2018 Fiscal Year Final Research Report
Elucidation of the control mechanism by Fbxw7 / Notch1 / chemokine in perineural invasion of pancreatic cancer
| Project/Area Number |
16K19910
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Digestive surgery
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | Fbxw7 / 胆道癌 / 膵癌 |
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| Outline of Final Research Achievements |
I examined to elucidate the influence of Fbxw7 and the substrates accumulation in pancreatic cancer nerve infiltration. However, there was no association between Fbxw7 downregulation and pathological factors in pancreatic cancer pathological specimens. For that reason, I analyzed the relationship between the expression of Fbxw7 and clinicopathological factors in cholangiocarcinoma, which had Fbxw7 mutation.
FBXW7 expression was associated with clinicopathological outcomes in cholangiocarcinoma patients. FBXW7 was the most important independent prognostic factor. I also demonstrate that the two FBXW7 substrates, NOTCH1 and MCL1), regulate cholangiocarcinoma progression. FBXW7 modulates the malignant potential of cholangiocarcinoma via independent regulation of NOTCH1 and MCL1.
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| Free Research Field |
消化器外科学
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| Academic Significance and Societal Importance of the Research Achievements |
膵癌神経浸潤でのFbxw7と基質の蓄積による影響を解明すべく実験を行ったが,膵癌病理検体Fbxw7 発現低下と病理学的因子の関連はなく,細胞株では基質の蓄積を確認できなかった.そのため、Fbxw7に変異を有する胆道癌で研究を行った.
胆道癌においてFbxw7の発現低下は臨床病理学的予後が不良であることを初めて確認した.また,それらのメカニズムとしてNotch1とMcl-1の蓄積の関与を明らかにした.
胆道癌において Fbxw7 と基質タンパク質の分子メカニズムを明らかにし、それらを標的とする新規治療を確立することは個別化治療へと繋がる研究であり,更なる治療成績向上への第一歩となると考えられる.
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