Development of the alkylating agent targeting intrahepatic cholangiocarcinoma -specific fusion gene
| Project/Area Number |
16K10583
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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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| Research Field |
Digestive surgery
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| Research Institution | Nihon University |
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Principal Investigator |
TAKAGI Keiko 日本大学, 医学部, 研究医員 (20339328)
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| Co-Investigator(Kenkyū-buntansha) |
緑川 泰 日本大学, 医学部, 准教授 (10292905)
尾崎 俊文 千葉県がんセンター(研究所), 発がん研究グループ DNA損傷シグナル研究室, 室長 (40260252)
藤原 恭子 日本大学, 歯学部, 准教授 (40595708)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 肝内胆管癌 / 融合遺伝子 / PIポリアミド / ChB-PIP / アルキル化剤 |
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| Outline of Final Research Achievements |
We aimed to develop chlorambucil-PI polyamide (ChB-PIP), which alkylates a fusion gene specific for intrahepatic cholangiocarcinoma (ICC) and kills only cells contain the fusion gene. ChB-PIP was prepared by purification and analysis by high performance liquid chromatography (HPLC), and the synthesis of ChB-PIP that specifically binds to the fusion gene was confirmed by gel shift assay. Then, a transient expression strain was prepared for the ICC cell line. Next, in order to establish a stable strain, after transfection, selection was performed using G418 (Geneticin) to scale up the cells.In the fusion gene plasmid-introduced group, the gene expression level was higher than that in the control group, and it was confirmed that a stable strain was produced.
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| Academic Significance and Societal Importance of the Research Achievements |
配列特異的にDNAに結合する性質を持つピロール・イミダゾール・ポリアミド(PIP)を用いて、融合領域を認識するPIPにアルキル化剤クロラムブシル(ChB)を付加したFGFR2-BICC1融合遺伝子認識ChB-PIPの合成を成功させた。また、融合遺伝子2種のいずれかの存在が確認されているICC細胞株が樹立されていないことから、安定株の作製を成功させた。
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Report
(5 results)
Research Products
(1 results)
