| Project/Area Number |
16K14615
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology
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| Research Institution | Japanese Red Cross Hokkaido college of Nursing |
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Principal Investigator |
Yamazaki Kohsuke 日本赤十字北海道看護大学, 看護学部, 教授 (20281884)
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| Research Collaborator |
Tanaka Hiroki
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 肝癌 / TMA / 血小板 / 血栓性微小血管障害 / 腫瘍随伴症候群 / Braf / 癌 / 血栓 / 微小血管 |
|---|
| Outline of Final Research Achievements |
The Braf mutation plays a pivotal role in hepatocarcinogenesis. The liver of transgenic mice with a hepatocyte-specific human BRAFV600E mutation was entirely consisted of preneoplastic hepatocytes. These transgenic mice died due to thrombotic microangiopathy (TMA). This study was aimed to clarify the causes of TMA. Blood/tissue specimens collected from the transgenic mice were analysed haematologically/pathologically. In the transgenic mice, the liver showed thrombopoietin (TPO) overexpression, which is associated with thrombocytosis, and platelets were activated in hepatic sinusoids. Podoplanin was expressed in the Kupffer cells in the liver of the transgenic mice, indicating that platelet activation occurred via the interaction of podoplanin. TPO overproduction by BRAFV600E-mutated hepatocytes may contribute to thrombocytosis, platelet activation, while TMA due to aberrant platelet activation led to spontaneous death in some of the transgenic mice.
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