A new strategy for treatment of HCC by regulating hepatic stellate cell

Research Project

Project/Area Number	15K10165
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Digestive surgery
Research Institution	Department of Clinical Research, National Hospital Organization Kure Medical Center
Principal Investigator	Tashiro Hirotaka 独立行政法人国立病院機構(呉医療センター臨床研究部), その他部局等, その他 (90359894)
Project Period (FY)	2015-04-01 – 2018-03-31
Project Status	Completed (Fiscal Year 2017)
Budget Amount *help	¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000) Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords	肝細胞癌 / 肝星細胞 / 癌間質 / アンチトロンビン / 肝線維化 / 脂肪肝 / 抗インテグリン抗体
Outline of Final Research Achievements	Antithrombin (AT) is not only a major regulator of hemostasis, but also has anti-inflammatory properties. We aimed to investigate whether AT is associated with development of HCC. Liver tumors were developed in ATIII-insufficient (AT＋/－) mice and wild-type (AT＋/＋) mice treated with DEN and CCl4. Tumor size and the number of DEN and CCl4-induced liver tumors were significantly enhanced in AT-insufficient mice compared with wild-type mice. The serum transaminases, cell death and expression of cleaved caspase-3 in livers were exaggerated in AT-insufficient mice compared with wild-type mice. The level of 8-OHdG, a marker of oxidative DNA damage, in liver was significantly increased in AT-insufficient mice compared with wild-type mice. AT insufficiency led to the increased susceptibility to liver-tumorigenesis through amplifying inflammation.