, 高桑 好一, 榎本 隆之

    日本遺伝カウンセリング学会誌34 ( 2 ) 46 - 46   2013年5月

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    記述言語:日本語   出版者・発行元:日本遺伝カウンセリング学会  

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  • Annexin A4-conferred platinum resistance is mediated by the copper transporter ATP7A

    Shinya Matsuzaki, Akiko Morimoto, Satoshi Serada, Takuhei Yokoyama, Toshihiro Kimura, Eiji Kobayashi, Yutaka Ueda, Kiyoshi Yoshino, Masami Fujita, Takayuki Enomoto, Tetsuji Naka, Tadashi Kimura

    CANCER RESEARCH73 ( 8 )   2013年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

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  • THE PROGNOSTIC SIGNIFICANCE OF MULTIPLE PELVIC NODE METASTASES IN CERVICAL CANCER PATIENTS TREATED WITH RADICAL HYSTERECTOMY PLUS ADJUVANT CHEMORADIOTHERAPY

    M. Okazawa, S. Mabuchi, E. Daimon, T. Iwamiya, T. Miyatake, Y. Ohta, K. Yoshino, M. Fujita, T. Enomoto, S. Kamiura, T. Kimura

    ANNALS OF ONCOLOGY23   126 - 126   2012年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:OXFORD UNIV PRESS  

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  • 治療抵抗性婦人科悪性腫瘍におけるWT1ペプチドワクチン第II相臨床試験(Phase II trial of WT1 peptide vaccine to gynecologic malignancies which are resistant to conventional therapies)

    森本 晶子, 上田 豊, 宮武 崇, 榎本 隆之, 岡 芳弘, 西田 純幸, 坪井 昭博, 白方 俊章, 尾路 祐介, 森田 智視, 坂本 純一, 杉山 治夫, 木村 正

    日本癌学会総会記事71回   145 - 145   2012年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • Establishment of cancer-tissue originated spheroids (CTOSs) and chemo-sensitivity test for endometrial cancer

    Toshihiro Kimura, Kiyoshi Yoshino, Kosuke Hiramatsu, Yumiko Kiyohara, Akiko Morimoto, Takuhei Yokoyama, Eiji Kobayashi, Yutaka Ueda, Masami Fujita, Masahiro Inoue, Takayuki Enomoto, Tadashi Kimura

    CANCER RESEARCH72   2012年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2012-4257

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  • Annexin A4 induces chemoresistance for multiple drugs in ovarian clear cell carcinoma

    Akiko Morimoto, Takayuki Enomoto, Satoshi Serada, Shinya Matsuzaki, Takuhei Yokoyama, Toshihiro Kimura, Yutaka Ueda, Kiyoshi Yoshino, Masami Fujita, Minoru Fujimoto, Tadashi Kimura, Tetsuji Naka

    CANCER RESEARCH72   2012年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2012-4225

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  • Lymphovascular space invasion and risk of lymph node metastasis in epithelial ovarian cancer

    K. Matsuo, T. Sheridan, T. Miyake, K. Yoshino, K. Hew, T. Enomoto, D. Im, N. Rosenshein, A. Sood, L. Roman

    GYNECOLOGIC ONCOLOGY125   S88 - S89   2012年3月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    DOI: 10.1016/j.ygyno.2011.12.214

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  • 治療抵抗性婦人科悪性腫瘍に対するWT1ペプチドワクチン第II相臨床試験

    森本 晶子, 榎本 隆之, 上田 豊, 宮武 崇, 吉野 潔, 藤田 征巳, 筒井 建紀, 白方 俊章, 西田 純幸, 岡 芳弘, 杉山 治夫, 木村 正

    日本産科婦人科学会雑誌64 ( 2 ) 453 - 453   2012年2月

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    記述言語:日本語   出版者・発行元:(公社)日本産科婦人科学会  

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  • Therapeutic strategies in epithelial ovarian cancer

    Ayako Kim, Yutaka Ueda, Tetsuji Naka, Takayuki Enomoto

    JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH31   2012年2月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:BIOMED CENTRAL LTD  

    Ovarian cancer is the most lethal gynecologic malignancy. It appears that the vast majority of what seem to be primary epithelial ovarian and primary peritoneal carcinomas is, in fact, secondary from the fimbria, the most distal part of the fallopian tube.
    Treatment of epithelial ovarian cancer is based on the combination of cytoreductive surgery and combination chemotherapy using taxane and platinum. Although clear cell type is categorized in indolent type, it is known to show relatively strong resistance to carboplatin and paclitaxel regimen and thus poor prognosis compared to serous adenocarcinoma, especially in advanced stages. Irinotecan plus cisplatin therapy may effective for the clear cell adenocarcinoma.
    The larger expectation for improved prognosis in ovarian carcinoma is related to the use of the new biological agents. One of the most investigated and promising molecular targeted drugs in ovarian cancer is bevacizumab, a monoclonal antibody directed against VEGF. PARP inhibitor is another one. A few recent studies demonstrated positive results of bevacizumab on progression-free survival in ovarian cancer patients, however, investigation of molecular targeting drugs in patients with ovarian cancer are still underway.

    DOI: 10.1186/1756-9966-31-14

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  • P1-11-9 治療抵抗性婦人科悪性腫瘍に対するWTIペプチドワクチン第II相臨床試験(Group11 婦人科腫瘍全般・症例3,一般演題,第64回日本産科婦人科学会学術講演会)

    森本 晶子, 榎本 隆之, 上田 豊, 宮武 崇, 吉野 潔, 藤田 征巳, 筒井 建紀, 白方 俊章, 西田 純幸, 岡 芳弘, 杉山 治夫, 木村 正

    日本産科婦人科學會雜誌64 ( 2 )   2012年

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    記述言語:日本語   出版者・発行元:日本産科婦人科学会  

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  • Quantitative proteomic analysis of cell-surface membrane proteins: Biomarker discovery in endometrial cancer

    Takuhei Yokoyama, Takayuki Enomoto, Satoshi Serada, Shinya Matsuzaki, Toshihiro Kimura, Yutaka Ueda, Masami Fujita, Kiyoshi Yoshino, Ayako Kim, Minoru Fujimoto, Tadashi Kimura, Tetsuji Naka

    CANCER RESEARCH71   2011年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2011-5108

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  • Targeting Src in mucinous ovarian carcinoma

    Koji Matsuo, Masato Nishimura, Rebbeca L. Stone, Kakajan Komurov, Mian M. K. Shahzad, Justin N. Bottsford-Miller, Takayuki Enomoto, Tadashi Kimura, Prahlad T. Ram, Kathleen M. Schmeler, Michael Frumovitz, Gary G. Gallick, Kwong K. Wong, Anil K. Sood

    CANCER RESEARCH71   2011年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2011-5032

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  • 定量的プロテオーム解析による子宮内膜癌抗原蛋白質の探索

    世良 田聡, 横山 拓平, 榎本 隆之, 松崎 慎哉, 森本 晶子, 金 雅子, 藤本 穣, 木村 正, Naka Tetsuji

    日本プロテオーム学会大会要旨集2011 ( 0 ) 170 - 170   2011年

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    記述言語:日本語   出版者・発行元:日本プロテオーム学会(日本ヒトプロテオーム機構)  

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  • Clinical trials of WT1 peptide vaccine to gynecologic malignancies that are resistant to conventional therapies.

    T. Miyatake, T. Enomoto, Y. Oka, S. Nishida, A. Tsuboi, T. Shirakata, S. Morita, J. Sakamoto, H. Sugiyama, T. Kimura

    JOURNAL OF CLINICAL ONCOLOGY28 ( 15 )   2010年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

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  • P2-245 本邦における広汎子宮頸部摘出術の現状 : 多施設アンケート調査結果(Group73 子宮頸部悪性腫瘍9,一般演題,第62回日本産科婦人科学会学術講演会)

    佐藤 慎也, 青木 大輔, 小林 裕明, 安藤 正明, 斎藤 豪, 西村 隆一郎, 永野 忠義, 八重樫 伸生, 榎本 隆之, 紀川 純三

    日本産科婦人科學會雜誌62 ( 2 )   2010年

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    記述言語:日本語   出版者・発行元:日本産科婦人科学会  

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  • 治療抵抗性婦人科癌を対象としたWT1ペプチドワクチン療法の有用性の検討

    宮武 崇, 榎本 隆之, 白方 俊章, 岡 芳弘, 西田 純幸, 尾路 祐介, 保仙 直毅, 坪井 昭博, 上田 豊, 藤田 征巳, 青笹 克之, 森田 智視, 坂本 純一, 杉山 哲夫, 木村 正

    日本癌治療学会誌44 ( 2 ) 415 - 415   2009年9月

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    記述言語:日本語   出版者・発行元:(一社)日本癌治療学会  

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  • Expression of Bcl11b in the developing mouse olfactory system

    Takayuki Enomoto, Ryo Kominami, Junji Hirota

    NEUROSCIENCE RESEARCH61   S106 - S106   2008年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

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  • 当科における若年子宮頸癌の臨床病理学的検討

    金 雅子, 木村 正, 高田 友美, 宇垣 弘美, 藤原 和子, 三宅 貴仁, 宮武 崇, 吉野 潔, 藤田 征巳, 榎本 隆之

    産婦人科の進歩59 ( 2 ) 102 - 104   2007年

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    記述言語:日本語   出版者・発行元:近畿産科婦人科学会  

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  • ネダプラチン毎週投与による放射線化学療法:Phase I /II study

    三宅 貴仁, 倉垣 千恵, 榎本 隆之, 村田 雄二, 中嶌 竜一, 藤原 和子, 岡澤 美佳, 上田 豊, 橋本 奈美子, 武田 卓, 筒井 建紀, 吉野 潔

    産婦人科の進歩58 ( 1 ) 30 - 32   2006年

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    記述言語:日本語   出版者・発行元:近畿産科婦人科学会  

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  • 子宮内膜癌におけるRUNX3の関与(子宮体部悪性腫瘍VII, 第57回日本産科婦人科学会学術講演会)

    吉崎 達郎, 榎本 隆之, 上田 豊, 岡澤 美佳, 中嶌 竜一, 三宅 貴仁, 藤原 和子, 吉野 潔, 村田 雄二

    日本産科婦人科學會雜誌57 ( 2 )   2005年

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    記述言語:日本語   出版者・発行元:日本産科婦人科学会  

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  • Correlation between p14(ARF)/p16(INK4A) expression and HPV infection in uterine cervical cancer

    H Kanao, T Enomoto, Y Ueda, M Fujita, R Nakashima, Y Ueno, T Miyatake, T Yoshizaki, GS Buzard, T Kimura, K Yoshino, Y Murata

    CANCER LETTERS213 ( 1 ) 31 - 37   2004年9月

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    記述言語:英語   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    The CDKN2A locus on human chromosome 9p21 encodes two tumor suppressors, p14(ARF) and p16(INK4A), which enhance the growth-suppressive functions of the retinoblastoma (Rb) and the p53 proteins, respectively. Conversely, the E6 and E7 oncoproteins of the high-risk human papillomaviruses (HPVs) causally associated with carcinogenesis of the uterine cervix contributes to tumor development by inactivating p53 and Rb. Nevertheless, a correlation between expression of P14(ARF)/p16(INK4A) and HPV infection in uterine cervix is less clear. To clarify this, we examined 25 cervical cancers and 11 normal uterine cervixes. HPV was detected in 21 of 25 cervical cancers (84%) and their subtype was determined by PCR-RFLP. Quantitative real-time RT-PCR assays showed overexpression of p14(ARF) mRNA in all 21 HPV-positive cases (100%). p16(INK4A) mRNA was overexpressed in 17 cases of the HPV-positive cases (81%). In four HPV-negative cancers, reduced expression of p14(ARF) mRNA was detected in two cases (50%) and reduced p16(INK4A) mRNA in three cases (75%). Our data indicate that the overexpression of p14(ARF) and p16(INK4A) strongly associates with HPV-positive cervical cancers and that reduced expression of p14(ARF) and p16(INK4A) correlates with HPV-negative cervical cancers. These findings may indicate that impaired P14(ARF) and p16(INK4A) mRNA expression contribute to tumor development in HPV-negative cervical cancers by failure to support p53 and Rb instead of their inactivation by HPV E6 and E7. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.canlet.2004.03.030

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  • Correlation between p14(ARF)/p16(INK4A) expression and HPV infection in uterine cervical cancer

    H Kanao, T Enomoto, Y Ueda, M Fujita, R Nakashima, Y Ueno, T Miyatake, T Yoshizaki, GS Buzard, T Kimura, K Yoshino, Y Murata

    CANCER LETTERS213 ( 1 ) 31 - 37   2004年9月

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    記述言語:英語   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    The CDKN2A locus on human chromosome 9p21 encodes two tumor suppressors, p14(ARF) and p16(INK4A), which enhance the growth-suppressive functions of the retinoblastoma (Rb) and the p53 proteins, respectively. Conversely, the E6 and E7 oncoproteins of the high-risk human papillomaviruses (HPVs) causally associated with carcinogenesis of the uterine cervix contributes to tumor development by inactivating p53 and Rb. Nevertheless, a correlation between expression of P14(ARF)/p16(INK4A) and HPV infection in uterine cervix is less clear. To clarify this, we examined 25 cervical cancers and 11 normal uterine cervixes. HPV was detected in 21 of 25 cervical cancers (84%) and their subtype was determined by PCR-RFLP. Quantitative real-time RT-PCR assays showed overexpression of p14(ARF) mRNA in all 21 HPV-positive cases (100%). p16(INK4A) mRNA was overexpressed in 17 cases of the HPV-positive cases (81%). In four HPV-negative cancers, reduced expression of p14(ARF) mRNA was detected in two cases (50%) and reduced p16(INK4A) mRNA in three cases (75%). Our data indicate that the overexpression of p14(ARF) and p16(INK4A) strongly associates with HPV-positive cervical cancers and that reduced expression of p14(ARF) and p16(INK4A) correlates with HPV-negative cervical cancers. These findings may indicate that impaired P14(ARF) and p16(INK4A) mRNA expression contribute to tumor development in HPV-negative cervical cancers by failure to support p53 and Rb instead of their inactivation by HPV E6 and E7. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.canlet.2004.03.030

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  • Analysis of clonality and HPV infection in benign, hyperplastic, premalignant, and malignant lesions of the Vulvar mucosa

    Y Ueda, T Enomoto, T Miyatake, KR Shroyer, T Yoshizaki, H Kanao, Y Ueno, HB Sun, R Nakashima, K Yoshino, T Kimura, T Haba, K Wakasa, Y Murata

    AMERICAN JOURNAL OF CLINICAL PATHOLOGY122 ( 2 ) 266 - 274   2004年8月

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    記述言語:英語   出版者・発行元:AMER SOC CLINICAL PATHOLOGY  

    To elucidate the pathogenesis of vulvar carcinomas, we studied clonality and human papillomavirus (HPV) infection in vulvar epithelial diseases. Monoclonal composition was demonstrated in all 9 invasive tumors (squamous cell carcinoma [SCC], 6; basal cell carcinoma, 1; malignant melanoma, 2), 15 of 20 cases of vulvar intraepithelial neoplasia (VIN), 7 of 9 cases of Paget disease, 2 of 6 cases of lichen sclerosus (LS), and 2 of 3 cases of squamous cell hyperplasia (SCH); high-risk type HPV was revealed in 5 of 6 SCCs and 17 of 20 VINs. These observations might imply that a subset of cases of LS and SCH result from a neoplastic proliferation, similar to VINs but not related to infection with high-risk type HPV In 1 case of SCC with concurrent VIN 3 in an adjacent lesion, both lesions showed the same pattern of X chromosome inactivation and the presence of HPV-16 in episomal and integrated forms, suggesting that monoclonal expansion triggered by high-risk type HPV integration is an early event for carcinogenesis of HPV-associated SCC.

    DOI: 10.1309/65MKPQT3E2BDM67E

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  • 初回paclitaxel/carboplatin治療後再発した上皮性悪性卵巣腫ように対する化学療法

    榎本 隆之, 脇本 昭憲, 中嶌 竜一, 佐治 文隆, 水谷 隆洋, 西崎 孝道, 亀田 隆, 光田 信明, 長松 正章, 加藤 治子, 東 千尋, 吉野 潔, 伊藤 公彦, 安藝 忠篤, 上浦 祥司, 藤田 征巳, 田坂 慶一, 村田 雄二, 山嵜 正人, 倉垣 千恵, 松崎 昇, 大槻 芳朗, 杉田 長敏, 池上 博雅, 小川 晴幾

    産婦人科の進歩56 ( 3 ) 322 - 324   2004年

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    記述言語:日本語   出版者・発行元:近畿産科婦人科学会  

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  • 当科で経験した子宮肉腫症例

    岡澤 美佳, 上田 豊, 吉野 潔, 中嶌 竜一, 榎本 隆之, 村田 雄二

    産婦人科の進歩56 ( 4 ) 478 - 480   2004年

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    記述言語:日本語   出版者・発行元:近畿産科婦人科学会  

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  • Monoclonal expansion with integration of high-risk type human papillomaviruses is an initial step for cervical carcinogenesis: Association of clonal status and human papillomavirus infection with clinical outcome in cervical intraepithelial neoplasia

    Y Ueda, T Enomoto, T Miyatake, K Ozaki, T Yoshizaki, H Kanao, Y Ueno, R Nakashima, KR Shroyer, Y Murata

    LABORATORY INVESTIGATION83 ( 10 ) 1517 - 1527   2003年10月

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    記述言語:英語   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    To define the natural history of cervical intraepithelial neoplasia (CIN) as related to clonal status, we evaluated 20 cases of CIN1 and 18 cases of CIN2 that had been clinically followed for 7 to 48 months at Osaka University Hospital. These included 10 cases that progressed, 15 cases that persisted, and 13 cases that regressed. We analyzed the clonal status of each case by analysis of the pattern of X-chromosomal inactivation. Human papillomavirus (HPV) infection was detected by PCR-RFLP analysis. CINs that are monoclonal or infected by high-risk HPVs are more likely to progress or persist than cases that are polyclonal or negative for high-risk HPVs (p = 0.009 for monoclonal vs polyclonal, p = 0.024 for high-risk HPV positive vs negative p = 0.024). Eighteen (90%) of 20 monoclonal, high-risk HPV-associated CINs progressed or persisted, whereas 9 (60%) of 15 polyclonal or high-risk HPV-negative CINs regressed. Therefore, the combination of clonality status and high-risk type HPV infection was significantly correlated with clinical outcome (p = 0.003). The physical status of the HPV genome was evaluated in 17 cases of HPV-16 positive CINs by real-time PCR. Of those, the HPV viral genome was present in both episomal and integrated forms in 14 CINs (84%), and 12 of these cases (86%) were monoclonal in composition. By contrast, all three CINs in which the HPV genome was present in episomal form were polyclonal. In one CIN1 that was polyclonal, HPV-16 was originally present in episomal form but after 24 months, the patient developed a monoclonal CIN3 in which the HPV-16 genome was present in mixed form. These results may imply that HPV viral integration into the host genomic DNA is associated with progression from polyclonal to monoclonal status in CIN. These events may play a fundamental role in the progression from low-grade to higher grade dysplasia of the cervical mucosa.

    DOI: 10.1097/01.LAB.0000092234.68751.83

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  • Monoclonal expansion with integration of high-risk type human papillomaviruses is an initial step for cervical carcinogenesis: Association of clonal status and human papillomavirus infection with clinical outcome in cervical intraepithelial neoplasia

    Y Ueda, T Enomoto, T Miyatake, K Ozaki, T Yoshizaki, H Kanao, Y Ueno, R Nakashima, KR Shroyer, Y Murata

    LABORATORY INVESTIGATION83 ( 10 ) 1517 - 1527   2003年10月

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    記述言語:英語   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    To define the natural history of cervical intraepithelial neoplasia (CIN) as related to clonal status, we evaluated 20 cases of CIN1 and 18 cases of CIN2 that had been clinically followed for 7 to 48 months at Osaka University Hospital. These included 10 cases that progressed, 15 cases that persisted, and 13 cases that regressed. We analyzed the clonal status of each case by analysis of the pattern of X-chromosomal inactivation. Human papillomavirus (HPV) infection was detected by PCR-RFLP analysis. CINs that are monoclonal or infected by high-risk HPVs are more likely to progress or persist than cases that are polyclonal or negative for high-risk HPVs (p = 0.009 for monoclonal vs polyclonal, p = 0.024 for high-risk HPV positive vs negative p = 0.024). Eighteen (90%) of 20 monoclonal, high-risk HPV-associated CINs progressed or persisted, whereas 9 (60%) of 15 polyclonal or high-risk HPV-negative CINs regressed. Therefore, the combination of clonality status and high-risk type HPV infection was significantly correlated with clinical outcome (p = 0.003). The physical status of the HPV genome was evaluated in 17 cases of HPV-16 positive CINs by real-time PCR. Of those, the HPV viral genome was present in both episomal and integrated forms in 14 CINs (84%), and 12 of these cases (86%) were monoclonal in composition. By contrast, all three CINs in which the HPV genome was present in episomal form were polyclonal. In one CIN1 that was polyclonal, HPV-16 was originally present in episomal form but after 24 months, the patient developed a monoclonal CIN3 in which the HPV-16 genome was present in mixed form. These results may imply that HPV viral integration into the host genomic DNA is associated with progression from polyclonal to monoclonal status in CIN. These events may play a fundamental role in the progression from low-grade to higher grade dysplasia of the cervical mucosa.

    DOI: 10.1097/01.LAB.0000092234.68751.83

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  • Genetic alterations in ovarian carcinoma: with specific reference to histological subtypes

    M Fujita, T Enomoto, Y Murata

    MOLECULAR AND CELLULAR ENDOCRINOLOGY202 ( 1-2 ) 97 - 99   2003年4月

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    記述言語:英語   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    Multiple genetic changes including activation of proto-oncogenes and inactivation of tumor suppressor gene are involved in the development of human ovarian cancer. We describe such genetic alterations with specific reference to histological subtypes. K-ras activation is specific for mucinous tumors including adenomas. Borderline tumors and carcinomas, suggesting that K-ras activation may be associated with the mucinous differentiation rather than malignant transformation. Inactivation of p53 is detected in 30-40% of ovarian carcinoma. Mutations are more frequently observed in serous carcinomas, but not found in adenomas or rarely found in borderline tumors, suggesting that p53 mutations may be directly involved in malignant transformation. TGFbeta-2 mutations are found in 50% of endometrioid carcinoma, but rarely in other type. Loss of DCC mRNA expression is found in 50% of serous carcinomas but less frequently in other type. Loss of DCC expression is rare in borderline tumors and adenomas, suggesting that inactivation of DCC may be directly involved in malignant transformation. Microsatellite instability (MI) is found in 17% of ovarian carcinomas, and is frequently found in endometrioid carcinomas. Although inactivation of p16 by point mutation or deletion is rare, p16 inactivation by loss of expression is relatively common. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

    DOI: 10.1016/S0303-7207(03)00069-8

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  • Genetic alterations in ovarian carcinoma: with specific reference to histological subtypes

    M Fujita, T Enomoto, Y Murata

    MOLECULAR AND CELLULAR ENDOCRINOLOGY202 ( 1-2 ) 97 - 99   2003年4月

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    記述言語:英語   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    Multiple genetic changes including activation of proto-oncogenes and inactivation of tumor suppressor gene are involved in the development of human ovarian cancer. We describe such genetic alterations with specific reference to histological subtypes. K-ras activation is specific for mucinous tumors including adenomas. Borderline tumors and carcinomas, suggesting that K-ras activation may be associated with the mucinous differentiation rather than malignant transformation. Inactivation of p53 is detected in 30-40% of ovarian carcinoma. Mutations are more frequently observed in serous carcinomas, but not found in adenomas or rarely found in borderline tumors, suggesting that p53 mutations may be directly involved in malignant transformation. TGFbeta-2 mutations are found in 50% of endometrioid carcinoma, but rarely in other type. Loss of DCC mRNA expression is found in 50% of serous carcinomas but less frequently in other type. Loss of DCC expression is rare in borderline tumors and adenomas, suggesting that inactivation of DCC may b