2002 Fiscal Year Final Research Report Summary
Gene therapy enhances chemotherapy induced apoptosis in a peritonitis carcinomatosa model with ovarian cancer
| Project/Area Number |
12671600
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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 School of Medicine |
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Principal Investigator |
KIGAWA Junzo Tottori Univ. Dept. Obstet. Gynecol., Associated Professor, 医学部, 助教授 (00177784)
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| Co-Investigator(Kenkyū-buntansha) |
ITAMOCHI Hiroaki Tottori Univ. Dept. Obstet. Gynecol., Research Associates, 医学部附属病院, 助手 (20314601)
KANAMORI Yasunobu Tottori Univ. Dept. Obstet. Gynecol., Research Associates, 医学部, 助手 (70283984)
TERAKAWA Naoki Tottori Univ. Dept. Obstet. Gynecol., Professor, 医学部, 教授 (90163906)
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| Project Period (FY) |
2000 – 2002
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| Keywords | P53 gene / apoptosis / lperitonitis carcinomatosa model / gene therapy / ovarian cancer |
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| Research Abstract |
We found that mutations of the p53 gene newly occurred in 47% of patients after recurrence. Nonresponders to chemotherapy had mutations of the p53 gene more frequently (83% for nonresponders vs. 16% for responders) in patients with epithelial ovarian cancer undergoing platinum-based chemotherapy. Apoptotic index was significantly greater in tumors with wild-type p53 gene than those without the gene. Therefore, p53-dependent apoptosis in tumors is strongly related to sensitivity to chemotherapy in ovarian cancer.
P53 gene transduction markedly enhanced the sensitivity to cisplatin (CDDP) and CDDP-induced apoptosis, but did not affect the sensitivity to paclitaxel (PTX) nor PTX-induced apoptosis. The combination treatment with a recombinant adenovirus carrying a wild-type p53 gene (AxCAp53) and CDDP significantly suppressed tumor growth of ovarian cancer xenograft with and without p53 gene, compared with a single treatment of either AxCAp53 or CDDP. Apoptotic index was significantly higher and proliferating cell nuclear antigen labeling index was relatively low in the xenograft without p53 gene receiving combination treatment, compared with a single treatment of either CDDP or AxCAp53, suggesting that the transduction of p53 gene induces apoptosis, but does not enhance the DNA repair system. Additionally, a significant survival advantage was observed in the combination treatment compared with other treatments.
It is concluded that p53 gene status contributes the sensitivity to CDDP in ovarian cancer. Additionally, combination treatment of p53 gene transduction and CDDP may be an effective therapeutic modality for ovarian cancer without wild-type p53 gene.
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