| Project/Area Number |
18K08634
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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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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
永坂 岳司 川崎医科大学, 医学部, 准教授 (30452569)
眞部 紀明 川崎医科大学, 医学部, 教授 (50403572)
上野 富雄 川崎医科大学, 医学部, 教授 (70284255)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 大腸癌 / TIGAR / インスリン抵抗性 / メチル化 / TIGAR遺伝子 / 大腸がん / インスリンシグナル |
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| Outline of Final Research Achievements |
TIGAR gene promoter methylation analysis using colorectal cancer clinical specimens demonstrated that there were no significant differences between methylated and unmethylated group about neither relapse free survival (RFS) or overall survival (OS). There was tendency that methylated group had better OS. Moreover, there were no significant differences between TIGAR protein expression and RFS or OS, but there was tendency that worse RFS was shown in the group of high expression of TIGAR. This study could demonstrate some definite relation between TIGAR and colorectal cancer, but could not elucidate unexplained parts of mechanism of carcinogenesis by TIGAR activation.
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| Academic Significance and Societal Importance of the Research Achievements |
p53の下流に位置するTIGARの活性化は糖新生を亢進し、そのノックアウトマウスでは腫瘍増殖能が減少する。本研究においてTIGARは大腸癌において有意にメチルされる遺伝子の一つの可能性であることが分かった。ただ我々の限定的な研究においてはメチル化群と長期予後との明らかな因果関係を認めることは出来なかった。またTIGARタンパク高発現群は再発が起こりやすい傾向にあった。今後TIGAR活性による発がん機構を解明することによりTIGAR標的新規創薬・治療の開発に向けたさらなる基礎研究と今後の臨床応用への礎を構築できると考える。
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