| Project/Area Number |
15K10710
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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 |
Obstetrics and gynecology
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| Research Institution | Shinshu University |
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Principal Investigator |
Oka Kenji 信州大学, 学術研究院医学系(医学部附属病院), 助教 (40345749)
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| Co-Investigator(Kenkyū-buntansha) |
塩沢 丹里 信州大学, 学術研究院医学系, 教授 (20235493)
山田 靖 信州大学, 学術研究院医学系(医学部附属病院), 助教 (60646652)
宮本 強 信州大学, 学術研究院医学系, 准教授 (70418721)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | ミスマッチ修復 / サイトカイン / TNFα / 子宮内膜症 / 卵巣癌 / 子宮内膜癌 / 卵巣子宮内膜症性嚢胞 / ミスマッチ修復異常 / 炎症性サイトカイン / 鉄イオン / マイクロサテライト不安定性 / ミスマッチ修復以上 / 癌化 |
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| Outline of Final Research Achievements |
The stimulation by 100 pg/mL TNFα for 72 hours suppressed the expression of MLH1 and MSH2 in the immortalized ovarian surface epithelial cells, OSE2a. Because this effect was canceled by the addition of NFκB inhibitor, it might be mediated by NFκB pathway. In the endometrial carcinoma cell lines, Ishikawa and HEC1B, the addition of TNFα or ferric ion suppressed the expression of MLH1 and MSH2. This result suggests that these factors abundantly accumulated in ovarian endometriotic cyst might be involved in the mismatch repair (MMR) dysfunction. In the mouse endometrial carcinogenesis model by intrauterine injection of the carcinogen, N-methyl-N-nitrosourea, we found that high serum estrogen level induces the strong expression of MMR proteins and may rather inhibit carcinogenesis.
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