| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
In obese diabetes/NASH model TSOD mice, a large number of altered foci (AF) and liver tumors were developed. Metabolome analysis revealed significant elevation of glucose metabolites and L-Arg in HCCs of TSOD mice. Furthermore, immunohistochemistry demonstrated rise in phosphokinases, P-mTOR and inhibition of arginase 1 (ARG1) in HCCs. It was concluded that elevation of glucose metabolites and L-Arg, decreased ARG1 expression and activation of mTOR pathway are main characteristics of NASH HCCs. In NASH model STAM mice, significant overexpression of CACHD1 was found in AF and tumors. Significant decrease of autophagy marker Atg12 and increase of p62 were detected in CACHD1+ precancerous lesions and tumors of STAM mice.In human NASH HCCs, the survival rate of ARG1- and CACHD1+ HCC patients was significantly reduced compared to ARG1+ and CACHD1- patients. It is suggested that ARG1 and CACHD1 are potential markers of NASH liver carcinogenesis.
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