p53-based gene therapy of ovarian cancer with chemo-resistance
| Project/Area Number |
07671785
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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 | Tottori University, Faculty of Medicine |
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Principal Investigator |
KIGAWA Junzo Tottori Univ.・Dept.Obstet.Gynecol., Assistant Professor, 医学部, 講師 (00177784)
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| Co-Investigator(Kenkyū-buntansha) |
MINAGAWA Yukihisa Tottori Univ.・Dept.Obstet.Gynecol., Assistant Professor, 医学部附属病院, 講師 (70190692)
TERAKAWA Naoki Tottori Univ.・Dept.Obstet.Gynecol., Professor, 医学部, 教授 (90163906)
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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 |
¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1996: ¥400,000 (Direct Cost: ¥400,000)
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| Keywords | ovarian cancer / chemoresistance / p53 gene / gene therapy / p53 / 遺伝子変異 |
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| Research Abstract |
The aim of this study was to know the role of p53-gene therapy for patients with chemoresistant ovarian cancer. To examine the role of p53 gene in the chemoresistance of epithelial ovarian cancer, we investigated p53 gene and its protein in tumors before and after chemotherapy in the same patients. Mutation of p53 gene was seen in 7 patients (2 responders and 5 nonresponders) before chemotherapy. After chemotherapy, another mutation of the gene was observed in 5 patients who were all the nonresponders. By Western blot analysis, p53 protein was detected in 10 patients (3 responders and 7 nonresponders) before chemotherapy. After chemotherapy, expression of p53protein increased in these nonresponders and became to be positive in another 2 nonresponders. These results suggest for the first time that p53 gene and expression of p53 protein in tumors are altered by chemotherapy and the alteration of p53 status may be involved in the mechanisms of chemoresistance in epithelial ovarian cancer.
… More
Additionally, expression of GST-l and concentration of glutathione in tumors before and after chemotherapy were examined. Then we found that increased levels of GST-l and GSH expression after chemotherapy were linked to drug-resistance in patients with epithelial ovarian cancer. Next, We developed wt-p53 expression vector as following. Recombinant adenovirus was grown and propagated in 293 cells, a human embryonic kidney cell line transformed by Ad5 E1A and E1B genes. Recombinant adenoviruses purified on the method of sequential centrifugation in CsCl step gradients. To construct the Adex p53, a 1.95-kb BamH l-EcoR l fragment containing the full-length complementary DNA (cDNA) for human wild-type p53 (wt-p53) was isolated from pProSp53. The p53 coding sequence was inserted into pAdex1CAwt adenovirus gene transfer cosmid cassette. The cosmid was cotransfected the EcoT22 l-digested Ad5-dlx by the calcium phosphate method to 293 cells. Then tranfect experimental study showed that tumor suppression in even tumor with wt- p53, although the relation between p53 gene therapy status and chemosenseitivity. The present study suggests that p53 gene therapy will be useful approach for ovarian cancer. Less
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Report
(3 results)
Research Products
(19 results)
