Role of oxidative stress response in cholangiocarcinoma
Project/Area Number |
17K09452
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | Tohoku University |
Principal Investigator |
Hamada Shin 東北大学, 医学系研究科, 助教 (20451560)
|
Co-Investigator(Kenkyū-buntansha) |
正宗 淳 東北大学, 医学系研究科, 教授 (90312579)
|
Project Period (FY) |
2017-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
|
Keywords | 胆管癌 / Keap1 / 酸化ストレス |
Outline of Final Research Achievements |
We crossed Alb-Cre mouse, LSL-Kras G12D mouse and LSL-p53 R172H mouse to generate mutant Kras/p53 expressing mouse. We further introduced Keap1 floxed background into this mouse, leading to the constitutive activation of Nrf2. As a result, addition of Keap1 deletion promoted cholangiocarcinoma development, with increased expression of Nrf2 target genes.
|
Academic Significance and Societal Importance of the Research Achievements |
本研究により、酸化ストレス応答機構の活性化は胆管発癌を促進することが明らかになった。ヒト胆管癌組織においてもKeap1欠損とNrf2標的分子の発現増加が併存する一群がみられ、胆管癌発癌過程への寄与が考えられる結果であった。 胆管癌の進展に寄与する分子機構は新たな治療標的となる可能性があり、Nrf2阻害による胆管癌治療の可能性を示唆する結果が得られたものと思われる。
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Report
(4 results)
Research Products
(2 results)