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Prospective analysis of DNA damage and repair markers in the patients with high risk of hepatocellular cancer

Research Project

Project/Area Number 21590835
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionNiigata University

Principal Investigator

MATSUDA Yasunobu  新潟大学, 医歯学系, 准教授 (40334669)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2009: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords肝臓病学 / 肝癌 / DNA二重鎖傷害
Research Abstract

Background : It has been widely considered that the DNA damage response is strongly involved in the step of early carcinogenesis. In case of hepatocellular carcinoma(HCC), however, it has been remained unclear whether DNA damage response molecules are useful for the tumor markers of the patients with high risk of HCC.
Methods : We evaluated the phosphorylation levels of DNA damage response markers in animal models with HCC by Western blotting or immunohistochemical staining. Based on the animal model experiments, we addressed whether any of the DNA-damage response molecules are involved in the cancer development of the patients with high risk of HCC.
Results : Western blotting and immunohistochemical analysis showed that the levels of gamma-H2A were significantly increased in HCC-prone mice. Interestingly, increase in the levels of gamma-H2AX was observed from several months before the development of HCC. The increase in the levels of gamma-H2AX and Wip1 activity was also observed in human liver tissues adjacent to HCC.
Conclusion : DNA damage response molecules gamma-H2AX and Wip1 might be useful markers for predicting the development of HCC.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (21 results)

All 2011 2010 2009 Other

All Journal Article (18 results) (of which Peer Reviewed: 18 results) Presentation (2 results) Book (1 results)

  • [Journal Article] Hepatocellular carcinoma and liver transplantation : clinical perspective on molecular targeted strategies2011

    • Author(s)
      Matsuda Y, Ichida T, Fukumoto M
    • Journal Title

      Med Mol Morphol

      Volume: 44(3) Pages: 117-124

    • NAID

      10030463626

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [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, Kurosaki I, Shirai Y, Okada M, Aoyagi Y
    • Journal Title

      World J Hepatol

      Volume: 3(1) Pages: 15-23

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of elevated alanine aminotransferase levels during pegylated-interferonα-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, Nomoto M, Aoyagi Y
    • Journal Title

      Hepatol Res

      Volume: 41(2) Pages: 118-125

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of NQO1 expression in intrahepatic cholangiocarcinoma2011

    • Author(s)
      Wakai T, Shirai Y, Sakata J, Matsuda Y, Korita PV, Takamura M, Ajioka Y, Hatakeyama K
    • Journal Title

      Int J Clin Exp Pathol

      Volume: 4(4) Pages: 363-370

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Alteration of p53-binding protein 1 expression as a risk factor for local recurrence in patients undergoing resection for extrahepatic cholangiocarcinoma2011

    • Author(s)
      Wakai T, Shirai Y, Sakata J, Korita PV, Matsuda Y, Takamura M, Ohashi R, Nagahashi M, Ajioka Y, Hatakeyama K
    • Journal Title

      Int J Oncol

      Volume: 38(5) Pages: 1227-1236

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hepatocellular carcinoma and liver transplantation : clinical perspective on molecular targeted strategies2011

    • Author(s)
      松田康伸、市田隆文
    • Journal Title

      Med Mol Morphol

      Volume: 44 Issue: 3 Pages: 117-124

    • DOI

      10.1007/s00795-011-0547-2

    • NAID

      10030463626

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sorafenib : complexities of Raf-dependent and-independent signaling are now unveiled2011

    • Author(s)
      松田康伸、福本学
    • Journal Title

      Med Mol Morphol

      Volume: 44 Issue: 4 Pages: 183-189

    • DOI

      10.1007/s00795-011-0558-z

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Alteration of p53-binding protein 1 expression as a risk factor for local recurrence in patients undergoing resection for extrahepatic cholangiocarcinoma2011

    • Author(s)
      若井俊文、松田康伸, 他8名
    • Journal Title

      Int J Oncol

      Volume: 38 Issue: 5 Pages: 1227-1236

    • DOI

      10.3892/ijo.2011.959

    • Related Report
      2011 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, Yamagiwa S, Yano M, Takahashi H, Aoki YH, Matsuda Y, Aoyagi Y
    • Journal Title

      Case Rep Gastroenterol

      Volume: 4(2) Pages: 261-266

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] MRP2 determines the efficacy of cisplatin in patients with hepatocellular carcinoma2010

    • Author(s)
      Korita PV, Wakai T, Shirai Y, Matsuda Y, Sakata J, Takamura M, Yano M, Sanpei A, Aoyagi Y, Hatakeyama K, Ajioka Y
    • Journal Title

      Oncol Rep

      Volume: 23(4) Pages: 965-972

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Loss of liver-intestine cadherin in human intrahepatic cholangiocarcinoma promotes angiogenesis by upregulating metal-responsive transcription factor-1 and placental growth factor2010

    • Author(s)
      Takamura M, Yamagiwa S, Wakai T, Tamura Y, Kamimura H, Kato T, Tsuchiya A, Matsuda Y, Shirai Y, Ichida T, Ajioka Y, Aoyagi Y
    • Journal Title

      Int J Oncol

      Volume: 36(1) Pages: 245-254

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Multidmg resistanoe-associated protein 2 determines the of efficacy of Cisplatin in patients with hepatocellular carcinoma.2010

    • Author(s)
      コリタ・プラベル, 若井俊文, 白井良夫, 松田康伸, 他7名
    • Journal Title

      Oncology Reports

      Volume: vol.23 Pages: 965-972

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of hepatitis B virus X protein on the DNA damage response during hepatocarcinogenesis2009

    • Author(s)
      Matsuda Y, Ichida T
    • Journal Title

      Med Mol Morphol

      Volume: 42(3) Pages: 138-142

    • NAID

      10025860136

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Loss of carcinoembryonic antigen-related cell adhesion molecule 1 expression predicts metachronous pulmonary metastasis and poor survival in patients with hepatoblastoma2009

    • Author(s)
      Tsukada M, Wakai T, Matsud Y, Korita PV, Shirai Y, Ajioka Y, Hatakeyama K, Kubota M
    • Journal Title

      J Pediatr Surg

      Volume: 44(8) Pages: 1522-1528

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Progression of hypermethylation of the p16(INK4A) gene from normal liver to nontumorous liver and hepatocellular carcinoma : an evaluation using quantitative PCR analysis2009

    • Author(s)
      Kurita S, Ohkoshi S, Yano M, Yamazaki K, Suzuki K, Aoki YH, Matsuda Y, Wakai T, Shirai Y, Ichida T, Aoyagi Y
    • Journal Title

      Dig Dis Sci

      Volume: 54(1) Pages: 80-88

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinicopathological analysis of CD133 and NCAM human hepatic stem/progenitor cells in damaged livers and hepatocellular carcinomas2009

    • Author(s)
      Tsuchiya A, Kamimura H, Takamura M, Yamagiwa S, Matsuda Y, Sato Y, Nomoto M, Ichida T, Aoyagi Y
    • Journal Title

      Hepatol Res

      Volume: 39(11) Pages: 1080-1090

    • NAID

      10027405577

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] complexities of Raf-dependent and Raf-independent signaling are now unveiled

    • Author(s)
      Matsuda Y, Fukumoto M.
    • Journal Title

      Med Mol Morphol

      Volume: (in press)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reduced NKG2D ligand expression in hepatocellular carcinoma correlates with early recurrence

    • Author(s)
      Kamimura H, Yamagiwa S, Tsuchiya A, Takamura M, Matsuda Y, Ohkoshi S, Inoue M, Wakai T, Shirai Y, Nomoto M, Aoyagi Y
    • Journal Title

      J Hepatol

      Volume: (in press)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Presentation] B型肝炎ウイルスX遺伝子によるDNA酸化傷害機構の解析および制御方法の検討2011

    • Author(s)
      松田康伸、大越章吾、青柳豊
    • Organizer
      第47回日本肝臓学会総会
    • Place of Presentation
      東京都港区(ホテルグランパシフィック)
    • Year and Date
      2011-06-02
    • Related Report
      2011 Annual Research Report
  • [Presentation] Hepatitis B Virus X Protein Activates Mammalian Target of Rapamycin mTOR via Reactive Species Generation.2010

    • Author(s)
      三瓶歩, 松田康伸, 他7名
    • Organizer
      米国肝臓学会
    • Place of Presentation
      ボストン(米国)
    • Year and Date
      2010-11-02
    • Related Report
      2010 Annual Research Report
  • [Book] Molecular mechanism of DNA damage response pathway during hepatic carcinogenesis(Hepatocellular Carcinoma/Book 1)

    • Author(s)
      Matsuda Y, Wakai T
    • Publisher
      (in press)
    • Related Report
      2011 Final Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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