| Project/Area Number |
12671286
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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 |
Digestive surgery
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| Research Institution | Fukuoka University |
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Principal Investigator |
SHIMURA Hideo School of Medicine, Fukuoka University Associate Professor, 医学部, 助教授 (80178996)
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| Co-Investigator(Kenkyū-buntansha) |
IKEDA Seiyo School of Medicine, Fukuoka University Professor, 医学部, 教授 (40038758)
NAKAMURA Hiroshi School of Medicine, Fukuoka University Assistant, 医学部, 助手 (60309911)
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| Project Period (FY) |
2000 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | gallbladder cancer / gene therapy / hepatocyte growth factor / antagonist / adenovires vector / cancer dissemination |
|---|
| Research Abstract |
Pancreatobiliary cancers are highly malignant and its prognosis is poor due to extensive invasion and metastasis of the cancer cells to surrounding tissues or organs. We previously revealed that hepatocyte growth factor (HGF) stimulates cancer invasion and metastasis via its receptor c-met protooncogene. To control invasion and metastasis of these cancers, we created an antagonist, HGF/NK4, and its inhibitory effect on invasion and cancer growth. We examined in this study whether HGF/NK4 gene transfer into the cells results in suppression of the invasion and metastasis or not. Transfection of a plasmid carrying HGF/NK4 gene into a gallbladder cancer cell line, GB-d1, could not suppress invasive nature of the parental GB-dl. An adenovirus vector carrying HGF/NK4 gene, AdCMV. NK4, was purified and used for therapy in a murine model. GB-d1 cells and mesothelial cells infected with the adenovirus vector produced substantial level of NK4 protein. And the invasion and migration of GB-d1 cells was extremely inhibited by the virus. In nude mouse model for peritoneal metastasis of GB-d1 cells, the size of the metastasis tumor was decreased after injection of the virus into peritoneal cavity. We concluded that the adenovirus vector carrying HGF/NK4 gene might be effective to control biliary cancer dissemination or metastasis by induction of HGF/NK4 protein.
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