Research on the breast cancer chemotherapy targeting synthetic lethality caused by the factors in the DNA damage repair pathways.
| Project/Area Number |
23300358
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Tumor diagnosis
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
OHTA Tomohiko 聖マリアンナ医科大学, 医学(系)研究科(研究院), 教授 (60233136)
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| Co-Investigator(Kenkyū-buntansha) |
BOKU Narikazu 聖マリアンナ医科大学, 医学部, 教授 (50505948)
TSUGAWA Koichiro 聖マリアンナ医科大学, 医学部, 教授 (60313657)
NAKADA Shinichiro 大阪大学, 医学(系)研究科(研究院), 准教授 (70548528)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥21,970,000 (Direct Cost: ¥16,900,000、Indirect Cost: ¥5,070,000)
Fiscal Year 2013: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2012: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2011: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
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| Keywords | DNA修復 / 合成致死性 / 癌化学療法 / 乳癌 / 非癌遺伝子依存性 |
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| Research Abstract |
In this project we studied the DNA damage repair pathways to employ the synthetic lethality caused by the factors in the pathway for breast cancer therapy. We found that promoter methylation of genes implicating in the homology-directed DNA repair are associated with chemosensitivity. We also discovered that overexpression of PLK1 causes cellular hypersensitivity to CPT-11 and PARP inhibitor through suppression of the E3 ubiquitin ligase activity of BRCA1, and that BARD1 interacts with Lys9-dimethylated Histone H3 through heterochromatin protein 1 (HP1) gamma in response to DNA damage.
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Report
(4 results)
Research Products
(32 results)
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[Journal Article] Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum : WJOG 4007 trial2013
Author(s)
Hironaka S, Ueda S, Yasui H, Nishina T, Tsuda M, Tsumura T, Sugimoto N, Shimodaira H, Tokunaga S, Moriwaki T, Esaki T, Nagase M, Fujitani K, Yamaguchi K, Ura T, Hamamoto Y, Morita S, Okamoto I, Boku N, Hyodo I
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Journal Title
J Clin Oncol
Volume: 31(35)
Issue: 35
Pages: 4438-44
DOI
Related Report
Peer Reviewed
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[Journal Article] A DNA-Damage Selective Role for BRCA1 E3 Ligase in Claspin Ubiquitylation, CHK1 Activation, and DNA Repair2012
Author(s)
Sato K, Sundaramoorthy E, Rajendra E, Hattori H, Jeyasekharan AD, Ayoub N, Schiess R, Aebersold R, Nishikawa H, Sedukhina AS, Wada H, Ohta T, Venkitaraman AR
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Journal Title
Curr Biol
Volume: 22
Issue: 18
Pages: 1659-66
DOI
Related Report
Peer Reviewed
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