| Project/Area Number |
07457282
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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 |
Digestive surgery
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| Research Institution | Hyogo College of Medicine |
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Principal Investigator |
FUJIMOTO Jiro Hyogo College of Medicine. Assistant Professor, 医学部, 講師 (90199373)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMA Tomoko Hyogo College of Medicine. Associate Professor, 医学部, 助教授 (10172868)
TANAKA Tsuneo Hyogo College of Medicine. Medical Instractor, 医学部, 助手 (80248137)
TOYOSAKA Akihiro Hyogo College of Medicine. Associate Professor, 医学部, 助教授 (20068498)
OKAMOTO Eizo Hyogo College of Medicine. Professor, 医学部, 教授 (50068425)
山中 若樹 兵庫医科大学, 医学部, 助教授 (90131599)
竹内 雅春 兵庫医科大学, 医学部, 助手 (00258162)
古川 一隆 兵庫医科大学, 医学部, 助手 (70219096)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1997: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1996: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | HVJ-liposome / AFP / HSV-TK / liver cirrhosis / HGF / CTL / AFPプロモーター / ヘルペスチミジンキナーゼ / 遺伝子導入 / センダイウイルス / 肝癌 |
|---|
| Research Abstract |
Most viral vectors are highly immunogenic and are of limited use for somatic gene therapy that requires repetitive administrations. We developed a highly efficient gene transduction procedure useful for repetitive transfection using HVJ-liposome. We revealed that LacZ gene was deliveredto and expressed with high effeciency to rat liver. Antibody response to HVJ-liposome or cytotoxic T lymphocyte were not elicited against autologous rat hepatocyte. Using genetrasduction method, we performed gene therapy for liver cirrhosis using hepatocyte growth factor (HGF) and for hepatocellular carcinoma (HCC) by HSV-TK gene. Established liver cirrhosis rat model which has been induced by dimethy lnitrosamine was treated with muscle directed HGF gene therapy. HGF protein was detected in the plasma of rats, and tyrosine phosphorylation of c-Met/HGF receptor was observed. Fibrous component in the cirrhotic liver disappeared and the mortality was completely abrogated in HGF gene transducted rats. Transgene of HSV-TK gene under the control of alpha-fetoprotein (AFP) promotor achieved tumor regression for AFP-producing human HCC tumor in athymic nude mice. The suicidal gene, HSV-TK,was specifically expressed in the AFP-producing cells but not in normal cells. These results indicated that these gene therapies can be novel molecular approaches for liver cirrhosis and for HCC.
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