| Project/Area Number |
15590700
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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 |
Gastroenterology
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| Research Institution | Kurume University |
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Principal Investigator |
TORIMURA Takuji Kurume University, Medicine, Associate Professor, 医学部, 助教授 (60197986)
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| Co-Investigator(Kenkyū-buntansha) |
UENO Takato Kurume University, Research Center for Innovative Cancer Therapy, Professor, 先端癌治療研究センター, 教授 (70176618)
OKAMURA Takashi Kurume University, Medicine, Professor, 医学部, 教授 (30136436)
TANIGUCHI Eitaro Kurume University, Medicine, Assistant, 医学部, 助手 (50341318)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Hepatocellular Carcinoma / Gene therapy / Anti-angiogenesis / Endothelial progenitor cell / Endostatin / Kringle 1-5 / Retrovirus / 骨髄移植 / トランスジェニックマウス / K1-5 |
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| Research Abstract |
Hepatocellular carcinoma is a hypervascular tumor. In the present study, we investigated whether gene therapy with anti-angiogenic factor cDNA could be effective or not for hepatocellular carcinoma.
Endostatin and Kringle1-5, which were potent anti-angiogenic factors, suppressed proliferation of endothelial progenitor cells in vitro. We transfected endostatin and kringle1-5 cDNAs to bone marrow cells with retrovirus fransfection system. Kringle1-5 cDNA was successfully transfected. However, endostatin was not transfected. Then we injected intravenously liposome-kringle1-5 cDNA complexes in nude mice implanted into the liver with hepatoma cell lines to study tumor growth, intrahepatic metastasis and survival. Gene transfer of kringle1-5 suppressed tumor growth of the three hepatoma cell lines. kringle1-5 gene transfer prolonged the survival period, reduced the number of intrahepatic metastases. Next, we performed bone marrow transfection to nude mice with kringle1-5 cDNA transfected bone marrow cells. Then, the nude mice were received hepatoma cell transplantation in the liver. After 4 weeks of the bone marrow transfection, the mice were sacrificed. In tumor tissues, about 10% of vascular endothelial cells were consisted with bone marrow derived endothelial progenitor cells. About 20% of vascular endothelial cells derived from endothelial progenitor cells produced kringle 1-5 protein. However, tumor volume and vascular density in tumor tissues were not suppressed by bone marrow transfection with kringle1-5 cDNA at all.
These results seems that the expression of kringle1-5 protein in tumor tissues was too weak to suppress the tumor development due to low transfection efficacy of retrovirus system.
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