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Gene therapy using apoptosis-inducer bax and suicide gene for chemically induced rat bladder cancer

Research Project

Project/Area Number 12671567
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionOsaka Medical College

Principal Investigator

SHIBATA Masa-aki  Osaka Medical College Faculty of Medicine, Associate Professor, 医学部, 助教授 (10319543)

Co-Investigator(Kenkyū-buntansha) OTSUKI Yoshinori  Osaka Medical College Faculty of Medicine, Professor, 医学部, 教授 (50140166)
伊藤 裕子  大阪医科大学, 医学部, 講師 (40148432)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥100,000 (Direct Cost: ¥100,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsUrinary bladder cancer / HSVtk / Cancer gene therapy / Electroporation / Apoptosis / Mitochondrial pathway / Caspase / Non-virus vector / Electroporation / ミトコンドリア膜電位 / Caspase / 単純性ヘルペスチミジンキナーゼ / bax / ラット / 非ウイルスベクター / Electro-gene transfer / in vitro / in vivo
Research Abstract

The effectiveness of in vivo electrogene transfer as a means of gene therapy for rat bladder cancers using the herpes simplex virus 1 thymidine kinase (HSVtk) gene in combination with ganciclovir (GCV) was investigated. In vitro studies demonstrated that 50-70% of the transitional cell carcinoma (TCC) cells died as a result of transfection with pHSVtk and GCV administration and that this treatment was associated with decreased DNA synthesis and elevated activities of caspase-3, -8 and -9. A significantly decreased mitochondrial membrane potential was also noted in TCC cells given pHSVtk+GCV. A direct single injection of HSVtk into bladder tumors using in vivo electrogene transfer followed by GCV administration resulted in significant increases in the levels of apoptosis and histopathological necrosis accompanied by marked inflammation. Active caspase-3 was strongly expressed in the cell death areas of the TCC in rats given pHSVtk/GCV therapy. In vivo electrogene transfer results in efficient gene transfer in chemically induced rat bladder tumors and the HSVtk/GCV producing system induces significant cell death which appears to be, at least, mediated via the mitochondrial apoptotic pathway.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (5 results)

All Other

All Publications (5 results)

  • [Publications] Shibata, M.A., Horiguchi, T., Morimoto, J., Otsuki, Y.: "Massive apoptotic cell death in chemically induced rat urinary bladder carcinomas following in situ HSVtk electrogene transfer"Journal of Gene Medicine. 5(in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 柴田雅朗, 森本純司, 伊藤裕子, 大槻勝紀: "Review : Electrogene transferによるHSVtk遺伝子を用いた移植乳癌および実験膀胱癌に対する遺伝子治療"乳癌基礎研究. 12(印刷中). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shibata, M.A., Horiguchi, T., Morimoto, J. and Otsuki, Y.: "Massive apoptotic cell death in chemically induced rat urinary bladder carcinomas following in situ HSVtk electrogene transfer"Journal of Gene Medicine. 5, in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shibata, MA., Horiguchi, T., Morimoto, J., Otsuki, Y.: "Massive apoptotic cell death in chemically induced rat urinary bladder carcinomas following in situ HSVtk electrogene transfer"Journal of Gene Medicine. 5(in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 柴田雅朗, 森本純司, 伊藤裕子, 大槻勝紀: "Review : Electrogene transferによるHSVtk遺伝子を用いた移植乳癌及び実験膀胱癌に対する遺伝子治療"乳癌基礎研究. 12(印刷中). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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