2021/03/31 更新

写真a

サカマキ アキラ
坂牧 僚
SAKAMAKI Akira
所属
教育研究院 医歯学系 医学系列 助教
医歯学総合研究科 分子細胞医学専攻 細胞機能 助教
職名
助教
外部リンク

学位

  • 博士(医学) ( 2012年3月   新潟大学 )

研究分野

  • ライフサイエンス / 消化器内科学

経歴(researchmap)

  • 新潟大学大学院医歯学総合研究科 消化器内科学分野 助教

    2018年11月 - 現在

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  • 新潟大学医歯学総合病院 肝疾患相談センター 特任助教

    2016年11月 - 2018年10月

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  • 新潟大学医歯学総合病院 消化器内科 医員

    2016年4月 - 2016年10月

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  • 新潟県立中央病院 消化器内科 医長

    2012年4月 - 2016年3月

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  • 新潟大学医歯学総合病院 消化器内科 医員

    2011年4月 - 2012年3月

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  • 新潟大学大学院医歯学総合研究科 分子細胞医学専攻

    2007年4月 - 2012年3月

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  • 新潟県厚生連長岡中央綜合病院 消化器内科 医員

    2006年4月 - 2008年3月

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  • 新潟県厚生連長岡中央綜合病院 初期臨床研修医

    2004年4月 - 2006年3月

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経歴

  • 新潟大学   医歯学総合研究科 分子細胞医学専攻 細胞機能   助教

    2018年11月 - 現在

  • 新潟大学   医歯学総合病院 消化器内科   特任助教

    2016年11月 - 2018年10月

所属学協会

  • 日本高齢消化器病学会

    2020年12月 - 現在

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  • 日本門脈圧亢進症学会

    2020年4月 - 現在

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  • 日本肝臓学会

    2014年3月 - 現在

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  • 日本消化器病学会

    2006年2月 - 現在

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  • 日本消化器内視鏡学会

    2006年2月 - 現在

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  • 日本内科学会

    2005年11月 - 現在

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  • アルコール医学生物学研究会

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  • 日本肥満学会

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委員歴

  • 新潟大学 感染管理マネージャー(ICM)委員  

    2020年4月 - 現在   

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  • 新潟大学倫理審査委員会 委員  

    2019年4月 - 現在   

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論文

  • Daily Monitoring of Serum Wisteria floribunda Agglutinin-Positive Mac-2 Binding Protein Is Useful for Predicting Therapeutic Effect of Tolvaptan in Cirrhotic Ascites.

    Masaaki Takamura, Akira Sakamaki, Yoshihisa Arao, Toru Setsu, Hiroteru Kamimura, Takeshi Yokoo, Kenya Kamimura, Atsunori Tsuchiya, Shuji Terai

    The Tohoku journal of experimental medicine   252 ( 4 )   287 - 296   2020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)  

    Wisteria floribunda agglutinin (WFA) is a lectin that binds to the sugar chain of Mac-2 binding protein (M2BP), and WFA-positive M2BP (WFA+-M2BP) has been reported as a useful marker for assessing liver fibrosis in chronic liver disease. Tolvaptan (TLV), a selective vasopressin V2 receptor antagonist, is used for cirrhotic ascites in Japan, but good predictors of treatment efficacy remain to be established. Our aim was to investigate whether WFA+-M2BP monitoring before and after TLV administration can predict treatment efficacy in patients with cirrhotic ascites. Twenty patients (10 men), with a median age of 72 years, were enrolled. Cirrhosis was caused by hepatitis B virus (n = 3), hepatitis C virus (n = 4), alcohol (n = 8), and others (n = 5). Responders were defined as having a body weight loss of ≥ 1.5 kg/week after TLV administration. Serum WFA+-M2BP levels were measured at baseline and days 1, 3, and 7 after TLV treatment. Twelve patients (60%) were responders. Baseline WFA+-M2BP levels were correlated with serum albumin levels (r = -0.544, P = 0.013). The baseline furosemide dose was lower and platelet count was higher in responders than in non-responders (P < 0.05). The ratio of WFA+-M2BP levels on day 1 after TLV administration to baseline was lower in responders than in non-responders (P < 0.05). The decrease in the ratio discriminated responders from non-responders (AUC = 0.844, P < 0.05). In conclusion, monitoring serum WFA+-M2BP is helpful for predicting the efficacy of TLV treatment in patients with cirrhotic ascites.

    DOI: 10.1620/tjem.252.287

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  • Usefulness of ultrasonography to assess the response to steroidal therapy for the rare case of type 2b immunoglobulin G4-related sclerosing cholangitis without pancreatitis: A case report. 国際誌

    Yuto Tanaka, Kenya Kamimura, Ryota Nakamura, Marina Ohkoshi-Yamada, Yohei Koseki, Takeshi Mizusawa, Satoshi Ikarashi, Kazunao Hayashi, Hiroki Sato, Akira Sakamaki, Junji Yokoyama, Shuji Terai

    World journal of clinical cases   8 ( 22 )   5821 - 5830   2020年11月

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    記述言語:英語  

    BACKGROUND: A type 2b immunoglobulin G4 (IgG4)-related sclerosing cholangitis (SC) without autoimmune pancreatitis is a rare condition with IgG4-SC. While the variety of the imaging modalities have tested its usefulness in diagnosing the IgG4-SC, however, the usage of ultrasonography for the assessment of the response to steroidal therapy on the changes of bile duct wall thickness have not been reported in the condition. Therefore, the information of our recent case and reported cases have been summarized. CASE SUMMARY: We report the case of an 82-year-old Japanese man diagnosed with isolated IgG4-related SC based on the increase of serum IgG4, narrowing of the bile duct, its wall thickness, no complication of autoimmune pancreatitis, and IgG4 positive inflammatory cell infiltration to the wall with the fibrotic changes. The cholangiogram revealed type 2b according to the classification. Corticosteroid treatment showed a favorable effect, with the smooth decrease in serum IgG4 and the improvement of the bile duct wall thickness. CONCLUSION: As isolated type 2b, IgG4-SC is rare, the images, histological findings, and clinical course of our case will be helpful for physicians to diagnose and treat the new cases appropriately.

    DOI: 10.12998/wjcc.v8.i22.5821

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  • Obesity and accumulation of subcutaneous adipose tissue are poor prognostic factors in patients with alcoholic liver cirrhosis. 査読 国際誌

    Akira Sakamaki, Kunihiko Yokoyama, Kyutaro Koyama, Shinichi Morita, Hiroyuki Abe, Kenya Kamimura, Masaaki Takamura, Shuji Terai

    PloS one   15 ( 11 )   e0242582   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)  

    In alcoholic liver cirrhosis (LC) patients, obesity has become a problem that progresses into liver dysfunction. Herein, we investigated the relationship between the prognosis of steatohepatitis and body weight, along with fat accumulation in patients with alcoholic LC. We conducted a single-center retrospective study, enrolled 104 alcoholic LC patients without hepatocellular carcinoma (HCC) based on histological and clinical evidence, and investigated factors related to poor prognosis using multivariate Cox regression and cluster analyses. Cox regression analysis revealed three independent relevant factors: subcutaneous adipose tissue (SAT) index (median 34.8 cm2/m2, P = 0.009, hazard ratio [HR] 1.017, 95% confidence interval [CI] 1.004-1.030), total bilirubin level (median 1.7 mg/dL, P = 0.003, HR 1.129, 95% CI 1.042-1.223), and prothrombin time value (median 64%, P = 0.007, HR 0.967, 95% CI 0.943-0.991). In the cluster analysis, we categorized the patients into three groups: no adipose tissue accumulation (NAT group), SAT prior accumulation (SAT group), and visceral adipose tissue prior accumulation (VAT group). The results of the three groups revealed that the SAT group displayed a significantly poor prognosis of the Kaplan-Meier curve (67.1 vs 21.2 vs 65.3, P<0.001) of a 5-year survival rate. Propensity score matching analysis of the SAT and VAT groups was performed to adjust the patient's background, but no significant differences were found between them; however, the prognosis was poorer (21.2 vs 66.3, P<0.001), and hemostatic factors were still at a lower level in the SAT group. These findings suggest that SAT accumulation type of obesity is a poor prognostic factor in alcoholic LC patients without HCC, and the hemorrhagic tendency might worsen the poor prognosis in such cases.

    DOI: 10.1371/journal.pone.0242582

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  • Efficacy and Safety of the Radiotherapy for Liver Cancer: Assessment of Local Controllability and its Role in Multidisciplinary Therapy. 国際誌

    Marina Ohkoshi-Yamada, Kenya Kamimura, Osamu Shibata, Shinichi Morita, Motoki Kaidu, Toshimichi Nakano, Katsuya Maruyama, Atsushi Ota, Hirotake Saito, Nobuko Yamana, Tomoya Oshikane, Yukiyo Goto, Natsumi Yoshimura, Satoshi Tanabe, Hisashi Nakano, Madoka Sakai, Yuto Tanaka, Yohei Koseki, Yoshihisa Arao, Hiroyuki Abe, Toru Setsu, Akira Sakamaki, Takeshi Yokoo, Hiroteru Kamimura, Hidefumi Aoyama, Shuji Terai

    Cancers   12 ( 10 )   2020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)  

    This study investigated the efficacy and safety of radiotherapy as part of multidisciplinary therapy for advanced hepatocellular carcinoma (HCC). Clinical data of 49 HCC patients treated with radiotherapy were assessed retrospectively. The efficacy of radiotherapy was assessed by progression-free survival, disease control rate, and overall survival. Safety was assessed by symptoms and hematological assay, and changes in hepatic reserve function were determined by Child-Pugh score and albumin-bilirubin (ALBI) score. Forty patients underwent curative radiotherapy, and nine patients with portal vein tumor thrombus (PVTT) underwent palliative radiotherapy as part of multidisciplinary therapy. Local disease control for curative therapy was 80.0% and stereotactic body radiotherapy was 86.7% which was greater than that of conventional radiotherapy (60.0%). Patients with PVTT had a median observation period of 651 days and 75% three-year survival when treated with multitherapy, including radiotherapy for palliative intent, transcatheter arterial chemoembolization, and administration of molecular targeted agents. No adverse events higher than grade 3 and no changes in the Child-Pugh score and ALBI score were seen. Radiotherapy is safe and effective for HCC treatment and can be a part of multidisciplinary therapy.

    DOI: 10.3390/cancers12102955

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  • Small Intestinal Bacterial Overgrowth Diagnosed by a Breath Test and Improved by Rifaximin in a Patient with Hepatic Encephalopathy and Alcoholic Liver Cirrhosis: A Case Report. 査読

    Akira Sakamaki, Kunihiko Yokoyama, Fusako Yamazaki, Hiroteru Kamimura, Kenya Kamimura, Masaaki Takamura, Junji Yokoyama, Shuji Terai

    Internal medicine (Tokyo, Japan)   2020年4月

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    担当区分:筆頭著者   記述言語:英語  

    A 66-year-old Japanese man was admitted to our hospital with grade 2 hepatic encephalopathy (HE). Abdominal computed tomography and laboratory examinations revealed decompensated liver cirrhosis. Intravenous administration of branched-chain amino acids immediately ameliorated the HE, and lactulose was initiated. However, a breath test revealed small intestinal bacterial overgrowth (SIBO); therefore, rifaximin was additionally initiated. The breath test was repeated after discharge, when no evidence of SIBO or overt HE was identified. This case suggested that a breath test is effective for the identification of SIBO and that the administration of a poorly absorbed antibiotic should be considered in SIBO-positive HE patients taking lactulose.

    DOI: 10.2169/internalmedicine.4593-20

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  • Effect of Diphtheria Toxin-Based Gene Therapy for Hepatocellular Carcinoma. 査読 国際誌

    Kenya Kamimura, Takeshi Yokoo, Hiroyuki Abe, Norihiro Sakai, Takuro Nagoya, Yuji Kobayashi, Masato Ohtsuka, Hiromi Miura, Akira Sakamaki, Hiroteru Kamimura, Norio Miyamura, Hiroshi Nishina, Shuji Terai

    Cancers   12 ( 2 )   2020年2月

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    記述言語:英語  

    Hepatocellular carcinoma (HCC) is a major global malignancy, responsible for >90% of primary liver cancers. Currently available therapeutic options have poor performances due to the highly heterogeneous nature of the tumor cells; recurrence is highly probable, and some patients develop resistances to the therapies. Accordingly, the development of a novel therapy is essential. We assessed gene therapy for HCC using a diphtheria toxin fragment A (DTA) gene-expressing plasmid, utilizing a non-viral hydrodynamics-based procedure. The antitumor effect of DTA expression in HCC cell lines (and alpha-fetoprotein (AFP) promoter selectivity) is assessed in vitro by examining HCC cell growth. Moreover, the effect and safety of the AFP promoter-selective DTA expression was examined in vivo using an HCC mice model established by the hydrodynamic gene delivery of the yes-associated protein (YAP)-expressing plasmid. The protein synthesis in DTA transfected cells is inhibited by the disappearance of tdTomato and GFP expression co-transfected upon the delivery of the DTA plasmid; the HCC cell growth is inhibited by the expression of DTA in HCC cells in an AFP promoter-selective manner. A significant inhibition of HCC occurrence and the suppression of the tumor marker of AFP and des-gamma-carboxy prothrombin can be seen in mice groups treated with hydrodynamic gene delivery of DTA, both 0 and 2 months after the YAP gene delivery. These results suggest that DTA gene therapy is effective for HCC.

    DOI: 10.3390/cancers12020472

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  • Ghrelin-insulin-like growth factor-1 axis is activated via autonomic neural circuits in the non-alcoholic fatty liver disease. 査読 国際誌

    Takuro Nagoya, Kenya Kamimura, Ryosuke Inoue, Masayoshi Ko, Takashi Owaki, Yusuke Niwa, Norihiro Sakai, Toru Setsu, Akira Sakamaki, Takeshi Yokoo, Hiroteru Kamimura, Yuka Nakamura, Masaki Ueno, Shuji Terai

    Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society   e13799   2020年1月

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    記述言語:英語  

    BACKGROUND: The correlation of the growth hormone (GH) and insulin-like growth factor-1 (IGF-1) with non-alcoholic fatty liver disease (NAFLD) has been reported in epidemiological studies. However, the mechanisms of molecular and inter-organ systems that render these factors to influence on NAFLD have not been elucidated. In this study, we examined the induction of ghrelin which is the GH-releasing hormone and IGF-1, and involvement of autonomic neural circuits, in the pathogenesis of NAFLD. METHODS: The expression of gastric and hypothalamic ghrelin, neural activation in the brain, and serum IGF-1 were examined in NAFLD models of choline-deficient defined l-amino-acid diet-fed, melanocortin 4 receptor knockout mice, and partial hepatectomy mice with or without the blockades of autonomic nerves to test the contribution of neural circuits connecting the brain, liver, and stomach. KEY RESULTS: The fatty changes in the liver increased the expression of gastric ghrelin through the autonomic pathways which sends the neural signals to the arcuate nucleus in the hypothalamus through the afferent vagal nerve which reached the pituitary gland to release GH and then stimulate the IGF-1 release from the liver. In addition, high levels of ghrelin expression in the arcuate nucleus were correlated with NAFLD progression regardless of the circuits. CONCLUSIONS: Our study demonstrated that the fatty liver stimulates the autonomic nervous signal circuits which suppress the progression of the disease by activating the gastric ghrelin expression, the neural signal transduction in the brain, and the release of IGF-1 from the liver.

    DOI: 10.1111/nmo.13799

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  • Methotrexate-related lymphoproliferative disorders in the liver: Case presentation and mini-review. 査読 国際誌

    Takeshi Mizusawa, Kenya Kamimura, Hiroki Sato, Takeshi Suda, Hiroyuki Fukunari, Go Hasegawa, Osamu Shibata, Shinichi Morita, Akira Sakamaki, Junji Yokoyama, Yu Saito, Yoshihisa Hori, Yuduru Maruyama, Fumitoshi Yoshimine, Takahiro Hoshi, Shinichi Morita, Tsutomu Kanefuji, Masaaki Kobayashi, Shuji Terai

    World journal of clinical cases   7 ( 21 )   3553 - 3561   2019年11月

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    記述言語:英語  

    BACKGROUND: Immunosuppression is effective in treating a number of diseases, but adverse effects such as bone marrow suppression, infection, and oncogenesis are of concern. Methotrexate is a key immunosuppressant used to treat rheumatoid arthritis. Although it is effective for many patients, various side effects have been reported, one of the most serious being methotrexate-related lymphoproliferative disorder. While this may occur in various organs, liver involvement is rare. Information on these liver lesions, including clinical characteristics, course, and imaging studies, has not been summarized to date. CASE SUMMARY: We present a case of 70-year-old woman presented with a 2-wk history of fever and abdominal pain. She had had rheumatoid arthritis for 5 years and was being treated with medication including methotrexate. Contrast-enhanced computed tomography revealed multiple low density tumors in the liver and the histological analyses showed significant proliferation of lymphocytes in masses that were positive on immunohistochemical staining for CD3, CD4, CD8, and CD79a but negative for CD20 and CD56. Staining for Epstein-Barr virus-encoded RNA was negative. And based on these findings, the liver tumors were diagnosed as Methotrexate-related lymphoproliferative disorders. A time-dependent disappearance of the liver tumors after stopping methotrexate supported the diagnoses. CONCLUSION: The information obtained from our case and a review of 9 additional cases reported thus far assist physicians who may face the challenge of diagnosing and managing this disorder.

    DOI: 10.12998/wjcc.v7.i21.3553

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  • Rare Mesenteric Arterial Diseases: A Case Report of Fibromuscular Dysplasia and Segmental Arterial Mediolysis and Literature Review. 査読

    Ko M, Kamimura K, Sakamaki A, Niwa Y, Tominaga K, Mizuno K, Terai S

    Internal medicine (Tokyo, Japan)   2019年7月

  • A case report of psychiatric symptoms following direct-acting antiviral and ribavirin combination therapy for chronic hepatitis C in a patient with innate anxiety. 査読

    Sakamaki A, Kamimura K, Fukui N, Watanabe H, Sakai N, Tominaga K, Mizuno K, Takamura M, Kawai H, Sugai T, Yamagiwa S, Someya T, Terai S

    BMC gastroenterology   19 ( 1 )   85   2019年6月

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    担当区分:筆頭著者  

    DOI: 10.1186/s12876-019-1013-1

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  • Considerations of elderly factors to manage the complication of liver cirrhosis in elderly patients. 査読

    Kamimura K, Sakamaki A, Kamimura H, Setsu T, Yokoo T, Takamura M, Terai S

    World journal of gastroenterology   25 ( 15 )   1817 - 1827   2019年4月

  • Inhibition of sodium glucose cotransporter 2 (SGLT2) delays liver fibrosis in a medaka model of nonalcoholic steatohepatitis (NASH). 査読

    Goto R, Kamimura K, Shinagawa-Kobayashi Y, Sakai N, Nagoya T, Niwa Y, Ko M, Ogawa K, Inoue R, Yokoo T, Sakamaki A, Kamimura H, Abe S, Nishina H, Terai S

    FEBS open bio   9 ( 4 )   643 - 652   2019年4月

  • Effective prevention of sorafenib-related vascular damage induced adverse events and maintenance of hepatic function by dried bonito broth and histidine. 査読

    Sakai N, Kamimura K, Shinagawa-Kobayashi Y, Nagoya T, Niwa Y, Ko M, Setsu T, Sakamaki A, Yokoo T, Abe S, Kamimura H, Sugitani S, Yanagi M, Terai S

    Cancer management and research   11   4437 - 4448   2019年

  • Diagnosis and management of fibromuscular dysplasia and segmental arterial mediolysis in gastroenterology field: A mini-review. 査読

    Ko M, Kamimura K, Ogawa K, Tominaga K, Sakamaki A, Kamimura H, Abe S, Mizuno K, Terai S

    World journal of gastroenterology   24 ( 32 )   3637 - 3649   2018年8月

  • Rapidly declining skeletal muscle mass predicts poor prognosis of hepatocellular carcinoma treated with transcatheter intra-arterial therapies. 査読

    Kobayashi T, Kawai H, Nakano O, Abe S, Kamimura H, Sakamaki A, Kamimura K, Tsuchiya A, Takamura M, Yamagiwa S, Terai S

    BMC cancer   18 ( 1 )   756   2018年7月

  • Renal Impairment in Chronic Hepatitis B: A Review. 査読

    Kamimura H, Setsu T, Kimura N, Yokoo T, Sakamaki A, Kamimura K, Tsuchiya A, Takamura M, Yamagiwa S, Terai S

    Diseases (Basel, Switzerland)   6 ( 2 )   2018年6月

  • Effect of a neural relay on liver regeneration in mice: activation of serotonin release from the gastrointestinal tract. 査読

    Inoue R, Kamimura K, Nagoya T, Sakai N, Yokoo T, Goto R, Ogawa K, Shinagawa-Kobayashi Y, Watanabe-Mori Y, Sakamaki A, Abe S, Kamimura H, Miyamura N, Nishina H, Terai S

    FEBS open bio   8 ( 3 )   449 - 460   2018年3月

  • Effect of histidine on sorafenib-induced vascular damage: Analysis using novel medaka fish model. 査読

    Shinagawa-Kobayashi Y, Kamimura K, Goto R, Ogawa K, Inoue R, Yokoo T, Sakai N, Nagoya T, Sakamaki A, Abe S, Sugitani S, Yanagi M, Fujisawa K, Nozawa Y, Koyama N, Nishina H, Furutani-Seiki M, Sakaida I, Terai S

    Biochemical and biophysical research communications   496 ( 2 )   556 - 561   2018年2月

  • Prognostic value of subcutaneous adipose tissue volume in hepatocellular carcinoma treated with transcatheter intra-arterial therapy. 査読

    Kobayashi T, Kawai H, Nakano O, Abe S, Kamimura H, Sakamaki A, Kamimura K, Tsuchiya A, Takamura M, Yamagiwa S, Terai S

    Cancer management and research   10   2231 - 2239   2018年

  • Effective prevention of sorafenib-induced hand-foot syndrome by dried-bonito broth. 査読

    Kamimura K, Shinagawa-Kobayashi Y, Goto R, Ogawa K, Yokoo T, Sakamaki A, Abe S, Kamimura H, Suda T, Baba H, Tanaka T, Nozawa Y, Koyama N, Takamura M, Kawai H, Yamagiwa S, Aoyagi Y, Terai S

    Cancer management and research   10   805 - 813   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2147/CMAR.S159370

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  • Efficacy and Safety of Pancreas-Targeted Hydrodynamic Gene Delivery in Rats 査読

    Kohei Ogawa, Kenya Kamimura, Yuji Kobayashi, Hiroyuki Abe, Takeshi Yokoo, Norihiro Sakai, Takuro Nagoya, Akira Sakamaki, Satoshi Abe, Kazunao Hayashi, Satoshi Ikarashi, Junji Kohisa, Masanori Tsuchida, Yutaka Aoyagi, Guisheng Zhang, Dexi Liu, Shuji Terai

    MOLECULAR THERAPY-NUCLEIC ACIDS   9   80 - 88   2017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:CELL PRESS  

    Development of an effective, safe, and convenient method for gene delivery to the pancreas is a critical step toward gene therapy for pancreatic diseases. Therefore, we tested the possibility of applying the principle of hydrodynamic gene delivery for successful gene transfer to pancreas using rats as a model. The established procedure involves the insertion of a catheter into the superior mesenteric vein with temporary blood flow occlusion at the portal vein and hydrodynamic injection of DNA solution. We demonstrated that our procedure achieved efficient pancreas-specific gene expression that was 2,000-fold higher than that seen in the pancreas after the systemic hydrodynamic gene delivery. In addition, the level of gene expression achieved in the pancreas by the pancreas-specific gene delivery was comparable to the level in the liver achieved by a liver-specific hydrodynamic gene delivery. The optimal level of reporter gene expression in the pancreas requires an injection volume equivalent to 2.0% body weight with flow rate of 1 mL/s and plasmid DNA concentration at 5 mu g/mL. With the exception of transient expansion of intercellular spaces and elevation of serum amylase levels, which recovered within 3 days, no permanent tissue damage was observed. These results suggest that pancreas-targeted hydrodynamic gene delivery is an effective and safe method for gene delivery to the pancreas and clinically applicable.

    DOI: 10.1016/j.omtn.2017.08.009

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  • Intraductal Papillary Neoplasm of the Bile Duct: A Rare Liver Tumor Complicated by Malignancy 査読

    Kentaro Tominaga, Kenya Kamimura, Akira Sakamaki, Shuji Terai

    HEPATOLOGY   66 ( 5 )   1695 - 1697   2017年11月

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    記述言語:英語   出版者・発行元:WILEY  

    DOI: 10.1002/hep.29266

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  • Lusutrombopag increases hematocytes in a compensated liver cirrhosis patient 査読

    Akira Sakamaki, Takayuki Watanabe, Satoshi Abe, Kenya Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Hirokazu Kawai, Satoshi Yamagiwa, Shuji Terai

    Clinical Journal of Gastroenterology   10 ( 3 )   261 - 264   2017年6月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Tokyo  

    A 56-year-old Japanese man with liver cirrhosis (LC) due to hepatitis C virus was admitted to our hospital for radiofrequency ablation of residual tumor following lusutrombopag administration. Laboratory tests revealed thrombocytopenia and leukopenia. The patient’s LC was managed, and he was classified as Child–Pugh A. After admission, lusutrombopag was administered for 7 days. The platelet count increased to over 50,000/mm3 after 7–14 days and returned to previous levels 50 days after administration. Leukocyte and erythrocyte counts also increased in response to the treatment and stayed elevated for over 120 days. Lusutrombopag acts selectively on human thrombopoietin (TPO) receptors and activates signaling pathways that promote the proliferation and differentiation of bone marrow progenitor cells into megakaryocytes, consequently increasing the blood platelet count. However, the patient treated with lusutrombopag in our case study showed increased blood leukocyte and erythrocyte counts as well. Given that TPO receptors are reportedly expressed in not only megakaryocyte progenitor cells but also hematopoietic progenitors, lusutrombopag may potentially improve pancytopenia caused by LC and can be used for the recovery of blood counts before other treatments.

    DOI: 10.1007/s12328-017-0735-2

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  • Long-term efficacy and safety of nalfurafine hydrochloride on pruritus in chronic liver disease patients: Patient-reported outcome based analyses 査読

    Kenya Kamimura, Takeshi Yokoo, Hiroteru Kamimura, Akira Sakamaki, Satoshi Abe, Atsunori Tsuchiya, Masaaki Takamura, Hirokazu Kawai, Satoshi Yamagiwa, Shuji Terai

    PLOS ONE   12 ( 6 )   e0178991   2017年6月

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

    Background and aim
    Among various symptoms accompanied with chronic liver disease, pruritus affects the quality of life of patients, causing physical and mental stress, and worsens hepatic function. Recently, kappa-opioid receptor agonist, nalfurafine hydrochloride was approved to treat central pruritus in patients with liver disease in Japan. This study aimed to assess the long-term efficacy and safety of nalfurafine hydrochloride on pruritus in chronic liver disease patients.
    Methods
    A patient-reported outcome using questionnaire-based methods was used for 41 liver disease patients with or without pruritus symptoms. Nalfurafine hydrochloride (2.5 mu g/day) was orally administered to 18 patients suffering from pruritus symptoms and whose current treatment was not effective. The same questionnaires and visual analogue scales (VAS) were repeatedly followed up for the patients for the entire follow-up period, and biochemical analyses were performed to evaluate the safety of the treatment.
    Results
    Pruritus completely disappeared in seven of 18 cases, and VAS scores showed a decreasing trend over time from the start of nalfurafine hydrochloride administration in all patients who received the medication. Among 11 patients who were followed up for more than 12 weeks, nine patients showed continuous improvement of symptoms, and this progress was still apparent at &gt;= 20 weeks after starting administration (p &lt; 0.0001). The medication was discontinued in four patients because of progression of primary disease, high cost, oral dryness, and anemia. No significant toxicity was observed on the serum biochemical analyses.
    Conclusions
    Nalfurafine hydrochloride contributed to long-term suppression of pruritus without significant safety problems.

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  • Effect of double platinum agents, combination of miriplatintransarterial oily chemoembolization and cisplatinhepatic arterial infusion chemotherapy, in patients with hepatocellular carcinoma: Report of two cases 査読

    Kohei Ogawa, Kenya Kamimura, Yukari Watanabe, Yosuke Motai, Daisuke Kumaki, Ryoya Seki, Akira Sakamaki, Satoshi Abe, Hirokazu Kawai, Takeshi Suda, Satoshi Yamagiwa, Shuji Terai

    WORLD JOURNAL OF CLINICAL CASES   5 ( 6 )   238 - 246   2017年6月

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

    Hepatocellular carcinoma (HCC) is one of the most common cancers and the third highest cause of cancerassociated mortality worldwide. The treatment of HCC is complicated by its variable biological behavior and the frequent coexistence of chronic liver disease, particularly cirrhosis. To date, multiple treatment modalities have been developed according to the stage of the tumor and the hepatic functional reserve, including transarterial treatments such as transarterial chemoembolization, transarterial oily chemoembolization (TOCE), and hepatic arterial infusion chemotherapy (HAIC). We conducted a phase I and II study of the combination therapy with double platinum agents, miriplatin and cisplatin, and confirmed its safety and efficacy. Here, we describe two cases of unresectable HCC who were successfully treated by miriplatin-TOCE/cisplatin-HAIC combination therapy, resulting in complete responses with no significant adverse events. This report will provide that the combination therapy can be the therapeutic option for HCC patients in the advanced stage.

    DOI: 10.12998/wjcc.v5.i6.238

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  • Spontaneous regression of hepatocellular carcinoma: A mini-review 査読

    Akira Sakamaki, Kenya Kamimura, Satoshi Abe, Atsunori Tsuchiya, Masaaki Takamura, Hirokazu Kawai, Satoshi Yamagiwa, Shuji Terai

    WORLD JOURNAL OF GASTROENTEROLOGY   23 ( 21 )   3797 - 3804   2017年6月

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    記述言語:英語   出版者・発行元:BAISHIDENG PUBLISHING GROUP INC  

    Spontaneous tumor regression is an extremely rare phenomenon in the oncology field. However, there are several case reports resulted in the regression of hepatocellular carcinoma (HCC) and the accumulation of clinical information and analyses of the mechanism can contribute to the development of a novel therapy. For this purpose, we have carefully reviewed 23 cases of spontaneously regressed HCC published in recent 5 years and our case. The information regarding the tumor size, tumor marker, treatments, etc., have been summarized. The mechanism of spontaneous regression has been discussed to date and presumed to be due to many factors, including hypoxia and immunological reactions. In this careful review of the 24 cases based on the clinical information, hypoxia, systemic inflammation, and both upon spontaneous regression were seen in 3, 8, and 4 cases, respectively among the 15 cases for which the information regarding the proposed mechanisms are available. Recent development of immunotherapeutic approaches in oncology shows promising results, therefore, accumulation of additional cases and analysis of mechanisms underlying the spontaneous regression of HCC are essential and could lead to the development of a new generation of immunotherapies including antibodies directed against immune reactions.

    DOI: 10.3748/wjg.v23.i21.3797

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  • Tumor markers for early diagnosis for brain metastasis of hepatocellular carcinoma: A case series and literature review for effective loco-regional treatment 査読

    Kenya Kamimura, Yuji Kobayashi, Yoshifumi Takahashi, Hiroyuki Abe, Daisuke Kumaki, Takeshi Yokoo, Hiroteru Kamimura, Norihiro Sakai, Akira Sakamaki, Satoshi Abe, Masaaki Takamura, Hirokazu Kawai, Satoshi Yamagiwa, Shuji Terai

    CANCER BIOLOGY & THERAPY   18 ( 2 )   79 - 84   2017年

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

    Intrahepatic lesions of hepatocellular carcinoma (HCC) have been controlled by significant advances in treatment using loco-regional therapies, including, surgery, ablative therapy, catheter-based chemotherapy, and embolization. Consequently, the number of patients with extrahepatic metastatic lesions has increased. Their prognosis remains poor with approximately &lt;1y of survival from the time of diagnosis. A molecularly targeted drug, sorafenib, have been used to treat extrahepatic lesions and shown the prolonged survival time. However, the therapeutic benefit for the brain metastasis remains unclear, since it causes intratumor bleeding leading to the severe brain damage. No guidelines for the brain metastasis of HCC have been developed to date due to the shortage of the experiences and evidences. Therefore, the development of standard therapy for brain metastasis following the early diagnosis is essential by accumulating the information of clinical courses and evidences. For this purpose, we reviewed cases of HCC brain metastasis reported to date and analyzed additional 8 cases from our hospital, reviewing 592 advanced HCC cases to estimate the possible metastatic lesions in the brain. With careful review of cases and literature, we suggest that the cases with lung metastasis with increase tendency of tumor markers within recent 3-6months have higher risks of brain metastasis. Therefore, they should be carefully followed by imaging modalities. In addition, the loco-regional treatment, including surgical resection and radiation therapy should be performed for better prognosis by preventing re-bleeding from the tumors.

    DOI: 10.1080/15384047.2016.1276134

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  • Bcl11b SWI/SNF-complex subunit modulates intestinal adenoma and regeneration after γ-irradiation through Wnt/β-catenin pathway. 査読

    Sakamaki A, Katsuragi Y, Otsuka K, Tomita M, Obata M, Iwasaki T, Abe M, Sato T, Ochiai M, Sakuraba Y, Aoyagi Y, Gondo Y, Sakimura K, Nakagama H, Mishima Y, Kominami R

    Carcinogenesis   36 ( 6 )   622 - 631   2015年6月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1093/carcin/bgv044

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  • Granulocytapheresis for the Treatment of Severe Alcoholic Hepatitis: A Case Series and Literature Review 査読

    Kenya Kamimura, Michitaka Imai, Akira Sakamaki, Shigeki Mori, Masaaki Kobayashi, Ken-ichi Mizuno, Manabu Takeuchi, Takeshi Suda, Minoru Nomoto, Yutaka Aoyagi

    DIGESTIVE DISEASES AND SCIENCES   59 ( 2 )   482 - 488   2014年2月

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    記述言語:英語   出版者・発行元:SPRINGER  

    Severe alcoholic hepatitis has a high mortality rate due to limited therapeutic methods. Although corticosteroids have been used to control the inflammatory response, the outcomes vary and no standardized therapy has been established. Novel therapeutic approaches, such as anti-TNF-alpha, pentoxifilline, and others have been tested clinically on the basis of their cytokinemic pathophysiology with limited success. However, treatment of leukocytosis that causes cytokinemia and hepatic inflammation in patients via granulocytapheresis and leukocytapheresis showed promising results in a number of reports. Here, we report two cases of severe alcoholic hepatitis treated with granulocytapheresis. The liver function and inflammation recovered after the therapy. A review of 35 cases treated with granulocytapheresis and leukocytapheresis demonstrated their efficacy in treating alcoholic hepatitis by controlling leukocytosis as well as cytokines such as IL-8. Multidisciplinary treatment for severe alcoholic hepatitis should be considered case by case on the basis of the complexity and severity of the condition.

    DOI: 10.1007/s10620-013-2871-y

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  • Alcoholic Liver Disease Complicated by Deep Bleeding into the Muscles or Retroperitoneum: Report of Three Cases and a Review of the Literature 査読

    Masaaki Takamura, Jun Watanabe, Akira Sakamaki, Yutaka Honda, Kenya Kamimura, Atsunori Tsuchiya, Satoshi Yamagiwa, Takeshi Suda, Yasunobu Matsuda, Yutaka Aoyagi

    INTERNAL MEDICINE   53 ( 16 )   1763 - 1768   2014年

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    記述言語:英語   出版者・発行元:JAPAN SOC INTERNAL MEDICINE  

    We herein report three cases of alcoholic cirrhosis complicated by deep bleeding. In two of the three cases, intramuscular or retroperitoneal hematomas developed spontaneously. In contrast, in the remaining case, an intramuscular hematoma developed after trauma. In the former two patients, the intramuscular hematomas recurred at other sites during hospitalization. All three patients received conservative therapy, and one patient with a retroperitoneal hematoma underwent transcatheter arterial embolization. All of the patients eventually died of liver failure. The occurrence of severe alcoholic liver disease with deep bleeding has recently been reported with increasing frequency, and clinicians should bear this condition in mind as a life-threatening complication of alcoholic liver disease.

    DOI: 10.2169/internalmedicine.53.2123

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  • Immunoglobulin G4-Related Disease with Several Inflammatory Foci 査読

    Akira Sakamaki, Kenya Kamimura, Kazuhiko Shioji, Junko Sakurada, Takeshi Nakatsue, Yoko Wada, Michitaka Imai, Ken-ichi Mizuno, Takashi Yamamoto, Manabu Takeuchi, Yuichi Sato, Masaaki Kobayashi, Makoto Naito, Ichiei Narita, Yutaka Aoyagi

    INTERNAL MEDICINE   52 ( 4 )   457 - 462   2013年

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    担当区分:筆頭著者   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  

    We herein report the case of a 62-year-old Japanese man who presented with jaundice, dry eyes and abdominal discomfort. Imaging studies revealed swelling of the periorbital tissue, parotid and submandibular glands, pulmonary hilar lymph nodes, pancreas, bile ducts, gall bladder walls, bilateral kidneys, arterial walls and prostate. A significant increase in the serum level IgG4 was seen, and the patient was diagnosed with IgG4-related disease after undergoing a biopsy of the pancreas and prostate. We herein report a case of IgG4-related disease with multiple ten organ involvement at the onset of the disease that was successfully treated with prednisolone (PSL) therapy.

    DOI: 10.2169/internalmedicine.52.9239

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MISC

  • 10年目を迎えた新潟県肝疾患相談センターの現況 査読

    上村 博輝, 薛 徹, 荒生 祥尚, 廣川 光, 澤栗 裕美, 渡邊 文子, 小師 優子, 坂牧 僚, 土屋 淳紀, 高村 昌昭, 五十嵐 正人, 青柳 豊, 菊田 玲, 渡辺 和仁, 中山 均, 田村 務, 寺井 崇二

    肝臓   61 ( 5 )   245 - 254   2020年5月

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  • 【難治性腹水の対策】肝腎症候群

    薛 徹, 荒生 祥尚, 上村 博輝, 坂牧 僚, 横尾 健, 上村 顕也, 土屋 淳紀, 高村 昌昭, 寺井 崇二

    消化器・肝臓内科   7 ( 2 )   169 - 174   2020年2月

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    記述言語:日本語   出版者・発行元:(有)科学評論社  

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  • 肝性脳症治療の変遷 肝臓と消化管―腸・肝・脳相関をベースに―各種肝疾患における腸内細菌叢の変化

    上村顕也, 坂牧僚, 薛徹, 横尾健, 上村博輝, 阿部聡司, 高村昌昭, 寺井崇二

    肝胆膵   78 ( 3 )   441‐446   2019年3月

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    記述言語:日本語  

    J-GLOBAL

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  • サルコペニア研究の最前線 (特集 肝疾患におけるサルコペニア)

    吉田 智彰, 横山 純二, 冨永 顕太郎, 上村 博輝, 坂牧 僚, 高村 昌昭, 寺井 崇二

    消化器・肝臓内科 = Gastroenterology & hepatology   5 ( 1 )   120 - 126   2019年1月

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    記述言語:日本語   出版者・発行元:科学評論社  

    CiNii Article

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  • 超高齢者における肝硬変診療

    上村 顕也, 坂牧 僚, 木村 成広, 薛 徹, 上村 博輝, 横尾 健, 阿部 聡司, 寺井 崇二

    消化器・肝臓内科   4 ( 4 )   344 - 347   2018年10月

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  • Acute on chronic―慢性病態の急性増悪―総論 Acute‐on‐chronic liver failureの病態―感染症,循環障害の焦点をあてて―

    寺井崇二, 上村博輝, 坂牧僚, 高村昌昭

    肝胆膵   76 ( 6 )   995‐1000   2018年6月

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    記述言語:日本語  

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  • 新しい肝性脳症の治療薬リファキシミン

    坂牧 僚, 寺井 崇二

    医学のあゆみ   263 ( 6 )   525 - 526   2017年11月

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    担当区分:筆頭著者  

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  • Trousseau症候群を合併した胆管細胞癌の2例 査読

    品川 陽子, 上村 顕也, 酒井 規裕, 熊木 大輔, 小川 光平, 安住 里英, 冨永 顕太郎, 坂牧 僚, 五十嵐 聡, 林 和直, 山本 幹, 水野 研一, 山際 訓, 寺井 崇二

    肝臓   58 ( 9 )   528 - 535   2017年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

    Trousseau症候群は、Trousseauによって1865年に報告された、悪性腫瘍に合併する血栓症である。その脳卒中症状は、重篤な神経症状を呈し、直接的に生命予後に関与しうる傍悪性腫瘍症候群の一つとして認識されている。今回、胆管細胞癌に脳卒中症状を呈するTrousseau症候群を合併し死亡した2例を経験したので報告する。症例1は90歳、男性、症例2は58歳、女性でいずれの症例も生活習慣病の危険因子を有し、40mm前後の肝腫瘍で初診、各種画像検査、胆汁細胞診、組織診にて胆管細胞癌の診断となった。経過中、腫瘍の急激な増大、胆道出血を合併し、本症候群を発症しやすい状況であった。担癌患者では、病態が急速に進行する場合、凝固線溶系の異常値などに留意し、抗凝固療法の開始を含む対応が本症候群の発症を予防し、原病に対する治療介入の機会を増やしうる方法論であると考え、報告する。(著者抄録)

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  • 【肝硬変を理解する-分子機構から実臨床に至るまで-】 合併症の病態と治療 腹水・浮腫

    坂牧 僚, 高村 昌昭, 寺井 崇二

    肝・胆・膵   73 ( 6 )   1150 - 1154   2016年12月

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    担当区分:筆頭著者   記述言語:日本語   出版者・発行元:(株)アークメディア  

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  • 肝局所治療におけるデクスメデトミジン塩酸塩の使用経験 査読

    津端 俊介, 有賀 諭生, 平野 正明, 坂牧 僚, 山川 雅史

    日本消化器病学会雑誌   112 ( 3 )   547 - 554   2015年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

    デクスメデトミジン塩酸塩(dexmedetomidine hydrochloride;DEX)による鎮静下に肝細胞癌局所治療を行った2例を報告する。症例1は経過中に血圧低下を認めたが経過観察にて対処し得た。症例2は、DEXの初期用量を減じて治療を行い血圧低下は軽度だった。いずれも鎮痛効果は十分だった。DEXは、用量設定などに課題があるものの有用な鎮静剤になりうると考えられた。(著者抄録)

    DOI: 10.11405/nisshoshi.112.547

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  • 治療に難渋した肝性脳症に対するレボカルニチン塩化物の使用経験 査読

    津端 俊介, 小川 光平, 平野 正明, 坂牧 僚, 有賀 諭生, 山川 雅史

    肝臓   55 ( 1 )   76 - 78   2014年

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

    高アンモニア血症および肝性脳症管理に難渋している肝硬変患者に対するレボカルニチン塩化物(L-CA)について検討した。L-CAの内服治療を開始し、3ヵ月以上の経過を観察することのできた肝硬変患者5例を対象とした。全例においてL-CAによる有害事象の発現はみられなかった。血清アンモニア値は、外来導入となった4例は導入後2ヵ月で基準値内にはいたらないものの有意に低下した。BCAA点滴の回数が全例減少し、病院受診の頻度も低下した。入院中に導入となった1例では、第32病日にL-CAが開始となった。血清アンモニア値は、基準値内には至らないものの低下傾向を示した。その後、BCAA輸液製剤の減量、脱却に成功し、第112病日に退院となった。

    DOI: 10.2957/kanzo.55.76

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  • 食道壁内偽憩室症の1例 査読

    坂牧 僚, 小林 正明, 今井 径卓, 水野 研一, 上村 顕也, 竹内 学, 成澤 林太郎, 青柳 豊

    Gastroenterological Endoscopy   55 ( 10 )   3368 - 3374   2013年10月

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    担当区分:筆頭著者   記述言語:日本語   出版者・発行元:(一社)日本消化器内視鏡学会  

    症例は63歳男性。長期のアルコール多飲・喫煙歴がある。嚥下困難を主訴に当院を紹介受診した。食道造影では、食道全体に多発する突出像を認めた。上部消化管内視鏡検査では、多発するピンホール状陥凹の周囲に白色調の付着物質を認め、生検組織でカンジダ感染が検出された。食道壁内偽憩室症と診断し、節酒指導および狭窄に対する内視鏡的拡張術を行い、症状は改善傾向にある。食道カンジダ感染を伴い、典型的な内視鏡像、食道造影像を呈した食道壁内偽憩室症の1例を経験したので、文献的考察を加えて報告する。(著者抄録)

    DOI: 10.11280/gee.55.3368

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  • 転写因子Bcl11bは腸管の恒常性維持に働き、Apc変異下の腫瘍発育を抑制する 査読

    坂牧 僚

    新潟医学会雑誌   126 ( 8 )   414 - 422   2012年8月

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    担当区分:筆頭著者   記述言語:日本語   出版者・発行元:新潟医学会  

    Bcl11bはヒトT細胞性白血病やそのモデルであるマウス胸腺リンパ腫において、ハプロ不全ながん抑制遺伝子として発症に寄与することがわかっている。本論文ではBcl11b機能低下モデルマウスおよびヒト大腸がん標本を利用し、Bcl11bが腸管腫瘍の発症に関与する可能性を検討した。Bcl11bの機能低下により、小腸陰窩サイズの増大と絨毛細胞の増殖が認められ、また放射線照射後の腸管細胞増殖抑制の減弱が観察された。腸管腫瘍発生にはβ-カテニンシグナルの関与が知られているが、機能低下マウスでは核内β-カテニン発現細胞数が上昇する像、すなわちβ-カテニンシグナルの亢進がみられた。培養細胞にBcl11bを導入した実験から、Bcl11bの転写抑制の標的にβ-カテニン遺伝子があることがわかった。一方、ヒト大腸がんの74検体の変異検索を行い、5検体に変異と15検体にLOHを見いだした。これら20のDNA変化では、LOHと変異の両方をもつ症例はなく、Bcl11bがハプロ不全ながん抑制遺伝子として働くことが示唆された。これらの結果から、Bcl11bタンパク質はWnt/β-カテニンシグナルを負に制御し、細胞増殖抑制に働く可能性が示唆された。また、ヒト大腸がんでBCL11Bはハプロ不全ながん抑制遺伝子として働くことが示された。(著者抄録)

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  • 幽門側胃切除後に発生した柿胃石によるイレウスの1例 査読

    坂牧 僚, 佐藤 知巳, 岡 宏充, 稲田 勢介, 波田野 徹, 富所 隆, 吉川 明, 西村 淳, 河内 保之, 新国 恵也, 清水 武昭

    ENDOSCOPIC FORUM for digestive disease   22 ( 1 )   6,55 - 11,55   2006年6月

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    担当区分:筆頭著者   記述言語:日本語   出版者・発行元:(株)癌と化学療法社  

    83歳男.4年前,早期胃癌に対して幽門側胃切除術+Billroth I法再建術を受けた.今回,嘔気・嘔吐が出現し,入院となった.胃管を留置し,腸管内減圧を行った.腹部造影CTで十二指腸水平部と上行部の境界に含気性のスポンジ様低濃度腫瘤を認め,閉塞の原因と考えられた.胃管からの造影では十二指腸水平部が完全途絶となっていた.小腸内視鏡検査では,表面が黄色調の食物残渣に覆われた腫瘤が十二指腸内に嵌頓していた.これらの所見から胃石によるイレウスと診断し,手術を施行した.開腹すると空腸内に5×9cm大の腫瘤が認められ,これを摘出した.術後経過は良好で,9日目に退院した.患者は症状発現の10日ほど前に多量の柿を摂取しており,摘出標本所見とあわせて柿胃石と診断した

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受賞

  • 第18回市田賞(基礎医学の分野)

    2015年6月  

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  • 第72回日本消化器内視鏡学会甲信越支部例会 優秀演題賞

    2012年11月  

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共同研究・競争的資金等の研究

  • 臓器選択的ハイドロダイナミック遺伝子導入法の新規膵癌遺伝子治療法への応用

    研究課題/領域番号:20K08379  2020年4月 - 2024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)

    上村 顕也, 寺井 崇二, 坂牧 僚, 横尾 健

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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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  • NASHを反映する改良型MC4RKOマウスでの線維化改善治療開発と発癌機構の解明

    研究課題/領域番号:19H03636  2019年4月 - 2022年3月

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

    寺井 崇二, 土屋 淳紀, 高村 昌昭, 上村 顕也, 坂牧 僚, 薛 徹, 横尾 健

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    配分額:17420000円 ( 直接経費:13400000円 、 間接経費:4020000円 )

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  • 新規NASH発癌モデルの開発とその機序解析

    研究課題/領域番号:18K15775  2018年4月 - 2021年3月

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    坂牧 僚

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    配分額:2470000円 ( 直接経費:1900000円 、 間接経費:570000円 )

    本研究はMC4R遺伝子欠損マウスを用いてMaid遺伝子の機能解析を行うことを目的としている。
    MC4R遺伝子欠損マウス、Maid遺伝子欠損マウスおよびMC4RおよびMaid両遺伝子欠損マウスについてはそれぞれ作成、生育に成功している。また既報通り当施設においてもMC4R遺伝子欠損マウスに高脂肪食投与を行うことにより肝線維化を来し、NASHモデルとして使用できることを確認できている。
    NASHモデルと考えられる高脂肪食投与のMC4R遺伝子欠損マウス、および対象として用いる通常食マウスの準備、育成及び標本摘出は終了しており、今後、摘出した標本を用い、免疫組織化学染色およびウエスタンブロット解析により機能解析を行う予定である。

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  • 肝臓特異的ハイドロダイナミック法による核酸医薬送達と肝癌遺伝子治療法への応用

    研究課題/領域番号:17K09408  2017年4月 - 2021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)

    上村 顕也, 寺井 崇二, 坂牧 僚, 横尾 健

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    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

    本研究は、ハイドロダイナミック遺伝子導入法(HGD)を肝癌治療に応用するための方法論、抗腫瘍効果を学術的に検証するためのステップと位置づけ、HGDパラメーターの確立、治療遺伝子の選択、効果と安全性の検証、肝癌モデル動物に対する治療効果の検証を行うことを目的としている。
    今年度はHGDによる肝癌に対する遺伝子治療確立のための候補遺伝子X(特許出願中)の検証をin vitroで継続し、その安全性、有効性を検討するため、肝癌モデルマウスを作製し、in vivoで腫瘍に対する治療効果を検証した。
    1. in vitroでは、候補遺伝子を含む複数の抗腫瘍効果を有する遺伝子を用いて、肝癌培養細胞株の細胞増殖の検討、肝癌で発現するAFP等のプロモーターを用いた腫瘍細胞特異的治療効果の評価を行ない、候補遺伝子Xが遺伝子導入により肝癌細胞の増殖を抑制することが明らかとなった。
    2. HGDで癌関連遺伝子の導入により作成した肝癌モデルマウスに対して、候補遺伝子XをHGDにより導入し、その抗腫瘍効果及びマウス個体に対する安全性の評価を行っている。
    これまでに、候補遺伝子Xによる効率的な抗腫瘍効果が示唆され、検証中である。以上の成果は安全で再現性のある肝癌遺伝子治療法を構築するための基盤となる、と考えられる。

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