| Project/Area Number |
07457133
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Kanazawa University |
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Principal Investigator |
KOBAYASHI Kenichi Medical department, Kanazawa University, Professor, 医学部, 教授 (70019933)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUSHITA Eiki Department of Neurosurgery, Kanazawa University Assistant professor, 医学部・附属病院, 講師 (00242545)
KANEKO Shuichi School of Medicine, Kanazawa University Associate Professor, 医学部, 助教授 (60185923)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1996: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1995: ¥4,900,000 (Direct Cost: ¥4,900,000)
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| Keywords | gene therapy / hepatocellular carcinoma / retroviral vector / herpes simplex thymidine kinase / ganciclovir |
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| Research Abstract |
Currently, clinical trials of suicide gene transfer with retroviral vector producer cells are being carried out for the treatment of brain tumors. The feasibility of applying this approach for the treatment of hepatocellular carcinoma is studied.
Methods : Five hepatoma cell lines were tested for retroviral mediated transduction efficiency with the herpes simplex thymidine kinase (HSV-TK) gene and for the induced drug sensitivity to ganciclovir. Different populations of HSV-TK transduced HuH7 cells were subcutaneously injected into athymic nude mice with non transduced HuH7 cells to analyze the "bystander" effect. The retroviral vector producer cells were intratumorally injected into pre-established HuH7 tumors to study the antitumor effect.
Results : Five hepatoma cell lines were transduced with the viral supernatant, and all resultant 50 transduced clones, except one, were sensitive to ganciclovir. Complete regression occurred in 21 out of 30 tumors when the inoculum consisted of as few as 10% of HSV-TK containing transduced cells. The producer cell injection into tumors and GCV treatment group was significantly smaller in size of the tumors compared to GCV treatment group (p<0.01).
Conclusions : This gene therapy approach could potentially be effective for the treatment of human hepatocellular carcinoma.
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