Establishment of transgenic HRAS medaka as a tumor model for in vivo drug screening
| Project/Area Number |
24591633
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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 |
Dermatology
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| Research Institution | Keio University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
SAYA Hideyuki 慶應義塾大学, 医学部, 教授 (80264282)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | がん遺伝子導入メダカ / 抗癌剤スクリーニング / メダカ腫瘍モデル / HRAS / HRAS高発現 / トランスジェニックメダカ / メダカ / トランスジェニック / RAS / 薬剤スクリーニング |
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| Outline of Final Research Achievements |
We have previously reported a transgenic medaka strain expressing human HRAS mutant gene. Here, we further intend to establish a novel drug screening system using this medaka. In the first screen using our drug library, we obtained 35 drugs which could decrease pigmentation of zebrafish embryos. Seven out of 35 drugs were selected as candidate drugs because they had affected the downregulation of the gene for marker of embryonic neural crest progenitors. Before the second screening, we tried to validate the experimental system using the transgenic HRAS medaka. Inhibitors for downstream molecules of RAS signaling were administered to the HRAS medaka. Treatment with sorafenib, an inhibitor of Raf kinase, improved their survival, and Trametinib, an inhibitor of MEK, decreased the levels of phosphorylated ERK in the tumor tissue. The in vivo system presented here is promising to screen potential anticancer drugs.
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Report
(4 results)
Research Products
(10 results)
