Sensitization for chemotherapy and radiation by gene induction which suppresses DNA repair in head and neck cancer
| Project/Area Number |
23592544
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | National Defense Medical College |
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Principal Investigator |
YAMASHITA Taku 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究, その他部局等, 准教授 (00296683)
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| Co-Investigator(Kenkyū-buntansha) |
ARAKI Koji 防衛医科大学校, 耳鼻咽喉科, 講師 (70317220)
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| Project Period (FY) |
2011-04-28 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 遺伝子治療 / 頭頸部癌 / 遺伝子修復 / DNA切断 / DNA修復遺伝子 / ウイルスベクター / DNA修復因子 |
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| Outline of Final Research Achievements |
We used reconbinant adenovirus vector(Ad-NBS1) introduced mutant type of NBS1 protein which is associated with double strand breaks(DSB) repair of DNA. We confirmed good introduction rate of Ad-NBS1 for tumor cells , significant antitumor effect of Ad-NBS1, and obvious sensitization in using with cisplatin in vitro. In addition, by using PARP inhibitor which suppresses the repair of single strand breaks (SSB) as well as the combination of cisplatin and Ad-NBS1, more significant sensitization of antitumor effect was observed. The increase of production in DNA repair proteins such as MRE11, NBS1 and RAD50(MRN) through a transcription factor p63 was associated with cisplatin resistant of tumor cells. However, the functional mechanism of Ad-NBS1 was not through p63, but directly suppressed MRN proteins and resulted in not working DNA repair function through γH2AX near DSB normally.
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Report
(5 results)
Research Products
(2 results)
