Molecular targeted and gene therapy using adeno-associated virus vector to suppress the peritoneal dissemination in ovarian cancer
| Project/Area Number |
17591755
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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 |
Obstetrics and gynecology
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| Research Institution | Jichi Medical University |
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Principal Investigator |
OHWADA Michitaka Jichi Medical University, Department Of Obstetrics and Gynecology, Associate Professor (40203955)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Mitsuaki Jichi Medical University, Department of Obstetrics and Gynecology, Professor (50110870)
SAGA Yasushi Jichi Medical University, Department of Obstetrics and Gynecology, Lecturer (70360071)
OZAWA Keiya Jichi Medical University, Department of Hematology, Professor (30137707)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,710,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | ovarian cancer / peritoneal dissemination / molecular targeted thera / gene therapy / adeno-associated virus / basic Research |
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| Research Abstract |
The main mode of progression is a peritoneal dissemination in ovarian cancer, and a peritoneal dissemination is involved of the angiogenesis factors those of vascular endothelial growth factor(VEGF), hepatocyte growth factor (HGF) and so on. We performed to investigate the molecular targeted and gene therapy using adeno-associated virus (AAV) vector for the purpose of the inhibition of peritoneal dissemination in ovarian cancer.
We revealed as follows ;
(1)AAV vectors are derived from a nonpathogenic virus, and a long-term transgene expression can be obtained after intramuscular vector injection and the serotype-1 was most useful.
(2)Soluble Flt-1 (sFlt-1) and interleukin-10 (IL-10) are potentially useful as an antagonist of VEGF. By using AAV-sFlt-land AAV-Il-10, inhibition of peritoneal dissemination and long-term survival were showed in tumor bearing mice by means of anti-angiogenesis. Rare adverse events were found.
(3)Ovarian cancer cell line overexpressed HGF/NK4 (HRA/NK4) showed that inhibitions of cell migration in virto and peritoneal dissemination in vivo. It suggested that inhibition of peritoneal dissemination of HGF/NK4 work by cell migration.
(4)HGF/NK4 was overexpressed of 22 genes including proline dehydrogenase and porin, and underexpressed of 12 genes including FLIP, EphB1 and tyrosine kinase DDR more than control by microarray analysis. EphB1 and tyrosine kinase DDR were involved cell migration.
These results indicated that sFlt-1, IL-10 and AAV-HGF/NK4 suppress tumor growth and peritoneal dissemination of ovarian cancer by inhibition of angiogenasis, and thus suggest the usefulness of gene therapy for ovarian cancer.
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Report
(4 results)
Research Products
(64 results)
