| Project/Area Number |
12671567
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Osaka Medical College |
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Principal Investigator |
SHIBATA Masa-aki Osaka Medical College Faculty of Medicine, Associate Professor, 医学部, 助教授 (10319543)
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| 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)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| 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)
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| Keywords | Urinary 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 |
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| 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.
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