Research of oncomiRs contributing to initiation process of inflammation-associated carcinogenesis in liver

• Project/Area Number: 19390198
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kanazawa University
• Principal Investigator: NAKAMOTO Yasunari Kanazawa University, 附属病院, 講師 (40293352)
• Co-Investigator(Kenkyū-buntansha): HIRAKU Yusuke 三重大学, 医学系研究科, 講師 (30324510)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000); Fiscal Year 2009: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2008: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2007: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
• Keywords: 癌 / 遺伝子 / マイクロアレイ / 動物 / 内科

Research Abstract

慢性肝炎から肝がんに至るがん化のイニシエーション過程に作用するマイクロRNA分子[oncogenic micro RNA ; oncomiR(s)]を同定することを目的とした。これまで確立したB型肝炎ウイルス(HBV)トランスジェニックマウスを用いた炎症性発がんモデルにおいて、経時的な遺伝子発現および酸化ストレスと相関する8個のoncomiR分子を明らかにした。これらの分子は、肝臓における前がん状態で悪性転化を制御する標的となる可能性が示唆された。

Research Products

• [Journal Article] Enhancement of tumor-specific T-cell responses by transcatheter arterial embolization with dendritic cell infusion for hepatocellular carcinoma. (2010)
  • Author(s): Mizukoshi E, Nakamoto Y, Arai K, Yamashita T, Mukaida N, Matsushima K, Matsui O, Kaneko S
  • Journal Title: Int. J. Cancer 126 Pages: 2164-2174
  • Peer Reviewed
• [Journal Article] Enhancement of tumor-specific T-cell responses by transcatheter arterial embolization with dendritic cell infusion for hepatocellular carcinoma (2010)
  • Author(s): Mizukoshi E, Nakamoto Y, et al.
  • Journal Title: Int.J.Cancer 126 Pages: 2164-2174
  • Peer Reviewed
• [Journal Article] Accelerated hepatocellular carcinoma development in mice expressing the Pim-3 transgene selectively in liver. (2009)
  • Author(s): Wu Y, Wang YY, Nakamoto Y, Li YY, Baba T, Kaneko S, Fujii C, Mukaida N
  • Journal Title: Oncogene (in press)
  • NAID: 120002165222
  • Peer Reviewed
• [Journal Article] Crucial contribution of thymic Sirp alpha+ conventional dendritic cells to central tolerance against blood-borne antigens in a CCR2-dependent manner (2009)
  • Author(s): Baba T, Nakamoto Y, Mukaida N
  • Journal Title: J. Immunol. 183 Pages: 3053-3063
  • Peer Reviewed
• [Journal Article] Accelerated hepatocellular carcinoma development in mice expressing the Pim-3 transgene selectively in liver (2009)
  • Author(s): Wu Y, Wang YY, Nakamoto Y, et al.
  • Journal Title: Oncogene Epub(in press)
  • NAID: 120002165222
  • Peer Reviewed
• [Journal Article] Crucial contribution of thymic Sirp alpha+ conventional dendritic cells to central tolerance against blood-borne antigens in a CCR2-dependent manner (2009)
  • Author(s): Baba T, Nakamoto Y, et al.
  • Journal Title: J.Immunol. 183 Pages: 3053-3063
  • Peer Reviewed
• [Journal Article] Common transcriptional signature of tumor-infiltrating mononuclear inflammatory cells and peripheral blood mononuclear cells in hepatocellular carcinoma patients (2008)
  • Author(s): Sakai Y, Honda M, Fujinaga H, Tatsumi I, Mizukoshi E, Nakamoto Y, Kaneko S
  • Journal Title: Cancer Res. 68 Pages: 10267-10279
  • Peer Reviewed
• [Journal Article] Optimal amount of monocyte chemoattractant protein-1 enhances antitumor effects of suicide gene therapy against hepatocellular carcinoma by M1 macrophage activation. (2008)
  • Author(s): Tsuchiyama T, Nakamoto Y, Sakai Y, Mukaida N, Kaneko S
  • Journal Title: Cancer Sci. 99 Pages: 2075-2082
  • NAID: 10024012389
  • Peer Reviewed
• [Journal Article] Tumor cell apoptosis induces tumor-specific immunity in a CC chemokine receptor 1-and 5-dependent manner in mice (2008)
  • Author(s): Iida N, Nakamoto Y, Baba T, Kakinoki K, Li YY, Wu Y, Matsushima K, Kaneko S, Mukaida N
  • Journal Title: J. Leukoc. Biol. 84 Pages: 1001-1010
  • NAID: 120000997200
  • Peer Reviewed
• [Journal Article] Expression of multidrug resistance-associated protein 3 and cytotoxic T cell responses in patients with hepatocellular carcinoma (2008)
  • Author(s): Mizukoshi E, Honda M, Arai K, Yamashita T, Nakamoto Y, Kaneko S
  • Journal Title: J. Hepatol. 49 Pages: 946-954
  • Peer Reviewed
• [Journal Article] Tumor cell apoptosis induces tumor-specific immunity in a CC chemokine receptor 1- and 5-dependent manner in mice. (2008)
  • Author(s): Iida N, Nakamoto Y, et al.
  • Journal Title: J. Leukoc. Biol. 84 Pages: 1001-1010
  • NAID: 120000997200
  • Peer Reviewed
• [Journal Article] Expression of multidrug resistance-associated protein 3 and cytotoxic T cell responses in patients with hepato cellular careinoma. (2008)
  • Author(s): Mizukoshi E, Nakamoto Y, et al.
  • Journal Title: J. Hepatol. 49 Pages: 946-954
  • Peer Reviewed
• [Journal Article] Common transcriptional signature of tumor-infiltrating mononuclear inflammatory cells and peripheral blood mononuclear cells in hepatocellular carcinoma patients. (2008)
  • Author(s): Sakai Y, Nakamoto Y, et al.
  • Journal Title: Cancer Res. 68 Pages: 10267-10279
  • Peer Reviewed
• [Journal Article] Optimal amount of monocyte chemoattractant protein-1 enhances antitumor effects of suicide gene therapy against hepatocellular carcinoma by M1 macrophage activation. (2008)
  • Author(s): Tsuchiyama T, Nakamoto Y, et al.
  • Journal Title: Cancer Sci. 99 Pages: 2075-2082
  • NAID: 10024012389
  • Peer Reviewed
• [Journal Article] Combined therapy of transcatheter hepatic arterial embolization with intratumoral dendritic cell infusion for hepatocellular carcinoma (2007)
  • Author(s): Nakamoto Y, Mizukoshi E, Tsuji H, Sakai Y, Kitahara M, Arai K, Yamashita T, Yokoyama K, Mukaida N, Matsushima K, Matsui O, Kaneko S
  • Journal Title: clinical safety. Clin. Exp. Immunol. 251 Pages: 36-42
  • Peer Reviewed
• [Journal Article] Intrahepatic interleukin-8 production during disease progression of chronic hepatitis C. (2007)
  • Author(s): Tachibana Y, Nakamoto Y, Mukaida N, Kaneko S
  • Journal Title: Cancer Lett. 251 Pages: 36-42
  • Peer Reviewed
• [Journal Article] Prolonged, NK cell-mediated antitumor effects of suicide gene therapy combined with monocyte chemoattractant protein-1 against hepatocellular carcinoma. (2007)
  • Author(s): Tsuchiyama T, Nakamoto Y, Sakai Y, Marukawa Y, Kitahara M, Mukaida N, Kaneko S
  • Journal Title: J. Immunol. 178 Pages: 574-583
  • NAID: 120000813306
  • Peer Reviewed
• [Journal Article] Analysis of hepatitis C virus-specific CD8+ T-cells with HLA-A*24 tetramers during phlebotomy and interferon therapy for chronic hepatitis C (2007)
  • Author(s): Kaji K, Nakamoto Y, Kaneko S
  • Journal Title: Oncol. Rep. 18 Pages: 993-998
  • Peer Reviewed
• [Journal Article] Impact of diabetes on recurrence of hepatocellular carcinoma after surgical treatment in patients with viral hepatitis (2007)
  • Author(s): Komura T, Mizukoshi E, Kita Y, Sakurai M, Takata Y, Arai K, Yamashita T, Ohta T, Shimizu K, Nakamoto Y, Honda M, Takamura T, Kaneko S
  • Journal Title: Am. J. Gastroenterol. 102 Pages: 1939-1946
  • Peer Reviewed
• [Journal Article] Hepatitis B virus X protein overcomes oncogenic RAS-induced senescence in human immortalized cells (2007)
  • Author(s): Oishi N, Shilagardi K, Nakamoto Y, Honda M, Kaneko S, Murakami S
  • Journal Title: Cancer Sci 98 Pages: 1540-1548
  • NAID: 10019997274
  • Peer Reviewed
• [Journal Article] Impact of diabetes mellitus on prognosis of patients infected with hepatitis C virus (2007)
  • Author(s): Kita Y, Mizukoshi E, Takamura T, Sakurai M, Takata Y, Arai K, Yamashita T, Nakamoto Y, Kaneko S
  • Journal Title: Metabolism 56 Pages: 1682-1688
  • Peer Reviewed
• [Journal Article] Combined Therpay of Transcatheter Hepatic Arterial Embolization with Intratumoral Dendritic Cell Infusion for Hepatocellular CarCinoma;Clinical Safety. (2007)
  • Author(s): Nakamoto Y, Mizukoshi E, et. al.
  • Journal Title: Clin. Exp. Immunol. 147 Pages: 296-305
  • Peer Reviewed
• [Journal Article] Prolonged, NK cell-mediated antitumor effects of suicide gene therapy combined with monocyte chemoattractant protein-1 against hepatocelular carcinoma. (2007)
  • Author(s): Tsuchiyama T, Nakamoto Y, et. al.
  • Journal Title: J. Immunol. 178 Pages: 574-583
  • Peer Reviewed
• [Journal Article] Analysis of hepatitis C virus-specific CD8^+ T-cells with HLA-A^*24 tetramers during phlebotomy and interferon therapy for chronic hepatitis C. (2007)
  • Author(s): Kaji K, Nakamoto Y, et. al.
  • Journal Title: Oncol. Rep. 18 Pages: 993-998
  • Peer Reviewed
• [Journal Article] Hepatitis B virus X protein overcomes oncogenic RAS-induced senescence in human immortalized cells. (2007)
  • Author(s): Oishi N, Shilagardi K, Nakamoto Y, et. al.
  • Journal Title: Cancer Sci. 98 Pages: 1540-1548
  • NAID: 10019997274
  • Peer Reviewed
• [Journal Article] Intrahepatic interleukin-8 production during disease progression of chronic hepatitts C. (2007)
  • Author(s): Tachibana Y, Nakamoto Y, et. al.
  • Journal Title: Cancer Lett. 251 Pages: 36-42
  • Peer Reviewed
• [Presentation] #1725; Immunological factors associated with prolonged recurrence-free survival following transcatheter hepatic arterial embolization with OK432-stimulated dendritic cell transfer into hepatocellular carcinoma. (2009)
  • Author(s): Nakamoto Y, Mizukoshi E, Kitahara M, Arihara F, Sakai Y, Kakinoki K, Fujita Y, Marukawa Y, Arai K, Yamashita T, Mukaida N, Matsushima K, Matsui O, Kaneko S
  • Organizer: 第60回American Association for the Study of Liver Diseases (AASLD) Annual Meeting (Boston, Massachusetts)
  • Place of Presentation: Hepatology
  • Year and Date: 2009-11-03
• [Presentation] Immunological factors associated with prolonged recurrence-free survival following transcatheter hepatic arterial embolization with OK432-stimulated dendritic cell transfer into hepatocellular carcinoma (2009)
  • Author(s): Nakamoto Y, et al.
  • Organizer: 60th American Association for the Study of Liver Diseases (AASLD) Annual Meeting ; poster session
  • Place of Presentation: Boston, Massachusetts (USA)
  • Year and Date: 2009-11-03
• [Presentation] #1280; Identification of hepatic stem cells by monitoring of nucleostemin promoter activity. (2009)
  • Author(s): Shugo H, Ohmura M, Naka K, Nakamoto Y, Kaneko S, Hirao A
  • Organizer: 第60回American Association for the Study of Liver Diseases (AASLD) Annual Meeting (Boston, Massachusetts)
  • Place of Presentation: Hepatology
  • Year and Date: 2009-11-01
• [Presentation] 125; Prolonged recurrence-free survival following combined therapy of transcatheter hepatic arterial embolization with OK432-stimulated dendritic cell transfer into hepatocellular carcinoma. (2008)
  • Author(s): Nakamoto Y, Mizukoshi E, Kitahara M, Sakai Y, Kakinoki K, Fujita Y, Arai K, Yamashita T, Mukaida N, Matsushima K, Matsui O, Kaneko S
  • Organizer: 第59回American Association for the Study of Liver Diseases (AASLD) Annual Meeting (San Francisco, California)
  • Place of Presentation: Hepatology
  • Year and Date: 2008-11-02
• [Presentation] #82; Cellular immune responses to multidrug resistance-associated protein 3 in the patients with hepatocellular carcinoma. ; (2008)
  • Author(s): Mizukoshi E, Arai K, Yamashita T, Nakamoto Y, Honda M, Kaneko S
  • Organizer: 第25回Internal Association for the Study of the Liver (IASL) Biennial Meeting (San Francisco, California)
  • Place of Presentation: Hepatology
  • Year and Date: 2008-11-02
• [Presentation] Prolonged recurrence-free survival following combined therapy of transcatheter hepatic arterial embolization with 0K432-stimulated dendritic cell transfer into hepatocellular carcinoma. (2008)
  • Author(s): Nakamoto Y, et al.
  • Organizer: 59^<th> AASLD Annual Meeting; Parallel (oral) session
  • Place of Presentation: San Francisco, California
  • Year and Date: 2008-11-02
• [Presentation] S-1;B型肝炎と獲得免疫 (2007)
  • Author(s): 中本安成, 金子周一
  • Organizer: 第44回日本消化器免疫学会総会(東京)
  • Place of Presentation: シンポ
  • Year and Date: 2007-07-08
• [Presentation] シンポジウム:B型慢性肝炎を構築する獲得免疫と病態進展の分子機構. (2007)
  • Author(s): 中本 安成、金子 周一
  • Organizer: 第43回日本肝臓学会総会
  • Place of Presentation: 東京
  • Year and Date: 2007-05-31
• [Presentation] S1-2;B型慢性肝炎を構築する獲得免疫と病態進展の分子機構 (2007)
  • Author(s): 中本安成, 金子周一
  • Organizer: 第43回日本肝臓学会総会(東京)
  • Place of Presentation: シンポ
  • Year and Date: 2007-05-03
• [Book] 別冊「医学のあゆみ」;感染症と発癌の分子メカニズム(千葉勉編).【感染症と発癌UPDATE】h b vによる発癌病態 (2009)
  • Author(s): 中本安成, 金子周一
  • Publisher: 医歯薬出版
• [Book] Liver Forum in Kyoto(第10回学術集会記録集編).b型慢性肝炎モデルを用いた肝癌細胞の起源と分子機構の研究 (2008)
  • Author(s): 中本安成
  • Publisher: メディカルトリビューン社
• [Book] Recent Development in Gene Therrapy (Xiang J, ed.). Enhanced antitumor effects of suicide gene therapy combined with adenovirally delivered monocyte chemoattractant protein-1. (2007)
  • Author(s): Nakamoto Y, Kaneko S
  • Publisher: Transworld Research Network
• [Book] 消化器発癌における炎症・再生・細胞応答の役割(小俣政男編).炎症性発癌モデルの肝細胞癌化プロセスを構築する分子病態の解析 (2007)
  • Author(s): 中本安成,金子周一
  • Publisher: アークメディア社
• [Book] Recent Development in Gene Therrapy.;Enhanced antitumor effects of suicide gene therapy combined with adenovirally delivered monocyte chemoattractant protein-1. (2007)
  • Author(s): Nakamoto Y and Kaneko S
  • Publisher: Transworld Research Network