2021/12/04 更新

写真a

ワタナベ サトシ
渡部 聡
WATANABE Satoshi
所属
医歯学総合病院 呼吸器・感染症内科 講師
職名
講師
外部リンク

学位

  • 博士(医学) ( 2004年3月   新潟大学 )

研究分野

  • ライフサイエンス / 腫瘍診断、治療学

経歴(researchmap)

  • 新潟大学 医歯学総合病院 呼吸器・感染症内科

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経歴

  • 新潟大学   医歯学総合病院 呼吸器・感染症内科   講師

    2018年6月 - 現在

  • 新潟大学   医歯学総合病院 呼吸器・感染症内科   助教

    2015年3月 - 2018年5月

  • 新潟大学   医歯学総合病院 生命科学医療センター   特任助教

    2011年4月 - 2015年2月

所属学協会

▶ 全件表示

留学歴

  • クリーブランドクリニック   リサーチフェロー

    2005年10月 - 2008年6月

 

論文

  • The Prognostic Significance of the Continuous Administration of Anti-PD-1 Antibody via Continuation or Rechallenge After the Occurrence of Immune-Related Adverse Events

    Toshiya Fujisaki, Satoshi Watanabe, Takeshi Ota, Kohei Kushiro, Yusuke Sato, Miho Takahashi, Aya Ohtsubo, Satoshi Shoji, Koichiro Nozaki, Kosuke Ichikawa, Satoshi Hokari, Rie Kondo, Takao Miyabayashi, Tetsuya Abe, Satoru Miura, Hiroshi Tanaka, Masaaki Okajima, Masaki Terada, Naoya Matsumoto, Takashi Ishida, Akira Iwashima, Kazuhiro Sato, Hirohisa Yoshizawa, Nobumasa Aoki, Masachika Hayashi, Yasuyoshi Ohshima, Toshiyuki Koya, Toshiaki Kikuchi

    Frontiers in Oncology   11   2021年9月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Frontiers Media SA  

    <sec><title>Objectives</title>Although immune checkpoint inhibitors (ICIs) have been shown to improve overall survival (OS) in advanced non-small-cell lung cancer (NSCLC) patients, ICIs sometimes cause various types of immune-related adverse events (irAEs), which lead to the interruption of ICI treatment. This study aims to evaluate the clinical significance of the continuation of ICIs in NSCLC patients with irAEs and to assess the safety and efficacy of the readministration of ICIs after their discontinuation due to irAEs.

    </sec><sec><title>Methods</title>We retrospectively identified patients with advanced NSCLC who were treated with first- to third-line anti-programmed cell death-1 (PD-1) therapy from January 2016 through October 2017 at multiple institutions belonging to the Niigata Lung Cancer Treatment Group. Progression-free survival (PFS) and OS from the initiation of ICI treatment were analyzed in patients with and without irAEs, with and without ICI interruption, and with and without ICI readministration. A 6-week landmark analysis of PFS and OS was performed to minimize the lead-time bias associated with time-dependent factors.

    </sec><sec><title>Results</title>Of 231 patients who received anti-PD-1 antibodies, 93 patients (40%) developed irAEs. Of 84 eligible patients with irAEs, 32 patients (14%) continued ICIs, and OS was significantly longer in patients who continued ICIs than that in patients who discontinued ICIs [not reached (95% CI: NE-NE) <italic>vs</italic>. not reached (95% CI: 22.4–NE); p = 0.025]. Of 52 patients who discontinued ICIs, 14 patients (6.1%) readministered ICIs, and OS in patients with ICI readministration was significantly longer than that in patients without ICI readministration [not reached (95% CI: NE-NE) <italic>vs</italic>. not reached (95% CI: 8.4–NE); p = 0.031].

    </sec><sec><title>Conclusion</title>The current study demonstrated that both the continuation and readministration of ICIs after irAE occurrence improved OS compared to the permanent interruption of ICIs in NSCLC patients with ICI-related irAEs.

    </sec>

    DOI: 10.3389/fonc.2021.704475

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  • Bevacizumab plus erlotinib versus erlotinib alone in Japanese patients with advanced, metastatic, EGFR-mutant non-small-cell lung cancer (NEJ026): overall survival analysis of an open-label, randomised, multicentre, phase 3 trial. 国際誌

    Yosuke Kawashima, Tatsuro Fukuhara, Haruhiro Saito, Naoki Furuya, Kana Watanabe, Shunichi Sugawara, Shunichiro Iwasawa, Yoshio Tsunezuka, Ou Yamaguchi, Morihito Okada, Kozo Yoshimori, Ichiro Nakachi, Masahiro Seike, Koichi Azuma, Futoshi Kurimoto, Yukari Tsubata, Yuka Fujita, Hiromi Nagashima, Gyo Asai, Satoshi Watanabe, Masaki Miyazaki, Koichi Hagiwara, Toshihiro Nukiwa, Satoshi Morita, Kunihiko Kobayashi, Makoto Maemondo

    The Lancet. Respiratory medicine   2021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)  

    BACKGROUND: Bevacizumab is a promising candidate for combination treatment with epidermal growth factor receptor tyrosine-kinase inhibitors (eg, erlotinib), which could improve outcomes for patients with metastatic EGFR-mutant non-small-cell lung cancer (NSCLC). We have previously shown in NEJ026, a phase 3 trial, that the combination of bevacizumab plus erlotinib significantly prolonged progression-free survival compared with erlotinib alone in these patients. In further analyses, we aimed to examine the effects of bevacizumab-erlotinib on overall survival, time from enrolment to progressive disease during second-line treatment or death, and quality of life. METHODS: This open-label, randomised, multicentre, phase 3 trial (NEJ026) was done in 69 hospitals and medical, community-based centres across Japan. Eligible patients had stage IIIB, stage IV, or postoperative recurrent, EGFR-mutant (exon 19 deletion or exon 21 Leu858Arg point mutation) NSCLC, had not previously received systemic chemotherapy, and were randomly assigned (1:1) by a computer-generated randomisation sequence and minimisation to receive either 150 mg oral erlotinib once daily plus 15 mg/kg intravenous bevacizumab once every 21 days, or 150 mg oral erlotinib once daily, until disease progression or intolerable toxicity. Randomisation was stratified according to sex, smoking status, EGFR mutation subtype, and clinical disease stage. All participants, investigators, and study personnel (including those assessing outcomes) were unmasked to treatment allocation. We report the secondary outcomes of overall survival and quality of life (the period from enrolment to confirmation of a minimally important difference on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30), and the exploratory outcome of time from enrolment to progressive disease during second-line treatment or death. Overall survival and the exploratory outcome were analysed in the modified intention-to-treat population, which comprised all randomly assigned patients who received at least one dose of the study drug and had response evaluations. Quality of life was analysed in patients in the modified intention-to-treat population who had completed the quality of life questionnaires. The trial is registered with the University Hospital Medical Information Network Clinical Trials Registry, UMIN000017069, and the Japan Registry of Clinical Trials, jRCTs031180056, and is currently closed. FINDINGS: Between June 3, 2015, and Aug 31, 2016, 228 patients were enrolled. 112 patients who received bevacizumab-erlotinib and 112 who received erlotinib only were included in the modified intention-to-treat population. At data cutoff (Nov 30, 2019) and a median follow-up of 39·2 months (IQR 23·9-43·5), the median overall survival was 50·7 months (95% CI 37·3-not estimable [NE]) in the bevacizumab-erlotinib group and 46·2 months (38·2-NE) in the erlotinib-only group (hazard ratio [HR] 1·007, 95% CI 0·681-1·490; p=0·97). In analysis of the exploratory outcome, after a median follow-up of 23·9 months (IQR 14·2-39·1), the median time from enrolment to progressive disease during second-line treatment or death was 28·6 months (95% CI 22·1-35·9) in the bevacizumab-erlotinib group and 24·3 months (20·4-29·1) in the erlotinib-only group (HR 0·773, 95% CI 0·562-1·065). The median time between enrolment and confirmation of a minimally important difference on the EORTC QLQ-C30 was 6·0 months (95% CI 5·2-11·3) in the bevacizumab-erlotinib group and 8·3 months (5·7-13·9) in the erlotinib-only group (p=0·47). INTERPRETATION: The addition of bevacizumab to erlotinib did not prolong survival in patients with metastatic EGFR-mutant NSCLC, but both treatment groups had relatively long survival durations. Why the addition of bevacizumab to erlotinib did not affect overall survival is unclear, but it is possible that the beneficial effects of combination therapy were not seen because overall survival was influenced by treatment regimens used after disease progression. FUNDING: Chugai Pharmaceutical.

    DOI: 10.1016/S2213-2600(21)00166-1

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  • Impact of tumor programmed death ligand-1 expression on osimertinib efficacy in untreated EGFR-mutated advanced non-small cell lung cancer: a prospective observational study

    Akihiro Yoshimura, Tadaaki Yamada, Yusuke Okuma, Akito Fukuda, Satoshi Watanabe, Naoya Nishioka, Takayuki Takeda, Yusuke Chihara, Shinnosuke Takemoto, Taishi Harada, Osamu Hiranuma, Yukina Shirai, Akihiro Nishiyama, Seiji Yano, Yasuhiro Goto, Shinsuke Shiotsu, Kei Kunimasa, Yoshie Morimoto, Masahiro Iwasaku, Yoshiko Kaneko, Junji Uchino, Hirotsugu Kenmotsu, Toshiaki Takahashi, Koichi Takayama

    TRANSLATIONAL LUNG CANCER RESEARCH   2021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:AME PUBL CO  

    Background: Osimertinib monotherapy is currently the standard of care as a first-line treatment for patients harboring epidermal growth factor receptor (EGFR) mutations; however, some EGFR-mutated non-small cell lung cancer (NSCLC) patients exhibit primary resistance and an insufficient response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Elevated programmed death-ligand 1 (PD-L1) expression in tumors was reported as a negative predictive factor for outcomes of first-or second-generation EGFR-TKIs. Methods: We prospectively assessed advanced NSCLC patients with EGFR mutations who were treated with osimertinib at 14 institutions in Japan between September 2019 and December 2020. Relationships between outcomes of osimertinib monotherapy and patients' characteristics were reviewed. Results: Seventy-one patients who underwent the tumor PD-L1 test were enrolled. Multivariate analysis identified tumor PD-L1 expression as an independent predictor for progression-free survival (PFS) with osimertinib treatment (P=0.029). The objective-response and disease-control rates for osimertinib treatment were significantly lower in patients demonstrating elevated PD-L1 levels relative to those with low or negative PD-L1 level (P=0.043 and P=0.007, respectively). Furthermore, among patients treated with osimertinib, those with high PD-L1 levels exhibited shorter PFS relative to those with low plus negative PD L1 level (median PFS: 5.0 vs. 17.4 months; P<0.001). Conclusions: Elevated tumor PD-L1 expression is associated with poor outcomes of osimertinib monotherapy in previously untreated advanced NSCLC patients with EGFR mutation. Further clinical trials are warranted to accumulate evidence demonstrating the effectiveness of combination therapy with osimertinib for EGFR-mutated advanced NSCLC patients with elevated tumor PD-L1 expression. Trial Registration: UMIN000043942.

    DOI: 10.21037/tlcr-21-461

    Web of Science

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  • Bevacizumab plus platinum-based chemotherapy in advanced non-squamous non-small-cell lung cancer: a randomized, open-label phase 2 study (CLEAR). 国際誌

    Hibiki Udagawa, Eri Sugiyama, Toshiyuki Harada, Shinji Atagi, Ryo Koyama, Satoshi Watanabe, Yukiko Nakamura, Daijiro Harada, Osamu Hataji, Fumihiro Tanaka, Hiroshi Kida, Miyako Satouchi, Ken Maeno, Akira Inoue, Kiyotaka Yoh, Yuki Yamane, Yoshiko Urata, Hiroshige Yoshioka, Takeharu Yamanaka, Koichi Goto

    Translational lung cancer research   10 ( 7 )   3059 - 3070   2021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: Atezolizumab combined with bevacizumab plus platinum-based chemotherapy is a standard treatment for advanced non-squamous non-small-cell lung cancer (nsNSCLC). We aimed to determine the most effective platinum-based combination, such that future studies with atezolizumab can be conducted to further improve patient outcomes. Methods: This phase 2 study enrolled treatment-naïve patients with advanced or recurrent nsNSCLC who were randomly assigned to either cisplatin (75 mg/m2) + pemetrexed (500 mg/m2) + bevacizumab (15 mg/kg) (CisPemBev) followed by maintenance PemBev (N=132) or carboplatin (area under the concentration-time curve of 6 mg/mL/min) + paclitaxel (200 mg/m2) + bevacizumab (15 mg/kg) (CarPacBev) followed by maintenance Bev (N=67). The primary endpoint was progression-free survival (PFS, by central review). Secondary endpoints included overall survival (OS) and overall response rate (ORR). Adverse events (AEs) were evaluated for safety. This study was designed with the point estimate of the hazard ratio (HR) for PFS calculated based on an expected HR <0.830 with a probability ≥80%. Results: The HR for PFS (CisPemBev/CarPacBev) was 0.825 [95% confidence interval (CI), 0.600-1.134, median PFS, 7.6 vs. 7.0 months]. Because the observed point estimate of the HR for PFS was <0.830, the primary endpoint was met, and CisPem doublet therapy was deemed to be more effective than CarPac in terms of PFS. Median OS was 23.4 months for CisPemBev and 21.6 months for CarPacBev (HR 0.845; 95% CI, 0.583-1.242). The ORR was 57% for CisPemBev and 55% for CarPacBev. Both CisPemBev and CarPacBev were well tolerated; grade ≥3 AEs were reported in 67% and 82% of patients, respectively. Conclusions: CisPem combined with Bev was more effective in improving PFS compared with CarPacBev in patients with advanced nsNSCLC. CisPemBev was also well tolerated by this patient population. A study to evaluate the efficacy of atezolizumab plus CisPemBev is warranted. Trial Registration: University hospital Medical Information Network Clinical Trial Registry (ID: UMIN000013354).

    DOI: 10.21037/tlcr-21-240

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  • Subsequent systemic therapy for non-small cell lung cancer patients with immune checkpoint inhibitor-related interstitial lung disease. 国際誌

    Yusuke Sato, Satoshi Watanabe, Takeshi Ota, Kohei Kushiro, Toshiya Fujisaki, Miho Takahashi, Aya Ohtsubo, Satoshi Shoji, Koichiro Nozaki, Kosuke Ichikawa, Satoshi Hokari, Rie Kondo, Masachika Hayashi, Hiroyuki Ishikawa, Takao Miyabayashi, Tetsuya Abe, Satoru Miura, Hiroshi Tanaka, Masaaki Okajima, Masaki Terada, Takashi Ishida, Akira Iwashima, Kazuhiro Sato, Hirohisa Yoshizawa, Nobumasa Aoki, Yasuyoshi Ohshima, Toshiyuki Koya, Toshiaki Kikuchi

    Translational lung cancer research   10 ( 7 )   3132 - 3143   2021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: Although immune checkpoint inhibitors (ICIs) are effective for advanced non-small cell lung cancer (NSCLC), ICIs may cause interstitial lung disease (ILD), which results in treatment discontinuation and is sometimes fatal. Despite the high incidence of ICI-related ILD, there are few cancer treatment options for patients. This study aimed to evaluate the safety and efficacy of subsequent systemic cancer therapy in NSCLC patients with ICI-related ILD. Methods: We retrospectively assessed NSCLC patients who received programmed cell death-1 (PD-1) inhibitors as first- to third-line therapy at participating institutions of the Niigata Lung Cancer Treatment Group from January 2016 to October 2017. Results: This analysis included 231 patients, 32 (14%) of whom developed ICI-related ILD. Of these patients, 16 (7%) received subsequent systemic cancer treatments. The median overall survival (OS) tended to be longer in the systemic cancer therapy group than in the no systemic cancer therapy group [22.2 months (95% CI: 1-NE) vs. 4.5 months (95% CI: 1-NE); P=0.067]. ICI-related ILD recurred in half of the patients who received systemic cancer therapy, and the median OS tended to be shorter in patients with recurrent ICI-related ILD [22.0 months (95% CI: 1-NE) vs. 7.0 months (95% CI: 1-NE); P=0.3154]. Conclusions: According to the current study, systemic cancer treatment is effective in patients with ICI-related ILD; however, its safety is uncertain because of the high risk of ICI-related ILD recurrence and poor survival outcome following ILD recurrence.

    DOI: 10.21037/tlcr-21-198

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  • Association of hepatitis B virus infection status with outcomes of non-small cell lung cancer patients undergoing anti-PD-1/PD-L1 therapy. 国際誌

    Xuanye Zhang, Dan Tian, Yue Chen, Chen Chen, Li-Na He, Yixin Zhou, Haifeng Li, Zuan Lin, Tao Chen, Yuhong Wang, Alessandro Russo, Ernest Nadal, Francesco Passiglia, Ross Andrew Soo, Satoshi Watanabe, Teresa Moran, In-Jae Oh, Sha Fu, Shaodong Hong, Li Zhang

    Translational lung cancer research   10 ( 7 )   3191 - 3202   2021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 aim of this study was to evaluate the safety and survival outcomes of anti-programmed cell death (PD)-1/programmed cell death-ligand 1 (PD-L1) monotherapy in patients with advanced non-small cell lung cancer (NSCLC) and different hepatitis B virus (HBV) infection status. Methods: Patients with advanced NSCLC and both chronic and/or resolved HBV infection who were treated with anti-PD-(L)1 monotherapy were retrospectively enrolled. The primary endpoint was the safety of PD-1/PD-L1 monotherapy, while the secondary endpoints included the survival outcomes. Results: Of the 62 eligible patients, 10 (16.1%) were hepatitis B surface antigen (HBsAg) positive [chronic hepatitis B (CHB) infection] and 52 (83.9%) were HBsAg negative and HBcAb positive [resolved hepatitis B (RHB) infection]; 42 (67.7%) patients had at least 1 treatment-related adverse event (AE), with 4 patients (6.5%) developing grade 3 AEs and 6 (9.7%) developing hepatic AEs. One CHB patient experienced HBV reactivation during anti-PD-1 immunotherapy due to the interruption of antiviral prophylaxis. The objective response rate and durable clinical benefit (DCB) rate were 17.7% and 29.0%, respectively. Median overall survival (OS) and progression-free survival (PFS) were 23.6 months [95% confidence interval (CI): 14.4-32.8] and 2.1 months (95% CI: 1.2-3.0), respectively. The DCB rate was significantly higher in the CHB group than in the RHB group (60% vs. 23.1%; P=0.048). Patients with CHB experienced a longer PFS (8.3 vs. 2.0 months; P=0.103) and OS (35.0 vs. 18.2 months, P=0.119) than did RHB patients. Conclusions: Anti-PD-(L)1 monotherapy was safe and effective in patients with NSCLC and HBV infection. This population should not be excluded from receiving immunotherapy in routine clinical practice or within clinical trials if HBV biomarkers are monitored and antiviral prophylaxis is properly used.

    DOI: 10.21037/tlcr-21-455

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  • International consensus on severe lung cancer-the first edition. 国際誌

    Chengzhi Zhou, Shiyue Li, Jun Liu, Qian Chu, Liyun Miao, Linbo Cai, Xiuyu Cai, Yu Chen, Fei Cui, Yuchao Dong, Wen Dong, Wenfeng Fang, Yong He, Weifeng Li, Min Li, Wenhua Liang, Gen Lin, Jie Lin, Xinqing Lin, Hongbing Liu, Ming Liu, Xinlin Mu, Yi Hu, Jie Hu, Yang Jin, Ziming Li, Yinyin Qin, Shengxiang Ren, Gengyun Sun, Yihong Shen, Chunxia Su, Kejing Tang, Lin Wu, Mengzhao Wang, Huijuan Wang, Kai Wang, Yuehong Wang, Ping Wang, Hongmei Wang, Qi Wang, Zhijie Wang, Xiaohong Xie, Zhanhong Xie, Xin Xu, Fei Xu, Meng Yang, Boyan Yang, Xiangjun Yi, Xiaoqun Ye, Feng Ye, Zongyang Yu, Dongsheng Yue, Bicheng Zhang, Jian Zhang, Jianqing Zhang, Xiaoju Zhang, Wei Zhang, Wei Zhao, Bo Zhu, Zhengfei Zhu, Wenzhao Zhong, Chunxue Bai, Liangan Chen, Baohui Han, Chengping Hu, Shun Lu, Weimin Li, Yong Song, Jie Wang, Caicun Zhou, Jianying Zhou, Yanbin Zhou, Yuichi Saito, Yoshinobu Ichiki, Hitoshi Igai, Satoshi Watanabe, Sara Bravaccini, Alfonso Fiorelli, Francesco Petrella, Takeo Nakada, Piergiorgio Solli, Nikolaos Tsoukalas, Yuki Kataoka, Taichiro Goto, Rossana Berardi, Jianxing He, Nanshan Zhong

    Translational lung cancer research   10 ( 6 )   2633 - 2666   2021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)  

    DOI: 10.21037/tlcr-21-467

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  • Pembrolizumab plus chemotherapy-induced pneumonitis in chemo-naïve patients with non-squamous non-small cell lung cancer: A multicentre, retrospective cohort study. 国際誌

    Daichi Fujimoto, Satoru Miura, Kenichi Yoshimura, Kazushige Wakuda, Yuko Oya, Toshihide Yokoyama, Takashi Yokoi, Tetsuhiko Asao, Motohiro Tamiya, Atsushi Nakamura, Hiroshige Yoshioka, Koji Haratani, Shunsuke Teraoka, Takaaki Tokito, Shuji Murakami, Akihiro Tamiya, Shoichi Itoh, Hiroshi Yokouchi, Satoshi Watanabe, Ou Yamaguchi, Keisuke Tomii, Nobuyuki Yamamoto

    European journal of cancer (Oxford, England : 1990)   150   63 - 72   2021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)  

    INTRODUCTION: Despite the extensive use of the combination of cytotoxic chemotherapy and programmed cell death protein 1/programmed death-ligand 1 checkpoint inhibitors for cancer treatment, the incidence and characteristics of pneumonitis caused by this combination therapy have not been examined in clinical settings. METHODS: We conducted a 36-centre, retrospective cohort study in patients with chemo-naïve advanced non-squamous non-small cell lung cancer who received a combination of platinum, pemetrexed and pembrolizumab between December 2018 and June 2019. RESULTS: The study comprised 299 patients. The most frequent grade ≥3 non-hematologic adverse event was pneumonitis. There were 37 patients (12.4%, 95% CI 8.9-16.7) with all-grade pneumonitis and 10 (3.3%, 95% CI 1.6-6.1) with grade ≥3 pneumonitis. Of these, 21 (7.0%, 95% CI 4.4-10.5) and 9 patients (3.0%, 95% CI 1.4-5.6) developed all-grade and grade ≥3 pneumonitis within 90 days after initiating the combination therapy, respectively. The median time to treatment failure and progression-free survival was 5.9 (95% CI 5.0-6.8) and 7.5 (95% CI 6.5-8.7) months, respectively. In the survival analysis after adjusting for immortal time bias, pneumonitis was independently associated with shorter progression-free survival (HR 1.99, 95% CI 1.07-3.69, P = 0.03) and overall survival (HR 3.03, 95% CI 1.12-8.20, P = 0.03). CONCLUSIONS: Treatment-related pneumonitis occurred at a higher rate in the real-world population than that reported previously; it led to worse survival outcomes. Pneumonitis requires more attention. Additional studies are required to improve the safety of this combination therapy. TRIAL REGISTRATION NUMBER: UMIN000038084.

    DOI: 10.1016/j.ejca.2021.03.016

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  • Safety and efficacy of anti-PD-1 inhibitors in Chinese patients with advanced lung cancer and hepatitis B virus infection: a retrospective single-center study. 国際誌

    Fei Xu, Zhu Zeng, Bing Yan, Yiqi Fu, Yilan Sun, Guangdie Yang, Lingfang Tu, Satoshi Watanabe, Salma K Jabbour, Sara Bravaccini, Francesca Fanini, Jianying Zhou, Yihong Shen

    Translational lung cancer research   10 ( 4 )   1819 - 1828   2021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)  

    Background: Programmed death protein (ligand) 1 [PD-(L)1] inhibitors have provided new therapeutic options for advanced lung cancer. However, patients with hepatitis B virus (HBV) infection have been traditionally excluded from most registered trials of this form of treatment. Methods: We performed a retrospective analysis of patients with HBV and advanced lung cancer who received anti-PD-1 immunotherapy from September 2018 to May 2020 in our department. Treatment-related hepatotoxicity was evaluated and recorded. Overall response rate and progression free survival were also assessed in the patients using iRECIST. Results: Seventeen patients were evaluated in this analysis. Of these, six (35.3%) experienced hepatic transaminase elevation during immunotherapy. Three of these patients developed Grade 3 hepatic immune-related adverse events and received systemic corticosteroids, following which aminotransferase levels recovered to normal in all patients and no adverse events were observed in subsequent treatment. No patient experienced HBV reactivation or flare. One patient developed active pulmonary tuberculosis (TB). Other adverse events were mild, well tolerated and short term. The objective response rate (ORR) of the cohort was 62.5%, and the median progression-free survival (PFS) was 3 months. Conclusions: Lung cancer patients can be treated safely with anti-PD-1 inhibitors in the context of HBV infection. Close monitoring for hepatotoxicity and prophylactic antiviral therapy is advised. Further studies on the use of anti-PD-1 inhibitors in HBV-infected patients are needed.

    DOI: 10.21037/tlcr-21-79

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  • EGFR遺伝子変異陽性肺がんのEGFR-TKI治療における腫瘍内AXL発現の意義

    解良 恭一, 山田 忠明, 吉村 彰紘, 安宅 信二, 谷口 寛和, 渡部 聡, 三浦 理, 山口 博之, 内野 順治, 高山 浩一, 矢野 聖二

    日本呼吸器学会誌   10 ( 増刊 )   208 - 208   2021年4月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

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  • 当院におけるCPAPアドヒアランスに影響する因子の検討

    倉科 健司, 穂苅 諭, 永井 明日香, 鈴木 涼子, 大嶋 康義, 青木 信将, 林 正周, 渡部 聡, 小屋 俊之, 菊地 利明

    日本呼吸器学会誌   10 ( 増刊 )   298 - 298   2021年4月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

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  • A phase II study of first-line afatinib for patients aged ≥75 years with EGFR mutation-positive advanced non-small cell lung cancer: North East Japan Study Group trial NEJ027. 国際誌

    Yuji Minegishi, Ou Yamaguchi, Shunichi Sugawara, Shoichi Kuyama, Satoshi Watanabe, Kazuhiro Usui, Masahide Mori, Osamu Hataji, Toshihiro Nukiwa, Satoshi Morita, Kunihiko Kobayashi, Akihiko Gemma

    BMC cancer   21 ( 1 )   208 - 208   2021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: Lung cancer is most common among older individuals. However, polypharmacy and comorbidities, which are also more common in older individuals, can limit treatment options. Previous studies suggest that afatinib can be used safely and effectively in elderly patients. This study investigated the anti-tumour activity and safety profile of first-line afatinib in previously-untreated elderly Japanese patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). METHODS: This was a single-arm, open-label, phase II study, performed in multiple centres in Japan. Previously untreated patients, aged ≥75 years, with EGFR mutation-positive (Del19 or L858R) advanced NSCLC were treated with afatinib 40 mg until disease progression or unacceptable toxicity. Adverse events (AEs) were managed with protocol-defined dose adjustments. The primary endpoint was objective response rate (ORR) by central review. RESULTS: In total, 38 patients received at least one dose of afatinib, and 37 were evaluable for response. Median age was 77.5 years (range 75-91), all patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, and 60.5% had Del19-positive disease. Median follow-up was 838 days. ORR was 75.7% (2 complete responses and 26 partial responses). Median progression-free survival was 14.2 months (95% confidence interval [CI], 9.5-19.0). Median overall survival (OS) was 35.2 months (95% CI, 35.2-not reached); the 2-year OS rate was 78.3%. The most common grade 3/4 treatment-related AEs (TRAEs) were diarrhoea (28.9%), paronychia (23.7%), and rash/acne (15.8%). Dose reductions due to TRAEs were reported in 78.9% of patients, and eight (21.1%) patients discontinued afatinib due to TRAEs. No treatment-related deaths were reported. CONCLUSION: Although dose adjustments were relatively common in this small group of Japanese patients aged ≥75 years with EGFR mutation-positive NSCLC, discontinuation occurred much less frequently, and most patients were able to stay on treatment for well over a year. Further, afatinib was associated with high response rates and prolonged PFS and OS. TRIAL REGISTRATION: The trial is registered with Japan Registry of Clinical Trials (JRCT) as trial number 031180136 (date of initial registration: 19 February 2019), and the University Hospital Network (UMIN) as trial number 000017877 (date of initial registration: 11 June 2015).

    DOI: 10.1186/s12885-021-07861-1

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  • Sequential therapy of crizotinib followed by alectinib for non-small cell lung cancer harbouring anaplastic lymphoma kinase rearrangement (WJOG9516L): A multicenter retrospective cohort study. 国際誌

    Kentaro Ito, Takeharu Yamanaka, Hidetoshi Hayashi, Yoshihiro Hattori, Kazumi Nishino, Haruki Kobayashi, Yuko Oya, Toshihide Yokoyama, Takashi Seto, Koichi Azuma, Tomoya Fukui, Toshiyuki Kozuki, Atsushi Nakamura, Kentaro Tanaka, Katsuya Hirano, Takashi Yokoi, Haruko Daga, Shinya Sakata, Daichi Fujimoto, Masahide Mori, Ken Maeno, Takuya Aoki, Atsuhisa Tamura, Satoru Miura, Satoshi Watanabe, Hiroaki Akamatsu, Osamu Hataji, Kensuke Suzuki, Shigeto Hontsu, Koji Azuma, Akihiro Bessho, Akihito Kubo, Motoyasu Okuno, Kazuhiko Nakagawa, Nobuyuki Yamamoto

    European journal of cancer (Oxford, England : 1990)   145   183 - 193   2021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: The data of sequential therapy of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) in clinical practice have been limited. METHODS: We reviewed the clinical data of patients with ALK-rearranged non-small cell lung cancer who received crizotinib (CRZ) or alectinib (ALEC) between May 2012 and December 2016. Patients were divided into two groups based on the first-administered ALK-TKI, the CRZ or ALEC group. The combined time-to-treatment failure (TTF) was defined as the sum of the 'TTF of CRZ' plus the 'TTF of ALEC' if patients were treated with CRZ followed by ALEC in the CRZ group. The primary end-point is the comparison between the combined TTF and the TTF of ALEC in the ALEC group. RESULTS: Of 864 patients enrolled from 61 institutions, 840 patients were analysed. There were 535 of 305 patients in the CRZ/ALEC groups. The combined TTF in the CRZ group was significantly longer than TTF in the ALEC group (median, 34.4 versus 27.2 months; hazard ratio [HR], 0.709; P = 0.0044). However, there was no significant difference in overall survival (OS) between the patients who received ALEC after CRZ in the CRZ group and the patients in the ALEC group (median, 88.4 months versus. not reached; HR, 1.048; P = 0.7770). In the whole population, the CRZ group had a significantly shorter OS than the ALEC group (median, 53.6 months versus not reached; HR, 1.821, P < 0.0001). CONCLUSION: The combined TTF in the CRZ group was significantly longer than the TTF in the ALEC group; however, OS benefit of sequential therapy against ALEC as the first ALK-TKI was not shown.

    DOI: 10.1016/j.ejca.2020.12.026

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  • ジアフェニルスルホンによる薬剤性メトヘモグロビン血症の3例

    穂苅 諭, 渡井 はづき[風間], 南雲 駿, 尾方 英至, 小泉 健, 市川 紘将, 青木 信将, 渡部 聡, 小屋 俊之, 菊地 利明

    日本内科学会雑誌   110 ( 3 )   622 - 626   2021年3月

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    記述言語:日本語   出版者・発行元:(一社)日本内科学会  

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  • Chronic Hypercapnic Respiratory Failure in an Adult Patient with Silver-Russell Syndrome: A Case Report.

    Mariko Hakamata, Satoshi Hokari, Yasuyoshi Ohshima, Masayo Kagami, Sakae Saito, Ikuko N Motoike, Taiki Abe, Nobumasa Aoki, Masachika Hayashi, Satoshi Watanabe, Toshiyuki Koya, Toshiaki Kikuchi

    Internal medicine (Tokyo, Japan)   2021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)  

    A 31-year-old woman who was clinically diagnosed with Silver-Russell syndrome (SRS) in childhood was admitted with complaints of dyspnea. She had hypercapnic respiratory failure accompanied by nocturnal hypoventilation. Computed tomography revealed systemic muscle atrophy and superior mesenteric artery syndrome; however, the bilateral lung fields were normal. She was treated with nocturnal noninvasive positive pressure ventilation and showed improvement of respiratory failure. In this case, loss of methylation on chromosome 11p15 and maternal uniparental disomy of chromosome 7, which are the common causes of SRS, were not detected. This is a rare case of adult SRS manifesting as chronic hypercapnic respiratory failure.

    DOI: 10.2169/internalmedicine.5479-20

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  • 2型呼吸不全と抗ミトコンドリアM2抗体の関係性

    大嶋 康義, 倉科 健司, 穂苅 諭, 永井 明日香, 鈴木 涼子, 青木 信将, 林 正周, 渡部 聡, 小屋 俊之, 菊地 利明

    日本呼吸ケア・リハビリテーション学会誌   30 ( Suppl. )   197s - 197s   2021年2月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸ケア・リハビリテーション学会  

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  • 2型呼吸不全と抗ミトコンドリアM2抗体の関係性

    大嶋 康義, 倉科 健司, 穂苅 諭, 永井 明日香, 鈴木 涼子, 青木 信将, 林 正周, 渡部 聡, 小屋 俊之, 菊地 利明

    日本呼吸ケア・リハビリテーション学会誌   30 ( Suppl. )   197s - 197s   2021年2月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸ケア・リハビリテーション学会  

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  • A case of bronchiolitis obliterans after living-donor renal transplantation. 国際誌

    Masachika Hayashi, Satoshi Hokari, Nobumasa Aoki, Yasuyoshi Ohshima, Satoshi Watanabe, Toshiyuki Koya, Masayuki Tasaki, Kazuhide Saito, Toshiaki Kikuchi

    Respiratory investigation   59 ( 3 )   367 - 371   2021年1月

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    記述言語:英語  

    We herein report the case of a 20 year-old-man who developed bronchiolitis obliterans after living-donor renal transplantation. The patient presented with dyspnea on exertion and wheezing two years after renal transplantation, and spirometry showed an obstructive pattern. Surgical lung biopsy revealed subepithelial fibrosis that constricted and obstructed the intrabronchiolar space. Based on these findings, the patient was diagnosed with bronchiolitis obliterans. He was prescribed bronchodilators and azithromycin, and he achieved stable respiratory function for two years. The differential diagnosis of respiratory symptoms after renal transplantation includes opportunistic infection and drug-induced lung injury; however, bronchiolitis obliterans should also be considered.

    DOI: 10.1016/j.resinv.2020.12.003

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  • IMpower132: Atezolizumab plus platinum-based chemotherapy vs chemotherapy for advanced NSCLC in Japanese patients. 国際誌

    Makoto Nishio, Haruhiro Saito, Koichi Goto, Satoshi Watanabe, Naoko Sueoka-Aragane, Yusuke Okuma, Kazuo Kasahara, Kenichi Chikamori, Yuki Nakagawa, Tomohisa Kawakami

    Cancer science   112 ( 4 )   1534 - 1544   2021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)  

    IMpower132 explored the safety and efficacy of atezolizumab plus pemetrexed and platinum-based chemotherapy as first-line treatment for advanced non-small-cell lung cancer (NSCLC). Key eligibility criteria for the phase 3, open-label, IMpower132 study included age ≥18 y, histologically or cytologically confirmed advanced non-squamous NSCLC per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Eastern Cooperative Oncology Group performance status of 0/1, and no prior systemic treatment for stage IV NSCLC. Patients received atezolizumab (1200 mg) plus pemetrexed (500 mg/m2 ) and cisplatin (75 mg/m2 ) or carboplatin (area under the concentration curve, 6 mg/mL/min) (APP arm) or chemotherapy alone (PP arm). The co-primary study endpoints were overall survival (OS) and investigator-assessed progression-free survival (PFS) per RECIST 1.1 in the intention-to-treat population. A subgroup analysis was conducted in Japanese patients. In the Japanese subgroup (n = 101), median OS was 30.8 (95% CI, 24.3 to not estimable) mo in the APP arm (n = 48) and 22.2 (95% CI, 15.7-30.8) mo in the PP arm (n = 53; hazard ratio [HR], 0.63 [95% CI, 0.36-1.14]). PFS was 12.8 (95% CI, 8.6-16.6) mo in the APP arm vs 4.5 (95% CI, 4.1-6.7) mo in the PP arm (HR, 0.33 [95% CI, 0.21-0.58]). Grade 3/4 treatment-related adverse events (TRAEs) occurred in 68.8% of APP arm patients and 44.2% of PP arm patients. Consistent with global study results, atezolizumab plus pemetrexed and platinum-based chemotherapy improved efficacy and was well tolerated in Japanese patients with advanced NSCLC despite a higher incidence of grade 3/4 TRAEs.

    DOI: 10.1111/cas.14817

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  • Combination therapy of cisplatin with cilastatin enables an increased dose of cisplatin, enhancing its antitumor effect by suppression of nephrotoxicity. 国際誌

    Masashi Arita, Satoshi Watanabe, Nobumasa Aoki, Shoji Kuwahara, Ryo Suzuki, Sawako Goto, Yuko Abe, Miho Takahashi, Miyuki Sato, Satoshi Hokari, Aya Ohtsubo, Satoshi Shoji, Koichiro Nozaki, Kosuke Ichikawa, Rie Kondo, Masachika Hayashi, Yasuyoshi Ohshima, Hideyuki Kabasawa, Michihiro Hosojima, Toshiyuki Koya, Akihiko Saito, Toshiaki Kikuchi

    Scientific reports   11 ( 1 )   750 - 750   2021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)  

    Cisplatin, one of the most active anticancer agents, is widely used in standard chemotherapy for various cancers. Cisplatin is more poorly tolerated than other chemotherapeutic drugs, and the main dose-limiting toxicity of cisplatin is its nephrotoxicity, which is dose-dependent. Although less toxic methods of cisplatin administration have been established, cisplatin-induced nephrotoxicity remains an unsolved problem. Megalin is an endocytic receptor expressed at the apical membrane of proximal tubules. We previously demonstrated that nephrotoxic drugs, including cisplatin, are reabsorbed through megalin and cause proximal tubular cell injury. We further found that cilastatin blocked the binding of cisplatin to megalin in vitro. In this study, we investigated whether cilastatin could reduce cisplatin-induced nephrotoxicity without influencing the antitumor effects of cisplatin. Nephrotoxicity was decreased or absent in mice treated with cisplatin and cilastatin, as determined by kidney injury molecule-1 staining and the blood urea nitrogen content. Combined with cilastatin, a twofold dose of cisplatin was used to successfully treat the mice, which enhanced the antitumor effects of cisplatin but reduced its nephrotoxicity. These findings suggest that we can increase the dose of cisplatin when combined with cilastatin and improve the outcome of cancer patients.

    DOI: 10.1038/s41598-020-80853-6

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  • A prospective phase II study of multimodal prophylactic treatment for afatinib-induced adverse events in advanced non-small cell lung cancer (Niigata Lung Cancer Treatment Group 1401). 国際誌

    Masaaki Okajima, Satoru Miura, Satoshi Watanabe, Hiroshi Tanaka, Kazuhiko Ito, Takashi Ishida, Masato Makino, Akira Iwashima, Naoya Matsumoto, Kazuhiro Sato, Kosuke Ichikawa, Tetsuya Abe, Hirohisa Yoshizawa, Toshiaki Kikuchi

    Translational lung cancer research   10 ( 1 )   252 - 260   2021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: Afatinib has shown clinical benefits in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Many patients treated with afatinib experience skin or gastrointestinal toxicity. However, an effective management strategy has not been established. This prospective study was conducted to evaluate the efficacy of multimodal prophylactic treatment for afatinib-induced toxicity. Methods: This single-arm prospective study was conducted to evaluate the efficacy of multimodal prophylactic treatment for afatinib-induced toxicity in patients with EGFR mutation positive advanced NSCLC who planned to receive a 40 mg dose of afatinib. Eligible patients were treated with oral loperamide (2 mg twice per day), prophylactic minocycline (100 mg once per day), topical medium-class steroids, and gargling with sodium azulene. The primary endpoint was the ability of prophylactic loperamide to prevent severe or intolerable diarrhea during the 4 weeks after the initial administration of afatinib. The incidence, severity and time to occurrence of diarrhea, rash, oral mucositis and paronychia were evaluated based on a daily patient questionnaire. Results: Forty-six patients were enrolled. The primary endpoint analysis was performed in 35 patients as the per-protocol (PP) population. The 4-week successful prophylaxis rate for severe or intolerable diarrhea was 82.9% (90% confidence interval: 70.1-91.9%). In the total population, the incidences of grade 3 or higher rash, oral mucositis and paronychia within 4 weeks were 4%, 2% and 4%, respectively. Conclusions: Prophylactic loperamide administration was not effective in preventing severe or intolerable diarrhea during afatinib treatment. Adequate dose reduction will be a better approach to manage afatinib-induced diarrhea. Multimodal prevention using minocycline, topical steroids and gargling with sodium azulene may be helpful to maintain compliance with afatinib treatment (UMIN000016167).

    DOI: 10.21037/tlcr-20-649

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  • A case of eosinophilic granulomatosis with polyangiitis showing multiple white lichen lesions on the airway mucosa. 国際誌

    Yosuke Kimura, Ryo Ito, Yoshiki Hayashi, Toshihiro Kazawa, Yoshiro Endo, Akira Iwashima, Yasuyoshi Ohshima, Satoshi Watanabe, Toshiyuki Koya, Toshiaki Kikuchi

    Respiratory medicine case reports   33   101451 - 101451   2021年

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    記述言語:英語  

    A 70-year-old man, treated for asthma for 2 years and chronic sinusitis for several months, presented with fever, numbness in the lower limbs, heaviness in the head, gross hematuria, and black stools. He also had eosinophilia, elevated serum IgG4 levels, high levels of myeloperoxidase-anti-neutrophil cytoplasmic antibodies (MPO-ANCA), and pulmonary infiltrative shadows. Bronchoscopy revealed multiple white flattened lesions (white moss) on the airway mucosa, suggesting mycobacterial infection or malignancy. A biopsy from tracheal mucosa revealed airway inflammation with marked eosinophil infiltration. The patient was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA) and treated with steroids, and all findings improved. However, a year and a half after the initiation of treatment, eosinophils and IgE gradually increased; subjective symptoms, such as asthma symptoms and numbness in the lower limbs, worsened; and ANCA, which had been negative, turned positive. Therefore, we suspected disease relapse and anti-IL-5 antibody (mepolizumab) treatment was initiated. Thereafter, ANCA turned negative again, eosinophils and IgE normalized, and subjective symptoms decreased. The presence of airway mucosal lesions in EGPA is relatively rare, and we report this case as a valuable case owing to the interesting bronchoscopic findings that are worth comprehending as a respiratory physician.

    DOI: 10.1016/j.rmcr.2021.101451

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  • Efficacy of the new β-D-glucan measurement kit for diagnosing invasive fungal infections, as compared with that of four conventional kits. 国際誌

    Yuuki Bamba, Kei Nagano, Hiroshi Moro, Hideyuki Ogata, Mariko Hakamata, Satoshi Shibata, Takeshi Koizumi, Nobumasa Aoki, Yasuyoshi Ohshima, Satoshi Watanabe, Takeshi Nakamura, Sugako Kobayashi, Yoshiki Hoshiyama, Toshiyuki Koya, Toshinori Takada, Toshiaki Kikuchi

    PloS one   16 ( 8 )   e0255172   2021年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Each of the currently available (1→3)-β-D-glucan (BDG) measurement kits follows a different measurement method and cut-off value. Comparisons of diagnostic performance for invasive fungal infections (IFIs) are desirable. Additionally, ecological considerations are becoming increasingly important in the development of new measurement kits. METHODS: The plasma BDG levels in clinical samples were measured using the following currently available kits: the Fungitec G test MKII, the Fungitec G test ES, Fungitell, the β-Glucan test Wako, and the newly developed Wako kit (Wako-Eu). Wako-Eu uses a pre-treatment solution that conforms to European regulations for the registration, evaluation, authorisation, and restriction of chemicals. The values obtained for the samples using each kit were studied and compared. RESULTS: Of the 165 patients evaluated, 12 had IFIs, including pneumocystis pneumonia, aspergillosis, and candidiasis. BDG values obtained using the kits were moderately correlated with each other. Clinical diagnoses of the evaluated cases indicated that 21 false positives were diagnosed by at least one kit. The sensitivity of the Fungitell kit was relatively low, but those of the other four were over 90%. The specificity was above 90% for all kits. For positive predictive value, the Wako and the Wako-Eu methods were superior to the others owing to fewer false positive results. CONCLUSIONS: The newly developed Wako-Eu method, which considers ecological concerns, shows diagnostic performance equivalent to that of its predecessor. To improve the diagnostic accuracy of IFIs, it is necessary to interpret the results carefully, giving due consideration to the characteristics of each measurement kit.

    DOI: 10.1371/journal.pone.0255172

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  • Disseminated Varicella-zoster Virus Infection Causing Fatal Pneumonia in an Immunocompromised Patient with Chronic Interstitial Pneumonia: A Case Report.

    Hiroshi Ueno, Masachika Hayashi, Shun Nagumo, Kosuke Ichikawa, Nobumasa Aoki, Yasuyoshi Ohshima, Satoshi Watanabe, Toshiyuki Koya, Tatsuya Abé, Riuko Ohashi, Yoichi Ajioka, Toshiaki Kikuchi

    Internal medicine (Tokyo, Japan)   2020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)  

    Viral pneumonia caused by varicella-zoster virus (VZV) infection is a rare but important complication, especially regarding varicella infections. Although disseminated cutaneous herpes zoster (DCHZ) is often associated with visceral diseases, there have been few reports of DCHZ-related pneumonia. We herein report a rare case of a lethal disseminated VZV infection that caused severe pneumonia in a Japanese patient who had chronic interstitial pneumonia. Physicians should consider the possibility of VZV-related pneumonia, especially in patients with a medical history of hematopoietic stem cell transplantation and immunosuppressive therapy.

    DOI: 10.2169/internalmedicine.5396-20

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  • Frequent Germline and Somatic Single Nucleotide Variants in the Promoter Region of the Ribosomal RNA Gene in Japanese Lung Adenocarcinoma Patients. 国際誌

    Riuko Ohashi, Hajime Umezu, Ayako Sato, Tatsuya Abé, Shuhei Kondo, Kenji Daigo, Seijiro Sato, Norikazu Hara, Akinori Miyashita, Takeshi Ikeuchi, Teiichi Motoyama, Masashi Kishi, Tadahiro Nagaoka, Keiko Horiuchi, Atsushi Shiga, Shujiro Okuda, Tomoki Sekiya, Aya Ohtsubo, Kosuke Ichikawa, Hiroshi Kagamu, Toshiaki Kikuchi, Satoshi Watanabe, Jun-Ichi Tanuma, Peter Schraml, Takao Hamakubo, Masanori Tsuchida, Yoichi Ajioka

    Cells   9 ( 11 )   2020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)  

    Ribosomal RNA (rRNA), the most abundant non-coding RNA species, is a major component of the ribosome. Impaired ribosome biogenesis causes the dysfunction of protein synthesis and diseases called "ribosomopathies," including genetic disorders with cancer risk. However, the potential role of rRNA gene (rDNA) alterations in cancer is unknown. We investigated germline and somatic single-nucleotide variants (SNVs) in the rDNA promoter region (positions -248 to +100, relative to the transcription start site) in 82 lung adenocarcinomas (LUAC). Twenty-nine tumors (35.4%) carried germline SNVs, and eight tumors (9.8%) harbored somatic SNVs. Interestingly, the presence of germline SNVs between positions +1 and +100 (n = 12; 14.6%) was associated with significantly shorter recurrence-free survival (RFS) and overall survival (OS) by univariate analysis (p < 0.05, respectively), and was an independent prognostic factor for RFS and OS by multivariate analysis. LUAC cell line PC9, carrying rDNA promoter SNV at position +49, showed significantly higher ribosome biogenesis than H1650 cells without SNV. Upon nucleolar stress induced by actinomycin D, PC9 retained significantly higher ribosome biogenesis than H1650. These results highlight the possible functional role of SNVs at specific sites of the rDNA promoter region in ribosome biogenesis, the progression of LUAC, and their potential prognostic value.

    DOI: 10.3390/cells9112409

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  • 気管支静脈瘤による喀血を来した気管支拡張症の1例

    倉科 健司, 穂苅 諭, 月岡 啓輔, 青木 信将, 上野 浩志, 大坪 亜矢, 庄子 聡, 近藤 利恵, 林 正周, 大嶋 康義, 渡部 聡, 小屋 俊之, 菊地 利明, 池田 裕里恵, 山崎 元彦, 堀井 陽祐

    気管支学   42 ( 6 )   577 - 577   2020年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器内視鏡学会  

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  • ペムブロリズマブによる大腸炎発症後、再投与で小腸炎を発症した非小細胞肺癌の一例

    庄子 聡, 高橋 美帆, 大坪 亜矢, 野嵜 幸一郎, 市川 紘将, 近藤 利恵, 青木 信将, 大嶋 康義, 林 正周, 渡部 聡, 小屋 俊之, 近藤 修平, 梅津 哉, 菊地 利明

    肺癌   60 ( 6 )   769 - 769   2020年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • シェーグレン症候群を有する非小細胞肺癌に対して免疫チェックポイント阻害薬を安全に使用できた一例

    大坪 亜矢, 久代 航平, 佐藤 佑輔, 高橋 美帆, 庄子 聡, 野嵜 幸一郎, 穂苅 諭, 市川 紘将, 近藤 利恵, 青木 信将, 大嶋 康義, 林 正周, 渡部 聡, 小屋 俊之, 菊地 利明

    肺癌   60 ( 6 )   724 - 724   2020年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • EGFR遺伝子変異陽性非小細胞肺がんの腫瘍内AXL発現とEGFR-TKI初回治療効果に関する多施設共同後方視的検討

    吉村 彰紘, 山田 忠明, 安宅 信二, 谷口 寛和, 解良 恭一, 松本 勲, 渡部 聡, 三浦 理, 北崎 健, 山口 博之, 内野 順治, 高山 浩一, 矢野 聖二

    肺癌   60 ( 6 )   563 - 563   2020年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 血液透析中の肺がん患者における化学療法の実態調査(NEJ-042)

    三浦 雄, 峯岸 裕司, 新井 誠人, 斎藤 良太, 荒井 大輔, 村瀬 享子, 三浦 啓太, 渡部 聡, 坂下 博之, 宮林 貴大, 本田 亮一, 神宮 大輔, 堀田 尚誠, 小林 国彦, 清家 正博

    日本癌治療学会学術集会抄録集   58回   O3 - 5   2020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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  • ニンテダニブはMDSCを抑制することでPD-1阻害剤の抗腫瘍効果を増強する

    鈴木 遼, 渡部 聡, 有田 将史, 関谷 友樹, 安部 悠子, 佐藤 美由紀, 高橋 美帆, 大坪 亜矢, 庄子 聡, 野嵜 幸一郎, 市川 紘将, 穂苅 諭, 近藤 利恵, 大嶋 康義, 小屋 俊之, 菊地 利明

    日本癌学会総会記事   79回   PJ12 - 9   2020年10月

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    記述言語:英語   出版者・発行元:(一社)日本癌学会  

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  • ALK陽性NSCLCに対するベバシズマブと併用したアレクチニブ療法の第2相およびバイオマーカー研究(A phase II and biomarker study of alectinib combined with bevacizumab in ALK-positive NSCLC)

    渡部 聡, 松本 尚哉, 古塩 純, 石田 晃, 阿部 徹哉, 石川 大輔, 田中 知宏, 高橋 美帆, 大坪 亜矢, 庄子 聡, 野嵜 幸一郎, 市川 紘将, 近藤 利恵, 青木 亜美, 梶原 大季, 小山 建一, 三浦 理, 吉澤 弘久, 西尾 和人, 菊地 利明

    肺癌   60 ( 6 )   562 - 562   2020年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 肺原発肉腫様癌における化学療法の有効性および安全性の検討(HOT1201/NEJ024)

    大泉 聡史, 高村 圭, 原田 敏之, 立原 素子, 森川 直人, 本田 亮一, 渡部 聡, 朝尾 哲彦, 國崎 守, 福原 達朗, 野呂 林太郎, 菊地 英毅, 津谷 康大, 天満 紀之, 小林 国彦, 秋田 弘俊, 北海道肺癌臨床研究会

    肺癌   60 ( 6 )   620 - 620   2020年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 第1世代EGFR-TKI耐性例に対するafatinibの効果と高感度PNA-LNA PCR clamp法による血漿EGFR変異との関連性

    渡邉 香奈, 渡部 聡, 宮内 栄作, 長島 広相, 菅原 俊一, 盛田 麻美, 鈴木 綾, 田中 伸幸, 寺崎 浩司, 福原 達朗, 前門戸 任

    肺癌   60 ( 6 )   670 - 670   2020年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 閉塞性睡眠時無呼吸におけるCPAPデータを用いた治療効果のモニタリングは有用か?

    穂苅 諭, 藤戸 信宏, 鈴木 涼子, 大嶋 康義, 青木 信将, 林 正周, 渡部 聡, 小屋 俊之, 菊地 利明

    日本呼吸器学会誌   9 ( 増刊 )   184 - 184   2020年8月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

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  • 閉塞性睡眠時無呼吸におけるCPAPデータを用いた治療効果のモニタリングは有用か?

    穂苅 諭, 藤戸 信宏, 鈴木 涼子, 大嶋 康義, 青木 信将, 林 正周, 渡部 聡, 小屋 俊之, 菊地 利明

    日本呼吸器学会誌   9 ( 増刊 )   184 - 184   2020年8月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

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  • Evaluation of plasma EGFR mutation as an early predictor of response of erlotinib plus bevacizumab treatment in the NEJ026 study. 査読 国際誌

    Tatsuro Fukuhara, Haruhiro Saito, Naoki Furuya, Kana Watanabe, Shunichi Sugawara, Shunichiro Iwasawa, Yoshio Tsunezuka, Ou Yamaguchi, Prof Morihito Okada, Kozo Yoshimori, Ichiro Nakachi, Prof Akihiko Gemma, Koichi Azuma, Futoshi Kurimoto, Yukari Tsubata, Yuka Fujita, Hiromi Nagashima, Gyo Asai, Satoshi Watanabe, Masaki Miyazaki, Prof Koichi Hagiwara, Prof Toshihiro Nukiwa, Prof Satoshi Morita, Prof Kunihiko Kobayashi, Prof Makoto Maemondo

    EBioMedicine   57   102861 - 102861   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)  

    BACKGROUND: The NEJ026 Phase 3 study demonstrated that erlotinib and bevacizumab (BE)-treated NSCLC patients with EGFR mutations had significantly better progression-free survival (PFS) than those treated with erlotinib alone (E). This study included a prospective analysis of the relationship between the mutational status of EGFR in plasma circulating tumor DNA (ctDNA) and the efficacy of TKI monotherapy or combination therapy. We describe these results herein. METHODS: Plasma samples were collected from patients enrolled in NEJ026 at the start of treatment (P0), 6 weeks after the start of treatment (P1), and upon confirmation of progressive disease (P2). Plasma ctDNA was analyzed using a modified PNA-LNA PCR clamp method. PFS and OS according to EGFR status at the time of plasma collection were evaluated. FINDINGS: Plasma activating EGFR mutation (aEGFR) at P0 was detected in 68% of cases; patients without plasma aEGFR had longer PFS. The frequency of T790M mutation at P2 was similar in both arms: 8 (19.0%) in BE and 11 (20.8%) in E. Based on the aEGFR profiles, PFS was evaluated among three groups: type A [P0(-), P1(-)], type B [P0(+), P1(-)], and type C [P0(+), P1(+)]. This revealed that BE was more efficacious than E, and that BE was associated with improved PFS in all types. INTERPRETATION: Pre-treatment plasma aEGFR status have a potential of early predictor of response of TKI efficacy. Monitoring plasma aEGFR mutation will contribute to selection and continuation of treatment with BE or E. FUNDING: Chugai Pharmaceutical.

    DOI: 10.1016/j.ebiom.2020.102861

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  • Cysteinyl Leukotriene Synthesis via Phospholipase A2 Group IV Mediates Exercise-induced Bronchoconstriction and Airway Remodeling. 査読 国際誌

    Hiroshi Ueno, Toshiyuki Koya, Hiroyuki Takeuchi, Keisuke Tsukioka, Akira Saito, Yosuke Kimura, Masachika Hayashi, Satoshi Watanabe, Takashi Hasegawa, Masaaki Arakawa, Toshiaki Kikuchi

    American journal of respiratory cell and molecular biology   63 ( 1 )   57 - 66   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)  

    It is well known that the prevalence of asthma is higher in athletes, including Olympic athletes, than in the general population. In this study, we analyzed the mechanism of exercise-induced bronchoconstriction by using animal models of athlete asthma. Mice were made to exercise on a treadmill for a total duration of 1 week, 3 weeks, or 5 weeks. We analyzed airway responsiveness, BAL fluid, lung homogenates, and tissue histology for each period. In mice that were treated (i.e., the treatment model), treatments were administered from the fourth to the fifth week. We also collected induced sputum from human athletes with asthma and analyzed the supernatants. Airway responsiveness to methacholine was enhanced with repeated exercise stimulation, although the cell composition in BAL fluid did not change. Exercise induced hypertrophy of airway smooth muscle and subepithelial collagen deposition. Cysteinyl-leukotriene (Cys-LT) levels were significantly increased with exercise duration. Montelukast treatment significantly reduced airway hyperresponsiveness (AHR) and airway remodeling. Expression of PLA2G4 (phospholipase A2 group IV) and leukotriene C4 synthase in the airway epithelium was upregulated in the exercise model, and inhibition of PLA2 ameliorated AHR and airway remodeling, with associated lower levels of Cys-LTs. The levels of Cys-LTs in sputum from athletes did not differ between those with and without sputum eosinophilia. These data suggest that AHR and airway remodeling were caused by repeated and strenuous exercise. Cys-LTs from the airway epithelium, but not inflammatory cells, may play an important role in this mouse model.

    DOI: 10.1165/rcmb.2019-0325OC

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  • Does the gut microbiota play a key role in PD-1/PD-L1 blockade therapy? 査読 国際誌

    Satoshi Watanabe, Toshiaki Kikuchi

    Translational lung cancer research   9 ( 3 )   438 - 440   2020年6月

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  • Prognostic significance of the radiologic features of pneumonitis induced by anti-PD-1 therapy. 査読 国際誌

    Satoshi Watanabe, Takeshi Ota, Masachika Hayashi, Hiroyuki Ishikawa, Aya Otsubo, Satoshi Shoji, Koichiro Nozaki, Kosuke Ichikawa, Rie Kondo, Takao Miyabayashi, Satoru Miura, Hiroshi Tanaka, Tetsuya Abe, Masaaki Okajima, Masaki Terada, Takashi Ishida, Akira Iwashima, Kazuhiro Sato, Hirohisa Yoshizawa, Toshiaki Kikuchi

    Cancer medicine   9 ( 9 )   3070 - 3077   2020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)  

    BACKGROUND: Interstitial lung disease (ILD) induced by anti-programmed-cell death-1 (PD-1) and anti-PD-ligand 1 (PD-L1) is potentially life-threatening and is a common reason of the discontinuation of therapy. In contrast, an enhancement in antitumor effects was reported in patients who developed immune-related adverse events, including ILD. Although recent evidence suggests that radiologic patterns of ILD may reflect the severity of ILD and the antitumor immune responses to anti-PD-1/PD-L1 therapies, the association between radiologic features and clinical outcomes remains unclear. METHODS: Patients with advanced non-small-cell lung cancer who were treated with 1st to 3rd line anti-PD-1 therapy from January 2016 through October 2017 were identified at multiple institutions belonging to the Niigata Lung Cancer Treatment Group. ILD was diagnosed by the treating physicians, and chest computed tomography scans were independently reviewed to assess the radiologic features of ILD. RESULTS: A total of 231 patients who received anti-PD-1 therapy were enrolled. Thirty-one patients (14%) developed ILD. Sixteen patients were classified as having ground glass opacities (GGO), 16 were classified as having cryptogenic organizing pneumonia (COP), and one was classified as having pneumonitis not otherwise specified. Patients with GGO had significantly worse overall survival time compared to patients with COP (7.8 months (95% CI: 2.2-NE) versus not reached (95% CI: 13.2-NE); P = 0.0175). Multivariate analysis of all 231 patients also revealed that PS = 1 and ≥2 and GGO were significant predictors of a worse overall survival. CONCLUSIONS: This study demonstrated that patients who developed GGO exhibited worse outcomes among non-small-cell lung cancer patients receiving anti-PD-1 therapies.

    DOI: 10.1002/cam4.2974

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  • Clinical Outcomes of Second-Line Chemotherapy in Patients with Previously Treated Advanced Thymic Carcinoma: A Retrospective Analysis of 191 Patients from the NEJ023 Study. 査読 国際誌

    Kazunari Tateishi, Ryo Ko, Takehito Shukuya, Yusuke Okuma, Satoshi Watanabe, Shoichi Kuyama, Kyoko Murase, Yoko Tsukita, Hironori Ashinuma, Taku Nakagawa, Kazutsugu Uematsu, Mika Nakao, Yoshiaki Mori, Kyoichi Kaira, Atsuto Mouri, Takao Miyabayashi, Hiroyuki Sakashita, Yoko Matsumoto, Tomoyuki Tanigawa, Tomonobu Koizumi, Satoshi Morita, Kunihiko Kobayashi, Toshihiro Nukiwa, Kazuhisa Takahashi

    The oncologist   25 ( 4 )   e668-e674   2020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)  

    BACKGROUND: Owing to the rarity of this tumor, there is limited information about second-line chemotherapy for patients with previously treated advanced thymic carcinoma. MATERIAL AND METHODS: We performed a multi-institutional, retrospective study named NEJ023 for patients with advanced thymic carcinoma. Patients without indications for curative treatment were treated with chemotherapy from 1995 to 2014 at 40 institutions in the North East Japan Study Group. Demographic and clinicopathologic characteristics, data on treatment methods, and outcomes of second-line chemotherapy were obtained from medical records. RESULTS: In total, 191 patients were enrolled in this study. Second-line chemotherapy included platinum-based doublets in 57.6% of patients, other multidrug chemotherapy (e.g., cisplatin, doxorubicin, vincristine, and cyclophosphamide) in 13.6%, and monotherapy in 28.8%. The median follow-up time was 50.5 months, and the median overall survival (OS) from the start of second-line chemotherapy was 22.4 (95% confidence interval, 17.5-26.7) months. The average response rate (RR) was 20.0% overall; it was 21.6% for patients treated with platinum-based doublet chemotherapy, 13.6% for those treated with other multidrug chemotherapy, and 19.6% for those treated with single agent chemotherapy. There was no significant difference in OS between platinum-based doublet chemotherapy, other multidrug chemotherapy, and monotherapy (the median OS was 22.4, 25.7, and 21.4 months, respectively). CONCLUSION: The median OS was 22.4 months in patients with advanced thymic carcinoma treated with second-line chemotherapy. There were no significant differences in RR and OS between monotherapy and multidrug chemotherapy in this study. IMPLICATIONS FOR PRACTICE: Owing to the rarity of this tumor, there is limited information about second-line chemotherapy for patients with previously treated advanced thymic carcinoma. This is the largest data for those patients treated with second-line chemotherapy. This study suggests there is no significant difference in efficacy between monotherapy and multidrug chemotherapy for previously treated advanced thymic carcinoma. This result can support the adequacy to select monotherapy as treatment of those patients.

    DOI: 10.1634/theoncologist.2019-0593

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  • First-line osimertinib treatment in patients with lung squamous cell carcinoma harboring active epidermal growth factor receptor mutations. 査読 国際誌

    Satoshi Shoji, Satoshi Watanabe, Kaori Takamura, Hajime Umezu, Toshiaki Kikuchi

    Lung cancer (Amsterdam, Netherlands)   140   113 - 115   2020年2月

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  • 閉塞性睡眠時無呼吸は尿細管障害のバイオマーカーである尿中NAGを増加させる

    森谷 梨加, 穂苅 諭, 藤戸 信宏, 鈴木 涼子, 大嶋 康義, 青木 信将, 林 正周, 渡部 聡, 小屋 俊之, 菊地 利明

    日本内科学会雑誌   109 ( Suppl. )   174 - 174   2020年2月

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    記述言語:日本語   出版者・発行元:(一社)日本内科学会  

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  • Final progression-free survival results from the J-ALEX study of alectinib versus crizotinib in ALK-positive non-small-cell lung cancer. 査読 国際誌

    Kazuhiko Nakagawa, Toyoaki Hida, Hiroshi Nokihara, Masahiro Morise, Koichi Azuma, Young Hak Kim, Takashi Seto, Yuichi Takiguchi, Makoto Nishio, Hiroshige Yoshioka, Toru Kumagai, Katsuyuki Hotta, Satoshi Watanabe, Koichi Goto, Miyako Satouchi, Toshiyuki Kozuki, Ryo Koyama, Tetsuya Mitsudomi, Nobuyuki Yamamoto, Takashi Asakawa, Morihiko Hayashi, Wakako Hasegawa, Tomohide Tamura

    Lung cancer (Amsterdam, Netherlands)   139   195 - 199   2020年1月

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    記述言語:英語  

    OBJECTIVES: The J-ALEX study compared the efficacy and safety of alectinib with crizotinib in Japanese patients with advanced ALK-positive non-small-cell lung cancer (NSCLC). Superiority in independent review facility (IRF)-assessed progression-free survival (PFS) was demonstrated for alectinib at the second pre-planned interim PFS analysis (data cutoff: December 3, 2015; hazard ratio [HR] 0.34, 99.7 % confidence interval [CI]: 0.17-0.71, P < 0.0001). We report final PFS data and the second pre-planned interim analysis of overall survival (OS) and safety (data cutoff: June 30, 2018). METHODS: Patients aged ≥20 years who were ALK inhibitor-naïve and chemotherapy-naïve, or had received one prior chemotherapy regimen, were randomized to receive alectinib 300 mg (n = 103) or crizotinib 250 mg (n = 104) twice daily. The primary end point was IRF-assessed PFS. Secondary end points included OS and safety. All patients entered survival follow-up in July 2018. RESULTS: Median follow-up was 42.4 months for alectinib and 42.2 months for crizotinib. Sustained improvement in IRF-assessed PFS with alectinib was shown (HR 0.37, 95 % CI: 0.26-0.52; median PFS 34.1 months vs 10.2 months crizotinib). At the second interim OS analysis, superiority of alectinib to crizotinib could not be concluded (stratified HR 0.80, 99.8799 % CI: 0.35-1.82, stratified log-rank P = 0.3860; median OS not reached alectinib vs 43.7 months crizotinib). Fewer alectinib-treated patients experienced grade ≥3 adverse events (36.9 % vs 60.6 % crizotinib). CONCLUSIONS: At the final PFS analysis, alectinib continued to demonstrate superiority in IRF-assessed PFS versus crizotinib in ALK-inhibitor-naïve ALK-positive NSCLC, with a favorable safety profile. OS follow-up continues.

    DOI: 10.1016/j.lungcan.2019.11.025

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  • Characterization of low adherence population in asthma patients from Japan using Adherence Starts with Knowledge-12. 査読 国際誌

    Yuka Kimura, Toshiyuki Koya, Takashi Hasegawa, Hiroshi Ueno, Kazutaka Yoshizawa, Yosuke Kimura, Masachika Hayashi, Satoshi Watanabe, Toshiaki Kikuchi

    Allergology international : official journal of the Japanese Society of Allergology   69 ( 1 )   61 - 65   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)  

    BACKGROUND: Adherence Starts with Knowledge-12 (ASK-12) is a useful indicator of drug adherence. In this study, we analyzed patient background including social and psychological factors in a low-adherence group of patients with asthma defined using ASK-12. METHODS: From a questionnaire survey for patients with asthma from the Niigata Prefecture, Japan, conducted in the fall of 2016, we enrolled patients who answered all ASK-12 items and underwent a measured respiratory function test within 1 year. The low-adherence group (ASK-12 ≥ 28) was compared with the control group (ASK-12 < 28), and we conducted a cluster analysis of the low-adherence group. RESULTS: There were 170 patients in the low-adherence group and 402 patients in the control group. There was a significant difference between age, gender, working status, smoking history, the percentage of forced expiratory volume in one second (%FEV1), asthma control test (ACT), and Patient Health Questionnaire-9 (PHQ-9) score between the two groups. Logistic analysis revealed that working status (working), % FEV1 (<90%), and PHQ-9 score (>5) were independent factors for the low-adherence group. The cluster analysis identified three clusters in the low-adherence group. Among these, one cluster was characterized by elderly males with chronic obstructive pulmonary disease and another by middle-aged nonsmoking females with a depression tendency, had problems with asthma control. CONCLUSIONS: Several factors were considered to be attributed to low drug-adherence. There were several phenotypes in the low-adherence population correlated with incomplete asthma control. Intervention with drug adherence should be a future goal for asthma treatment.

    DOI: 10.1016/j.alit.2019.07.006

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  • Hypothesis generative head-to-head study comparing efficacy of afatinib and osimertinib based on immunological biomarkers in Japanese NSCLC patients with EGFR mutations (Heat on Beat study). 国際誌

    Kei Morikawa, Hisashi Tanaka, Hidetoshi Itani, Saori Takata, Satoshi Watanabe, Kazuma Kishi, Kenzo Soejima, Kyoichi Kaira, Hiroshi Kagamu, Kenichi Yoshimura, Noriyuki Matsutani, Nobuhiko Seki

    Therapeutic advances in medical oncology   12   1758835920967254 - 1758835920967254   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: In the FLAURA trial, superiority of osimertinib over the standard of care (SOC) was not demonstrated in Asian patients; SOC seemed favorable among Japanese patients (hazard ratio 1.39, 95% confidence interval 0.82-2.33). Three reasons are suggested: since rechallenge with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is covered by health insurance in Japan, EGFR-TKI rechallenge rate was higher in SOC than in the osimertinib group, which resulted in a long-term sequential administration of EGFR-TKIs; treatment discontinuation rate was high in the osimertinib group due to adverse events such as interstitial pneumonia among Japanese patients. EGFR-TKIs enhance tumor antigen-specific cytotoxicity of T cells, especially first- and second-generation EGFR-TKIs, which are more active against various cells with wild-type EGFR, including regulatory T cells. Consequently, subsequent immune checkpoint inhibitor therapy seemed more promising in the SOC group. Therefore, optimal first-line EGFR-TKI for EGFR-mutant advanced lung cancer may not have been identified in Japanese patients. Methods: The Heat on Beat study is a randomized, open-label, multicenter, phase II study to compare OS between initial treatment with afatinib and osimertinib in treatment-naïve patients with advanced or recurrent EGFR-mutant NSCLC. Exploration of immunomonitoring through peripheral blood mononuclear cells will also be performed, before, during, and after treatment. Treatment-naïve EGFR mutation-positive non-small cell lung cancer (NSCLC) patients (N = 100) will be randomized to two groups in a 1:1 ratio. The co-primary endpoints are 3-year survival rate and characterization of immune environment associated with response to afatinib, osimertinib, or immune checkpoint inhibitors. Enrollment will start in May 2020 at 28 sites in Japan and continue for 1 year, with 3-year follow-up. Discussion: Because there is no clinical trial comparing second- with third-generation EGFR-TKI for advanced EGFR-mutant NSCLC, our study would provide a major impact on clinical practice. Trial registration Japan Registry of Clinical Trials, jRCTs031190221, registered date: 25 February 2020, https://jrct.niph.go.jp/en-latest-detail/jRCTs031190221.

    DOI: 10.1177/1758835920967254

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  • Correlation of prechemotherapy urinary megalin ectodomain (A-megalin) levels with the development of cisplatin-induced nephrotoxicity: a prospective observational study. 査読 国際誌

    Satoshi Shoji, Michihiro Hosojima, Hideyuki Kabasawa, Rie Kondo, Satoru Miura, Satoshi Watanabe, Nobumasa Aoki, Ryohei Kaseda, Shoji Kuwahara, Naohito Tanabe, Yoshiaki Hirayama, Ichiei Narita, Toshiaki Kikuchi, Hiroshi Kagamu, Akihiko Saito

    BMC cancer   19 ( 1 )   1170 - 1170   2019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)  

    BACKGROUND: Cisplatin is a potent chemotherapeutic agent used to treat a variety of solid tumors. One of the major side effects of cisplatin is dose-limiting nephrotoxicity. We recently demonstrated that the renal uptake of cisplatin and resultant cisplatin-induced nephrotoxicity are mediated in part by megalin, an endocytic receptor in proximal tubule epithelial cells (PTECs). We also developed sandwich enzyme-linked immunosorbent assays to measure the megalin ectodomain (A-megalin) and full-length megalin (C-megalin) in urine using monoclonal antibodies against the amino- and carboxyl-termini of megalin, respectively. The present study examined the correlation of urinary megalin level with cisplatin-induced nephrotoxicity and its utility as a biomarker in patients with thoracic cancer. METHODS: This prospective observational study involved 45 chemotherapy-naïve patients scheduled to receive chemotherapy with ≥60 mg/m2 cisplatin for histologically diagnosed small cell lung cancer, non-small cell lung cancer, or malignant pleural mesothelioma. Before and after the first course of chemotherapy, we measured urinary A- and C-megalin and other markers of PTEC injury, such as N-acetyl-β-D-glucosaminidase, α1-microglobulin, β2-microglobulin, neutrophil gelatinase-associated lipocalin, and liver-type fatty acid-binding protein, and compared the values with the change in the estimated glomerular filtration rate (eGFR) and clinical risk factors for renal impairment. RESULTS: A negative correlation was found between baseline urinary A-megalin levels and change in eGFR (r = - 0.458, P = 0.002). According to Kaplan-Meier survival curves, eGFR decline was associated with the baseline urinary A-megalin quartile (P = 0.038). In addition, according to the hazard ratios (HRs) for eGFR decline > 10 mL/min/1.73 m2 calculated using a Cox proportional hazard model, the highest quartile had a significantly higher risk of eGFR decline compared with the lowest quartile (HR 7.243; 95% confidence interval 1.545-33.962). Other baseline urinary markers showed no correlation with eGFR decline. CONCLUSIONS: This is the first report demonstrating that prechemotherapy urinary A-megalin levels are correlated with the development of cisplatin-induced nephrotoxicity. This finding has clinical implications for the identification of patients at risk for cisplatin-induced nephrotoxicity and the development of possible prophylactic therapies.

    DOI: 10.1186/s12885-019-6398-2

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  • Efficacy of EGFR-TKIs with or without upfront brain radiotherapy for EGFR-mutant NSCLC patients with central nervous system metastases. 査読 国際誌

    Yu Saida, Satoshi Watanabe, Tetsuya Abe, Satoshi Shoji, Koichiro Nozaki, Kosuke Ichikawa, Rie Kondo, Kenichi Koyama, Satoru Miura, Hiroshi Tanaka, Masaaki Okajima, Masaki Terada, Takashi Ishida, Hiroki Tsukada, Masato Makino, Akira Iwashima, Kazuhiro Sato, Naoya Matsumoto, Hirohisa Yoshizawa, Toshiaki Kikuchi

    Thoracic cancer   10 ( 11 )   2106 - 2116   2019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)  

    BACKGROUND: Although the clinical efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC) patients has been demonstrated, their efficacy in EGFR-mutant NSCLCs with central nervous system (CNS) metastases and the role of radiotherapy remain unclear. This study aimed to determine if it is preferable to add upfront cranial radiotherapy to EGFR-TKIs in patients with EGFR-mutant NSCLC with newly diagnosed brain metastases. METHODS: We retrospectively analyzed the data of EGFR-mutant NSCLC patients with CNS metastases who received EGFR-TKIs as a first-line therapy. RESULTS: A total of 104 patients were enrolled and 39 patients received upfront brain radiotherapy, while 65 patients received first and second generation EGFR-TKIs first. The median time to treatment failure (TTF) was 7.8 months (95% confidence interval [CI]: 6.3-9.4). The median survival time (MST) was 24.0 months (95% CI: 20.1-30.1). The overall response rate of the CNS was 37%. The median CNS progression-free survival (PFS) was 13.2 months (95% CI: 10.0-16.2). Brain radiotherapy prior to EGFR-TKI prolonged TTF (11.2 vs. 6.8 months, P = 0.038) and tended to prolong CNS-PFS (15.6 vs. 11.1 months, P = 0.096) but was not significantly associated with overall survival (MST 26.1 vs. 24.0 months, P = 0.525). Univariate and multivariate analyses indicated that poor performance status and the presence of extracranial metastases were poor prognostic factors related to overall survival. CONCLUSION: EGFR-TKI showed a favorable effect for EGFR-mutant NSCLC patients with CNS metastases. Prolonged TTF and CNS-PFS were observed with upfront brain radiotherapy.

    DOI: 10.1111/1759-7714.13189

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  • CBDCA+Pemetrexed+Pembrolizumabが奏効したTrousseau症候群合併肺腺癌の一例

    野嵜 幸一郎, 島津 翔, 尾形 英至, 吉澤 和孝, 近藤 利恵, 木村 陽介, 青木 信将, 渡部 聡, 大嶋 康義, 庄子 聡, 大坪 亜矢, 市川 紘将, 菊地 利明

    肺癌   59 ( 6 )   814 - 814   2019年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • Osimertinibによる奏効が認められたEGFR遺伝子Exon20 insertionを有する肺腺癌の一例

    市川 紘将, 渡部 聡, 大坪 亜矢, 庄子 聡, 野嵜 幸一郎, 近藤 利恵, 青木 信将, 林 正周, 大嶋 康義, 小屋 俊之, 菊地 利明

    肺癌   59 ( 6 )   763 - 763   2019年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • シラスタチンによりシスプラチン腎症を抑制することでシスプラチン投与を増量できる(Cilastatin suppresses cisplatin-induced nephrotoxicity and enables to increase the dose of cisplatin for cancer therapy)

    有田 将史, 渡部 聡, 青木 信将, 高橋 美帆, 庄子 聡, 野嵜 幸一郎, 市川 紘将, 近藤 利恵, 桑原 頌治, 田中 純太, 小屋 俊之, 斎藤 亮彦, 菊地 利明

    日本癌学会総会記事   78回   P - 1398   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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  • Corrigendum to "Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line treatment for stage IV squamous non-small cell lung cancer: A phase 1b and randomized, open-label, multicenter, phase 2 trial in Japan" [Lung C 査読 国際誌

    Watanabe S, Yoshioka H, Sakai H, Hotta K, Takenoyama M, Yamada K, Sugawara S, Takiguchi Y, Hosomi Y, Tomii K, Niho S, Yamamoto N, Nishio M, Ohe Y, Kato T, Takahashi T, Kamada A, Suzukawa K, Omori Y, Enatsu S, Nakagawa K, Tamura T

    Lung cancer (Amsterdam, Netherlands)   132   157 - 158   2019年6月

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  • 睡眠呼吸障害に対して、PAP療法の適応を探索する! 多系統萎縮症に対するPAP療法の探索

    大嶋 康義, 穂苅 諭, 渡部 聡, 小屋 俊之, 菊地 利明, 中山 秀章, 下畑 享良

    日本睡眠学会定期学術集会プログラム・抄録集   44回   159 - 159   2019年6月

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    記述言語:日本語   出版者・発行元:(一社)日本睡眠学会  

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  • Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial. 査読 国際誌

    Haruhiro Saito, Tatsuro Fukuhara, Naoki Furuya, Kana Watanabe, Shunichi Sugawara, Shunichiro Iwasawa, Yoshio Tsunezuka, Ou Yamaguchi, Morihito Okada, Kozo Yoshimori, Ichiro Nakachi, Akihiko Gemma, Koichi Azuma, Futoshi Kurimoto, Yukari Tsubata, Yuka Fujita, Hiromi Nagashima, Gyo Asai, Satoshi Watanabe, Masaki Miyazaki, Koichi Hagiwara, Toshihiro Nukiwa, Satoshi Morita, Kunihiko Kobayashi, Makoto Maemondo

    The Lancet. Oncology   20 ( 5 )   625 - 635   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)  

    BACKGROUND: Resistance to first-generation or second-generation EGFR tyrosine kinase inhibitor (TKI) monotherapy develops in almost half of patients with EGFR-positive non-small-cell lung cancer (NSCLC) after 1 year of treatment. The JO25567 phase 2 trial comparing erlotinib plus bevacizumab combination therapy with erlotinib monotherapy established the activity and manageable toxicity of erlotinib plus bevacizumab in patients with NSCLC. We did a phase 3 trial to validate the results of the JO25567 study and report here the results from the preplanned interim analysis. METHODS: In this prespecified interim analysis of the randomised, open-label, phase 3 NEJ026 trial, we recruited patients with stage IIIB-IV disease or recurrent, cytologically or histologically confirmed non-squamous NSCLC with activating EGFR genomic aberrations from 69 centres across Japan. Eligible patients were at least 20 years old, and had an Eastern Cooperative Oncology Group performance status of 2 or lower, no previous chemotherapy for advanced disease, and one or more measurable lesions based on Response Evaluation Criteria in Solid Tumours (1.1). Patients were randomly assigned (1:1) to receive oral erlotinib 150 mg per day plus intravenous bevacizumab 15 mg/kg once every 21 days, or erlotinib 150 mg per day monotherapy. Randomisation was done by minimisation, stratified by sex, smoking status, clinical stage, and EGFR mutation subtype. The primary endpoint was progression-free survival. This study is ongoing; the data cutoff for this prespecified interim analysis was Sept 21, 2017. Efficacy was analysed in the modified intention-to-treat population, which included all randomly assigned patients who received at least one dose of treatment and had at least one response evaluation. Safety was analysed in all patients who received at least one dose of study drug. The trial is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN000017069. FINDINGS: Between June 3, 2015, and Aug 31, 2016, 228 patients were randomly assigned to receive erlotinib plus bevacizumab (n=114) or erlotinib alone (n=114). 112 patients in each group were evaluable for efficacy, and safety was evaluated in 112 patients in the combination therapy group and 114 in the monotherapy group. Median follow-up was 12·4 months (IQR 7·0-15·7). At the time of interim analysis, median progression-free survival for patients in the erlotinib plus bevacizumab group was 16·9 months (95% CI 14·2-21·0) compared with 13·3 months (11·1-15·3) for patients in the erlotinib group (hazard ratio 0·605, 95% CI 0·417-0·877; p=0·016). 98 (88%) of 112 patients in the erlotinib plus bevacizumab group and 53 (46%) of 114 patients in the erlotinib alone group had grade 3 or worse adverse events. The most common grade 3-4 adverse event was rash (23 [21%] of 112 patients in the erlotinib plus bevacizumab group vs 24 [21%] of 114 patients in the erlotinib alone group). Nine (8%) of 112 patients in the erlotinib plus bevacizumab group and five (4%) of 114 patients in the erlotinib alone group had serious adverse events. The most common serious adverse events were grade 4 neutropenia (two [2%] of 112 patients in the erlotinib plus bevacizumab group) and grade 4 hepatic dysfunction (one [1%] of 112 patients in the erlotinib plus bevacizumab group and one [1%] of 114 patients in the erlotinib alone group). No treatment-related deaths occurred. INTERPRETATION: The results of this interim analysis showed that bevacizumab plus erlotinib combination therapy improves progression-free survival compared with erlotinib alone in patients with EGFR-positive NSCLC. Future studies with longer follow-up, and overall survival and quality-of-life data will be required to further assess the efficacy of this combination in this setting. FUNDING: Chugai Pharmaceutical.

    DOI: 10.1016/S1470-2045(19)30035-X

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  • 動物モデル2:アレルギー性気道炎症の治療 コレラトキシンBを用いた舌下免疫療法の増強効果

    上野 浩志, 小屋 俊之, 齋藤 暁, 竹内 寛之, 林 正周, 大嶋 康義, 渡部 聡, 菊地 利明, 長谷川 隆志

    アレルギー   68 ( 4-5 )   507 - 507   2019年5月

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    記述言語:日本語   出版者・発行元:(一社)日本アレルギー学会  

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  • Retrospective efficacy analysis of immune checkpoint inhibitors in patients with EGFR-mutated non-small cell lung cancer. 査読 国際誌

    Tadaaki Yamada, Soichi Hirai, Yuki Katayama, Akihiro Yoshimura, Shinsuke Shiotsu, Satoshi Watanabe, Toshiaki Kikuchi, Kazuki Hirose, Yutaka Kubota, Yusuke Chihara, Taishi Harada, Keiko Tanimura, Takayuki Takeda, Nobuyo Tamiya, Yoshiko Kaneko, Junji Uchino, Koichi Takayama

    Cancer medicine   8 ( 4 )   1521 - 1529   2019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)  

    BACKGROUND: Treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) leads to initial response in most patients with EGFR-mutated non-small cell lung cancer (NSCLC). In contrast, little is known of the subpopulation of patients with NSCLC with EGFR mutations who exhibit clinical outcomes that require treatment with immune checkpoint inhibitors (ICIs). Therefore, to identify eligible cases to treat with ICIs, we retrospectively analyzed the correlation between clinical features and the efficacy of ICIs in patients with EGFR mutations. PATIENTS AND METHODS: We retrospectively analyzed patients with advanced NSCLC harboring EGFR mutations who were treated with ICIs after developing resistance to EGFR-TKIs between February 2016 and April 2018 at 6 institutions in Japan. The association between clinical outcomes and the efficacy of ICIs was investigated. RESULTS: We enrolled 27 patients who harbored EGFR-activating mutations. The objective response and disease control rates were higher in patients with uncommon EGFR mutations than in those with common EGFR mutations (71% vs 35.7% and 57% vs 7%, P = 0.14 and P < 0.01, respectively). Patients with uncommon EGFR mutations or without T790M mutations exhibited a significantly longer median progression-free survival than those with common EGFR mutations or with T790M mutations (P = 0.003 and P = 0.03, respectively). CONCLUSION: Patients with uncommon EGFR mutations and without T790M mutations are associated with the best outcomes for treatment with immunotherapy among those with EGFR-mutated NSCLC, based on retrospective analysis. Further research is needed to validate the clinical biomarkers involved in ICI responders with EGFR mutations.

    DOI: 10.1002/cam4.2037

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  • Multiplex cytokine analysis in Mycobacterium avium complex lung disease: relationship between CXCL10 and poor prognostic factors. 査読 国際誌

    Yuuki Bamba, Hiroshi Moro, Nobumasa Aoki, Takeshi Koizumi, Yasuyoshi Ohshima, Satoshi Watanabe, Takuro Sakagami, Toshiyuki Koya, Toshinori Takada, Toshiaki Kikuchi

    BMC infectious diseases   19 ( 1 )   263 - 263   2019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: Mycobacterium avium complex lung disease (MAC-LD) can deteriorate rapidly to become fatal. Reported poor prognostic factors include radiographic findings, undernutrition, anemia and high inflammation test values. However, the association of these prognostic factors with the pathophysiology of the disease remains unknown. We aimed to clarify the pathophysiology of MAC-LD and develop a new biomarker that reflects the immune response to the disease. METHODS: We performed the cytokine panel analyses of serum from patients with MAC-LD and compared each cytokine level with clinically negative prognostic factors (radiographic disease type, body mass index, albumin, C-reactive protein and hemoglobin) and high-resolution CT scores. RESULTS: We analyzed 27 patients with MAC-LD, 6 with the fibrocavitary form and 21 with the nodular bronchiectatic form on high-resolution CT. Serum CXC motif ligand 10 (CXCL10) concentration was significantly elevated in patients with the fibrocavitary form (p = 0.008). CXCL10 levels correlated with body mass index (r = - 0.60, p = 0.0008), serum albumin concentration (r = - 0.45, p = 0.016) and high-resolution CT scores (r = 0.61, p = 0.0006). Among 14 patients initially untreated, antibiotic therapy was initiated for five during the study period. CXCL10 concentration was significantly higher in these patients (p = 0.046), and receiver operating characteristic analysis for CXCL10 concentration on treatment initiation produced an area under the curve of 0.844, with a sensitivity of 100%, specificity of 66.7%, and cut-off value of 366.5 pg/mL. CONCLUSION: We revealed cytokine profiles in patients with MAC-LD. Serum CXCL10 levels probably reflect the severity of MAC-LD. Our findings suggest that CXCL10 concentration may be a promising biomarker for managing treatment for patients with MAC disease of the lung.

    DOI: 10.1186/s12879-019-3888-4

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  • Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line treatment for stage IV squamous non-small cell lung cancer: A phase 1b and randomized, open-label, multicenter, phase 2 trial in Japan. 査読 国際誌

    Watanabe S, Yoshioka H, Sakai H, Hotta K, Takenoyama M, Yamada K, Sugawara S, Takiguchi Y, Hosomi Y, Tomii K, Niho S, Yamamoto N, Nishio M, Ohe Y, Kato T, Takahashi T, Kamada A, Suzukawa K, Omori Y, Enatsu S, Nakagawa K, Tamura T

    Lung cancer (Amsterdam, Netherlands)   129   55 - 62   2019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)  

    DOI: 10.1016/j.lungcan.2019.01.005

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  • 小細胞肺癌患者におけるプロカルシトニンの臨床的意義に関する解析

    市川 紘将, 渡部 聡, 柳村 尚寛, 庄子 聡, 野嵜 幸一郎, 近藤 利恵, 青木 信将, 林 正周, 大嶋 康義, 小屋 俊之, 菊地 利明

    日本呼吸器学会誌   8 ( 増刊 )   336 - 336   2019年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

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  • AXL confers intrinsic resistance to osimertinib and advances the emergence of tolerant cells. 査読 国際誌

    Hirokazu Taniguchi, Tadaaki Yamada, Rong Wang, Keiko Tanimura, Yuta Adachi, Akihiro Nishiyama, Azusa Tanimoto, Shinji Takeuchi, Luiz H Araujo, Mariana Boroni, Akihiro Yoshimura, Shinsuke Shiotsu, Isao Matsumoto, Satoshi Watanabe, Toshiaki Kikuchi, Satoru Miura, Hiroshi Tanaka, Takeshi Kitazaki, Hiroyuki Yamaguchi, Hiroshi Mukae, Junji Uchino, Hisanori Uehara, Koichi Takayama, Seiji Yano

    Nature communications   10 ( 1 )   259 - 259   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)  

    A novel EGFR-tyrosine kinase inhibitor (TKI), osimertinib, has marked efficacy in patients with EGFR-mutated lung cancer. However, some patients show intrinsic resistance and an insufficient response to osimertinib. This study showed that osimertinib stimulated AXL by inhibiting a negative feedback loop. Activated AXL was associated with EGFR and HER3 in maintaining cell survival and inducing the emergence of cells tolerant to osimertinib. AXL inhibition reduced the viability of EGFR-mutated lung cancer cells overexpressing AXL that were exposed to osimertinib. The addition of an AXL inhibitor during either the initial or tolerant phases reduced tumor size and delayed tumor re-growth compared to osimertinib alone. AXL was highly expressed in clinical specimens of EGFR-mutated lung cancers and its high expression was associated with a low response rate to EGFR-TKI. These results indicated pivotal roles for AXL and its inhibition in the intrinsic resistance to osimertinib and the emergence of osimertinib-tolerant cells.

    DOI: 10.1038/s41467-018-08074-0

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  • Retrospective analysis of antitumor effects and biomarkers for nivolumab in NSCLC patients with EGFR mutations. 査読 国際誌

    Miyuki Sato, Satoshi Watanabe, Hiroshi Tanaka, Koichiro Nozaki, Masashi Arita, Miho Takahashi, Satoshi Shoji, Kosuke Ichikawa, Rie Kondo, Nobumasa Aoki, Masachika Hayashi, Yasuyoshi Ohshima, Toshiyuki Koya, Riuko Ohashi, Yoichi Ajioka, Toshiaki Kikuchi

    PloS one   14 ( 4 )   e0215292   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Although the blockade of programmed cell death 1 (PD-1)/PD-ligand (L) 1 has demonstrated promising and durable clinical responses for non-small-cell lung cancers (NSCLCs), NSCLC patients with epidermal growth factor receptor (EGFR) mutations responded poorly to PD-1/PD-L1 inhibitors. Previous studies have identified several predictive biomarkers, including the expression of PD-L1 on tumor cells, for PD-1/PD-L1 blockade therapies in NSCLC patients; however, the usefulness of these biomarkers in NSCLCs with EGFR mutations has not been elucidated. The present study was conducted to evaluate the predictive biomarkers for PD-1/PD-L1 inhibitors in EGFR-mutated NSCLCs. We retrospectively analyzed 9 patients treated with nivolumab for EGFR-mutated NSCLCs. All but one patient received EGFR-tyrosine kinase inhibitors before nivolumab treatment. The overall response rate and median progression-free survival were 11% and 33 days (95% confidence interval (CI); 7 to 51), respectively. Univariate analysis revealed that patients with a good performance status (P = 0.11; hazard ratio (HR) 0.183, 95% CI 0.0217 to 1.549), a high density of CD4+ T cells (P = 0.136; HR 0.313, 95% CI 0.045 to 1.417) and a high density of Foxp3+ cells (P = 0.09; HR 0.264, 95% CI 0.0372 to 1.222) in the tumor microenvironment tended to have longer progression-free survival with nivolumab. Multivariate analysis revealed that a high density of CD4+ T cells (P = 0.005; HR<0.001, 95% CI <0.001 to 0.28) and a high density of Foxp3+ cells (P = 0.003; HR<0.001, 95% CI NA) in tumor tissues were strongly correlated with better progression-free survival. In contrast to previous studies in wild type EGFR NSCLCs, PD-L1 expression was not associated with the clinical benefit of anti-PD-1 treatment in EGFR-mutated NSCLCs. The current study indicated that immune status in the tumor microenvironment may be important for the effectiveness of nivolumab in NSCLC patients with EGFR mutations.

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  • 進行非扁平上皮非小細胞肺癌を対象としたCBDCA+PTX+BEVとCDDP+PEM+BEVのランダム化第II相試験(CLEAR study) 査読

    原田 大二郎, 宇田川 響, 杉山 栄里, 原田 敏之, 安宅 信二, 小山 良, 渡部 聡, 中村 有希子, 畑地 治, 田中 文啓, 新実 彰男, 木田 博, 里内 美弥子, 山中 竹春, 後藤 功一

    肺癌   58 ( 6 )   478 - 478   2018年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • Common driver mutations and smoking history affect tumor mutation burden in lung adenocarcinoma. 査読 国際誌

    Nagahashi M, Sato S, Yuza K, Shimada Y, Ichikawa H, Watanabe S, Takada K, Okamoto T, Okuda S, Lyle S, Takabe K, Tsuchida M, Wakai T

    The Journal of surgical research   230   181 - 185   2018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)  

    DOI: 10.1016/j.jss.2018.07.007

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  • 新潟市における慢性閉塞性肺疾患に対する地域医療連携の取り組み

    藤戸 信宏, 大嶋 康義, 坂井 邦彦, 横田 樹也, 大平 徹郎, 渡部 聡, 小屋 俊之, 菊地 利明

    日本呼吸ケア・リハビリテーション学会誌   28 ( Suppl. )   239s - 239s   2018年10月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸ケア・リハビリテーション学会  

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  • 小細胞肺癌患者におけるプロカルシトニンの臨床的意義に関する解析

    市川 紘将, 渡部 聡, 柳村 尚寛, 庄子 聡, 野嵜 幸一郎, 近藤 利恵, 青木 信将, 林 正周, 大嶋 康義, 小屋 俊之, 菊地 利明

    肺癌   58 ( 6 )   589 - 589   2018年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 気道炎症による抗PD-1抗体の抗腫瘍効果への影響の解析(Inflammation of the lung enhances antitumor effects of anti-PD-1 immunotherapy)

    有田 将史, 渡部 聡, 高橋 美帆, 庄子 聡, 野嵜 幸一郎, 市川 紘将, 近藤 利恵, 田中 純太, 小屋 俊之, 菊地 利明

    日本癌学会総会記事   77回   1628 - 1628   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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  • Phase I Study Evaluating the Combination of Afatinib with Carboplatin and Pemetrexed After First-line EGFR-TKIs. 査読 国際誌

    Satoshi Watanabe, O U Yamaguchi, A I Masumoto, Yuri Maeno, Yosuke Kawashima, Osamu Ishimoto, Shunichi Sugawara, Hirohisa Yoshizawa, Toshiaki Kikuchi, Toshihiro Nukiwa, Kunihiko Kobayashi

    Anticancer research   38 ( 8 )   4699 - 4704   2018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)  

    BACKGROUND/AIM: Promising reports have described the combination of first-generation epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) with carboplatin plus pemetrexed or bevacizumab. However, no analysis of afatinib with platinum-doublet chemotherapies has been performed. PATIENTS AND METHODS: We evaluated the safety and antitumor efficacy of afatinib combined with carboplatin and pemetrexed in EGFR-mutated non-small-cell lung cancer (NSCLC) patients who progressed during first-generation EGFR-TKIs. RESULTS: Ten patients received 20 or 30 mg/day afatinib with carboplatin (area under the curve, 5) and pemetrexed (500 mg/m2). Dose-limiting toxicities included delay of afatinib ≥14 days, grade 3 diarrhea, grade 3 hypokalemia, grade 3 serum amylase increase and grade 4 thrombocytopenia. The recommended dose of afatinib was 20 mg/day in this combination therapy. Overall response rate was 30% and median progression-free survival was 13.7 months. CONCLUSION: This is the first study to investigate the combination of afatinib, carboplatin and pemetrexed. At the recommended dose, this combination was well tolerated and had a good clinical efficacy.

    DOI: 10.21873/anticanres.12776

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  • Clinical and Genetic Implications of Mutation Burden in Squamous Cell Carcinoma of the Lung. 査読 国際誌

    Tatsuro Okamoto, Kazuki Takada, Seijiro Sato, Gouji Toyokawa, Tetsuzo Tagawa, Fumihiro Shoji, Ryota Nakanishi, Eiji Oki, Terumoto Koike, Masayuki Nagahashi, Hiroshi Ichikawa, Yoshifumi Shimada, Satoshi Watanabe, Toshiaki Kikuchi, Kouhei Akazawa, Stephen Lyle, Kazuaki Takabe, Shujiro Okuda, Kenji Sugio, Toshifumi Wakai, Masanori Tsuchida, Yoshihiko Maehara

    Annals of surgical oncology   25 ( 6 )   1564 - 1571   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:Springer New York LLC  

    BACKGROUND: Lung squamous cell carcinoma (LSCC) is a major histological subtype of lung cancer. In this study, we investigated genomic alterations in LSCC and evaluated the clinical implications of mutation burden (MB) in LSCC. METHODS: Genomic alterations were determined in Japanese patients with LSCC (N = 67) using next-generation sequencing of 415 known cancer genes. MB was defined as the number of non-synonymous mutations per 1 Mbp. Programmed death-ligand 1 (PD-L1) protein expression in cancer cells was evaluated by immunohistochemical analysis. RESULTS: TP53 gene mutations were the most common alteration (n = 51/67, 76.1%), followed by gene alterations in cyclin-dependent kinase inhibitor 2B (CDKN2B; 35.8%), CDKN2A (31.3%), phosphatase and tensin homolog (30.0%), and sex-determining region Y-box 2 (SOX2, 28.3%). Histological differentiation was significantly poorer in tumors with high MB (greater than or equal to the median MB) compared with that in tumors with low MB (less than the median MB; p = 0.0446). The high MB group had more tumors located in the upper or middle lobe than tumors located in the lower lobe (p = 0.0019). Moreover, cancers in the upper or middle lobes had significantly higher MB than cancers in the lower lobes (p = 0.0005), and tended to show higher PD-L1 protein expression (p = 0.0573). SOX2 and tyrosine kinase non-receptor 2 amplifications were associated with high MB (p = 0.0065 and p = 0.0010, respectively). CONCLUSIONS: The MB level differed according to the tumor location in LSCC, suggesting that the location of cancer development may influence the genomic background of the tumor.

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  • [A Case of Drug-Induced Organizing Pneumonia Caused by Dasatinib]. 査読

    Miyuki Sato, Satoshi Watanabe, Nobumasa Aoki, Katsuaki Asakawa, Hiroshi Moriyama, Yasuyoshi Oshima, Toshiyuki Koya, Kiyoshi Okazuka, Toshiaki Kikuchi

    Gan to kagaku ryoho. Cancer & chemotherapy   45 ( 5 )   851 - 854   2018年5月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    A 52-year-old man with chronic myelogenous leukemia (CML) received dasatinib after the failure of imatinib and nilotinib therapy. Two years after the initiation of dasatinib, he developed shortness of breath that gradually worsened. Chest X-ray and computed tomography scan showed pulmonary infiltrative shadows and bilateral pleural effusion. We performed a transbronchial lung biopsy and diagnosed organizing pneumonia caused by dasatinib treatment. Corticosteroid therapy was initiated after the discontinuation of dasatinib and all his symptoms were significantly improved. Because of the exacerbation of CML, the patient was treated with imatinib and then nilotinib; however, these drugs failed to decrease the leukemic cells. Re - administration of dasatinib in combination with corticosteroid therapy successfully controlled CML without recurrence of organizing pneumonia.

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  • Clinical Significance of Interferon-γ Neutralizing Autoantibodies Against Disseminated Nontuberculous Mycobacterial Disease. 査読 国際誌

    Aoki A, Sakagami T, Yoshizawa K, Shima K, Toyama M, Tanabe Y, Moro H, Aoki N, Watanabe S, Koya T, Hasegawa T, Morimoto K, Kurashima A, Hoshino Y, Trapnell BC, Kikuchi T

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America   66 ( 8 )   1239 - 1245   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)  

    DOI: 10.1093/cid/cix996

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  • Impact of Concurrent Genomic Alterations Detected by Comprehensive Genomic Sequencing on Clinical Outcomes in East-Asian Patients with EGFR-Mutated Lung Adenocarcinoma. 査読 国際誌

    Seijiro Sato, Masayuki Nagahashi, Terumoto Koike, Hiroshi Ichikawa, Yoshifumi Shimada, Satoshi Watanabe, Toshiaki Kikuchi, Kazuki Takada, Ryota Nakanishi, Eiji Oki, Tatsuro Okamoto, Kouhei Akazawa, Stephen Lyle, Yiwei Ling, Kazuaki Takabe, Shujiro Okuda, Toshifumi Wakai, Masanori Tsuchida

    Scientific reports   8 ( 1 )   1005 - 1005   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:Nature Publishing Group  

    Next-generation sequencing (NGS) has enabled comprehensive detection of genomic alterations in lung cancer. Ethnic differences may play a critical role in the efficacy of targeted therapies. The aim of this study was to identify and compare genomic alterations of lung adenocarcinoma between Japanese patients and the Cancer Genome Atlas (TCGA), which majority of patients are from the US. We also aimed to examine prognostic impact of additional genomic alterations in patients harboring EGFR mutations. Genomic alterations were determined in Japanese patients with lung adenocarcinoma (N = 100) using NGS-based sequencing of 415 known cancer genes, and correlated with clinical outcome. EGFR active mutations, i.e., those involving exon 19 deletion or an L858R point mutation, were seen in 43% of patients. Some differences in driver gene mutation prevalence were observed between the Japanese cohort described in the present study and the TCGA. Japanese cohort had significantly more genomic alterations in cell cycle pathway, i.e., CDKN2B and RB1 than TCGA. Concurrent mutations, in genes such as CDKN2B or RB1, were associated with worse clinical outcome in patients with EGFR active mutations. Our data support the utility of comprehensive sequencing to detect concurrent genomic variations that may affect clinical outcomes in this disease.

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  • A Phase II Study of Irinotecan for Patients with Previously Treated Small-Cell Lung Cancer. 査読 国際誌

    Rie Kondo, Satoshi Watanabe, Satoshi Shoji, Kosuke Ichikawa, Tetsuya Abe, Junko Baba, Junta Tanaka, Hiroki Tsukada, Masaki Terada, Kazuhiro Sato, Yoshie Maruyama, Masato Makino, Akira Hirata, Hiroshi Tanaka, Toshiyuki Koya, Hirohisa Yoshizawa, Toshiaki Kikuchi

    Oncology   94 ( 4 )   223 - 232   2018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:S. Karger AG  

    OBJECTIVE: Chemotherapy with irinotecan plus cisplatin has shown promise in chemo-naïve small-cell lung cancer (SCLC) patients. However, irinotecan treatment for relapsed or refractory SCLC has not been adequately evaluated. This phase II study evaluated the appropriate treatment schedule of irinotecan as a single agent. This study was designed to determine the antitumor activity, toxicity, and survival in previously treated SCLC patients. METHODS: Previously treated SCLC patients with at least one platinum-based regimen received irinotecan (100 mg/m2) on days 1 and 8, every 3 weeks, until disease progression. The assessment of the response rate was the primary endpoint. RESULTS: Thirty patients were enrolled, with an objective response rate of 41.3% (95% confidence interval [CI] 25.5-59.3), and a disease control rate of 69%. Median progression-free and overall survival was 4.1 months (95% CI, 2.2-5.4) and 10.4 months (95% CI, 8.1-14), respectively. The grade 3/4 hematological toxicities were neutropenia (36.7%), thrombocytopenia (3.3%), anemia (13.3%), and febrile neutropenia (6.6%). There were no grade 4 nonhematological toxicities. Frequent grade 3 nonhematological toxicities included diarrhea (10%), anorexia (6.6%), and hyponatremia (6.6%). CONCLUSIONS: This phase II study showed a high objective response rate and long survival. Irinotecan monotherapy schedule used was well tolerated, and could be an active treatment option for these patients.

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  • Usefulness of EBUS-TBNA in the staging of lung cancer in patients with sarcoidosis and sarcoid reactions 査読

    Kosuke Ichikawa, Satoshi Watanabe, Rie Kondo, Satoshi Shoji, Nobumasa Aoki, Yasuyoshi Ohshima, Takuro Sakagami, Hiroshi Moro, Toshiyuki Koya, Toshiaki Kikuchi

    Japanese Journal of Lung Cancer   58 ( 2 )   88 - 92   2018年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japan Lung Cancer Society  

    Objective. Sarcoidosis is a systemic disease that causes the formation of noncaseating epithelioid granuloma in various organs and which often exhibits hilar and mediastinal lymphadenopathy. Among lung cancer patients with sarcoidosis or sarcoid reactions, it is difficult to evaluate the lymph node status and stage by CT and FDG-PET/CT scans. In this study, we examined the usefulness of EBUS-TBNA in the staging of the lung cancer in patients with sarcoidosis or sarcoid reactions. Materials and Methods. We evaluated the effectiveness of EBUS-TBNA in lung cancer patients with sarcoidosis or sarcoid reactions from January 2009 to December 2016. Results. We found 4 patients who were diagnosed with lung cancer accompanied by sarcoidosis and sarcoid reactions by EBUS-TBNA. All of these patients had hilar and mediastinal lymphadenopathy. EBUS-TBNA was useful for the differential diagnosis of lymph-node metastasis of lung cancer. Three of the 4 patients were diagnosed with stage I non-small cell lung cancer and surgery was performed in 2 cases. The histopathological examination of the surgical specimens confirmed that these patients had sarcoid reactions with no lymph-node metastasis. One of the 4 patients was diagnosed with stage III non-small cell lung cancer with systemic sarcoidosis. Conclusion. EBUS-TBNA seems to be useful for the evaluation of the lymph-node status of lung cancer patients with sarcoidosis and sarcoid reactions.

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  • Updated survival outcomes of NEJ005/TCOG0902: a randomised phase II study of concurrent versus sequential alternating gefitinib and chemotherapy in previously untreated non-small cell lung cancer with sensitive EGFR mutations. 査読 国際誌

    Satoshi Oizumi, Shunichi Sugawara, Koichi Minato, Toshiyuki Harada, Akira Inoue, Yuka Fujita, Makoto Maemondo, Satoshi Watanabe, Kazuhiko Ito, Akihiko Gemma, Yoshiki Demura, Shinichi Fukumoto, Hiroshi Isobe, Ichiro Kinoshita, Satoshi Morita, Kunihiko Kobayashi, Koichi Hagiwara, Keisuke Aiba, Toshihiro Nukiwa

    ESMO open   3 ( 2 )   e000313   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: The North-East Japan Study Group (NEJ) 005/Tokyo Cooperative Oncology Group (TCOG) 0902 study has reported that first-line concurrent and sequential alternating combination therapies of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (gefitinib) plus platinum-based doublet chemotherapy (carboplatin/pemetrexed) offer promising efficacy with predictable toxicities for patients with EGFR-mutant non-small cell lung cancer. However, overall survival (OS) data were insufficient in the primary report because of the lack of death events. Patients and methods: Progression-free survival (PFS) and OS were re-evaluated at the final data cut-off point (March 2017) for the entire population (n=80). Results: At the median follow-up time of 35.6 months, 88.8% of patients had progressive disease and 77.5% of patients had died. Median PFS was 17.5 months for the concurrent regimen and 15.3 months for the sequential alternating regimen (P=0.13). Median OS was 41.9 and 30.7 months, respectively (P=0.036). Updated response rates were similar in both groups (90.2% and 82.1%, respectively; P=0.34). Patients with Del19 tumours displayed relatively better OS (median: 45.3 vs 33.3 months, respectively) than those with L858R (31.4 vs 28.9 months, respectively). No severe adverse events, including interstitial lung disease, occurred in the period since the primary report. Conclusions: This updated analysis confirms that PFS is improved with first-line combination therapy compared with gefitinib monotherapy and that the concurrent regimen, in particular, offers an OS benefit of 42 months in the EGFR-mutated setting. Our ongoing NEJ009 study will clarify whether this combination strategy can be incorporated into routine clinical practice. Trial registration number: UMIN C000002789, Post-results.

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  • Increased presepsin levels are associated with the severity of fungal bloodstream infections. 査読 国際誌

    Yuuki Bamba, Hiroshi Moro, Nobumasa Aoki, Takeshi Koizumi, Yasuyoshi Ohshima, Satoshi Watanabe, Takuro Sakagami, Toshiyuki Koya, Toshinori Takada, Toshiaki Kikuchi

    PloS one   13 ( 10 )   e0206089   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Presepsin is a widely recognized biomarker for sepsis. However, little is known about the usefulness of presepsin in invasive fungal infection. The aim of this study was to determine the plasma levels of presepsin in fungal bloodstream infections and to investigate whether it reflects the disease severity, similar to its utility in bacterial infections. METHODS: We prospectively measured presepsin in plasma samples from participants with fungemia from April 2016 to December 2017. The associations of C-reactive protein, procalcitonin, and presepsin concentrations with the severity of fungemia were statistically analyzed. In vitro assay was performed by incubating Escherichia coli, Candida albicans, and lipopolysaccharide to whole blood cells collected from healthy subjects; after 3 h, the presepsin concentration was measured in the supernatant and was compared among the bacteria, fungi, and LPS groups. RESULTS: Presepsin was increased in 11 patients with fungal bloodstream infections. Serial measurement of presepsin levels demonstrated a prompt decrease in 7 patients in whom treatment was effective, but no decrease or further increase in the patients with poor improvement. Additionally, presepsin concentrations were significantly correlated with the Sequential Organ Failure Assessment score (r = 0.89, p < 0.001). In vitro assay with co-incubation of C. albicans and human whole blood cells indicated that the viable cells of C. albicans caused an increase in presepsin, as seen with E. coli. CONCLUSIONS: Plasma presepsin levels increased in patients with fungal bloodstream infection, with positive association with the disease severity. Presepsin could be a useful biomarker of sepsis secondary to fungal infections.

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  • Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial 査読

    Toyoaki Hida, Hiroshi Nokihara, Masashi Kondo, Young Hak Kim, Koichi Azuma, Takashi Seto, Yuichi Takiguchi, Makoto Nishio, Hiroshige Yoshioka, Fumio Imamura, Katsuyuki Hotta, Satoshi Watanabe, Koichi Goto, Miyako Satouchi, Toshiyuki Kozuki, Takehito Shukuya, Kazuhiko Nakagawa, Tetsuya Mitsudomi, Nobuyuki Yamamoto, Takashi Asakawa, Ryoichi Asabe, Tomohiro Tanaka, Tomohide Tamura

    LANCET   390 ( 10089 )   29 - 39   2017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:ELSEVIER SCIENCE INC  

    Background Alectinib, a potent, highly selective, CNS-active inhibitor of anaplastic lymphoma kinase (ALK), showed promising efficacy and tolerability in the single-arm phase 1/2 AF-001JP trial in Japanese patients with ALK-positive non-small-cell lung cancer. Given those promising results, we did a phase 3 trial to directly compare the efficacy and safety of alectinib and crizotinib.
    Methods J-ALEX was a randomised, open-label, phase 3 trial that recruited ALK inhibitor-naive Japanese patients with ALK-positive non-small-cell lung cancer, who were chemotherapy-naive or had received one previous chemotherapy regimen, from 41 study sites in Japan. Patients were randomly assigned (1: 1) via an interactive web response system using a permuted-block method stratified by Eastern Cooperative Oncology Group performance status, treatment line, and disease stage to receive oral alectinib 300 mg twice daily or crizotinib 250 mg twice daily until progressive disease, unacceptable toxicity, death, or withdrawal. The primary endpoint was progression-free survival assessed by an independent review facility. The efficacy analysis was done in the intention-to-treat population, and safety analyses were done in all patients who received at least one dose of the study drug. The study is ongoing and patient recruitment is closed. This study is registered with the Japan Pharmaceutical Information Center (number JapicCTI-132316).
    Findings Between Nov 18, 2013, and Aug 4, 2015, 207 patients were recruited and assigned to the alectinib (n=103) or crizotinib (n=104) groups. At data cutoff for the second interim analysis, 24 patients in the alectinib group had discontinued treatment compared with 61 in the crizotinib group, mostly due to lack of efficacy or adverse events. At the second interim analysis (data cutoff date Dec 3, 2015), an independent data monitoring committee determined that the primary endpoint of the study had been met (hazard ratio 0.34 [99.7% CI 0.17-0.71], stratified log-rank p&lt; 0.0001) and recommended an immediate release of the data. Median progression-free survival had not yet been reached with alectinib (95% CI 20.3-not estimated) and was 10.2 months (8.2-12.0) with crizotinib. Grade 3 or 4 adverse events occurred at a greater frequency with crizotinib (54 [52%] of 104) than alectinib (27 [26%] of 103). Dose interruptions due to adverse events were also more prevalent with crizotinib (77 [74%] of 104) than with alectinib (30 [29%] of 103), and more patients receiving crizotinib (21 [20%]) than alectinib (nine [9%]) discontinued the study drug because of an adverse event. No adverse events with a fatal outcome occurred in either treatment group.
    Interpretation These results provide the first head-to-head comparison of alectinib and crizotinib and have the potential to change the standard of care for the first-line treatment of ALK-positive non-small-cell lung cancer. The dose of alectinib (300 mg twice daily) used in this study is lower than the approved dose in countries other than Japan; however, this limitation is being addressed in the ongoing ALEX study.

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  • Updated survival outcomes of NEJ005/TCOG0902, a randomized phase II study of concurrent (C) versus sequential alternating (S) gefitinib and chemotherapy in previously untreated non-small cell lung cancer (NSCLC) with sensitive epidermal growth factor receptor (EGFR) mutations. 査読

    Satoshi Oizumi, Shunichi Sugawara, Koichi Minato, Toshiyuki Harada, Akira Inoue, Yuka Fujita, Makoto Maemondo, Satoshi Watanabe, Kazuhiko Ito, Akihiko Gemma

    JOURNAL OF CLINICAL ONCOLOGY   35 ( 2 )   e000313   2017年5月

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    記述言語:英語   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

    DOI: 10.1200/JCO.2017.35.15_suppl.9038

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  • Effects of sublingual immunotherapy in a murine asthma model sensitized by intranasal administration of house dust mite extracts. 査読 国際誌

    Kenjiro Shima, Toshiyuki Koya, Keisuke Tsukioka, Takuro Sakagami, Takashi Hasegawa, Chiharu Fukano, Katsuyo Ohashi-Doi, Satoshi Watanabe, Eiichi Suzuki, Toshiaki Kikuchi

    Allergology international : official journal of the Japanese Society of Allergology   66 ( 1 )   89 - 96   2017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:JAPANESE SOCIETY ALLERGOLOGY  

    BACKGROUND: Sublingual immunotherapy (SLIT) has received attention as a method for allergen immunotherapy. However, the mechanism of SLIT has not yet been fully investigated. Therefore, we evaluated the effects of SLIT in a murine asthma model, sensitized by intranasal administration of house dust mite (HDM) extracts. METHODS: Female BALB/c mice were intranasally exposed to HDM for either 3 or 5 weeks (5 consecutive days per week). Mice were administered either low-dose (0.5 mg/day) or high-dose (5 mg/day) sublingual HDM extracts for 2 weeks, followed by an additional week of intranasal exposure. Airway hyperresponsiveness (AHR), bronchoalveolar lavage fluid (BALF) cell count, cytokine levels in the BALF and lymph node cell culture supernatants, and allergen-specific antibodies were measured. Lung histology was also investigated. RESULTS: In mice sensitized for 5 weeks, high-dose SLIT ameliorated AHR, airway eosinophilia and goblet cell metaplasia. In mice sensitized for 3 weeks, even low dose SLIT ameliorated AHR and airway eosinophilia. Th2 cytokine levels in culture supernatants of submandibular lymph node cells in high-dose SLIT mice decreased, whereas IL-10 levels increased. Total IgA in BALF increased in mice sensitized for 3 or 5 weeks, and high-dose SLIT also increased allergen-specific IgG2a in mice sensitized for 5 weeks. CONCLUSIONS: These data suggest that earlier induction of SLIT in HDM-sensitized mice provides superior suppression of AHR and goblet cell metaplasia. The modulation of allergen specific IgG2a and local IgA might play a role in the amelioration of AHR and airway inflammation.

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  • Transfer of in vitro-expanded naïve T cells after lymphodepletion enhances antitumor immunity through the induction of polyclonal antitumor effector T cells. 査読 国際誌

    Tanaka T, Watanabe S, Takahashi M, Sato K, Saida Y, Baba J, Arita M, Sato M, Ohtsubo A, Shoji S, Nozaki K, Ichikawa K, Kondo R, Aoki N, Ohshima Y, Sakagami T, Abe T, Moro H, Koya T, Tanaka J, Kagamu H, Yoshizawa H, Kikuchi T

    PloS one   12 ( 8 )   e0183976   2017年

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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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  • Effect of Lymphodepletion on Donor T Cells and the Role of Recipient Cells Persisting after Cytotoxic Treatments in Cancer Immunotherapies. 査読 国際誌

    Satoshi Watanabe, Masashi Arita, Miho Takahashi, Yu Saida, Toshiyuki Koya, Toshiaki Kikuchi

    Critical reviews in immunology   37 ( 1 )   59 - 73   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:Begell House Inc.  

    The effectiveness of lymphodepletion in antitumor immunity has been well established. Although recent studies have elucidated some of the broad mechanisms underlying the augmentation of antitumor immunity by lymphodepletion, such as increased availability of cytokines due to the elimination of cellular elements and improvement in tumor antigen presentation, the precise mechanisms remain unclear. Previous studies have focused on the enhancement of the functions of transferred antitumor CD8+ T cells after lymphodepletion. In this review, we discuss the important role of other immune cells in the effectiveness of lymphodepletion. Recent studies have demonstrated that lymphodepletion enhances not only transferred tumor-specific CD8+ T cells but also tumor-specific CD4+ T cells and polyclonal naïve T cells. Moreover, recipient immune cells, including CD8+ T cells, regulatory T cells, dendritic cells, and macrophages, are involved in the augmentation of antitumor effects by lymphodepletion. These host cells can survive lymphodepletive therapies and play a role in the development of antitumor immunity after lymphodepletion. Improvements in the understanding of lymphodepletion allow us to design effective cancer immunotherapy.

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  • Hypermutation and microsatellite instability in gastrointestinal cancers 査読

    Kizuki Yuza, Masayuki Nagahashi, Satoshi Watanabe, Kazuaki Takabe, Toshifumi Wakai

    Oncotarget   8 ( 67 )   112103 - 112115   2017年

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    記述言語:英語   出版者・発行元:Impact Journals LLC  

    Recent progress in cancer genome analysis using next-generation sequencing has revealed a high mutation burden in some tumors. The particularly high rate of somatic mutation in these tumors correlates with the generation of neo-antigens capable of eliciting an immune response. Identification of hypermutated tumors is therefore clinically valuable for selecting patients suitable for immunotherapy treatment. There are several known causes of hypermutation in tumors, such as ultraviolet light in melanoma, tobacco smoke in lung cancer, and excessive APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) activity in breast and gastric cancer. In gastrointestinal cancers, one of the leading causes of hypermutation is a defect in DNA mismatch repair, which results in microsatellite instability (MSI). This review will focus on the frequency, characteristics and genomic signature of hypermutated gastrointestinal cancers with MSI. Detection of tumor hypermutation in cancer is expected to not only predict the clinical benefit of immune checkpoint inhibitor treatment, but also to provide better surgical strategies for the patients with hypermutated tumors. Thus, in an era of precision medicine, identification of hypermutation and MSI will play an important role directing surgical and chemotherapeutic treatment.

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  • Nephrotoxicity of cisplatin combination chemotherapy in thoracic malignancy patients with CKD risk factors 査読

    Ko Sato, Satoshi Watanabe, Aya Ohtsubo, Satoshi Shoji, Daisuke Ishikawa, Tomohiro Tanaka, Koichiro Nozaki, Rie Kondo, Masaaki Okajima, Satoru Miura, Junta Tanaka, Takuro Sakagami, Toshiyuki Koya, Hiroshi Kagamu, Hirohisa Yoshizawa, Ichiei Narita

    BMC CANCER   16   222   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:BIOMED CENTRAL LTD  

    Background: Nephrotoxicity is the major side effect that limits the dose of cisplatin that can be safely administered, and it is a clinical problem in cancer patients who received cisplatin combination chemotherapy. Recent evidence has demonstrated that patients with chronic kidney disease (CKD) have an increased risk of developing acute kidney injury (AKI). The present study was conducted to evaluate the prevalence of CKD risk factors in patients who received cisplatin and to assess the correlation between CKD risk factors and cisplatin-induced AKI.
    Methods: We retrospectively analyzed 84 patients treated with cisplatin combination chemotherapy for thoracic malignancies. AKI was defined as a decrease in the estimated glomerular filtration rate (eGFR) &gt; 25 % from base line, an increase in the serum creatinine (sCre) level of &gt; 0.3 mg/dl or &gt;= 1.5 times the baseline level.
    Results: Eighty of the 84 patients (95.2 %) had at least one risk factor for CKD. All enrolled patients received cisplatin with hydration, magnesium supplementation and mannitol. Cisplatin-induced AKI was observed in 18 patients (21.4 %). Univariate analysis revealed that cardiac disease and use of non-steroidal anti-inflammatory drugs (NSAIDs) were associated with cisplatin-induced nephrotoxicity (odds ratios [OR] 6 and 3.56, 95 % confidence intervals [CI] 1.21-29.87 and 1.11-11.39, p = 0.04 and p = 0.04, respectively). Multivariate analysis revealed that cisplatin nephrotoxicity occurred significantly more often in patients with both risk factors (OR 13.64, 95 % CI 1.11-326.83, p = 0.04). Patients with more risk factors for CKD tended to have a greater risk of developing cisplatin-induced AKI.
    Conclusions: We should consider avoiding administration of cisplatin to patients with CKD risk factors, particularly cardiac disease and NSAID use.

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  • Comparison of Gefitinib Versus Chemotherapy in Patients with Non-small Cell Lung Cancer with Exon 19 Deletion. 査読 国際誌

    Satoshi Watanabe, Akira Inoue, Toshihiro Nukiwa, Kunihiko Kobayashi

    Anticancer research   35 ( 12 )   6957 - 61   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:INT INST ANTICANCER RESEARCH  

    BACKGROUND: Second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) afatinib as first-line treatment has been demonstrated to improve overall survival (OS) in patients with non-small cell lung cancer (NSCLC) harboring an exon 19 deletion (del19) of EGFR compared to platinum-doublet chemotherapy. However, it is unclear whether first-generation EGFR-TKIs improve OS in patients with del19 in the first-line treatment. PATIENTS AND METHODS: We performed a post-hoc analysis of patients with del19 or L858R mutation of EGFR who received gefitinib in the NEJ002 study, which compared gefitinib to carboplatin-paclitaxel. RESULTS: A total of 58 patients and 57 patients with del19 EGFR received gefitinib and carboplatin-paclitaxel, respectively. No OS differences were observed between patients receiving gefitinib and carboplatin-paclitaxel irrespective of del19 (29.3 months vs. 29.7 months, p=0.53) or L858R (28.4 months vs. 25.1 months, p=0.45). CONCLUSION: In contrast to afatinib, it is suggested that first-line gefitinib does not improve OS in patients with del19 of EGFR compared with platinum-doublet chemotherapy.

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  • A case of pneumatosis cystoides intestinalis secondary to gefitinib therapy for lung adenocarcinoma 査読

    Takuya Ando, Jun Sakata, Tomohiro Maruyama, Yuki Hirose, Yasuyuki Okabe, Kazuyasu Takizawa, Masayuki Nagahashi, Yoshifumi Shimada, Takashi Ishikawa, Hitoshi Kameyama, Takashi Kobayashi, Masahiro Minagawa, Shinichi Kosugi, Yu Koyama, Aya Ohtsubo, Satoshi Watanabe, Toshifumi Wakai

    Japanese Journal of Cancer and Chemotherapy   42 ( 7 )   847 - 849   2015年7月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Journal of Cancer and Chemotherapy Publishers Inc.  

    Pneumatosis cystoides intestinalis (PCI) is a relatively rare condition, characterized by subserosal or submucosal air within the bowel wall. Herein, we report a rare case of PCI secondary to treatment with an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). A 71-year-old man, who had received gefitinib therapy for 2 years and 5 months for lung adenocarcinoma with metastases to the bones and brain, presented with abdominal pain, diarrhea, and vomiting. Computed tomography of the abdomen revealed intramural air in the small bowel, free air in the abdomen, and moderate ascites. A diagnosis of PCI was made, and the patient was managed conservatively by discontinuing gefitinib treatment, because his vital signs were stable and there was no sign of peritonitis. The patient's symptoms gradually improved, and follow-up CT after 1 week revealed that the initial findings had almost completely resolved. Clinicians should note that treatment with gefitinib might cause PCI.

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  • Critical Roles of Chemoresistant Effector and Regulatory T Cells in Antitumor Immunity after Lymphodepleting Chemotherapy 査読

    Yu Saida, Satoshi Watanabe, Tomohiro Tanaka, Junko Baba, Ko Sato, Satoshi Shoji, Natsue Igarashi, Rie Kondo, Masaaki Okajima, Jun Koshio, Kosuke Ichikawa, Koichiro Nozaki, Daisuke Ishikawa, Toshiyuki Koya, Satoru Miura, Junta Tanaka, Hiroshi Kagamu, Hirohisa Yoshizawa, Koh Nakata, Ichiei Narita

    JOURNAL OF IMMUNOLOGY   195 ( 2 )   726 - 735   2015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:AMER ASSOC IMMUNOLOGISTS  

    Antitumor immunity is augmented by cytotoxic lymphodepletion therapies. Adoptively transferred naive and effector T cells proliferate extensively and show enhanced antitumor effects in lymphopenic recipients. Although the impact of lymphodepletion on transferred donor T cells has been well evaluated, its influence on recipient T cells is largely unknown. The current study demonstrates that both regulatory T cells (Tregs) and effector CD8(+) T cells from lymphopenic recipients play critical roles in the development of antitumor immunity after lymphodepletion. Cyclophosphamide (CPA) treatment depleted lymphocytes more efficiently than other cytotoxic agents; however, the percentage of CD4(+)CD25(+) Foxp3(+) Tregs was significantly increased in CPA-treated lymphopenic mice. Depletion of these chemoresistant Tregs following CPA treatment and transfer of naive CD4(+) T cells augmented the antitumor immunity and significantly suppressed tumor progression. Further analyses revealed that recipient CD8(+) T cells were responsible for this augmentation. Using Rag2(-/-) mice or depletion of recipient CD8(+) T cells after CPA treatment abrogated the augmentation of antitumor effects in CPA-treated reconstituted mice. The transfer of donor CD4(+) T cells enhanced the proliferation of CD8(+) T cells and the priming of tumor-specific CD8(+) T cells originating from the lymphopenic recipients. These results highlight the importance of the recipient cells surviving cytotoxic regimens in cancer immunotherapies.

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  • 肺腺癌に対するGefitinib投与中に発症した腸管嚢腫様気腫症の1例

    安藤 拓也, 坂田 純, 丸山 智宏, 廣瀬 雄己, 岡部 康之, 滝沢 一泰, 永橋 昌幸, 島田 能史, 石川 卓, 亀山 仁史, 小林 隆, 皆川 昌広, 小杉 伸一, 小山 諭, 大坪 亜矢, 渡部 聡, 若井 俊文

    癌と化学療法   42 ( 7 )   847 - 849   2015年7月

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    記述言語:日本語   出版者・発行元:(株)癌と化学療法社  

    症例は71歳、男性。骨転移、脳転移を伴う肺腺癌に対して、2年5ヵ月前よりgefitinib(250mg/日)を連日投与され、安定(stable disease:SD)を維持中に腹痛、下痢、嘔吐を発症した。腹部骨盤造影CT検査を施行すると小腸壁内ガス像、腹腔内遊離ガス像、中等量の腹水を認め、腸管嚢腫様気腫症(pneumatosis cystoides intestinalis:PCI)の診断となった。バイタルサインが安定し、腹部理学所見で腹膜炎を疑う所見がみられなかったため、gefitinibを休薬して保存的に治療を開始した。自覚症状は徐々に改善し、治療開始7日後の腹部骨盤造影CT検査では画像所見も著明に改善した。(著者抄録)

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  • The Effects of All-Trans Retinoic Acid on the Induction of Oral Tolerance in a Murine Model of Bronchial Asthma 査読

    Hirotaka Sakamoto, Toshiyuki Koya, Keisuke Tsukioka, Kenjiro Shima, Satoshi Watanabe, Hiroshi Kagamu, Yosuke Kimura, Takuro Sakagami, Takashi Hasegawa, Eiichi Suzuki, Ichiei Narita

    INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY   167 ( 3 )   167 - 176   2015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: Active suppression induced by regulatory T (Treg) cells is reported to be one of the mechanisms involved in oral tolerance. All-trans retinoic acid (ATRA) has been reported to affect Treg cell differentiation. The present study examined the effects of ATRA on the induction of oral tolerance in a murine model of bronchial asthma. Methods: BALB/c mice were sensitized to and challenged with ovalbumin (OVA) through feeding followed by OVA challenges. In some study groups ATRA was orally administered concomitantly with OVA feeding either in the presence or absence of the retinoic acid receptor antagonist LE135. Lung CD4(+) T cells were isolated from mice exposed to ATRA and/or OVA, and transferred to control mice. Airway hyperresponsiveness (AHR), cell counts and cytokine levels in bronchoalveolar lavage (BAL) fluid, and lung histology were assessed. Results: Concomitant administration of ATRA with OVA ameliorated AHR, airway eosinophilia, elevation of cytokines in BAL fluid and goblet cell metaplasia. The proportion of Treg cells in the lungs was increased in mice treated with OVA and ATRA, as compared to those treated with OVA only. Transfer of lung CD4(+) T cells from mice treated with OVA and ATRA induced suppression of AHR and airway inflammation. LE135 completely reversed the effects of ATRA on AHR, airway allergic inflammation and the number of Treg cells in the lungs. Conclusion: These data suggested that oral administration of ATRA with OVA had the potential to enhance oral tolerance in this murine model of bronchial asthma. These effects were mediated, at least in part, by Treg cell expansion. (C) 2015 S. Karger AG, Basel

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  • Advanced Thymic Cancer Treated with Carboplatin and Paclitaxel in a Patient Undergoing Hemodialysis 査読

    Satoru Miura, Hiroshi Kagamu, Takehito Sakai, Koichiro Nozaki, Katsuaki Asakawa, Hiroshi Moro, Masaaki Okajima, Satoshi Watanabe, Suguru Yamamoto, Noriaki Iino, Shin Goto, Junichiro James Kazama, Hirohisa Yoshizawa, Ichiei Narita

    INTERNAL MEDICINE   54 ( 1 )   55 - 58   2015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:JAPAN SOC INTERNAL MEDICINE  

    A 53-year-old man with an asymptomatic anterior mediastinal tumor undergoing hemodialysis was referred to our institution. He was diagnosed with thymic basaloid carcinoma based on the findings of a chest tomography-guided biopsy and successfully treated with carboplatin (300 mg/m(2)/day) and paclitaxel (200 mg/ m2/day) on day 1 for six three-week cycles. To our knowledge, this is the first report regarding the efficiency of a carboplatin dose-definition method based on the body surface area with paclitaxel in a hemodialysis patient. This report may therefore be useful for treating hemodialysis patients who are candidates for carboplatin and paclitaxel therapy.

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  • A case of thymic cancer effectively treated by weekly paclitaxel combined with carboplatin 査読

    Rie Kondo, Satoshi Watanabe, Daisuke Ishikawa, Tomohiro Tanaka, Yasuyoshi Ohshima, Katsuaki Asakawa, Takuro Sakagami, Masaaki Okajima, Satoru Miura, Yoshiki Hayashi, Junta Tanaka, Hiroshi Kagamu, Hirohisa Yoshizawa, Ichiei Narita

    Japanese Journal of Cancer and Chemotherapy   41 ( 13 )   2607 - 2609   2014年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Journal of Cancer and Chemotherapy Publishers Inc.  

    A 65-year-old woman with left chest pain, back pain, and palpitation that had persisted for 2 months was referred to our hospital. Computed tomography of her chest showed an anterior mediastinal tumor with mediastinal lymphadenopathy, left pleural effusion, and pericardial effusion. Endobronchial ultrasound-guided transbronchial needle aspiration of the subcarinal lymphadenopathy was performed. The pathological findings and other examinations such as bone scintigraphy suggested advanced thymic cancer (stage IVb according to the Masaoka classification of thymic epithelial tumors). The patient was treated with combination chemotherapy of carboplatin (area under the curve [AUC]=6, 656mg/body, day 1) and weekly paclitaxel (70 mg/m2, 100 mg/body, days 1, 8, and 15). After 4 cycles of chemotherapy, a partial response was achieved and the pericardial effusion disappeared. The patient did not experience any severe toxicity, except for grade 1 nausea, grade 2 anemia, and grade 2 alopecia. Weekly paclitaxel combined with carboplatin appears to be a useful regimen with minimal toxicity for advanced thymic cancer.

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  • DDX3X Induces Primary EGFR-TKI Resistance Based on Intratumor Heterogeneity in Lung Cancer Cells Harboring EGFR-Activating Mutations 査読

    Koichiro Nozaki, Hiroshi Kagamu, Satoshi Shoji, Natsue Igarashi, Aya Ohtsubo, Masaaki Okajima, Satoru Miura, Satoshi Watanabe, Hirohisa Yoshizawa, Ichiei Narita

    PLOS ONE   9 ( 10 )   e111019   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)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    The specific mechanisms how lung cancer cells harboring epidermal growth factor receptor (EGFR) activating mutations can survive treatment with EGFR-tyrosine kinase inhibitors (TKIs) until they eventually acquire treatment-resistance genetic mutations are unclear. The phenotypic diversity of cancer cells caused by genetic or epigenetic alterations (intratumor heterogeneity) confers treatment failure and may foster tumor evolution through Darwinian selection. Recently, we found DDX3X as the protein that was preferentially expressed in murine melanoma with cancer stem cell (CSC)-like phenotypes by proteome analysis. In this study, we transfected PC9, human lung cancer cells harboring EGFR exon19 deletion, with cDNA encoding DDX3X and found that DDX3X, an ATP-dependent RNA helicase, induced CSC-like phenotypes and the epithelial-mesenchymal transition (EMT) accompanied with loss of sensitivity to EGFR-TKI. DDX3X expression was associated with upregulation of Sox2 and increase of cancer cells exhibiting CSC-like phenotypes, such as anchorage-independent proliferation, strong expression of CD44, and aldehyde dehydrogenase (ALDH). The EMT with switching from E-cadherin to N-cadherin was also facilitated by DDX3X. Either ligand-independent or ligand-induced EGFR phosphorylation was inhibited in lung cancer cells that strongly expressed DDX3X. Lack of EGFR signal addiction resulted in resistance to EGFR-TKI. Moreover, we found a small nonadherent subpopulation that strongly expressed DDX3X accompanied by the same stem cell-like properties and the EMT in parental PC9 cells. The unique subpopulation lacked EGFR signaling and was highly resistant to EGFR-TKI. In conclusion, our data indicate that DDX3X may play a critical role for inducing phenotypic diversity, and that treatment targeting DDX3X may overcome primary resistance to EGFR-TKI resulting from intratumor heterogeneity.

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  • Effectiveness of gefitinib against non-small-cell lung cancer with the uncommon EGFR mutations G719X and L861Q. 査読 国際誌

    Satoshi Watanabe, Yuji Minegishi, Hirohisa Yoshizawa, Makoto Maemondo, Akira Inoue, Shunichi Sugawara, Hiroshi Isobe, Masao Harada, Yoshiki Ishii, Akihiko Gemma, Koichi Hagiwara, Kunihiko Kobayashi

    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer   9 ( 2 )   189 - 94   2014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:LIPPINCOTT WILLIAMS & WILKINS  

    INTRODUCTION: In non-small-cell lung cancer, an exon 19 deletion and an L858R point mutation in the epidermal growth factor receptor (EGFR) are predictors of a response to EGFR-tyrosine kinase inhibitors. However, it is uncertain whether other uncommon EGFR mutations are associated with sensitivity to EGFR-tyrosine kinase inhibitors. METHODS: A post-hoc analysis to assess prognostic factors was performed with the use of patients with EGFR mutations (exon 19 deletion, L858R, G719X, and L861Q) who were treated with gefitinib in the NEJ002 study, which compared gefitinib with carboplatin-paclitaxel as the first-line therapy. RESULTS: In the NEJ002 study, 225 patients with EGFR mutations received gefitinib at any treatment line. The Cox proportional hazards model indicated that performance status, response to chemotherapy, response to gefitinib, and mutation types were significant prognostic factors. Overall survival (OS) was significantly shorter among patients with uncommon EGFR mutations (G719X or L861Q) compared with OS of those with common EGFR mutations (12 versus 28.4 months; p = 0.002). In the gefitinib group (n = 114), patients with uncommon EGFR mutations had a significantly shorter OS (11.9 versus 29.3 months; p < 0.001). By contrast, OS was similar between patients with uncommon mutations and those with common mutations in the carboplatin-paclitaxel group (n = 111; 22.8 versus 28 months; p = 0.358). CONCLUSIONS: The post-hoc analyses clearly demonstrated shorter survival for gefitinib-treated patients with uncommon EGFR mutations compared with the survival of those with common mutations and suggest that the first-line chemotherapy may be relatively effective for non-small-cell lung cancer with uncommon EGFR mutations.

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  • Morphine and breast tumor metastasis: the role of matrix-degrading enzymes 査読

    Banafsheh Afsharimani, JoAnne Baran, Satoshi Watanabe, Daniel Lindner, Peter J. Cabot, Marie-Odile Parat

    CLINICAL & EXPERIMENTAL METASTASIS   31 ( 2 )   149 - 158   2014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  

    Opioids including morphine are commonly used in pain management during and after cancer surgery but have been linked to a variety of pro- and anti-tumor effects. In the present study the effect of morphine administration on the localization and growth of breast tumor cells in lungs and the level of extracellular matrix (ECM) proteases were investigated. In a mouse syngeneic model of intravenously inoculated breast cancer cells, morphine administration led to a reduction in the localization and growth of tumors in the lungs and a reduction in circulating matrix metalloproteinase-9 (MMP-9) and urokinase-like plasminogen activator (uPA). To model the involvement of non-malignant cells of the tumor microenvironment in the changes we observed in the level of proteases, we co-cultured breast cancer cells with macrophages, endothelial cells and fibroblasts. We found a significant elevation of matrix proteases as well as matrix protease inhibitors in co-cultures of breast cancer cells with macrophages or endothelial cells. Interestingly, morphine treatment of these co-cultures reduced the level of MMP-9 and increased its endogenous inhibitor, TIMP-1, thereby altering the proteolytic profile. Morphine affected the level of enzymes in co-cultures but not in cells grown individually. This suggests that anti-tumor effects of morphine observed in our in vivo model could be mediated at least in part through modulation of paracrine communication between cancer cells and non-malignant cells in the tumor microenvironment.

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  • DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked is an immunogenic target of cancer stem cells 査読

    Jun Koshio, Hiroshi Kagamu, Koichiro Nozaki, Yu Saida, Tomohiro Tanaka, Satoshi Shoji, Natsue Igarashi, Satoru Miura, Masaaki Okajima, Satoshi Watanabe, Hirohisa Yoshizawa, Ichiei Narita

    Cancer Immunology, Immunotherapy   62 ( 10 )   1619 - 1628   2013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)  

    Accumulating evidence suggests that most solid malignancies consist of heterogeneous tumor cells and that a relatively small subpopulation, which shares biological features with stem cells, survives through potentially lethal stresses such as chemotherapy and radiation treatment. Since the survival of this subpopulation of cancer stem cells (CSC) plays a critical role in recurrence, it must be eradicated in order to cure cancer. We previously reported that vaccination with CD133+ murine melanoma cells exhibiting biological CSC features induced CSC-specific effector T cells. These were capable of eradicating CD133+ tumor cells in vivo, thereby curing the parental tumor. In the current study, we indicated that DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked (DDX3X) is an immunogenic protein preferentially expressed in CD133+ tumor cells. Vaccination with DDX3X primed specific T cells, resulting in protective and therapeutic antitumor immunity. The DDX3X-primed CD4+ T cells produced CD133 + tumor-specific IFNγ and IL-17 and mediated potent antitumor therapeutic efficacy. DDX3X is expressed in various human cancer cells, including lung, colon, and breast cancer cells. These results suggest that anti-DDX3X immunotherapy is a promising treatment option in efforts to eradicate CSC in the clinical setting. © 2013 Springer-Verlag Berlin Heidelberg.

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  • The efficacy of triplet antiemetic therapy with 0.75 mg of palonosetron for chemotherapy-induced nausea and vomiting in lung cancer patients receiving highly emetogenic chemotherapy 査読

    Satoru Miura, Satoshi Watanabe, Kazuhiro Sato, Masato Makino, Osamu Kobayashi, Hiromi Miyao, Akira Iwashima, Masaaki Okajima, Junta Tanaka, Hiroshi Tanaka, Hiroshi Kagamu, Akira Yokoyama, Ichiei Narita, Hirohisa Yoshizawa

    SUPPORTIVE CARE IN CANCER   21 ( 9 )   2575 - 2581   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:SPRINGER  

    Chemotherapy-induced nausea and vomiting (CINV) are some of the most problematic symptoms for cancer patients. Triplet therapy consisting of a 5HT3 receptor antagonist, aprepitant, and dexamethasone is a guideline-recommended antiemetic prophylaxis for highly emetogenic chemotherapy (HEC). The efficacy and safety of triplet therapy using a 0.75-mg dose of palonosetron have not yet been investigated. We performed a prospective phase II study using triplet antiemetic therapy with 0.75 mg of palonosetron.
    Chemotherapy-na &lt; ve lung cancer patients scheduled to receive HEC were enrolled. The eligible patients were pretreated with antiemetic therapy consisting of the intravenous administration of 0.75 mg of palonosetron, and 9.9 mg of dexamethasone and the oral administration of 125 mg of aprepitant on day 1, followed by the oral administration of 80 mg of aprepitant on days 2-3 and the oral administration of 8 mg of dexamethasone on days 2-4. The primary endpoint was the complete response rate (the CR rate; no vomiting and no rescue medication) during the overall phase (0-120 h).
    The efficacy analysis was performed in 63 patients. The CR rates during the overall, acute and delayed phases were 81.0, 96.8, and 81.0 %, respectively. The no nausea and no significant nausea rate during the overall phase were 54.0 and 66.7 %, respectively. The most common adverse event was grade 1 or 2 constipation.
    Triplet antiemetic therapy using a 0.75-mg dose of palonosetron shows a promising antiemetic effect in preventing CINV in lung cancer patients receiving HEC.

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  • Epitope diversification driven by non-tumor epitope-specific Th1 and Th17 mediates potent antitumor reactivity 査読

    Kosuke Ichikawa, Hiroshi Kagamu, Kenichi Koyama, Takao Miyabayashi, Jun Koshio, Satoru Miura, Satoshi Watanabe, Hirohisa Yoshizawa, Ichiei Narita

    VACCINE   30 ( 43 )   6190 - 6197   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:ELSEVIER SCI LTD  

    MHC class I-restricted peptide-based vaccination therapies have been conducted to treat cancer patients, because CD8(+) CTL can efficiently induce apoptosis of tumor cells in an MHC class I-restricted epitope-specific manner. Interestingly, clinical responders are known to demonstrate reactivity to epitopes other than those used for vaccination: however, the mechanism underlying how antitumor T cells with diverse specificity are induced is unclear. In this study, we demonstrated that dendritic cells (DCs) that engulfed apoptotic tumor cells in the presence of non-tumor MHC class II-restricted epitope peptides, OVA(323-339), efficiently presented tumor-associated antigens upon effector-dominant CD4(+) T cell balance against regulatory T cells (Treg) for the OVA(323-339) epitope. Th1 and Th17 induced tumor-associated antigens presentation of DC, while Th2 ameliorated tumor-antigen presentation for CD8(+) T cells. Blocking experiments with anti-IL-23p19 antibody and anti-IL-23 receptor indicated that an autocrine mechanism of IL-23 likely mediated the diverted tumor-associated antigens presentation of DC. Tumor-associated antigens presentation of DC induced by OVA(323-339) epitope-specific CD4(+) T cells resulted in facilitated antitumor immunity in both priming and effector phase in vivo. Notably, this immunotherapy did not require pre-treatment to reduce Treg induced by tumor. This strategy may have clinical implications for designing effective antitumor immunotherapies. (c) 2012 Elsevier Ltd. All rights reserved.

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  • Depletion of radio-resistant regulatory T cells enhances antitumor immunity during recovery from lymphopenia 査読

    Junko Baba, Satoshi Watanabe, Yu Saida, Tomohiro Tanaka, Takao Miyabayashi, Jun Koshio, Kosuke Ichikawa, Koichiro Nozaki, Toshiyuki Koya, Katsuya Deguchi, Chunrui Tan, Satoru Miura, Hiroshi Tanaka, Junta Tanaka, Hiroshi Kagamu, Hirohisa Yoshizawa, Ko Nakata, Ichiei Narita

    BLOOD   120 ( 12 )   2417 - 2427   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:AMER SOC HEMATOLOGY  

    Cytotoxic lymphodepletion therapies augment antitumor immune responses. The generation and therapeutic efficacy of antitumor effector T cells (T(E)s) are enhanced during recovery from lymphopenia. Although the effects of lymphodepletion on naive T cells (T(N)s) and T(E)s have been studied extensively, the influence of lymphodepletion on suppressor cells remains poorly understood. In this study, we demonstrate a significant increase of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) in sublethally irradiated lymphopenic mice. These radio-resistant Tregs inhibited the induction of T(E)s in tumor-draining lymph-nodes (TDLNs) during recovery from lymphopenia. The transfer of T(N)s into lymphopenic tumor-bearing mice resulted in some antitumor effects; however, Treg depletion after whole-body irradiation and reconstitution strongly inhibited tumor progression. Further analyses revealed that tumor-specific T cells were primed from the transferred T(N)s, whereas the Tregs originated from irradiated recipient cells. As in irradiated lymphopenic mice, a high percentage of Tregs was observed in cyclophosphamide-treated lymphopenic mice. The inhibition of Tregs in cyclophosphamide-treated mice significantly reduced tumor growth. These results indicate that the Tregs that survive cytotoxic therapies suppress antitumor immunity during recovery from lymphopenia and suggest that approaches to deplete radio and chemo-resistant Tregs can enhance cancer immunotherapies. (Blood. 2012;120(12):2417-2427)

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  • Vaccination with CD133(+) melanoma induces specific Th17 and Th1 cell-mediated antitumor reactivity against parental tumor 査読

    Takao Miyabayashi, Hiroshi Kagamu, Jun Koshio, Kosuke Ichikawa, Junko Baba, Satoshi Watanabe, Hiroshi Tanaka, Junta Tanaka, Hirohisa Yoshizawa, Koh Nakata, Ichiei Narita

    CANCER IMMUNOLOGY IMMUNOTHERAPY   60 ( 11 )   1597 - 1608   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:SPRINGER  

    Accumulating evidence suggests that cancer cells possess a small subpopulation that survives during potentially lethal stresses, including chemotherapy, radiation treatment, and molecular-targeting therapy. CD133 is a putative marker that distinguishes a minor subpopulation from normal differentiated tumor cells in many cancers. Although it is necessary to eradicate all cancer cells to obtain a cure, effective treatment to eliminate the CD133(+) treatment-tolerant cells has not been elucidated. In this study, we demonstrated that a CD133(+) subpopulation in murine melanoma is immunogenic and that effector T cells specific for the CD133(+) melanoma cells mediated potent antitumor reactivity, curing the mice of the parental melanoma. CD133(+) melanoma antigens preferentially induced type 17 T helper (Th17) cells and Th1 cells but not Th2 cells. CD133(+) melanoma cell-specific CD4(+) T-cell treatment eradicated not only CD133(+) tumor cells but also CD133(-) tumor cells while inducing long-lasting accumulation of lymphocytes and dendritic cells with upregulated MHC class II in tumor tissues. Further, the treatment prevented regulatory T-cell induction. These results indicate that T-cell immunotherapy is a promising treatment option to eradicate CD133(+) drug-tolerant cells to obtain a cure for cancer.

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  • Clinical responses to EGFR-tyrosine kinase inhibitor retreatment in non-small cell lung cancer patients who benefited from prior effective gefitinib therapy: a retrospective analysis 査読

    Satoshi Watanabe, Junta Tanaka, Takeshi Ota, Rie Kondo, Hiroshi Tanaka, Hiroshi Kagamu, Kosuke Ichikawa, Jun Koshio, Junko Baba, Takao Miyabayashi, Ichiei Narita, Hirohisa Yoshizawa

    BMC CANCER   11   1   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:BIOMED CENTRAL LTD  

    Background: Gefitinib was the first epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) approved for the treatment of advanced non-small cell lung cancer (NSCLC). Few treatment options are available for NSCLC patients who have responded to gefitinib treatment and demonstrated tumor progression. The present study was conducted to evaluate the efficacy and toxicity of the 2(nd) EGFR-TKI administration.
    Methods: We retrospectively analyzed 11 patients who had obtained a partial response (PR) or stable disease (SD) with gefitinib treatment and were re-treated with EGFR-TKI after failure of the initial gefitinib treatment.
    Results: Three patients (27%) were treated with gefitinib as the 2(nd) EGFR-TKI, and 8 patients (73%) received erlotinib. Only one patient (9%) showed PR, 7 (64%) achieved SD, and 3 (27%) had progressive disease. The disease control rate was 73% (95% CI, 43% - 91%) and the median progression-free survival was 3.4 months (95% CI, 2 - 5.2). The median overall survival from the beginning of the 2(nd) EGFR-TKI and from diagnosis were 7.3 months (95% CI, 2.7 - 13) and 36.7 months (95% CI, 23.6 - 43.9), respectively. No statistical differences in PFS or OS were observed between gefitinib and erlotinib as the 2(nd) EGFR-TKI (PFS, P = 0.23 and OS, P = 0.052). The toxicities associated with the 2(nd) EGFR-TKI were generally acceptable and comparable to those observed for the initial gefitinib therapy.
    Conclusions: Our results indicate that a 2(nd) EGFR-TKI treatment can be an effective treatment option for gefitinib responders.

    DOI: 10.1186/1471-2407-11-1

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  • Henoch Schönlein purpura associated with pulmonary adenocarcinoma. 査読

    Mifune D, Watanabe S, Kondo R, Wada Y, Moriyama H, Kagamu H, Yoshizawa H, Tetsuka T, Matsuyama A, Ito K, Narita I

    Journal of medical case reports   5   226   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1186/1752-1947-5-226

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  • Paraneoplastic neurological syndrome and polyglandular autoimmune syndrome type 2 in a case of small cell lung cancer 査読

    S. Watanabe, J. Tanaka, T. Ohta, H. Yoshizawa, F. Gejyo

    THORAX   63 ( 12 )   1118 - 1119   2008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:B M J PUBLISHING GROUP  

    We report a female patient with small cell lung cancer (SCLC) and clinical findings consistent with polyglandular autoimmune syndrome type 2 (PGA2) and paraneoplastic neurological syndrome (PNS). To the best of our knowledge, this is the first reported case of SCLC associated with PGA2 and PNS. All of the autoantibodies detected before anticancer treatment decreased below the upper normal limits after serial treatment, and the patient&apos;s clinical symptoms also improved. Cross reactivity of autoantibodies may have contributed to the complicated clinical picture of this patient.

    DOI: 10.1136/thx.2007.093211

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  • Tumor-induced CD11b+Gr-1+ myeloid cells suppress T cell sensitization in tumor-draining lymph nodes. 査読 国際誌

    Satoshi Watanabe, Katsuya Deguchi, Rongxiu Zheng, Hidemasa Tamai, Li-Xin Wang, Peter A Cohen, Suyu Shu

    Journal of immunology (Baltimore, Md. : 1950)   181 ( 5 )   3291 - 300   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:AMER ASSOC IMMUNOLOGISTS  

    Suppression of tumor-specific T cell sensitization is a predominant mechanism of tumor escape. To identify tumor-induced suppressor cells, we transferred spleen cells from mice bearing progressive MCA205 sarcoma into sublethally irradiated mice. These mice were then inoculated subdermally with tumor cells to stimulate T cell response in the tumor-draining lymph-node (TDLN). Tumor progression induced splenomegaly with a dramatic increase (22.1%) in CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSC) compared with 2.6% of that in normal mice. Analyses of therapeutic effects by the adoptive immunotherapy revealed that the transfer of spleen cells from tumor-bearing mice severely inhibited the generation of tumor-immune T cells in the TDLN. We further identified MDSC to be the dominant suppressor cells. However, cells of identical phenotype from normal spleens lacked the suppressive effects. The suppression was independent of CD4(+)CD25(+) regulatory T cells. Intracellular IFN-gamma staining revealed that the transfer of MDSC resulted in a decrease in numbers of tumor-specific CD4(+) and CD8(+) T cells. Transfer of MDSC from MCA207 tumor-bearing mice also suppressed the MCA205 immune response indicating a lack of immunologic specificity. Further analyses demonstrated that MDSC inhibited T cell activation that was triggered either by anti-CD3 mAb or by tumor cells. However, MDSC did not suppress the function of immune T cells in vivo at the effector phase. Our data provide the first evidence that the systemic transfer of MDSC inhibited and interfered with the sensitization of tumor-specific T cell responses in the TDLN.

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  • Effective treatment of spontaneous metastases derived from a poorly immunogenic murine mammary carcinoma by combined dendritic-tumor hybrid vaccination and adoptive transfer of sensitized T cells. 査読 国際誌

    Hidemasa Tamai, Satoshi Watanabe, Rongxiu Zheng, Katsuya Deguchi, Peter A Cohen, Gary K Koski, Suyu Shu

    Clinical immunology (Orlando, Fla.)   127 ( 1 )   66 - 77   2008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:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Curative immunotherapy against spontaneous metastases of poorly immunogenic tumors has been difficult to demonstrate, but it is highly relevant to clinical disease conditions. The 4T1 mammary carcinoma shares many characteristics of human mammary cancer. Here, mice with 4T1 spontaneous metastases were treated effectively with a combination of dendritic (DC)-tumor hybrid vaccination and adoptive transfer of tumor-draining lymph node-derived immune T cells. This strategy significantly prolonged survival and cured some mice. In this model, the combined immunotherapy induced a dramatic increase of T cells in the lung where metastases were located and in the spleen where tumor was not present. The mechanism of increasing numbers of T cells is likely attributed to the ability of DC-tumor hybrids to stimulate vigorous proliferation of adoptively transferred T cells rather than to promote their infiltration into tumor-harboring and lymphoid organs. Taken together, the combined approach may be useful for clinical development of cancer immunotherapy.

    DOI: 10.1016/j.clim.2007.12.001

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  • Generation of anti-tumour effector T cells from naïve T cells by stimulation with dendritic/tumour fusion cells. 査読

    Ishida A, Tanaka H, Hiura T, Miura S, Watanabe S, Matsuyama K, Kuriyama H, Tanaka J, Kagamu H, Gejyo F, Yoshizawa H

    Scandinavian journal of immunology   66 ( 5 )   546 - 554   2007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)  

    DOI: 10.1111/j.1365-3083.2007.02012.x

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  • [A case of squamous cell carcinoma of unknown primary site with involvement of cervico-mediastinal lymph nodes successfully treated by chemoradiotherapy]. 査読

    Watanabe S, Tanaka J, Tsuboi K, Tanaka H, Kagamu H, Yoshizawa H, Suzuki E, Gejyo F

    Gan to kagaku ryoho. Cancer & chemotherapy   33 ( 10 )   1493 - 1495   2006年10月

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  • Mechanism of third signals provided by IL-12 and OX-40R ligation in eliciting therapeutic immunity following dendritic-tumor fusion vaccination. 査読 国際誌

    Hideyuki Kuriyama, Satoshi Watanabe, Jorgen Kjaergaard, Hidemasa Tamai, Rongxiu Zheng, Andrew D Weinberg, Hong-Ming Hu, Peter A Cohen, Gregory E Plautz, Suyu Shu

    Cellular immunology   243 ( 1 )   30 - 40   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:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Dendritic-tumor heterokaryons generated by electrofusion are highly immunogenic. In animal studies, a single vaccination was therapeutic for tumors established in the lung, skin, and brain. However, effective therapy required a third signal which could be provided by exogenous IL-12 or the agonistic anti-OX-40R monoclonal antibody (mAb). In this study, we investigated the mechanism and mode of actions of these two seemingly distinct adjuvants. In immunotherapy of the MCA205 sarcoma, administration of the neutralizing anti-IL-12 mAb nearly completely blocked the adjuvant effect of IL-12, but had minimal inhibitory effects on anti-OX-40R mAb. By contrast, in vivo administration of the antagonistic anti-OX-40L mAb inhibited the adjuvant effects of both IL-12 and anti-OX-40R mAb. Thus, a common pathway of endogenous OX-40 interaction is critical for the development of a therapeutic immune response. Analysis of the third signal mechanism revealed that in the absence of an adjuvant, vaccination with fusion hybrids led to IL-10 production without eliciting IFN-gamma secreting cells. The addition of IL-12 to vaccination suppressed IL-10 production and initiated sensitization of specific IFN-gamma secreting cells, resulting in a type 1-like antitumor immunity. These findings underscore the significance of the third signal in the design of dendritic cell-based cancer vaccines.

    DOI: 10.1016/j.cellimm.2006.11.002

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  • [A case of recurrent pulmonary lymphoepithelioma-like carcinoma responding to treatment with CBDCA/paclitaxel combined chemotherapy]. 査読

    Abe T, Tanabe Y, Watanabe S, Fujita N, Matsumoto N, Moriyama H, Kagamu H, Yokota T, Yoshizawa H, Gejyo F

    Gan to kagaku ryoho. Cancer & chemotherapy   31 ( 8 )   1215 - 1217   2004年8月

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  • The duration of signaling through CD40 directs biological ability of dendritic cells to induce antitumor immunity 査読

    S Watanabe, H Kagamu, H Yoshizawa, N Fujita, H Tanaka, J Tanaka, F Gejyo

    JOURNAL OF IMMUNOLOGY   171 ( 11 )   5828 - 5836   2003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:AMER ASSOC IMMUNOLOGISTS  

    Although it has been demonstrated that the functions of dendritic cells (DCs), including Ag capture, Ag presentation, and migratory activity, change dynamically with their maturation, the most appropriate conditioning of DCs for anticancer immunotherapy is still unclear. The help signal is one of the most potent stimuli for DC maturation and is provided by the interaction of CD40 expressed on DCs with CD40 ligand on CD4(+) T cells. To elucidate the appropriate conditioning of DCs for anticancer immunotherapy, we examined the biological activity of DCs stimulated with immobilized anti-CD40 Ab. DCs stimulated for 3 h (3h-DCs) still showed an immature phenotype, but exhibited augmented migration toward secondary lymphoid tissues. Subcutaneous injection of 3h-DCs facilitated priming of T cells, which could mediate potent antitumor therapeutic efficacy, in draining lymph nodes and successfully induced protective immunity. In contrast, 24h-DCs showed a mature phenotype with good Ag presentation ability to induce cell killing by adoptively transferred CD8(+) T cells when injected at tumor sites; however, they showed no migratory activity and were unable to induce protective immunity when injected s.c.. This is the first report that functionally distinct I)Cs, either for the priming phase or for the effector phase, could be obtained by conditioning with CD40 stimulation and that the duration of stimulation determines the biological outcome. The usage of DCs conditioned for the priming phase might provide significant advantages in anticancer immunotherapy.

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  • Successful liquid storage of peripheral blood stem cells at subzero non-freezing temperature 査読

    N Matsumoto, H Yoshizawa, H Kagamu, T Abe, N Fujita, S Watanabe, H Kuriyama, T Ishiguro, J Tanaka, E Suzuki, K Kobayashi, A Gemma, S Kudoh, F Gejyo

    BONE MARROW TRANSPLANTATION   30 ( 11 )   777 - 784   2002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  

    Although non-frozen storage of peripheral blood stem cells (PBSC) has been extensively studied and utilized clinically, the optimal storage conditions have not been determined. In order to improve the maintenance of clonogenic capacity during storage, we evaluated the feasibility of subzero non-freezing preservation of PBSC and attempted to determine the optimal conditions. Human PBSC were stored in different non-cryopreserved conditions. University of Wisconsin (UW) solution was used as the storage medium for PBSC. The stem cell integrity was optimally maintained when PBSC were preserved in a supercooled state at -2degreesC in UW solution without any cryoprotectants, and the highest values for nucleated cell survival (91.6%), CFU-GM survival (67.3%) and trypan blue viability (92%) were achieved at 72 h. CFU-GM survival in our storage conditions was significantly better than the survival achieved with hypothermic preservation in autologous serum and ACD-A solution at 4degreesC (67.3 +/- 9.2% vs 42.9 +/- 15.3%; P &lt; 0.01) or cryopreservation at -80&DEG;C (67.3 &PLUSMN; 9.2% vs 52.7 &PLUSMN; 10.7%; P &lt; 0.01). Thus, the combination of supercooling and UW solution was the optimal non-freezing method of preserving transplantable PBSC tested here. This method is of clinical utility in peripheral blood stem cell transplantation (PBSCT) for its simplicity and storage efficiency, and has value as a short-term storage method for PBSC to support dose-intensive multicyclic chemotherapy.

    DOI: 10.1038/sj.bmt.1703692

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MISC

  • ONO-7475, a Novel AXL Inhibitor, Suppresses the Adaptive Resistance to Initial EGFR-TKI Treatment in EGFR-Mutated Non-Small Cell Lung Cancer. 査読 国際誌

    Naoko Okura, Naoya Nishioka, Tadaaki Yamada, Hirokazu Taniguchi, Keiko Tanimura, Yuki Katayama, Akihiro Yoshimura, Satoshi Watanabe, Toshiaki Kikuchi, Shinsuke Shiotsu, Takeshi Kitazaki, Akihiro Nishiyama, Masahiro Iwasaku, Yoshiko Kaneko, Junji Uchino, Hisanori Uehara, Mano Horinaka, Toshiyuki Sakai, Kohei Tanaka, Ryohei Kozaki, Seiji Yano, Koichi Takayama

    Clinical cancer research : an official journal of the American Association for Cancer Research   26 ( 9 )   2244 - 2256   2020年5月

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    記述言語:英語  

    PURPOSE: Currently, an optimal therapeutic strategy comprising molecularly targeted agents for treating EGFR-mutated non-small cell lung cancer (NSCLC) patients with acquired resistance to osimertinib is not available. Therefore, the initial therapeutic intervention is crucial for the prolonged survival of these patients. The activation of anexelekto (AXL) signaling is known to be associated with intrinsic and acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). In this study, we investigated the best therapeutic strategy to combat AXL-induced tolerance to EGFR-TKIs using the novel AXL inhibitor ONO-7475. EXPERIMENTAL DESIGN: We examined the efficacy of ONO-7475 in combination with EGFR-TKIs in EGFR-mutated NSCLC cells using in vitro and in vivo experiments. We investigated the correlation between AXL expression in tumors and clinical outcomes with osimertinib for EGFR-mutated NSCLC patients with acquired resistance to initial EGFR-TKIs. RESULTS: ONO-7475 sensitized AXL-overexpressing EGFR-mutant NSCLC cells to the EGFR-TKIs osimertinib and dacomitinib. In addition, ONO-7475 suppressed the emergence and maintenance of EGFR-TKI-tolerant cells. In the cell line-derived xenograft models of AXL-overexpressing EGFR-mutated lung cancer treated with osimertinib, initial combination therapy of ONO-7475 and osimertinib markedly regressed tumors and delayed tumor regrowth compared with osimertinib alone or the combination after acquired resistance to osimertinib. AXL expression in EGFR-TKI refractory tumors did not correlate with the sensitivity of osimertinib. CONCLUSIONS: These results demonstrate that ONO-7475 suppresses the emergence and maintenance of tolerant cells to the initial EGFR-TKIs, osimertinib or dacomitinib, in AXL-overexpressing EGFR-mutated NSCLC cells, suggesting that ONO-7475 and osimertinib is a highly potent combination for initial treatment.

    DOI: 10.1158/1078-0432.CCR-19-2321

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  • 閉塞性睡眠時無呼吸は尿細管障害のバイオマーカーである尿中NAGを増加させる

    森谷 梨加, 穂苅 諭, 藤戸 信宏, 鈴木 涼子, 大嶋 康義, 青木 信将, 林 正周, 渡部 聡, 小屋 俊之, 菊地 利明

    日本内科学会雑誌   109 ( Suppl. )   174 - 174   2020年2月

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    記述言語:日本語   出版者・発行元:(一社)日本内科学会  

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  • ALK陽性非小細胞肺癌を対象としたベバシズマブとアレクチニブの併用療法の第II相およびバイオマーカー研究

    渡部聡, 松本尚哉, 古塩純, 石田晃, 阿部徹哉, 石川大輔, 田中知宏, 高橋美帆, 大坪亜矢, 庄子聡, 野嵜幸一郎, 市川紘将, 近藤利恵, 青木亜美, 梶原大季, 小山建一, 三浦理, 吉澤弘久, 西尾和人, 菊地利明

    日本肺癌学会総会号   61st   2020年

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  • 閉塞性睡眠時無呼吸におけるCPAP機器の残存呼吸イベント判定の有用性

    穂苅 諭, 藤戸 信宏, 鈴木 涼子, 大嶋 康義, 青木 信将, 林 正周, 渡部 聡, 小屋 俊之, 菊地 利明

    日本呼吸ケア・リハビリテーション学会誌   29 ( Suppl. )   213s - 213s   2019年10月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸ケア・リハビリテーション学会  

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  • CPAPアドヒアランスと鼻腔通気度との関係

    藤戸 信宏, 穂苅 諭, 鈴木 涼子, 大嶋 康義, 渡部 聡, 小屋 俊之, 菊地 利明

    日本呼吸ケア・リハビリテーション学会誌   29 ( Suppl. )   213s - 213s   2019年10月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸ケア・リハビリテーション学会  

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  • The efficacy of immune checkpoint inhibitors in patients with EGFR mutated non small cell lung cancer in retrospective analysis

    Tadaaki Yamada, Soichi Hirai, Akihiro Yoshimura, Satoshi Watanabe, Junji Uchino, Koichi Takayama

    CANCER RESEARCH   79 ( 13 )   2019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.AM2019-4036

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  • 睡眠呼吸障害に対して、PAP療法の適応を探索する! 多系統萎縮症に対するPAP療法の探索

    大嶋 康義, 穂苅 諭, 渡部 聡, 小屋 俊之, 菊地 利明, 中山 秀章, 下畑 享良

    日本睡眠学会定期学術集会プログラム・抄録集   44回   159 - 159   2019年6月

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    記述言語:日本語   出版者・発行元:(一社)日本睡眠学会  

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  • EGFR遺伝子陽性肺がん患者における免疫チェックポイント阻害薬の効果に関する多施設共同後方視検討

    塩津 伸介, 山田 忠明, 渡部 聡, 久保田 豊, 原田 大司, 竹田 隆之, 内野 順治, 高山 浩一

    日本呼吸器学会誌   8 ( 増刊 )   206 - 206   2019年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

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  • EGFR遺伝子陽性肺がん患者における免疫チェックポイント阻害薬の効果に関する多施設共同後方視検討

    塩津 伸介, 山田 忠明, 渡部 聡, 久保田 豊, 原田 大司, 竹田 隆之, 内野 順治, 高山 浩一

    日本呼吸器学会誌   8 ( 増刊 )   206 - 206   2019年3月

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  • EGFR遺伝子変異陽性肺がん患者における免疫チェックポイント阻害薬の効果に関する多施設共同後方視的検討

    平井 聡一, 山田 忠明, 塩津 伸介, 渡部 聡, 久保田 豊, 原田 大司, 竹田 隆之, 千原 佑介, 金子 美子, 田宮 暢代, 内野 順治, 高山 浩一

    肺癌   58 ( 6 )   545 - 545   2018年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • ダサチニブによる器質化肺炎の1例

    佐藤 美由紀, 渡部 聡, 青木 信将, 朝川 勝明, 森山 寛史, 大嶋 康義, 小屋 俊之, 岡塚 貴世志, 菊地 利明

    癌と化学療法   45 ( 5 )   851 - 854   2018年5月

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    記述言語:日本語   出版者・発行元:(株)癌と化学療法社  

    症例は52歳、男性。慢性骨髄性白血病(CML)に対してX-4年からメシル酸イマチニブ(imatinib mesylate、以下イマチニブ)、X-2年からニロチニブ、X-1年からダサチニブを開始された。X年11月ごろより息切れが出現し、胸部X線、胸部CTで浸潤影、両側胸水を認めた。抗菌薬と利尿剤を開始されたが改善を認めず、当科を紹介受診した。経気管支肺生検で得られた生検組織で肺胞腔内にポリープ状線維化巣を認め、器質化肺炎と診断した。ダサチニブを中止してステロイド治療を行い、臨床症状、画像所見の改善を認めた。その後CMLに対して、イマチニブ、ニロチニブを投与したが治療効果を認めなかった。ステロイド併用下でダサチニブを再投与し、器質化肺炎の再燃なくCMLをコントロールすることができた。ダサチニブによる器質化肺炎はまれであり、これまで報告はない。ステロイド治療によりダサチニブの再投与が可能であった器質化肺炎の症例を経験したので、文献的考察を含め報告する。(著者抄録)

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00296&link_issn=&doc_id=20180528410016&doc_link_id=%2Fab8gtkrc%2F2018%2F004505%2F017%2F0851-0854%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2018%2F004505%2F017%2F0851-0854%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • ガイドシースを用いた経気管支ドレナージが有効であった肺化膿症の1例

    柳村 尚寛, 青木 信将, 庄子 聡, 近藤 利恵, 林 正周, 大嶋 康義, 渡部 聡, 坂上 拓郎, 小屋 俊之, 菊地 利明

    気管支学   40 ( Suppl. )   S354 - S354   2018年5月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器内視鏡学会  

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  • 免疫チェックポイント阻害剤による薬剤性肺障害の気管支肺胞洗浄所見の検討

    里方 真理子, 近藤 利恵, 青木 信将, 市川 紘将, 林 正周, 大嶋 康義, 渡部 聡, 坂上 拓郎, 小屋 俊之, 菊地 利明

    気管支学   40 ( Suppl. )   S377 - S377   2018年5月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器内視鏡学会  

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  • サルコイドーシス/サルコイド反応合併肺癌の病期決定におけるEBUS-TBNAの有用性

    市川 紘将, 渡部 聡, 近藤 利恵, 庄子 聡, 青木 信将, 大嶋 康義, 坂上 拓郎, 茂呂 寛, 小屋 俊之, 菊地 利明

    肺癌   58 ( 2 )   88 - 92   2018年4月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

    目的. サルコイドーシスやサルコイド反応は肺門・縦隔リンパ節腫大を呈し、これらを合併した肺癌症例には、リンパ節病変の評価が治療方針決定上で問題となる。本研究では、これらサルコイド反応合併肺癌症例の病期診断におけるEBUS-TBNAの有用性を検討した。対象と方法. 2009年1月から2016年12月に気管支鏡検査を実施され、サルコイドーシス/サルコイド反応と肺癌の合併と診断された症例におけるEBUS-TBNAの有効性について検討した。結果. EBUS-TBNAにより、サルコイドーシス/サルコイド反応と肺癌との合併と診断された症例は4例であった。造影CT、FDG-PET/CTでは癌のリンパ節転移とサルコイドーシス/サルコイド反応の鑑別は困難であった。4例中3例はI期の非小細胞肺癌と診断され、2例は手術が施行された。術後検体でも転移はなく、granulomaが認められたことから、サルコイド反応と診断された。4例中1例は全身性サルコイドーシスに合併したIII期の肺癌症例であった。結論. サルコイドーシス/サルコイド反応合併肺癌症例におけるN因子の評価に、EBUS-TBNAは有用であると考えられる。(著者抄録)

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J01244&link_issn=&doc_id=20180515270004&doc_link_id=%2Fec7jaluc%2F2018%2F005802%2F004%2F0088-0092%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fec7jaluc%2F2018%2F005802%2F004%2F0088-0092%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • NPPV導入を必要としたSilver-Russell症候群の一例

    里方 真理子, 大嶋 康義, 西山 佑樹, 森谷 梨加, 才田 優, 市川 紘将, 朝川 勝明, 青木 信将, 渡部 聡, 坂上 拓郎, 小屋 俊之, 菊地 利明

    日本呼吸器学会誌   7 ( 増刊 )   336 - 336   2018年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

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  • EGFR遺伝子変異陽性NSCLCのゲフィチニブ/化学療法併用の第二相試験(NEJ005/TCOG0902) 最新アップデート解析

    宮林 貴大, 大泉 聡史, 菅原 俊一, 湊 浩一, 原田 敏之, 井上 彰, 藤田 結花, 前門戸 任, 渡部 聡, 弦間 昭彦, 出村 芳樹, 原田 眞雄, 磯部 宏, 木下 一郎, 森田 智視, 小林 国彦, 萩原 弘一, 相羽 惠介, 貫和 敏博

    日本呼吸器学会誌   7 ( 増刊 )   128 - 128   2018年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

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  • NPPV導入を必要としたSilver-Russell症候群の一例

    里方 真理子, 大嶋 康義, 西山 佑樹, 森谷 梨加, 才田 優, 市川 紘将, 朝川 勝明, 青木 信将, 渡部 聡, 坂上 拓郎, 小屋 俊之, 菊地 利明

    日本呼吸器学会誌   7 ( 増刊 )   336 - 336   2018年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

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  • Efficacy of EGFR tyrosine kinase inhibitors for EGFR mutatnt nonsmall cell lung cancer with brain metastases

    Yu Saida, Tetsuya Abe, Ko Sato, Kosuke Ichikawa, Ryo Ito, Masaaki Okajima, Satoru Miura, Satoshi Watanabe, Hiroshi Tanaka, Toshiaki Kikuchi

    ANNALS OF ONCOLOGY   28   2017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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  • 進行再発非扁平上皮非小細胞肺癌を対象としたCBDCA+PTX+BEV療法とCDDP+PEM+BEV療法のランダム化第II相試験

    渡部 聡, 宇田川 響, 杉山 栄里, 原田 敏之, 安宅 信二, 小山 良, 中村 有希子, 原田 大二郎, 山中 竹春, 後藤 功一

    肺癌   57 ( 5 )   440 - 440   2017年9月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 再発非小細胞肺癌に対するnab-パクリタキセル単剤療法の第II相試験(NLCTG1302)

    野嵜 幸一郎, 三浦 理, 渡部 聡, 石田 卓士, 宮林 貴大, 佐藤 和弘, 岡島 正明, 樋浦 徹, 市川 紘将, 阿部 徹哉, 田中 洋史, 吉澤 弘久, 菊地 利明

    肺癌   57 ( 5 )   476 - 476   2017年9月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • EGFR遺伝子変異陽性NSCLCのゲフィチニブ/化学療法併用の第II相試験(NEJ005/TCOG0902)最新アップデート結果

    渡部 聡, 大泉 聡史, 菅原 俊一, 湊 浩一, 原田 敏之, 井上 彰, 藤田 結花, 前門戸 任, 伊藤 和彦, 弦間 昭彦, 出村 芳樹, 原田 眞雄, 磯部 宏, 木下 一郎, 森田 智視, 小林 国彦, 萩原 弘一, 栗原 稔, 貫和 敏博

    肺癌   57 ( 5 )   442 - 442   2017年9月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • アファチニブ投与に伴う下痢、皮膚障害、口内炎に対する予防投与の第II相試験(NLCTG1401) 抗腫瘍効果解析

    小山 建一, 岡島 正明, 三浦 理, 石田 卓士, 佐藤 和弘, 塚田 弘樹, 市川 紘将, 渡部 聡, 阿部 徹哉, 田中 洋史, 菊地 利明

    肺癌   57 ( 5 )   442 - 442   2017年9月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 制御性T細胞調節と抗腫瘍エフェクターT細胞誘導による抗PD-1抗体療法の治療効果増強

    有田 将史, 渡部 聡, 高橋 美帆, 佐藤 美由紀, 庄子 聡, 市川 紘将, 近藤 利恵, 田中 純太, 坂上 拓郎, 小屋 俊之, 菊地 利明

    日本癌学会総会記事   76回   P - 1250   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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  • 多系統萎縮症患者に合併した睡眠関連呼吸障害の経時的変化の検討

    大嶋 康義, 中山 秀章, 松山 菜穂, 穂苅 諭, 渡部 聡, 坂上 拓郎, 茂呂 寛, 小屋 俊之, 菊地 利明, 下畑 享良

    日本睡眠学会定期学術集会プログラム・抄録集   42回   180 - 180   2017年6月

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    記述言語:日本語   出版者・発行元:(一社)日本睡眠学会  

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  • サルコイド反応合併肺癌症例の病期決定におけるEBUS-TBNAの有用性の検討

    市川 紘将, 渡部 聡, 大坪 亜矢, 近藤 利恵, 林 正周, 阿部 徹哉, 田中 純太, 小屋 俊之, 菊地 利明, 林 芳樹

    気管支学   39 ( Suppl. )   S301 - S301   2017年5月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器内視鏡学会  

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  • Updated efficacy and safety of the j-alex study comparing alectinib (ALC) with crizotinib (CRZ) in ALK-inhibitor naive ALK fusion positive non-small cell lung cancer (ALK plus NSCLC).

    Yuichi Takiguchi, Toyoaki Hida, Hiroshi Nokihara, Masashi Kondo, Young Hak Kim, Koichi Azuma, Takashi Seto, Makoto Nishio, Hiroshige Yoshioka, Fumio Imamura, Katsuyuki Hotta, Satoshi Watanabe, Koichi Goto, Kazuhiko Nakagawa, Tetsuya Mitsudomi, Nobuyuki Yamamoto, Hiroshi Kuriki, Naohito Inagaki, Tomohiro Tanaka, Tomohide Tamura

    JOURNAL OF CLINICAL ONCOLOGY   35   2017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  

    DOI: 10.1200/JCO.2017.35.15_suppl.9064

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  • PD-L1陰性腫瘍の肺・皮膚転移モデルに対する抗PD-1抗体併用細胞療法の開発

    有田 将史, 高橋 美帆, 渡部 聡, 佐藤 美由紀, 大坪 亜矢, 市川 紘将, 近藤 利恵, 阿部 徹哉, 田中 純太, 小屋 俊之, 菊地 利明

    日本呼吸器学会誌   6 ( 増刊 )   157 - 157   2017年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

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  • 肺抗酸菌症 病態解析 肺MAC症におけるサイトカインの網羅的解析

    番場 祐基, 茂呂 寛, 青木 信将, 朝川 勝明, 林 正周, 大嶋 康義, 渡部 聡, 坂上 拓郎, 阿部 徹哉, 小屋 俊之, 高田 俊範, 菊地 利明

    日本呼吸器学会誌   6 ( 増刊 )   121 - 121   2017年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

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  • Alectinib (ALC) versus Crizotinib (CRZ) in ALK-Positive Non-Small Cell Lung Cancer (ALK plus NSCLC): Primary Results from Phase III Study (J-ALEX)

    Young Kim, Toyoaki Hida, Hiroshi Nokihara, Masashi Kondo, Koichi Azuma, Takashi Seto, Yuichi Takiguchi, Makoto Nishio, Hiroshige Yoshioka, Fumio Imamura, Katsuyuki Hotta, Satoshi Watanabe, Koichi Goto, Kazuhiko Nakagawa, Tetsuya Mitsudomi, Nobuyuki Yamamoto, Hiroshi Kuriki, Ryoichi Asabe, Tomohiro Tanaka, Tomohide Tamura

    JOURNAL OF THORACIC ONCOLOGY   12 ( 1 )   S378 - S379   2017年1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 SCIENCE INC  

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  • 肺MAC症におけるサイトカインの網羅的解析

    番場祐基, 茂呂寛, 青木信将, 朝川勝明, 林正周, 大嶋康義, 渡部聡, 坂上拓郎, 阿部徹哉, 小屋俊之, 高田俊範, 菊地利明

    日本呼吸器学会誌(Web)   6   2017年

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  • 抗腫瘍エフェクター細胞の誘導による免疫療法の治療効果増強に関する検討

    渡部 聡, 有田 将史, 高橋 美帆, 菊地 利明

    新潟県医師会報   ( 801 )   11 - 12   2016年12月

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    記述言語:日本語   出版者・発行元:新潟県医師会  

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  • ALK陽性肺癌を対象としたアレクチニブ(ALC)とクリゾチニブ(CRZ)の比較第III相試験(J-ALEX試験)

    東 公一, 樋田 豊明, 軒原 浩, 近藤 征史, 金 永学, 瀬戸 貴司, 滝口 裕一, 西尾 誠人, 吉岡 弘鎮, 今村 文生, 堀田 勝幸, 渡部 聡, 後藤 功一, 中川 和彦, 光冨 徹哉, 山本 信之, 田中 智宏, 田村 友秀

    肺癌   56 ( 6 )   432 - 432   2016年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 胸部放射線治療後に合併した慢性進行性肺アスペルギルス症の2例

    上野 浩志, 坂上 拓郎, 大嶋 康義, 渡部 聡, 茂呂 寛, 菊地 利明

    日本呼吸器学会誌   5 ( 6 )   341 - 345   2016年11月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

    症例1は75歳、男性。症例2は64歳、男性。いずれも、術後再発非小細胞肺癌に対する胸部照射後に出現した浸潤影を放射線肺炎と診断し、ステロイド治療を行った。陰影は急速に増大したために抗菌薬治療を行ったが不応性であった。喀痰または肺洗浄検体よりアスペルギルス属を検出し、その後長期にわたる抗真菌薬治療を必要とした。呼吸器内科医として日常遭遇する可能性が高く、鑑別診断に慎重を要する2症例と考えられ報告する。(著者抄録)

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  • 小腸転移による急性腹症を来したALK陽性肺癌の2例

    里方 真理子, 渡部 聡, 佐藤 美由紀, 穂苅 諭, 渡邊 伸, 林 正周, 近藤 利恵, 市川 紘将, 阿部 徹哉, 小屋 俊之, 菊地 利明, 小山 建一, 田中 洋史

    肺癌   56 ( 6 )   858 - 858   2016年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • サルコイドーシス合併肺癌症例の病期決定におけるEBUS-TBNAの有用性の検討

    尾方 英至, 市川 紘将, 渡部 聡, 近藤 利恵, 阿部 徹哉, 小屋 俊之, 菊地 利明, 林 芳樹, 田中 洋史

    肺癌   56 ( 6 )   689 - 689   2016年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • Nivolumabによる腫瘍縮小前にpseudo-progressionをきたした非小細胞肺癌4例の検討

    齋藤 暁, 阿部 徹哉, 大坪 亜矢, 市川 紘将, 近藤 利恵, 渡部 聡, 坂上 拓郎, 小屋 俊之, 菊地 利明

    肺癌   56 ( 6 )   798 - 798   2016年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 当院でのオシメルチニブ倫理供給の使用経験

    小山 建一, 庄子 聡, 樋浦 徹, 三浦 理, 田中 洋史, 横山 晶, 市川 紘将, 渡部 聡, 阿部 徹哉, 菊地 利明, 伊藤 竜, 岩島 明

    肺癌   56 ( 6 )   659 - 659   2016年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • アレクチニブが奏効したALK陽性肺大細胞神経内分泌癌(LCNEC)の1例

    岡島 正明, 市川 紘将, 渡部 聡, 阿部 徹哉, 近藤 利恵, 小山 建一, 三浦 理, 田中 洋史, 菊地 利明

    肺癌   56 ( 6 )   667 - 667   2016年11月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • PD-1抗体療法は殺細胞性治療後の回復期におけるエフェクターT細胞の導入を増強する(PD-1 blockade enhances priming of effector T cells during homeostatic proliferation after cytotoxic therapy)

    高橋 美帆, 渡部 聡, 菊地 利明

    日本癌学会総会記事   75回   P - 1159   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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  • 気管支温熱療法を施行した重症気管支喘息の1例

    林 正周, 渡邊 伸, 佐藤 美由紀, 穂苅 諭, 近藤 利恵, 渡部 聡, 青木 信将, 大嶋 康義, 坂上 拓郎, 阿部 徹哉, 茂呂 寛, 小屋 俊之, 菊地 利明

    気管支学   38 ( 4 )   347 - 347   2016年7月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器内視鏡学会  

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  • Programmed death receptor-1/programmed death receptor ligand-1 blockade improves priming of antitumor effector T cells after cytotoxic therapies

    Miho Takahashi, Satoshi Watanabe, Ko Sato, Tomohiro Tanaka, Yu Saida, Junko Baba, Aya Ohtsubo, Miyuki Sato, Rie Kondo, Masaaki Okajima, Junta Tanaka, Hiroshi Kagamu, Hirohisa Yoshizawa, Toshiaki Kikuchi

    CANCER RESEARCH   76   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.AM2016-3206

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  • 当院における胸水貯留例に対する局所麻酔下胸腔鏡検査の有用性と安全性の検討

    吉澤 和孝, 近藤 利恵, 佐藤 美由紀, 上野 浩志, 穂苅 諭, 朝川 勝明, 林 正周, 青木 信将, 岡島 正明, 大嶋 康義, 渡邊 伸, 渡部 聡, 坂上 拓郎, 阿部 徹哉, 茂呂 寛, 小屋 俊之, 田中 純太, 森山 寛史, 菊地 利明, 田島 俊児

    気管支学   38 ( Suppl. )   S271 - S271   2016年5月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器内視鏡学会  

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  • 当院におけるEBUS-TBNAによるサルコイドーシス診断の後方視的検討

    林 正周, 上野 浩志, 吉澤 和孝, 佐藤 美由紀, 穂苅 諭, 青木 信将, 朝川 勝明, 大嶋 康義, 岡島 正明, 近藤 利恵, 渡邊 伸, 渡部 聡, 坂上 拓郎, 阿部 徹哉, 茂呂 寛, 小屋 俊之, 田中 純太, 森山 寛史, 菊地 利明, 田島 俊児

    気管支学   38 ( Suppl. )   S197 - S197   2016年5月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器内視鏡学会  

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  • 気管支鏡施行時の大量出血により気道確保を要した症例の検討

    近藤 利恵, 佐藤 美由紀, 吉澤 和孝, 上野 浩志, 穂苅 諭, 朝川 勝明, 林 正周, 青木 信将, 岡島 正明, 大嶋 康義, 渡邊 伸, 渡部 聡, 坂上 拓郎, 阿部 徹哉, 茂呂 寛, 小屋 俊之, 森山 寛史, 菊地 利明

    気管支学   38 ( Suppl. )   S256 - S256   2016年5月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器内視鏡学会  

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  • Alectinib (ALC) versus crizotinib (CRZ) in ALK-inhibitor naive ALK-positive non-small cell lung cancer (ALK plus NSCLC): Primary results from the J-ALEX study.

    Hiroshi Nokihara, Toyoaki Hida, Masashi Kondo, Young Hak Kim, Koichi Azuma, Takashi Seto, Yuichi Takiguchi, Makoto Nish Jo, Hiroshige Yoshioka, Fumio Imamura, Katsuyuki Hotta, Satoshi Watanabe, Koichi Goto, Kazuhiko Nakagawa, Tetsuya Mitsudomi, Nobuyuki Yamamoto, Hiroshi Kuriki, Ryoichi Asabe, Tomohiro Tanaka, Tomohide Tamura

    JOURNAL OF CLINICAL ONCOLOGY   34 ( 15 )   2016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  

    DOI: 10.1200/JCO.2016.34.15_suppl.9008

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  • シスプラチン腎症発症予測マーカーとしての尿中メガリン

    近藤 利恵, 各務 博, 渡部 聡, 阿部 徹哉, 細島 康宏, 忰田 亮平, 小屋 俊之, 菊地 利明, 成田 一衛, 斎藤 亮彦

    日本内科学会雑誌   105 ( Suppl. )   170 - 170   2016年2月

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    記述言語:日本語   出版者・発行元:(一社)日本内科学会  

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  • A randomized phase II trial of triplet or doublet antiemetic therapy in lung cancer patients receiving MEC (NLCTG1002)

    Takao Miyabayashi, Satoru Miura, Hiroshi Tanaka, Takashi Ishida, Satoshi Watanabe, Masato Makino, Masaaki Okajima, Junta Tanaka, Hiroshi Kagamu, Hirohisa Yoshizawa

    ANNALS OF ONCOLOGY   26   93 - 93   2015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:OXFORD UNIV PRESS  

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  • クリゾチニブの中止により急激な病勢増悪(disease flare)を来したALK陽性肺癌の一例

    有田 将史, 渡部 聡, 大坪 亜矢, 佐藤 昂, 田中 知宏, 石川 大輔, 大嶋 康義, 近藤 利恵, 岡島 正明, 三浦 理, 坂上 拓郎, 茂木 充, 小屋 俊之, 各務 博, 菊地 利明

    肺癌   55 ( 5 )   662 - 662   2015年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • クリゾチニブ耐性症例に対するアレクチニブの有効性に関する検討

    番場 祐基, 岡島 正明, 佐藤 昂, 近藤 利恵, 三浦 理, 渡部 聡, 田中 純太, 各務 博, 菊地 利明

    肺癌   55 ( 5 )   490 - 490   2015年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • アレクチニブによる薬剤性肺障害を来したALK陽性肺癌の一例

    藤戸 信宏, 渡部 聡, 有田 将史, 竹内 寛之, 鈴木 涼子, 渡邊 伸, 林 正周, 大坪 亜矢, 佐藤 昂, 岡島 正明, 三浦 理, 田島 俊児, 坂上 拓郎, 小屋 俊之, 各務 博, 菊地 利明

    肺癌   55 ( 5 )   657 - 657   2015年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • QOL 肺癌患者に対するカルボプラチン併用療法施行時の悪心嘔吐に対する予防的制吐療法の無作為化第II相試験

    河辺 昌哲, 三浦 理, 田中 洋史, 伊藤 和彦, 石田 卓士, 渡部 聡, 牧野 真人, 岡島 正明, 田中 純太, 各務 博, 吉澤 弘久, 菊地 利明

    肺癌   55 ( 5 )   395 - 395   2015年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 小細胞肺癌患者末梢血中循環腫瘍細胞とDDX3X特異的エフェクターT細胞

    大坪 亜矢, 各務 博, 岡島 正明, 三浦 理, 渡部 聡, 菊地 利明

    日本癌学会総会記事   74回   P - 1263   2015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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  • 再発非小細胞肺癌に対するnab-パクリタキセル単剤療法の第2相試験(NLCTG1302)

    三浦 理, 田中 洋史, 伊藤 和彦, 佐藤 和弘, 石田 卓士, 市川 紘将, 岡島 正明, 渡部 聡, 田中 純太, 各務 博, 吉澤 弘久, 菊地 利明

    肺癌   55 ( 5 )   679 - 679   2015年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 標準的制吐療法抵抗性の悪心に対するオランザピンの有効性に関する後方視的検討

    三科 悠子, 三浦 理, 庄子 聡, 近藤 利恵, 岡島 正明, 渡部 聡, 坂上 拓郎, 小屋 俊之, 各務 博, 菊地 利明

    肺癌   55 ( 5 )   714 - 714   2015年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • ゲフィチニブによる腸管気腫症発症後に安全にエルロチニブを投与しえた肺腺癌の1例

    大坪 亜矢, 渡部 聡, 田中 知宏, 石川 大輔, 近藤 利恵, 大嶋 康義, 坂上 拓郎, 野嵜 幸一郎, 岡島 正明, 三浦 理, 田中 純太, 各務 博, 吉澤 弘久, 成田 一衛, 峠 弘治, 丸山 智宏, 若井 俊文

    新潟医学会雑誌   129 ( 9 )   534 - 538   2015年9月

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    記述言語:日本語   出版者・発行元:新潟医学会  

    症例は71歳、男性。X-3年9月13日から左肺腺癌に対しゲフィチニブの内服治療を開始された。X年2月21日に腹痛、嘔吐を主訴に当科を受診。腹部造影CTで小腸腸管壁内ガス像および腹腔内遊離ガス像を指摘された。ゲフィチニブによる腸管気腫症と診断され、内服を中止し保存的治療で軽快した。ゲフィチニブ中止後、原病の増悪を認めたためX年4月15日からエルロチニブの内服を開始した。エルロチニブ内服開始後も腸管気腫症の再燃はなく、腫瘍の縮小を認めた。ゲフィチニブによる腸管気腫症は過去2例の報告のみである。今回我々は、ゲフィチニブにて腸管気腫症を発症し、エルロチニブにて安全に治療を再開可能であった症例を経験した。極めて稀な症例であり、文献的考察を含め報告した。(著者抄録)

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  • 中等度催吐性化学療法施行時の悪心嘔吐に対する予防的制吐療法の無作為化第II相試験

    石川 大輔, 三浦 理, 田中 洋史, 塚田 弘樹, 石田 卓士, 渡部 聡, 牧野 真人, 河辺 昌哲, 岩島 明, 宮尾 浩美, 岡島 正明, 田中 純太, 各務 博, 吉澤 弘久, 菊地 利明

    日本癌治療学会誌   50 ( 3 )   2239 - 2239   2015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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  • Critical roles of chemo-resistant effector and regulatory T cells in cancer immunotherapy during hemostatic proliferation

    Ko Sato, Satoshi Watanabe, Yu Saida, Tomohiro Tanaka, Junko Baba, Aya Ohtsubo, Satoshi Shoji, Daisuke Ishikawa, Rie Kondo, Masaaki Okajima, Satoru Miura, Junta Tanaka, Hiroshi Kagamu, Hirohisa Yoshizawa, Ichiei Narita

    CANCER RESEARCH   75   2015年8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.AM2015-3153

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  • 気管支鏡で診断し化学療法が奏効した肺肉腫の一例

    渡部 聡, 大坪 亜矢, 近藤 利恵, 田中 知宏, 石川 大輔, 佐藤 昂, 岡島 正明, 三浦 理, 大嶋 康義, 坂上 拓郎, 各務 博, 吉澤 弘久, 成田 一衛

    気管支学   37 ( Suppl. )   S267 - S267   2015年5月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器内視鏡学会  

    DOI: 10.18907/jjsre.37.Special_S267_3

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  • 当院における間質性肺炎合併肺癌例の後方視的検討

    石川 大輔, 坂上 拓郎, 朝川 勝明, 岡島 正明, 三浦 理, 渡部 聡, 小屋 俊之, 森山 寛史, 田中 純太, 各務 博, 高田 俊範, 成田 一衛, 土田 正則

    日本呼吸器学会誌   4 ( 増刊 )   201 - 201   2015年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

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  • Intra-tumor heterogeneityに基づくEGFR-TKI初期耐性機序の解明

    庄子 聡, 各務 博, 大坪 亜矢, 野嵜 幸一郎, 岡島 正明, 三浦 理, 渡部 聡, 小屋 俊之, 成田 一衛

    日本内科学会雑誌   104 ( Suppl. )   268 - 268   2015年2月

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    記述言語:日本語   出版者・発行元:(一社)日本内科学会  

    DOI: 10.2169/naika.104.268

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  • Carboplatin、Weekly Paclitaxel併用化学療法が奏効した胸腺癌の1例

    近藤 利恵, 渡部 聡, 石川 大輔, 田中 知宏, 大嶋 康義, 朝川 勝明, 坂上 拓郎, 岡島 正明, 三浦 理, 林 芳樹, 田中 純太, 各務 博, 吉澤 弘久, 成田 一衛

    癌と化学療法   41 ( 13 )   2607 - 2609   2014年12月

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    記述言語:日本語   出版者・発行元:(株)癌と化学療法社  

    症例は65歳、女性。約2ヵ月間続く左胸背部痛と動悸を主訴に前医を受診した。胸部CTで前縦隔腫瘤、縦隔リンパ節腫脹、左胸水、心嚢液貯留を認め、当院に紹介された。気管分岐下リンパ節に対する超音波気管支内視鏡下針生検および全身検索にて胸腺癌(正岡分類IVb期)と診断した。carboplatin(CBDCA)+weekly paclitaxel(PTX)療法を4サイクル施行後、腫瘍は著明に縮小し、心嚢液減少、左胸水消失を認めた。grade 1の嘔気、grade 2の貧血と脱毛以外に重篤な副作用は認められなかった。毒性が少なく、かつ腫瘍縮小効果が得られる治療法として、CBDCA+weekly PTX療法は胸腺癌に対する有用な治療選択肢の一つと考えられた。(著者抄録)

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  • 進展型小細胞肺癌に対するシスプラチン、ノギテカン、パクリタキセル、アムルビシン交替療法の第I相試験

    渡部 聡, 田中 純太, 佐藤 昂, 田中 知宏, 石川 大輔, 野嵜 幸一郎, 近藤 利恵, 岡島 正明, 三浦 理, 各務 博, 成田 一衛, 吉澤 弘久

    肺癌   54 ( 5 )   633 - 633   2014年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • ゾレドロン酸、デノスマブを投与された非小細胞肺癌骨転移症例と、非骨転移症例の検討

    岡島 正明, 石川 大輔, 田中 知宏, 野嵜 幸一郎, 近藤 利恵, 三浦 理, 渡部 聡, 田中 純太, 吉澤 弘久, 各務 博, 成田 一衛

    肺癌   54 ( 5 )   541 - 541   2014年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 両側副腎転移により副腎不全症状を呈した非小細胞肺癌の1例

    石川 大輔, 渡部 聡, 西山 佑樹, 木村 陽介, 才田 優, 市川 紘将, 堀 好寿, 青木 信将, 大嶋 康義, 坂上 拓郎, 小屋 俊之, 森山 寛史, 各務 博, 吉澤 弘久, 成田 一衛

    新潟医学会雑誌   128 ( 10 )   531 - 536   2014年10月

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    記述言語:日本語   出版者・発行元:新潟医学会  

    症例は54歳、男性。非小細胞肺癌(腺癌)、stage IV、上皮成長受容体遺伝子変異陽性と診断された。3次化学療法目的に入院した際、発熱、嘔気、低ナトリウム血症などの症状を認められた。血中コルチゾル低値、血中ACTH高値などから、急性副腎不全と診断した。両側副腎に巨大な肺癌の転移巣を認めており、副腎不全の原因と考えられた。ヒドロコルチゾン投与で症状は速やかに軽快した。肺癌は高率に副腎転移を来すが、両側副腎転移により副腎不全に至った報告例は少ない。我々は肺癌の両側副腎転移により副腎不全を来し、ステロイドホルモン補充により化学療法を再開しえた症例を経験したため、文献的考察を加え報告する。(著者抄録)

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  • DDX3X induces signal switching to stem cell-specific Wnt/beta-catenin signaling, resulting in EGFR-TKI resistance in lung cancer cells harboring EGFR activating mutation

    Satoshi Shoji, Hiroshi Kagamu, Koichiro Nozaki, Natsue Igarashi, Masaaki Okajima, Satoru Miura, Satoshi Watanabe, Hrohisa Yoshizawa, Ichiei Narita

    CANCER RESEARCH   74 ( 19 )   2014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:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2014-200

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  • Dendritic cell vaccination and regulatory T-cell depletion augment antitumor immunity after cytotoxic therapy

    Tomohiro Tanaka, Satoshi Watanabe, Ko Sato, Yu Saida, Junko Baba, Koichiro Nozaki, Daisuke Ishikawa, Natsue Igarashi, Satoshi Shoji, Masaaki Okajima, Satoru Miura, Junta Tanaka, Hiroshi Tanaka, Hiroshi Kagamu, Hirohisa Yoshizawa, Ichiei Narita

    CANCER RESEARCH   74 ( 19 )   2014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:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2014-2818

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  • PROGNOSTIC SIGNIFICANCE OF PROCALCITONIN IN SMALL CELL LUNG CANCER

    Satoshi Watanabe, Ko Sato, Satoru Miura, Hiroshi Kagamu, Tomohiro Tanaka, Yu Saida, Rie Kondo, Masaaki Okajima, Ichiei Narita, Hirohisa Yoshizawa

    ANNALS OF ONCOLOGY   25   2014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  

    DOI: 10.1093/annonc/mdu435.119

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  • DDX3X-specific effector T cells in small cell lung cancer patients reflect disease stage

    Natsue Igarashi, Hiroshi Kagamu, Koichiro Nozaki, Satoshi Shoji, Masaaki Okajima, Satoru Miura, Satoshi Watanabe, Hirohisa Yoshizawa, Ichiei Narita

    CANCER RESEARCH   74 ( 19 )   2014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:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.AM2014-2554

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  • 肺末梢病変に対するEBUS-GSを用いた気管支鏡検査の有用性の検討

    佐藤 昂, 渡部 聡, 岡島 正明, 石川 大輔, 田中 知宏, 野嵜 幸一郎, 近藤 利恵, 三浦 理, 田中 純太, 各務 博, 吉澤 弘久

    気管支学   36 ( 5 )   456 - 460   2014年9月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器内視鏡学会  

    背景. 近年、肺末梢の病変に対するガイドシース併用気管支腔内超音波断層法(EBUS-GS)の有用性と安全性が報告されている。また、肺癌治療の進歩に伴い組織型の確定や遺伝子検索の必要性が増し、組織採取が重要になってきている。目的. 今回我々は肺末梢病変に対するEBUS-GS併用気管支鏡検査の有用性を検討した。対象と方法. 2011年8月から2013年3月の20ヵ月間に、肺末梢病変に対してEBUS-GS併用下に気管支鏡検査を施行した64例を評価した。結果. 悪性腫瘍に対する正診率、感度はそれぞれ72.6%、66.7%であった。気管支鏡検査で肺腺癌と診断された症例でのEGFR遺伝子変異陽性率は33.3%であった。結論. EBUS-GS併用にて得られた検体は、肺癌組織型の確定診断や遺伝子検索に有用であると考えられた。(著者抄録)

    DOI: 10.18907/jjsre.36.5_456

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  • 癌多様性に基づいた新規EGFR-TKI耐性メカニズム(A novel EGFR-TKI resistance mechanism based on intratumor heterogeneity)

    庄子 聡, 各務 博, 野嵜 幸一郎, 岡島 正明, 三浦 理, 渡部 聡, 成田 一衛

    日本癌学会総会記事   73回   J - 1035   2014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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  • 化学療法抵抗性のエフェクターCD8+T細胞、CD4+CD25+Foxp3+抑制性T細胞は化学療法後の抗腫瘍免疫応答に重要な役割を果たす(Critical roles of chemo-resistant effector and regulatory T cells in antitumor immunity after cytotoxic therapy)

    佐藤 昂, 渡部 聡, 才田 優, 馬場 順子, 近藤 利恵, 田中 知宏, 庄子 聡, 岡島 正明, 三浦 理, 田中 純太, 各務 博, 吉沢 弘久, 成田 一衛

    日本癌学会総会記事   73回   P - 1245   2014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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  • 仮想気管支鏡を使用した医学・医療教育

    各務 博, 三浦 理, 渡部 聡, 坂上 拓郎, 小屋 俊之

    日本シミュレーション医療教育学会雑誌   2   83 - 83   2014年6月

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    記述言語:日本語   出版者・発行元:日本シミュレーション医療教育学会  

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  • Phase I study of dose-dense chemotherapy (DDC) alternating cisplatin (CDDP), topotecan (TPT), and paclitaxel (PTX) with CDDP, anrubicin (AMR), and PTX under granulocyte colony-stimulating factor support for extensive-stage small-cell lung cancer (ES-SCLC)

    Junta Tanaka, Satoshi Watanabe, Hiroshi Kagamu, Daisuke Ishikawa, Koichiro Nozakl, Tomohiro Tanaka, Masaaki Okajima, Satoru Miura, Ichlel Narita, Hirohisa Yoshizawa

    JOURNAL OF CLINICAL ONCOLOGY   32 ( 15 )   2014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  

    Web of Science

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  • 肺末梢病変に対するEBUS-GSを用いた気管支鏡検査の有用性と安全性の検討

    岡島 正明, 佐藤 昂, 石川 大輔, 田中 知宏, 野嵜 幸一郎, 三浦 理, 渡部 聡, 田中 純太, 各務 博, 吉澤 弘久

    気管支学   36 ( Suppl. )   S190 - S190   2014年3月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器内視鏡学会  

    DOI: 10.18907/jjsre.36.Special_S190_1

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  • 合併症を有する胸部悪性腫瘍患者に対する、シスプラチン併用化学療法の腎障害のリスク解析

    渡部 聡, 佐藤 昂, 近藤 利恵, 岡島 正明, 三浦 理, 田中 純太, 各務 博, 成田 一衛, 吉澤 弘久

    日本内科学会雑誌   103 ( Suppl. )   164 - 164   2014年2月

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    記述言語:日本語   出版者・発行元:(一社)日本内科学会  

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  • The Addition of bevacizumab to erlotinib for malignant pleural effusion: A case report with pharmacokinetic analysis 査読

    Miura S, Kagamu H, Imamura CK, Kondo R, Okajima M, Watanabe S, Tanaka J, Narita I, Tanigawara Y, Yoshizawa H

    Ann Oncol   25 ( Supplement 5 )   v75 - 109   2014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(全国大会,その他学術会議)  

    Poster session (P1-35-1)in The Japanese Society of Medical Oncology 2014 Annual Meeting, Fukuoka, Japan

    DOI: 10.1093/annonc/mdu436.71

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  • ペメトレキセドを含むプラチナ併用化学療法により長期生存が得られた原発性心膜悪性中皮腫の1例

    田中 知宏, 才田 優, 庄子 聡, 野嵜 幸一郎, 五十嵐 夏恵, 佐藤 昂, 岡島 正明, 三浦 理, 田中 純太, 青木 信将, 小屋 俊之, 各務 博, 成田 一衛, 渡部 聡, 吉澤 弘久, 篠原 博彦, 土田 正則, 清水 崇

    新潟医学会雑誌   127 ( 12 )   689 - 696   2013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  

    症例は71歳男性。上縦隔腫瘤、左胸水、心嚢液貯留の精査目的に当科を紹介され入院した。心嚢水セルブロック法による組織学的診断で上皮型原発性心膜悪性中皮腫と診断された。ペメトレキセドとプラチナ併用化学療法を計4コース施行し、stable diseaseが得られた。2013年5月現在、抗癌剤の最終投与日から約18ヵ月間が経過し無増悪生存中である。原発性心膜悪性中皮腫は稀であり、標準治療は確立されていない。本症例から、ペメトレキセドを含むプラチナ併用化学療法が有効である可能性が示唆された。(著者抄録)

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  • 化学療法が奏効した進行期二相性肺芽腫の1例

    岡島 正明, 佐藤 昂, 才田 優, 三浦 理, 渡部 聡, 田中 純太, 各務 博, 吉澤 弘久, 成田 一衛

    肺癌   53 ( 5 )   595 - 595   2013年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • ゲフィチニブで病勢抑制後進行した非小細胞肺癌に対するゲフィチニブ継続ドセタキセル併用療法の第I相試験

    渡部 聡, 田中 純太, 佐藤 昂, 才田 優, 岡島 正明, 三浦 理, 各務 博, 牧野 真人, 伊藤 和彦, 岩島 明, 佐藤 和弘, 横山 晶, 吉澤 弘久

    肺癌   53 ( 5 )   595 - 595   2013年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 血液透析施行中の慢性腎不全患者に合併した肺癌症例の検討

    三浦 理, 佐藤 昂, 才田 優, 岡島 正明, 渡部 聡, 田中 純太, 各務 博, 後藤 眞, 風間 順一郎, 吉澤 弘久, 成田 一衛

    肺癌   53 ( 5 )   582 - 582   2013年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • DDX3Xにより誘導される癌幹細胞様形質と新規EGFR-TKI耐性化メカニズム(DDX3X plays a critical role in a novel EGFR-TKI resistance mechanism correlating with CSC-like properties)

    庄子 聡, 各務 博, 野嵜 幸一郎, 五十嵐 夏恵, 才田 優, 田中 知宏, 近藤 利恵, 岡島 正明, 三浦 理, 渡部 聡, 吉澤 弘久, 成田 一衛

    日本癌学会総会記事   72回   332 - 332   2013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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  • 新潟大学の臨床研究を活性化するためにはどのような仕組みが必要か? 多施設臨床研究はどのように行うか?肺癌に対する新薬多施設臨床試験 新潟肺癌治療研究会の試み

    渡部 聡

    新潟医学会雑誌   127 ( 7 )   343 - 344   2013年7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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  • 肺癌における高度催吐性化学療法実施時の悪心嘔吐に対する2剤併用制吐療法と3剤併用制吐療法 2つの前向き試験の比較

    阿部 徹哉, 三浦 理, 松本 尚也, 石田 晃, 河辺 昌哲, 伊藤 和彦, 渡部 聡, 田中 純太, 各務 博, 成田 一衛, 吉澤 弘久

    日本緩和医療学会学術大会プログラム・抄録集   18回   303 - 303   2013年6月

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    記述言語:日本語   出版者・発行元:(NPO)日本緩和医療学会  

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  • エルロチニブによる急性肺障害の軽快後、各種癌治療により肺障害の再燃を繰り返した1例

    古塩 純, 星野 芳史, 田邊 嘉也, 成田 一衛, 渡部 聡, 吉澤 弘久, 田島 俊児, 張 仁美, 馬場 順子, 阿部 徹哉, 田中 洋史

    新潟医学会雑誌   127 ( 4 )   204 - 209   2013年4月

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    記述言語:日本語   出版者・発行元:新潟医学会  

    症例は39歳、男性。非小細胞肺癌(腺癌)、stage IV、上皮成長因子受容体遺伝子変異陰性と診断された。4次化学療法としてエルロチニブの内服を開始し、8日目に急性肺障害を発症した。副腎皮質ステロイド治療で急性肺障害は改善したが、骨転移巣に対する放射線照射、イリノテカン投与により急性肺障害の再燃を繰り返した。抗癌剤による急性肺障害の軽快後に照射や化学療法を行う際には、肺障害再燃の可能性を念頭におく必要がある。(著者抄録)

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  • Chemo-resistantregulatory T cells suppress the development of antitumor immunity aftercytotoxic regimens.

    Yu Saida, Satoshi Watanabe, Tomohiro Tanaka, Junko Baba, Koh Satoh, Satoshi Shoji, Natsue Igarashi, Koichirou Nozaki, Masaaki Okajima, Satoru Mura, Junta Tanaka, Hiroshi Kagamu, Hirohisa Yoshizawa, Ichiei Narita

    CANCER RESEARCH   73 ( 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  

    DOI: 10.1158/1538-7445.AM2013-3963

    Web of Science

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  • ステロイド治療により再投与が可能であったdasatinibによる器質化肺炎の1例

    渡部 聡, 青木 信将, 朝川 勝明, 森山 寛史, 大嶋 康義, 岡島 正明, 三浦 理, 小屋 俊之, 岡塚 貴世志, 田中 純太, 各務 博, 成田 一衛, 吉澤 弘久

    日本呼吸器学会誌   2 ( 増刊 )   273 - 273   2013年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

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  • 肺癌治療における緩和療法の役割 肺癌における高度催吐性化学療法実施時の2剤併用療法と3剤併用制吐療法の有効性に関する比較

    宮林 貴大, 三浦 理, 石田 卓士, 佐藤 和弘, 平田 明, 阿部 徹哉, 松本 尚也, 石田 晃, 河辺 昌哲, 伊藤 和彦, 渡部 聡, 田中 純太, 田中 洋史, 各務 博, 成田 一衛, 吉澤 弘久

    肺癌   52 ( 5 )   513 - 513   2012年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • Minor EGFR遺伝子変異陽性の非小細胞肺癌に対するGefitinibの治療効果

    渡部 聡, 吉澤 弘久, 前門戸 任, 井上 彰, 菅原 俊一, 磯部 宏, 原田 眞雄, 石井 芳樹, 萩原 弘一, 小林 国彦

    肺癌   52 ( 5 )   557 - 557   2012年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 肺癌における高度催吐性化学療法時のPALO、APR、DEXの3剤併用制吐療法の第II相試験

    牧野 真人, 三浦 理, 佐藤 和弘, 小林 理, 宮尾 浩美, 阿部 徹哉, 岩島 明, 寺田 正樹, 才田 優, 渡部 聡, 田中 純太, 田中 洋史, 各務 博, 成田 一衛, 吉澤 弘久

    日本癌治療学会誌   47 ( 3 )   1418 - 1418   2012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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  • シクロフォスファミドと化学療法耐性免疫抑制細胞の除去の組み合わせは優れた抗腫瘍効果を示す(Combination of cyclophosphamide and inhibition of chemo-resistant suppressor cells successfully treated advanced rumors)

    才田 優, 渡部 聡, 田中 知宏, 馬場 順子, 野嵜 幸一郎, 市川 紘将, 古塩 純, 三浦 理, 田中 純太, 各務 博, 吉沢 弘久, 成田 一衛

    日本癌学会総会記事   71回   282 - 282   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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  • DEAD/H(Asp-Glu-Ala-Asp/His)box polypeptide 3、X-linkedの癌幹細胞における役割(Oncogenic roles of DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked)

    野嵜 幸一郎, 各務 博, 古塩 純, 市川 紘将, 才田 優, 田中 知宏, 渡部 聡, 吉沢 弘久, 成田 一衛

    日本癌学会総会記事   71回   135 - 135   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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  • Successful treatment of advanced tumors with chemo-immunotherapy: a combination of cyclophosphamide and inhibition of chemo-resistant immune suppressor cells

    Yu Saida, Satoshi Watanabe, Tomohiro Tanaka, Junko Baba, Koichiro Nozaki, Kosuke Ichikawa, Jun Koshio, Satoru Miura, Junta Tanaka, Hiroshi Kagamu, Hirohisa Yoshizawa, Ichiei Narita

    CANCER RESEARCH   72   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.AM2012-1550

    Web of Science

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  • 副腎転移巣から出血をきたした肺癌と胃癌の重複癌の1例

    才田 優, 田中 知宏, 野嵜 幸一郎, 市川 紘将, 古塩 純, 三浦 理, 各務 博, 成田 一衛, 渡部 聡, 田中 純太, 吉澤 弘久, 櫛谷 幸嗣, 阿部 徹哉, 丸山 佳重

    新潟医学会雑誌   126 ( 3 )   155 - 160   2012年3月

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    記述言語:日本語   出版者・発行元:新潟医学会  

    症例は60歳、男性。2008年8月より湿性咳嗽が出現した。10月のCTで左肺上葉に45mm大の腫瘤影と両側肺門・縦隔・噴門部・傍大動脈リンパ節の腫大を認めた。気管支鏡検査、上部消化管内視鏡検査により、非小細胞肺癌、胃癌の同時重複癌と診断した。全身化学療法を施行したが徐々に原病は進行し、2009年7月1日のCTでは新たに両側副腎転移巣を認めた。2009年7月24日から腹痛、7月28日から発熱が出現した。7月29日のCTで右副腎転移巣の著明な増大、内部に高濃度域を認め、副腎出血と診断した。悪性腫瘍の副腎転移巣から出血を来す症例は稀であり、文献的考察を加え報告する。(著者抄録)

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  • エンドトキシン吸着療法が奏功したゲフィチニブによる急性肺障害の1例

    馬場 順子, 渡部 聡, 羽深 将人, 朝川 勝明, 古川 俊貴, 三浦 理, 田島 俊児, 小屋 俊之, 田中 純太, 各務 博, 吉澤 弘久, 成田 一衛

    肺癌   51 ( 5 )   549 - 549   2011年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 癌幹細胞特異的蛋白質を用いた抗腫瘍免疫療法(DEAD/H box polypeptide 3, X-linked is a CD133+ tumor-specific protein and induces antitumor immunity)

    古塩 純, 各務 博, 成田 一衛, 中田 光, 吉澤 弘久, 田中 純太, 渡部 聡, 三浦 理, 宮林 貴大, 市川 紘将, 才田 優, 野嵜 幸一郎, 田中 知宏

    日本癌学会総会記事   70回   334 - 334   2011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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  • 癌免疫療法のコンディショニング 生体外で増やしたT細胞はリンパ球減少状態の宿主でエフェクター細胞に分化し抗腫瘍効果を示す(Conditioning for cancer immunotherapy: ex vivo expanded T cells effectively develop into effectors in lymphopenic hosts)

    才田 優, 渡部 聡, 馬場 順子, 田中 知宏, 野嵜 幸一郎, 市川 紘将, 古塩 純, 田中 純太, 各務 博, 吉澤 弘久, 成田 一衛

    日本癌学会総会記事   70回   260 - 260   2011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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  • 肺がん化学療法時の悪心・嘔吐の実態

    田中 洋史, 佐藤 和弘, 丸山 佳重, 横山 晶, 小林 理, 成田 淳一, 岩島 明, 牧野 真人, 小山 建一, 栗山 英之, 江部 佑輔, 河辺 昌哲, 山岸 格史, 石田 晃, 松本 尚也, 太田 毅, 阿部 徹哉, 宮林 貴大, 松山 弘紀, 渡部 聡, 田中 純太, 各務 博, 中田 光, 成田 一衛, 吉澤 弘久, 新潟肺癌治療研究会

    臨床腫瘍プラクティス   7 ( 3 )   329 - 336   2011年8月

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    記述言語:日本語   出版者・発行元:(株)ヴァンメディカル  

    がん化学療法時の悪心・嘔吐は患者QOLを低下させることはもとよりコンプライアンス低下を招き、治療に悪影響を与える可能性がある。今回、肺がん化学療法を受けた患者101名を対象に悪心・嘔吐の実態調査を実施した。その結果、悪心・嘔吐の「つらさ」に対して医師と患者の間での認識に乖離が認められ、遅発期の摂食障害がシスプラチン群で66%、カルボプラチン群で44%に発現することがわかった。制吐療法を行う際、遅発期まで含めた認識と対応が必要だと考えられる。(著者抄録)

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  • サイトメガロウイルス感染症 両肺生体移植後の経過観察中にARDSをきたし、サイトメガロウイルス感染とともにTMAを発症した1例

    古川 俊貴, 馬場 順子, 朝川 勝明, 渡部 聡, 小屋 俊之, 中山 秀章, 鈴木 栄一, 成田 一衛

    今日の移植   24 ( 4 )   397 - 404   2011年8月

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    記述言語:日本語   出版者・発行元:(株)日本医学館  

    30歳女。16歳時にALL L1と診断され、19歳時にURBMTを施行された。21歳時にIPS after BMTを発症し、PSLを開始されたが徐々に増悪し、28歳時に妹、母親をドナーとする両肺生体移植を施行された。状態は安定していたが、その後急性拒絶反応を生じステロイド治療で改善した。今回、感冒様症状、発熱、呼吸困難が出現し、検査所見および画像所見よりARDSと診断して人工呼吸管理の上、ステロイドパルス療法、抗菌薬等を開始したが悪化した。PCPS導入して未分化ヘパリンを開始したところ改善傾向となったが、改善は不十分で徐々に悪化し、CMV抗原の上昇、LDH、FERの著明上昇、凝固マーカーの上昇などを来たし、VODを示唆する所見を認めた。ADAMTS13活性の低下やインヒビターを認めないことから、CMV感染、TMAの合併と判断してCHDF、血漿交換、次いでFFP連日投与を行い、抗凝固療法を再開して更に抗ウイルス療法を開始した。CMV抗原の減少とともに改善傾向となったが、脳内イベントによる突然の散瞳と完全房室ブロックで心肺停止となり永眠された。

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  • Irradiation and reconstitution with in vitro-expanded polyclonal T cells from na ve mice augments antitumor response

    Junko Baba, Satoshi Watanabe, Yu Saida, Kosuke Ichikawa, Jun Koshio, Junta Tanaka, Hiroshi Tanaka, Hiroshi Kagamu, Hirohisa Yoshizawa, Ichiei Narita

    CANCER RESEARCH   71   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.AM2011-2685

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  • DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked is a CD133+tumor-specific protein and induces antitumor immunity

    Jun Koshio, Hiroshi Kagamu, Kosuke Ichikawa, Junko Baba, Yu Saida, Satoshi Watanabe, Junta Tanaka, Hiroshi Tanaka, Hirohisa Yoshizawa, Ichiei Narita

    CANCER RESEARCH   71   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.AM2011-2694

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  • Erlotinibによる急性肺障害の軽快後、各種抗癌治療により肺障害の再燃を繰り返した1例

    渡部 聡, 馬場 順子, 星野 芳史, 田島 俊児, 田邊 嘉也, 各務 博, 成田 一衛, 田中 洋史, 田中 純太, 吉澤 弘久, 張 仁美, 阿部 徹哉

    肺癌   50 ( 7 )   952 - 952   2010年12月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 既治療小細胞肺癌に対するイリノテカン単剤化学療法の第II相試験

    馬場 順子, 渡部 聡, 田中 純太, 塚田 弘樹, 成田 淳一, 佐藤 和弘, 阿部 徹哉, 栗山 英之, 田中 洋史, 各務 博, 吉澤 弘久, 成田 一衛

    肺癌   50 ( 5 )   583 - 583   2010年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 癌幹細胞特異的蛋白質を用いた抗腫瘍免疫療法(Cancer stem cells express specific immunogenic proteins that induce Th17-dominant immunity)

    古塩 純, 各務 博, 市川 紘将, 渡部 聡, 田中 純太, 田中 洋史, 吉澤 弘久, 成田 一衛

    日本癌学会総会記事   69回   489 - 489   2010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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  • 殺細胞性治療に抵抗性な抑制T細胞群はリンパ球減少状態からの回復期における抗腫瘍免疫を阻害する(Regulatory T cells resistant to cytotoxic regimens prevent antitumor immunity during T cell homeostatic proliferation)

    馬場 順子, 渡部 聡, 才田 優, 市川 紘将, 古塩 純, 宮林 貴大, 田中 洋史, 田中 純太, 各務 博, 吉澤 弘久, 成田 一衛

    日本癌学会総会記事   69回   75 - 75   2010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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  • 喫煙再開により再燃を認めた急性好酸球性肺炎の1例

    三船 大樹, 渡部 聡, 近藤 利恵, 森山 寛史, 各務 博, 高田 俊範, 成田 一衛, 長谷川 隆志, 鈴木 栄一, 手塚 貴文

    新潟医学会雑誌   124 ( 7 )   407 - 412   2010年7月

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    記述言語:日本語   出版者・発行元:新潟医学会  

    症例は22歳、男性。2008年9月中旬より喫煙を開始した。同月下旬より乾性咳嗽、労作時の息切れが出現。同年10月1日、38℃台の発熱が加わり前医を受診した。低酸素血症と両肺野のびまん性すりガラス影を認め緊急入院したが、翌日には呼吸状態がさらに悪化したため当科へ転院した。気管支肺胞洗浄液にて好酸球増多の所見が得られ、その他の臨床所見をふまえ、急性好酸球性肺炎の診断に至った。ステロイド療法へ良好に反応し、呼吸不全の著明な改善が得られた。その後、喫煙の再開時期に一致して咳嗽や息切れの再燃、及び末梢血好酸球数の再上昇を認めた。急性好酸球性肺炎は病因不明の疾患概念であるが、吸入抗原に対するアレルギー反応の関与が疑われている。吸入抗原のチャレンジテストにより原因物質の特定が可能であると考えられるが、安全な負荷試験は確立されておらず施行は困難である。本例は喫煙の再開により急性好酸球性肺炎が再燃しており、発症の原因を特定し得た貴重な症例であった。(著者抄録)

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  • Chemo-resistant regulatory T cells inhibit the augmentation of antitumor immunity during homeostatic T cell proliferation

    Junko Baba, Satoshi Watanabe, Kosuke Ichikawa, Jun Koshio, Takao Miyabayashi, Junta Tanaka, Hiroshi Tanaka, Hiroshi Kagamu, Hirohisa Yoshizawa, Ichiei Narita

    CANCER RESEARCH   70   2010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.AM10-1920

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  • Reciprocal CD4+T cell balance of Th17 and Treg in small cell lung cancer reflects disease stage

    T. Miyabayashi, H. Kagamu, K. Koyama, S. Miura, S. Watanabe, H. Tanaka, J. Tanaka, H. Yoshizawa, I. Narita

    EJC SUPPLEMENTS   7 ( 2 )   540 - 540   2009年9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:PERGAMON-ELSEVIER SCIENCE LTD  

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  • 照射後回復期における照射抵抗性抑制性T細胞除去による抗腫瘍免疫の増強(Depletion of radio-resistant regulatory T cells enhances antitumor immunity during homeostatic proliferation)

    馬場 順子, 渡部 聡, 宮林 貴大, 各務 博, 田中 洋史, 太田 毅, 近藤 利恵, 栗山 英之, 田中 純太, 出口 勝也, 吉澤 弘久

    日本癌学会総会記事   68回   286 - 286   2009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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  • 癌幹細胞標的免疫療法はparental melanomaに対し強力な抗腫瘍反応性を介在する(Cancer stem cell targeted immunotherapy mediates potent antitumor reactivity against established parental melanoma)

    宮林 貴大, 各務 博, 小山 建一, 馬場 順子, 渡部 聡, 田中 純太, 田中 洋史, 吉澤 弘久, 中田 光, 成田 一衛

    日本癌学会総会記事   68回   399 - 399   2009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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  • EGFR-TKI再導入を行ったゲフィチニブ治療後再発・不応の非小細胞肺癌症例の検討

    渡部 聡, 太田 毅, 近藤 利恵, 栗山 英之, 各務 博, 田中 洋史, 田中 純太, 吉澤 弘久

    肺癌   49 ( 3 )   333 - 333   2009年6月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • Depletion of radio-resistatnt regulatory T cells enhances anti-tumor immunity during homeostatic proliferation

    Junko Baba, Satoshi Watanabe, Takao Miyabayashi, Hiroshi Kagamu, Hiroshi Tanaka, Katsuya Deguchi, Chunrui Tan, Suyu Shu, Hirohisa Yoshizawa, Fumitake Gejyo

    CANCER RESEARCH   69   2009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 ASSOC CANCER RESEARCH  

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  • Intratracheal administration of DC-based vaccine cells for tumor immunotherapy

    Takeshi Ota, Hiroshi Tanaka, Takao Miyabayashi, Junko Baba, Satoshi Watanabe, Hideyuki Kuriyama, Junta Tanaka, Hiroshi Kagamu, Koh Nakata, Fumitake Gejyo, Hirohisa Yoshizawa

    CANCER RESEARCH   69   2009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 ASSOC CANCER RESEARCH  

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  • Phase I Study of S-1 Combined with Gemcitabine in Relapsed or Refractory Non-Small Cell Lung Cancer.

    S. Watanabe, R. Ito, J. Tanaka, T. Ohta, K. Sato, H. Miyao, H. Kuriyama, H. Tanaka, H. Kagamu, H. Yoshizawa, K. Nakata, F. Gejyo

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   179   2009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:AMER THORACIC SOC  

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  • Reciprocal CD4(+) T Cell Balance of Effector CD62L(low) CD4(+) and CD62L(high)CD25(+) CD4(+) Regulatory T Cells in Small Cell Lung Cancer Reflects Disease Stage.

    T. Miyabayashi, H. Kagamu, K. Koyama, S. Miura, S. Watanabe, H. Kuriyama, H. Tanaka, J. Tanaka, H. Yoshizawa, K. Nakata, F. Gejyo

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   179   2009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:AMER THORACIC SOC  

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  • 頸部リンパ節結核と悪性リンパ腫の同時合併例

    佐藤 和弘, 渡部 聡, 村山 直也, 三上 理

    結核   80 ( 7 )   551 - 551   2005年7月

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    記述言語:日本語   出版者・発行元:(一社)日本結核病学会  

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  • 当院におけるDOTSの現状

    佐藤 和弘, 渡部 聡, 村山 直也, 三上 理

    日本呼吸器学会雑誌   43 ( 増刊 )   152 - 152   2005年4月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

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  • 当院におけるDOTSの現状

    佐藤 和弘, 渡部 聡, 村山 直也, 三上 理

    結核   80 ( 1 )   51 - 52   2005年1月

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    記述言語:日本語   出版者・発行元:(一社)日本結核病学会  

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  • 高齢者進行期非小細胞肺癌に対するカルボプラチン(C)+ゲムシタビン(G)併用化学療法の第I相試験

    渡部 聡, 田中 純太, 松山 弘紀, 広瀬 貴之, 田中 洋史, 各務 博, 吉澤 弘久, 下條 文武

    肺癌   44 ( 5 )   552 - 552   2004年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • 進行期非小細胞肺癌に対するシスプラチン+ドセタキセル併用biweekly化学療法の第I相試験

    松山 弘紀, 田中 純太, 渡部 聡, 広瀬 貴之, 田中 洋史, 各務 博, 吉澤 弘久, 下条 文武

    肺癌   44 ( 5 )   536 - 536   2004年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本肺癌学会  

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  • Total RNAパルスとCD40刺激による抗腫瘍樹状細胞療法の検討

    三浦 理, 各務 博, 樋浦 徹, 石田 晃, 渡部 聡, 田中 洋史, 田中 純太, 吉澤 弘久, 下条 文武

    日本癌治療学会誌   39 ( 2 )   842 - 842   2004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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  • 腫瘍所属リンパ節でプライミングされるCD62Lhigh CD4+regulatory T細胞

    樋浦 徹, 各務 博, 三浦 理, 石田 晃, 渡部 聡, 田中 洋史, 田中 純太, 吉澤 弘久, 下条 文武

    日本癌学会総会記事   63回   288 - 288   2004年9月

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    記述言語:日本語   出版者・発行元:日本癌学会  

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  • Naive T細胞からの抗腫瘍エフェクターT細胞の誘導 樹状細胞と腫瘍細胞の融合細胞を用いた試み

    石田 晃, 田中 洋史, 樋浦 徹, 三浦 理, 渡部 聡, 田中 純太, 各務 博, 吉澤 弘久, 下条 文武

    日本癌学会総会記事   63回   302 - 302   2004年9月

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    記述言語:日本語   出版者・発行元:日本癌学会  

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  • 肺原発リンパ上皮腫様癌の術後再発に対し化学療法が奏効した1例

    阿部 徹哉, 田邊 嘉也, 渡部 聡, 藤田 七恵, 松本 尚也, 森山 寛史, 各務 博, 横田 樹也, 吉沢 弘久, 下条 文武

    癌と化学療法   31 ( 8 )   1215 - 1217   2004年8月

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    記述言語:日本語   出版者・発行元:(株)癌と化学療法社  

    57歳女.胸部X線で異常陰影を指摘された.胸部CTで左肺下葉に腫瘤を認めた.術前に確定診断は得られなかったが,画像上遠隔転移は認めず,左肺下葉切除および縦隔リンパ節郭清を行った.病理組織でリンパ上皮腫様癌と診断した.経過観察していたが,胸部X線で左胸膜の肥厚が出現した.その後増大傾向を認め,左背部痛も出現した.carboplatin/paclitaxel併用化学療法を開始した.血液毒性としてgrade 2〜3の好中球減少と貧血を認めたが,いずれも重篤なものではなく輸血は必要としなかった.非血液毒性はgrade 1の筋痛,末梢神経障害とGOT,GPT上昇が認められたが,いずれも一過性で特に治療を必要としなかった.左背部痛は軽減し,疼痛コントロールのために内服していたloxoprofenを中止した.画像上も徐々に胸水は減少,胸膜肥厚もほぼ消失し,新病変も認められなかったのでCRと判定した

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  • 集学的治療が奏効した胸腺癌の一例

    佐野 博繁, 渡部 聡, 田中 純太, 松山 弘紀, 平田 明, 広瀬 貴之, 田中 洋史, 各務 博, 吉澤 弘久, 下条 文武, 渡辺 マヤ, 小池 輝元, 橋本 毅久, 土田 正則, 林 純一, 笹本 龍太, 笹井 啓資

    新潟医学会雑誌   118 ( 7 )   347 - 354   2004年7月

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    記述言語:日本語   出版者・発行元:新潟医学会  

    44歳男.声のかすれが出現し,前胸部の腫瘤を自覚した.胸部CTで上縦隔に腫瘍を指摘された.前胸部腫瘍の生検を施行し,胸腺癌(扁平上皮癌)と診断した.画像上,腕頭動脈への腫瘍の直接浸潤が疑われ,正岡分類III期と診断した.PACE療法を施行した.副作用としては,grade 4の好中球減少,grade 2の便秘が出現したが,補助療法にていずれも短期間で改善した.PRと判定した.腫瘍摘出術,胸腺摘出術を施行した.術後は合併症なく順調に経過し退院した.術後放射線療法を外来にて施行した.外来で経過観察中であり,これまでのところ再発を認めていない

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  • 再発・前治療無効非小細胞肺癌に対するCarboplatin,Paclitaxel併用化学療法第II相試験

    渡部 聡, 田中 純太, 吉澤 弘久, 松山 弘紀, 田中 洋史, 各務 博, 下条 文武

    気管支学   26 ( 3 )   255 - 255   2004年5月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器内視鏡学会  

    DOI: 10.18907/jjsre.26.3_255_3

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  • 切除不能III期非小細胞肺癌に対するCarboplatin(C),5-fluorouracil(F),胸部放射線療法(TRT)同時併用第I/II相試験

    田中 純太, 吉澤 弘久, 松山 弘紀, 渡部 聡, 田中 洋史, 各務 博, 下条 文武

    日本内科学会雑誌   93 ( Suppl. )   189 - 189   2004年2月

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    記述言語:日本語   出版者・発行元:(一社)日本内科学会  

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  • Carboplatin and paclitaxel in patients with non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy: A phase II study from the Niigata Lung Cancer Treatment Group

    Hirohisa Yoshizawa, Satoshi Watanabe, Junta Tanaka, Koki Matsuyama, Takayuki Hirose, Hiroshi Tanaka, Hiroshi Kagamu, Kazuhiko Ito, Yoshie Maruyama, Fumitake Gejyo

    ANNALS OF ONCOLOGY   15   177 - 177   2004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:OXFORD UNIV PRESS  

    Web of Science

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  • マウス樹状細胞と癌細胞の電気融合による新しい癌ワクチン作成の試み:モデル抗原を用いての検討

    田中 洋史, 石田 晃, 渡部 聡, 田中 純太, 各務 博, 吉澤 弘久, 下条 文武

    日本癌学会総会記事   62回   436 - 436   2003年8月

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    記述言語:日本語   出版者・発行元:日本癌学会  

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  • Total RNAパルスと成熟刺激による抗腫瘍樹状細胞療法

    渡部 聡, 各務 博, 石田 晃, 田中 洋史, 田中 純太, 吉澤 弘久, 下条 文武

    日本癌学会総会記事   62回   99 - 99   2003年8月

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    記述言語:日本語   出版者・発行元:日本癌学会  

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  • in vitro conditioningされた樹状細胞を用いた抗腫瘍エフェクター細胞の誘導

    渡部 聡, 各務 博, 吉沢 弘久, 藤田 七恵, 松本 尚也, 阿部 徹哉, 鈴木 栄一, 下条 文武

    日本癌学会総会記事   61回   350 - 351   2002年10月

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    記述言語:日本語   出版者・発行元:日本癌学会  

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  • 抗腫瘍療法に最適化することを目的とした抗CD40抗体による樹状細胞ex vivo conditioningの検討

    各務 博, 渡部 聡, 藤田 七恵, 松本 尚也, 石黒 卓朗, 田中 純太, 吉澤 弘久, 鈴木 栄一, 下条 文武

    日本癌学会総会記事   60回   189 - 189   2001年9月

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    記述言語:日本語   出版者・発行元:日本癌学会  

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共同研究・競争的資金等の研究

  • メガリンを標的とした薬剤性腎障害治療戦略の開発

    研究課題/領域番号:19K08673  2019年4月 - 2023年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    青木 信将, 渡部 聡, 斎藤 亮彦

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

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  • 化学療法後の免疫再構成を利用した進行期肺癌に対する新規免疫療法の開発

    研究課題/領域番号:15K09168  2015年4月 - 2018年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    渡部 聡, 各務 博, 吉澤 弘久, 三浦 理, 中田 光

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    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

    マウスを用いてhomeostatic proliferationを利用したナイーブT細胞からのTeffの誘導と抗PD-1抗体治療を組み合わせることで、高い治療効果が得られることを発見した。この治療効果は腫瘍のPD-L1発現に関係なく得られていた。腫瘍組織に浸潤している免疫細胞の検討により、PD-L1は腫瘍浸潤リンパ球に主に発現しており、Teff上のPD-1を介して免疫を抑制している可能性が考えられた。今後はさらに検討を進め、免疫抑制系細胞の解除による治療効果増強を目指している。

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  • 腫瘍免疫の再構築をコンディショニングとした進行期肺癌に対する新たな免疫療法の開発

    研究課題/領域番号:24591157  2012年4月 - 2015年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    渡部 聡, 各務 博, 吉澤 弘久, 中田 光, 三浦 理

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    化学療法、放射線療法後のリンパ球減少状態からの回復期には、抗腫瘍エフェクターT細胞の誘導が増強されることが知られている。我々は担癌マウスモデルを用いて、この回復期において殺細胞性治療抵抗性の免疫抑制細胞が増加することを発見した。これら免疫抑制細胞を、抗体を用いて除去すると抗腫瘍免疫応答が増強され、腫瘍の成長が抑制された。
    当院で治療を受けた進展型小細胞肺癌患者の末梢血検体を化学療法前後で解析すると、マウス同様に免疫抑制細胞が増加していた。今後は、化学療法後のリンパ球減少状態からの回復期を利用して、免疫抑制細胞を効率よく除去して抗腫瘍エフェクターT細胞を誘導する免疫療法の開発を検討している。

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  • 肺癌分子標的治療における新たな効果予測因子、治療ターゲットの探索

    研究課題/領域番号:24591156  2012年4月 - 2015年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    吉澤 弘久, 渡部 聡, 中田 光

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    配分額:5070000円 ( 直接経費:3900000円 、 間接経費:1170000円 )

    感受性EGFR遺伝子変異陽性の非小細胞肺癌患者でEGFR-TKIによる初回治療例を対象として、各種免疫学的パラメーターについて測定した。腫瘍 退縮時にはCD4+CD25+ Foxp3+Regulatory T細胞の末梢血中の出現頻度が低下する傾向を認めた。MDSCsの解析、各種液性因子では 一定の傾向は認めなかった。本研究を推進中にEGFR-TKIに対する腫瘍の抵抗性獲 得のメカニズムにCD4+ CD25+ Foxp3+Regulatory T細胞がかかわること、その背景にDDX3Xの関与を明らかとしてPLoS One, 2014. 9(10): p . e111019に報告した。

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  • 進行期肺癌に対する抗腫瘍免疫再構成を利用した画期的免疫療法の開発

    研究課題/領域番号:21590984  2009年 - 2011年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    渡部 聡, 各務 博, 吉澤 弘久, 中田 光

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    配分額:3900000円 ( 直接経費:3000000円 、 間接経費:900000円 )

    我々は全身照射後のマウスで照射抵抗性の抑制性T細胞(Treg)が存在し、リンパ球減少状態でのエフェクター(Teff)誘導を阻害していることを発見し報告した。同様にシクロフォスファミド投与後のマウスにおいても治療抵抗性なTregが存在し、Teffの誘導を阻害していることが分かった。シクロフォスファミド治療、ナイーブT細胞の移入、治療抵抗性なTregの除去により、進行腫瘍モデルも治癒可能であった。マウスではTregの除去に抗CD25抗体を使用したが、CD25はTeffにも中等度発現しており効率が悪い。抗TGF-β抗体や抗CTLA-4抗体などを用いて、より効率の良いTregの除去についても検討している。

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  • 末梢血循環腫瘍細胞を用いた肺癌術後再発予測・オーダーメード治療の開発

    研究課題/領域番号:21590983  2009年 - 2011年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    吉澤 弘久, 中田 光, 渡部 聡

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    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

    肺癌患者のcirculating tumor cells(CTC)は術後再発の予測因子と成り得るか?を解析し、さらに術後アジュバント治療のオーダーメード化を目指して研究を進めた。circulating tumor cells高感度検出法の確立のための、EpCAM、抗cytokeratin抗体を含めた単離及び最も感度を高められるビーズ等の条件設定を用いて、肺癌患者におけるCTC定量を試みた。正常白血球細胞とPC9との混合比率は約1/100000まで高められたが、進行期肺癌の末梢血検体での検出率は3%,術後肺癌での検討では検出されなかった。さらなる検出感度の向上のため、現在条件設定を再検討している。またAllele specific PCR、Real time PCRを用いてERCC gene family、β-Tubulin、RRM1の検討についても同様に進めている。

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