Development of new IFN-strategy that based on DNA repair mechanism

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590722
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Showa University (2011-2012); Niigata University (2010)
• Principal Investigator: OHKOSHI Shogo 昭和大学, 医学部, 講師 (70231199)
• Co-Investigator(Kenkyū-buntansha): MATSUDA Yasunobu 新潟大学, 医歯学系, 准教授 (40334669) ; YAMAGIWA Satoshi 新潟大学, 医歯学総合病院, 助教 (10419327) ; YANO Masahiko 昭和大学, 医学部, 助教 (70529693)
• Project Period (FY): 2010 – 2012
• Keywords: 肝臓学

Research Abstract

The aim of this study is to clarify the molecular mechanisms of preventive effect of IFN-beta for the occurrence of hepatocellular carcinoma (HCC) and to establish the strategy of chemoprevention of HCC. We found that aberrant expression of p21, that was a known cyclin-dependent kinase (CDK) inhibitor, was a key mechanism for hepatocarcinogenesis and it’s prevention. IFN-beta shifted cytoplasmic p21, which was oncogenic, to nucleus, making them to exert original anti-proliferative function. We may explore this anti-cancer mechanism of IFN-beta in order to apply to clinical studies.

Research Products

• [Journal Article] Hepatitis B virus X induces cell proliferation in the hepatocarcinogenesis via up-regulation of cytoplasmic p21 expression (2013)
  • Author(s): Yano M, Ohkoshi S, Aoki YH, Takahashi H, Kurita S, Yamazaki K, Suzuki K, Yamagiwa S, Sanpei A, Fujimaki S, Wakai T, Kudo SE, Matsuda Y,Aoyagi Y
  • Journal Title: Liver Int
• [Journal Article] Blockade of ataxia telangiectasia mutated sensitizes hepatoma cell lines to sorafenib by interfering with Akt signaling (2012)
  • Author(s): Fujimaki S, Matsuda Y, Wakai T, Sanpei A, Kubota M, Takamura M, Yamagiwa S, Yano M, Ohkoshi S, Aoyagi Y
  • Journal Title: Cancer Lett Volume: 319(1) Pages: 98-108
• [Journal Article] Characterization of elevated alanine aminotransferase levels during pegylated-interferon α-2b plus ribavirin treatment for chronic hepatitis C (2011)
  • Author(s): Aoki YH, Ohkoshi S, Yamagiwa S, Yano M, Takahashi H, Waguri N, Igarashi K, Sugitani S, Takahashi T, Ishikawa T, Kamimura T, Wakabayashi H, Watanabe T, Matsuda Y,(2)Nomoto M, Aoyagi Y
  • Journal Title: Hepatol Res Volume: 41(2) Pages: 118-25
• [Journal Article] A case with chronic hepatitis C who developed liver cirrhosis due to liver dysfunction caused by pegylated interferon plus ribavirin treatment despite negativity of serum HCV RNA, during therapy (2011)
  • Author(s): Ohkoshi S, Morita S, Tanaka Y, Yano M, Takeuchi M, Takahashi H, Ikeda H, Yamagiwa S, Matsuda Y, Nomoto M, Aoyagi Y
  • Journal Title: Nihon Shokakibyo Gakkai Zasshi Volume: 108(2) Pages: 267-74
• [Journal Article] Multicentric occurrence of hepatocellular carcinoma with nonalcoholic steatohepatitis (2011)
  • Author(s): Kawai H, Nomoto M, Suda T, Kamimura K, Tsuchiya A, Tamura Y, Yano M, Takamura M, Igarashi M, Wakai T, Yamagiwa S, Matsuda Y, Ohkoshi S, (4)Kurosaki I, Shirai Y, Okada M, Aoyagi Y
  • Journal Title: World J Hepatol Volume: 3(1) Pages: 15-23
• [Journal Article] Failure to achieve 2-log10 viral decrease in first four weeks of peg-IFNalpha-2b plus ribavirin therapy for chronic hepatitis C with genotype 1b and high viral titer is useful in predicting non-response: evaluation of response-guided therapy (2011)
  • Author(s): Ohkoshi S, Yamagiwa S, Yano M, Takahashi H, Aoki YH, Waguri N, Igarashi K, Sugitani S, Takahashi T, Ishikawa T, Kamimura T, Wakabayashi H, Watanabe T, Matsuda Y,Aoyagi Y.
  • Journal Title: Hepatogastroenterology Volume: 58(107-108) Pages: 965-70
• [Presentation] Retinol Binding Protein 4 induces interferon resistance in cells and it's serum levels can be a good marker to predict SVR in chronic hepatitis C patients treated by PegIFN/ RIB (2012)
  • Author(s): Ohkoshi S
  • Organizer: 全米肝臓学会総会
  • Place of Presentation: Boston
  • Year and Date: 20121109-13
• [Presentation] C型慢性肝炎とインスリン抵抗性因子RBP4RBP4 はインターフェロン治療抵抗性をもたらす (2012)
  • Author(s): 高橋 弘道, 大越 章吾, 矢野 雅彦, 山際 訓, 松田 康伸, 池田 正徳, 加藤 宣之, 青柳豊
  • Organizer: 日本肝臓学会総会
  • Place of Presentation: 金沢
  • Year and Date: 20120607-08
• [Presentation] p21細胞内局在制御によるIFN-βのシスプラチン制癌効果増強機構 (2012)
  • Author(s): 矢野 雅彦, 大越 章吾, 高橋 弘道, 藤巻 隼, 松田 康伸, 青柳 豊, 工藤進英
  • Organizer: 日本肝臓学会総会
  • Place of Presentation: 金沢
  • Year and Date: 20120607-08
• [Presentation] DNA傷害修復因子ATMによる肝癌細胞の細胞死抑制機構の解析 (2011)
  • Author(s): 藤巻 隼, 松田 康伸, 矢野 雅彦, 大越 章吾, 若井 俊文, 白井 良夫, 三瓶 歩, 平野 茂樹
  • Organizer: 日本肝臓学会総会
  • Year and Date: 20110000
• [Presentation] HBx誘導性肝発癌に対するIFN-βの制御機構の分子学的解析 (2010)
  • Author(s): 矢野 雅彦, 大越 章吾, 青木洋平, 山崎 和秀, 栗田 聡, 鈴木 健太, 三瓶 歩, 松田 康伸, 青柳 豊
  • Organizer: 日本肝臓学会総会
  • Year and Date: 20100000
• [Remarks] 大学のホームページに掲載予定