• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

The relationship between mtDNA injury and hepalocarcinogenesis in chronic hepatitis.

Research Project

Project/Area Number 13670546
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionOsaka City University

Principal Investigator

NISHIGUCHI Shuhei  Osaka City University, Medical School, Associate Professor, 大学院・医学研究科, 助教授 (10192246)

Co-Investigator(Kenkyū-buntansha) NISHIKAWA Manabu  Osaka City University, Medical School, Assistant Professor, 大学院・医学研究科, 助手 (00347494)
TAMORI Akihiro  Osaka City University, Medical School, Lecturer, 大学院・医学研究科, 講師 (30291595)
SHIOMI Susumu  Osaka City University, Medical School, Professor, 大学院・医学研究科, 教授 (30170848)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordschronic hepatitis / hepatoma / mitochondria / mitochondrial DNA / oxidative stress / 塩基変異 / 肝発癌 / インターフェロン
Research Abstract

The causal relation is not clear though the relation between mitochondrial DNA mutation and carcinogenesis is paid attention worldwide. We discovered, for the first time in the world, extremely a lot of mitochondria DNA mutations accumulation in the carcinogenesis based on inflammation. Surprisingly, this mutation passed due to chronic inflammation even if it was a normal tissue, and when the threshold that accumulated in the target was exceeded, it was ascertained to get cancer. Extremely a lot of mitochondria DNA mutations were found in the liver tissues from individuals with chronic hepatitis. Although the molecular mechanism is not clearly understood, interferon-therapy has been reported to inhibit hepatocarcinogenesis. Then, we analyzed mitochondria DNA mutation before and after the interferon-treatment. Interestingly, interferon decreased the number of mutation. Moreover, protection of mitochondria and prevention of mitochondrial DNA mutation by oral administration of L-carnitine clearly inhibited hepatocarcinogenesis in LEC rats with spontaneous occurrence of hepatoma. L-Carnitine used as a medicine for protecting mitochondria is included in specific food a lot, and is a material that exists widely in the natural world that can be even in vivo synthesized. As for administering a genuine quality, it is extremely safe, and the effect in vivo is clear also in the molecule theory. A clinical of genuine quality application of it will be expected.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (21 results)

All 2005 2004 2003 2002 2001 Other

All Journal Article (10 results) Book (1 results) Publications (10 results)

  • [Journal Article] L-carnitine inhibits hepatocarcinogenesis via protection of mitochondria.2005

    • Author(s)
      Chang B, Nishikawa M, Nishiguchi S, Inoue M.
    • Journal Title

      Int J Cancer 113

      Pages: 719-729

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] L-carnitine inhibits hepatocarcinogenesis via protection of mitochondria.2005

    • Author(s)
      Chang B, Nishikawa M, Nishiguchi S, Inoue M.
    • Journal Title

      Int J Cancer. 113(5)

      Pages: 719-729

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Interferon reduces Somatic Mutation of Mitochondrial DNA in Liver Tissues from Chronic Viral Hepatitis Patients.2004

    • Author(s)
      Nishikawa M, Nishiguchi S, Kioka K, Tamori A, Inoue M.
    • Journal Title

      J.Vral Hepatitis 11

      Pages: 1-5

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Correlation between clinical characteristics and mitochondrial D-loop DNA mutations in hepatocellular carcinoma.2004

    • Author(s)
      Tamori A, Nishiguchi S, Nishikawa M, Kubo S, Koh N, Hirohashi K, Shiomi S, Inoue M.
    • Journal Title

      J Gastroenterol. 39

      Pages: 1063-1068

    • NAID

      10014116216

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Multicentric occurrence of hepatocellular carcinoma in patients with a somatic mutation of mitochondorial DNA and hepatitis C virus.2004

    • Author(s)
      Kubo S, Nishikawa M, Hirohashi K, Tanaka H, Shuto T, Tamori A, Kinoshita H, Inoue M, Nishiguchi S.
    • Journal Title

      Hepatol Res. 25

      Pages: 78-82

    • NAID

      10016176177

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Correlation between clinical characteristics and mitochondrial D-loop DNA mutations in hepatocellular carcinoma.2004

    • Author(s)
      Tamori A, Nishiguchi S, Nishikawa M, Kubo S, Koh N, Hirohashi K, Shiomi S, Inoue M.
    • Journal Title

      J Gastroenterol. 39(11)

      Pages: 1063-1068

    • NAID

      10014116216

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Multicentric occurrence of hepatocellular carcinoma in patients with a somatic mutation of mitochondorial DNA and hepatitis C virus.2003

    • Author(s)
      Kubo S, Nishikawa M, Hirohashi K, Tanaka H, Shuto T, Tamori A, Kinoshita H, Inoue M, Nishiguchi S.
    • Journal Title

      Hepatol Res. 25(1)

      Pages: 78-82

    • NAID

      10016176177

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Somatic mutation of mitochondrial DNA in cancerous and noncancerous liver tissue in individuals with hepatocelluar carcinoma.2001

    • Author(s)
      Nishikawa M, Nishiguchi S, Shiomi S, Tamori A, Koh N, Takeda T, Kubo S, Hirohashi K, Kinoshita H, Sato E, Inoue M.
    • Journal Title

      Cancer Res. 61

      Pages: 1843-1845

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Somatic mutation of mitochondrial DNA in cancerous and noncancerous liver tissue in individuals with hepatocellular carcinoma.2001

    • Author(s)
      Nishikawa M, Nishiguchi S, Shiomi S, Tamori A, Koh N, Takeda T, Kubo S, Hirohashi K, Kinoshita H, Sato E, Inoue M.
    • Journal Title

      Cancer Res. 61(5)

      Pages: 1843-1845

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Interferon reduces Somatic Mutation of Mitochondrial DNA in Liver Tissues from Chronic Viral Hepatitis Patients.

    • Author(s)
      Nishikawa M, Nishiguchi S, Kioka K, Tamori A, Inoue M.
    • Journal Title

      J.Viral Hepatitis. (In press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Book] ミトコンドリアとミトコンドリア病「発癌とミトコンドリア遺伝子」2002

    • Author(s)
      西川 学, 井上正康
    • Total Pages
      804
    • Publisher
      日本臨床社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kubo S, Nishikawa M, Hirohashi K et al.: "Multicentric occurrence of hepatocellular carcinoma in patients with a somatic mutation of mitochondorial DNA and hepatitis C virus"Hepatol.Res.. 25. 78-82 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Chang B, Nishikawa M, Sato E et al.: "Mice lacking inducible nitric oxide synthase show strong resistance to anti-Fas antibody-induced fulminant hepatitis"Arch Biochem Biophys.. 411. 63-72 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Iguchi T, Nishikawa M, Chang B et al.: "Edaravone inhibits acute renal injury and cyst formation in cisplatin treated rat kidney"Free Rad.Res.. In press.

    • Related Report
      2003 Annual Research Report
  • [Publications] 西川 学, 井上正康: "ミトコンドリアとミトコンドリア病「発癌とミトコンドリア遺伝子」"日本臨床社. 804 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kubo S, Nishikawa M, Hirohashi K et al.: "Multicentric occurrence of hepatocellular carcinoma in patients with a somatic mutation of mitochondorial DNA and hepatitis C virus"Hepatol. Res.. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Chang B, Nishikawa M, Sato E et al.: "Mice lacking inducible nitric oxide synthase show strong resistance to anti-Fas antibody-induced fulminant hepatitis"Arch. Biochem. Biophys.. 411. 63-72 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Chang B, Nishikawa M, Sato E et al.: "L-Carnitine inhibits cisplatin-induced injury of the kidney and small intestine"Arch. Biochem. Biophys.. 405. 55-64 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 西川 学, 井上正康: "ミトコンドリアとミトコンドリア病「発癌とミトコンドリア遺伝子」"日本臨床社. 804 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 西口修平: "肝癌切除例における癌部と非癌部のミトコンドリアDNAにおける塩基変異に関する研究"非A非B型肝炎の臨床的総合研究 平成10年〜12年度総合研究報告書. 142-144 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 西口修平: "ミトコンドリアDNA塩基変異に対するIFN投与の影響に関する研究"非A非B型肝炎の臨床的総合研究 平成10年〜12年度総合研究報告書. 145-147 (2001)

    • Related Report
      2001 Annual Research Report

URL: 

Published: 2001-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi