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

Research Project

Project/Area Number 22590722
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionShowa 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
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2010: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Keywords肝臓学 / 肝癌 / インターフェロン / HBV / p21 / 細胞内局在 / 発がん抑制 / 分子機序 / IFNβ / 発癌予防 / DNA修復 / 肝細胞癌 / ウイルス発癌 / DNA修復機構 / HBx遺伝子 / ATM / トランスジェニックマウス
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.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (22 results)

All 2013 2012 2011 2010 Other

All Journal Article (12 results) (of which Peer Reviewed: 6 results) Presentation (9 results) Remarks (1 results)

  • [Journal Article] Hepatitis B virus X induces cell proliferation in the hepatocarcinogenesis via up-regulation of cytoplasmic p21 expression2013

    • 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

    • Related Report
      2012 Final Research Report
  • [Journal Article] Hepatitis B virus X induces cell proliferation in the hepatocarcinogenesis2013

    • Author(s)
      Yano M
    • Journal Title

      Liv Int

      Volume: in press Issue: 8 Pages: 2018-2029

    • DOI

      10.1111/liv.12176

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blockade of ataxia telangiectasia mutated sensitizes hepatoma cell lines to sorafenib by interfering with Akt signaling2012

    • 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

    • Related Report
      2012 Final Research Report
  • [Journal Article] Blockade of ataxia telangiectasia mutated sensitizes hepatoma cell lines to sorafenib by interfering with Akt signaling2012

    • Author(s)
      Fujimaki S
    • Journal Title

      Cancer Lett.

      Volume: 319 Issue: 1 Pages: 98-108

    • DOI

      10.1016/j.canlet.2011.12.043

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blockade of ataxia telangiectasia mutated sensitizes hepatoma eell lines to sorafenib by interfering with Akt signaling2012

    • Author(s)
      Fujimaki S, Matsuda Y, Ohkoshi S, et al
    • Journal Title

      Cancer Lett

      Volume: 319 Pages: 98-108

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of elevated alanine aminotransferase levels during pegylated-interferon α-2b plus ribavirin treatment for chronic hepatitis C2011

    • 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

    • Related Report
      2012 Final Research Report
  • [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 therapy2011

    • 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

    • NAID

      10029388211

    • Related Report
      2012 Final Research Report
  • [Journal Article] Multicentric occurrence of hepatocellular carcinoma with nonalcoholic steatohepatitis2011

    • 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

    • Related Report
      2012 Final Research Report
  • [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 therapy2011

    • 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

    • Related Report
      2012 Final Research Report
  • [Journal Article] Characterization of elevated alanine aminotransferase levels during pegylated-interferon (α-2b plus ribavirin treatment for chronic hepatitis C2011

    • Author(s)
      Aoki Y, et al.
    • Journal Title

      Hepatology Research

      Volume: 41 Pages: 118-25

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Failure to achieve 2-log_<10> viral decrease in first 4 weeks of peg-IFN α 2b plus ribavirin therapy for chronic hepatitis C with genotype lb and high viral titer is useful in predictingnon-response-Evaluation of response-guided therapy-2011

    • Author(s)
      Ohkoshi S, et al.
    • Journal Title

      Hepatogas troenterology

      Volume: In Press

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Very low-dose pegylated interferon a2a plus ribavirin therapy for advanced liver cirrhosis type C-A possible therapeutic alternative without splenic intervention2010

    • Author(s)
      Ohkoshi S, et al.
    • Journal Title

      Case Report in Gastroenterology

      Volume: 4 Pages: 261-66

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [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
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [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/ RIB2012

    • Author(s)
      Ohkoshi S
    • Organizer
      全米肝臓学会総会
    • Place of Presentation
      Boston
    • Related Report
      2012 Final Research Report
  • [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/ RIB2012

    • Author(s)
      Shogo Ohkoshi
    • Organizer
      全米肝臓学会(AASLD)
    • Place of Presentation
      Boston
    • Related Report
      2012 Annual Research Report
  • [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抑制作用2012

    • Author(s)
      矢野 雅彦
    • Organizer
      日本肝臓学会総会
    • Place of Presentation
      金沢
    • Related Report
      2012 Annual Research Report
  • [Presentation] HBx誘導性肝発癌にタイするIFN-βの制御機構の分子学的解析2011

    • Author(s)
      矢野雅彦
    • Organizer
      第48回日本肝臓学会総会
    • Place of Presentation
      金沢
    • Year and Date
      2011-06-07
    • Related Report
      2011 Annual Research Report
  • [Presentation] IFN-beta prevents HBx-triggered Hepatocarcinogenesis by dowm-regulating cytoplasmic p21 expression2011

    • Author(s)
      Yano M, etal.
    • Organizer
      全欧肝臓学会
    • Place of Presentation
      ベルリン
    • Year and Date
      2011-04-02
    • Related Report
      2010 Annual Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [Remarks] 大学のホームページに掲載予定

    • Related Report
      2012 Final Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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