| Project/Area Number |
18K16318
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Kyushu University |
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Principal Investigator |
KUBO Nobuhide 九州大学, 医学研究院, 共同研究員 (20811748)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 食道癌 / 酸化的DNA損傷 / 8oxoG / OGG1 / MutYH / アポトーシス抑制 / 分子標的治療 / 8-oxoG |
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| Outline of Final Research Achievements |
Our research results was consistent with the hypothesis that the oxidative DNA damage repair factor MutYH suppresses cancer apoptosis by fluorescent double staining with TUNEL. MutYH was significantly overexpressed in the cancerous part. The results of cell lines showed differences in the expression levels of OGG1 and MutYH among various esophageal cancer cell lines and fibroblast cell lines, and the cell viability under oxidative stress was decreased in siOGG1 and increased in siMutYH. When clinical specimens were used, the tumor size was large and the prognosis was poor in the MutYH strong expression group. These results are consistent with the hypothesis that MutYH suppresses cancer apoptosis. It was considered to be a molecular target candidate in the search for therapeutic targets (current research purpose).
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| Academic Significance and Societal Importance of the Research Achievements |
食道癌は悪性度が高く予後不良の消化器癌であり、手術療法は標準治療であるが極めて侵襲が大きく、薬物療法（抗癌剤）の役割は非常に大きい。しかし、食道癌治療の薬物療法は選択肢が少なく、新たな薬物療法の開発は急務である。食道癌は酸化的DNA損傷と関わりが深いことが推測されている。過度の8-oxoGのゲノム蓄積は細胞死を誘発し，結果として発癌頻度の低下をもたらすはずであるが、MutYHが酸化的DNA損傷の蓄積を排除することで癌の存続に寄与している可能性が報告されていた。本研究では同因子を抑制することなどで癌細胞の生存を抑制する結果を得たことで治療ターゲット因子としての可能性を示唆することができた。
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