2012 Fiscal Year Final Research Report
DNA damage detected with γH2AX induced by anticancer drugs on ovarian clear cell carcinoma
| Project/Area Number |
22591864
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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 | Iwate Medical University |
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Principal Investigator |
SUGIYAMA Toru 岩手医科大学, 医学部, 教授 (40162903)
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| Co-Investigator(Kenkyū-buntansha) |
KUROSE Akira 弘前大学, 医学研究科, 教授 (70244910)
KUMAGAI Seisuke 岩手医科大学, 医学部, 講師 (20289474)
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| Project Period (FY) |
2010 – 2012
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| Keywords | 癌 / 病理学 / 酵素 / 核酸 |
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| Research Abstract |
Differences in the incidences and types of DNA damage induced by antitumor agents for clear cell carcinoma (CCC) of the ovary, endometrioid adenocar cinoma of the uterine corpus, and squamous cell carcinoma of the cervix were determined using phosphory- lation of histon H2AX (γH2AX).1. Clear cell adenocarcinoma of the ovary (CCC): After administration of cisplatin(CDDP), DNA damage was frequent in S -phase cells, while cell-cycle arrest occurred in the G1 and G2/M phases and γH2AX did not increase in CDDP-resistant cells. Sensitivities to CDDP and carboplatin(CBDCA) differed between the two cell lines. The antitumor effect of paclitaxel(PTX) is induced by G2/M arrest, and combination treatment with CBDCA, inducing DNA damage in G2/M-phase cells, might be effective.This is the first study in Japan to evaluate the antitumor activity of anticancer agents by focusing on the relationship between the cell cycle and DNA damage using γH2AX as an indicator. The immunocytochemical method used in
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this study detects γH2AX, which indicates DNA damage even at very low concentrations and with high sensitivity. Therefore, a promising method of easily and rapidly identifying agents potentially effective against CCC. 2.Endometrioid adenocarcinoma of the uterine corpus: The study revealed significant differences among the cell lines in the effects of DNA damage vis-a-vis cell cycle phasespecificity, induction of apoptosis or senescence following drug treatment. doxorubicin (DOX) treatment showed little cell cycle specificity in terms of induction of γH2AX, and its mechanism, which is similar to another anthracycline DNA topoisomerase II inhibitor mitoxantrone, may involve oxidative DNA damage modulated by other factors. Treatment with CDDP and 5-fluorouracil (5-FU) led to phosphorylation of H2AXpreferentially in S -phase cells, consistent with the induction of replication stress. The response of Ishikawa cells expressing wt p53 was different compared to other cell lines. The data suggest that the treatment of endometrioid adenocarcinoma with these drugs may have to be customized to individual patients. Less
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Research Products
(15 results)
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[Journal Article] Transcriptional and post-transcriptional regulation of βIII-tubulin protein expression in relation with cell cycle -dependent regulation of tumor cells.2011
Author(s)
Masahiko Shibazaki, Chihaya Maesawa, Kiyomi Akasaka, Shuya Kasai, Shinji Yasuhira, Kiminori Kanno, Ikue Nakayama, Toru Sugiyama, Go Wakabayasi, Tomoyuki Masuda, Nozomu Mori.
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Journal Title
International Journal of Oncology;
Volume: 40(3)
Pages: 695-702
Peer Reviewed
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