| Project/Area Number |
16K09391
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Saitama Medical University (2017-2018)
The University of Tokyo (2016) |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
立石 敬介 東京大学, 医学部附属病院, 講師 (20396948)
伊佐山 浩通 東京大学, 医学部附属病院, 准教授 (70376458)
|
|---|
| Research Collaborator |
FUJIWARA hiroaki
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | 胆管癌 / 胆管がん / 胆道癌 / エピジェネテイクス |
|---|
| Outline of Final Research Achievements |
Cholangiocarcinoma is a life-threatening disease of poor prognosis.Mutations in IDH1 are found in almost 20% of intrahepatic cholangiocarcinoma (ICC).In this study, we report that the anti-growth effect of JQ1 differs among ICC cells and IDH1 mutation sensitizes ICC cells to JQ1. RBE cells harboring IDH1 mutation was more sensitive to JQ1 than HuCCT1 or HuH28 cells with wild-type IDH1. In addition, AGI-5198, a selective inhibitor of mutant IDH1 partially reversed the decrease in viability after JQ1 treatment and also suppressed the JQ1-induced apoptosis in RBE cells. These data suggested that IDH1 mutation contributed to the growth inhibitory effect of JQ1 in RBE cells. Our findings propose a new stratified therapeutic strategy based on IDH1 mutation in ICC.
|
| Academic Significance and Societal Importance of the Research Achievements |
肝内胆管癌は有効な治療薬が限られ、ゲノム医療への期待は大きい。その20%に認められるIDH1変異は、興味深いことに肝炎ウイルスや寄生虫など肝内胆管癌の発症における他の危険因子の無い症例群に集積する。よってIDH1変異は独自の特性を持つ肝内胆管癌のサブグループを形成する可能性が考えられる。本研究は肝内胆管におけるIDH変異の意義を解明し、IDH変異陽性の肝内胆管癌の特性や特異的な治療薬の同定を試みた点で意義がある。
|
