Development of new prophylactic reagent of hepatocellular carcinoma using thrombopoietin/platelets

• Project/Area Number: 21791240
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General surgery
• Research Institution: University of Tsukuba
• Principal Investigator: MURATA Soichiro University of Tsukuba, 大学院・人間総合科学研究科, 講師 (40436275)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: トロンボポチン / 血小板 / 肝細胞癌 / Pten / トロンボポエチン

Research Abstract

The aim of this research is to develop new prophylactic method of hepatocellular carcinoma using thrombopoietin to induce thrombocytosis. We clarified that thrombopoietin has no effect of proliferating hepatocellular carcinoma cell lines. We also investigated the prophylaxis of hepatocellular carcinoma in Pten liver conditional knockout mice by administrating thrombopoietin. As a result, thrombopoietin reduce hepatocellular carcinoma in female mice. Thrombopoietin has some effect of prophylaxis of hepatocellular carcinoma.

Research Products

• [Journal Article] Platel ets Prevent Acute Hepatitis Induced by Anti-Fas Antibody. (2011)
  • Author(s): Hisakura K, Murata S, Matsuo R, Paku S, Ikeda N, Kawasaki T, Kohno K, Myronovych A, Nakano Y, Ikeda O, Watanabe M, Ohkohchi N.
  • Journal Title: Journal of Gas troenterology and Hepatology. 26(2) Pages: 348-355
  • Peer Reviewed
• [Journal Article] Elevation andcharacteristics of Rab30 and S100a8/S100a9 expression in an early phase of liver regeneration in the mouse. (2011)
  • Author(s): Chiba M, Murata S, Myronovych A, Kohno K, Hiraiwa N, Nishibori M, Yasue H, Ohkohchi N.
  • Journal Title: International Journal of molecular medicine. Epub ahead of print.
  • Peer Reviewed
• [Journal Article] Platelets Prevent Acute Hepatitis Induced by Anti-Fas Antibody. (2011)
  • Author(s): Hisakura K, Murata S, Matsuo R, Paku S, Ikeda N, Kawasaki T, Kohno K, Myronovych A, Nakano Y, Ikeda O, Watanabe M, Ohkohchi N.
  • Journal Title: Journal of Gastroenterology and Hepatology Volume: 26(2) Pages: 348-355
  • Peer Reviewed
• [Journal Article] Elevation and characteristics of Rab30 and S100a8/S100a9 expression in an early phase of liver regeneration in the mouse. (2011)
  • Author(s): Chiba M, Murata S, Myronovych A, Kohno K, Hiraiwa N, Nishibori M, Yasue H, Ohkohchi N.
  • Journal Title: International Journal of molecular medicine. Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Activation of human liver sinusoidal endothelial cell by human platelets induces hepatocyte proliferation. (2010)
  • Author(s): Kawasaki T, Murata S, Takahashi K, Nozaki R, Ohshiro Y, Ikeda N, Paku S, Myronovych A, Hisakura K, Fukunaga K, Oda T, Sasaki R, Ohkohchi N.
  • Journal Title: Journal of Hepatology. 53(4) Pages: 648-654
  • NAID: 120007137912
  • Peer Reviewed
• [Journal Article] Platelets Prevent Acute Liver Damage after Extended Hepatectomy in Pigs. (2010)
  • Author(s): Hisakura K, Murata S, Fukunaga K, Myronovych A, Tadano S, Kawasaki T, Kohno K, Ikeda O, Paku S, Ikeda N, Nakano Y, Matsuo R, Kohno K,Kobayashi E, Saito T, Yasue H, Ohkohchi N.
  • Journal Title: Journal of hepato-biliary-pancreatico surgery. 17(6) Pages: 855-864
  • NAID: 10027664195
  • Peer Reviewed
• [Journal Article] Platelet adhesion in the sinusoid caused hepatic injury by neutrophils after hepatic ischemia reperfusion. (2010)
  • Author(s): Paku S, Kondo T, Nakano Y, Murata S, Fukunaga K, oda T, Sasaki R, Ohkohchi N.
  • Journal Title: Platelets. 21(4) Pages: 282-288
  • NAID: 120007130823
  • Peer Reviewed
• [Journal Article] Activation of human liver sinusoidal endothelial cell by human platelets induces hepatocyte proliferation. (2010)
  • Author(s): Kawasaki T, Murata S, Takahashi K, Nozaki R, Ohshiro Y, Ikeda N, Paku S, Myronovych A, Hisakura K, Fukunaga K, Oda T, Sasaki R, Ohkohchi N.
  • Journal Title: Journal of Hepatology. Volume: 53(4) Pages: 648-654
  • NAID: 120007137912
  • Peer Reviewed
• [Journal Article] Platelets Prevent Acute Liver Damage after Extended Hepatectomy in Pigs. (2010)
  • Author(s): Hisakura K, Murata S, Fukunaga K, Myronovych A, Tadano S, Kawasaki T, Kohno K, Ikeda O, Paku S, Ikeda N, Nakano Y, Matsuo R, Kohno K, Kobayashi E, Saito T, Yasue H, Ohkohchi N.
  • Journal Title: Journal of hepato-biliary-pancreatico surgery. Volume: 17(6) Pages: 855-864
  • NAID: 10027664195
  • Peer Reviewed
• [Journal Article] Platelet adhesion in the sinusoid caused hepatic injury by neutrophils after hepatic ischemia reperfusion. (2010)
  • Author(s): Paku S, Kondo T, Nakano Y, Murata S, Fukunaga K, oda T, Sasaki R, Ohkohchi N.
  • Journal Title: Platelets Volume: 21(4) Pages: 282-288
  • NAID: 120007130823
  • Peer Reviewed
• [Journal Article] Prevention of leukocyte activation by the neutrophil elastase inhibitor, sivelestat, in the hepatic microcirculationafter ischemia-reperfusion. (2009)
  • Author(s): Nakano Y, Kondo T, Matsuo R, Murata S, Fukunaga K, Ohkohchi N.
  • Journal Title: Journal of Surgical Research. 155(2) Pages: 311-317
  • Peer Reviewed
• [Journal Article] Platelets contribute to the reduction of liver fibrosis in mice. (2009)
  • Author(s): Watanabe M, Murata S, Hashimoto I,Nakano Y, Ikeda O, Aoyagi Y, Matsuo R, Fukunaga K, Yasue H, Ohkohchi N.
  • Journal Title: Journal of Gastroenterology and Hepatology. 24(1) Pages: 78-89
  • Peer Reviewed
• [Journal Article] Autonomic regulation of liver regeneration after partial hepatectomy in mice. (2009)
  • Author(s): Ikeda O, Ozaki M. Murata S, Matsuo R, Nakano Y, Watanabe M, Hisakura K, Myronovych A, Kawasaki T, Kohno K, Ohkohchi N.
  • Journal Title: Journal of Suegical Research. 152(2) Pages: 218-223
  • Peer Reviewed
• [Presentation] 血小板による肝類洞内皮細胞からのIL-6分泌促進作用の検討 (2010)
  • Author(s): 川崎卓也、村田聡一郎、田村孝史、丸山岳人、大城幸雄、柴崎佑樹、高橋一広、野崎礼史、池田直哉、朴秀吉、福永潔、大河内信弘
  • Organizer: 第24回肝類洞壁細胞研究会学術集会
  • Place of Presentation: 福島
  • Year and Date: 2010-11-27
• [Presentation] 血小板による肝硬変の再生療法:基礎から臨床 (2010)
  • Author(s): 村田聡一郎、川崎卓也、大河内信弘
  • Organizer: 第14回日本肝臓学会大会
  • Place of Presentation: 金沢
  • Year and Date: 2010-10-13
• [Presentation] 血小板による肝類洞内皮細胞からのIL-6分泌促進作用の検討 (2010)
  • Author(s): 川崎卓也、村田聡一郎、高橋一広、野崎礼史、大城幸雄、池田直哉、朴秀吉、Myronovych Andriy、久倉勝治、福永潔、大河内信弘
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形
  • Year and Date: 2010-05-27
• [Presentation] 肝再生促進・線維化抑制療法に濃厚血小板輸血療法を行った肝硬変の4症例 (2010)
  • Author(s): 大河内信弘、村田聡一郎、福永潔、安部井誠人
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形
  • Year and Date: 2010-05-27
• [Presentation] Activation of human liver sinusoidal endothelial cell by human platelets induces hepatocyte proliferation. (2010)
  • Author(s): Kawasaki T, Murata S, Takahashi K, Nozaki R, Ohshiro Y, Ikeda N, Pak S, Myronovych A, Hisakura K, Fukunaga K, Oda T, Sasaki R, Ohkohchi N.
  • Organizer: The Internaional Liver CongressTM 2010 45th Annual Meeting of the European Association for the Study of the Liver
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2010-04-14
• [Presentation] 血小板は肝星細胞の活性化を抑制する (2010)
  • Author(s): 池田直哉、村田聡一郎、高橋一広、大城幸雄、川崎卓也、Andriy Myronovych、大河内信弘
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-04-08
• [Presentation] 血小板は肝類洞内皮細胞を活性化しその結果肝細胞増殖を促進する(ヒト細胞を用いたin vitroでのメカニズムの検討) (2010)
  • Author(s): 川崎卓也、村田聡一郎、柴崎佑樹、大城幸雄、高橋一広、池田直哉、朴秀吉、Andriy Myronovych、久倉勝治、大河内信弘
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-04-08
• [Presentation] 脂肪酸合成酵素阻害剤セルレニンはマウス大腸癌肝転移を抑制する (2010)
  • Author(s): 村田聡一郎、川崎卓也、池田直哉、大城幸雄、高橋一広、大河内信弘
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋
• [Presentation] Activation of human liver sinusoidal endothelial cell by human platelets induces hepatocyte proliferation (2010)
  • Author(s): Kawasaki T, Murata S, Takahashi K, Nozaki R, Ohshiro Y, Ikeda N, Pak S, Myronovych A, Hisakura K, Fukunaga K, Oda T, Sasaki R, Ohkohchi N.
  • Organizer: The Internaional Liver Congress^<TM> 2010 45^<th> Annual Meeting of the European Association for the Study of the Liver
  • Place of Presentation: Vienna, Austria
• [Presentation] 3種類の肝切除モデルを用いた血小板による肝再生促進効果の検討 (2010)
  • Author(s): 村田聡一郎、Andriy Myronovych、中野順隆、大河内信弘
  • Organizer: 第22回日本肝胆膵外科学会・学術集会
  • Place of Presentation: 仙台
• [Presentation] 肝虚血再灌流障害におけるKupffer細胞と好中球動態のin vivoイメージングシステムの開発 (2010)
  • Author(s): 朴秀吉、近藤匡、中野順隆、村田聡一郎、福永潔、大河内信弘
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形
• [Presentation] 脂肪酸合成酵素阻害剤による大腸癌肝転移抑制効果の検討 (2010)
  • Author(s): 村田聡一郎、柳澤和彦、大河内信弘
  • Organizer: 第65回日本大腸肛門病学会学術集会
  • Place of Presentation: 浜松
• [Presentation] Platelets keep human hepatic stellate cell in stable state by the ERK signaling pathway. (2009)
  • Author(s): N Ikeda, S Murata, K Takahashi, Y Ohshiro, T Kawasaki, A Myronovych, N Ohkohchi.
  • Organizer: International Symposium on Cellular Singaling~principles and functions~.
  • Place of Presentation: tsukuba.
  • Year and Date: 2009-11-18
• [Presentation] 血小板は肝星細胞活性を抑制する (2009)
  • Author(s): 池田直哉, 村田聡一郎, 川崎卓也, アンドリーミロノヴィチ, 久倉勝治, 大河内信弘
  • Organizer: 第13回日本肝臓学会大会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-14
• [Presentation] 脾摘による慢性肝炎モデルの肝線維化抑制効果と過大肝切除モデルの肝障害抑制効果の検討 (2009)
  • Author(s): 村田聡一郎, 渡辺基信, 久倉勝治, アンドリーミロノヴィチ, 福永潔, 齋藤敏之, 安江博, 大河内信弘
  • Organizer: 第64回日本消化器外科学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2009-07-16
• [Presentation] 血小板は肝星細胞のαSMA発現を抑制する (2009)
  • Author(s): 池田直哉, 村田聡一郎, 柴崎佑樹, アンドリーミロノヴィチ, 川崎卓也, 久倉勝治, 小林直哉, 大河内信弘
  • Organizer: 第45回日本肝臓学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2009-06-04
• [Presentation] 血小板は肝類洞内皮細胞を活性化し肝細胞を増殖させる (2009)
  • Author(s): 川崎卓也, 村田聡一郎, 柴崎佑樹, 池田直哉, アンドリーミロノヴィチ, 久倉勝治, 大河内信弘
  • Organizer: 第45回日本肝臓学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2009-06-04
• [Patent(Industrial Property Rights)] 肝線維化抑制剤 (2011)
  • Inventor(s): 大河内信弘, 村田聡一郎, 渡辺基信, 中野順隆, 橋本育佳
  • Industrial Property Rights Holder: 国立大学法人筑波大学
  • Acquisition Date: 2011-03-11