26 Given the role of miR-122 in the developmental liver, we believe that loss of miR-122 expression may Carfilzomib ic50 be primarily involved in the misregulation of the balance between cell proliferation and differentiation during hepatocarcinogenesis. We thank Stephen J. Elledge (Howard Hughes Medical Institute) for graciously providing the p203 (pPRIME-TREX-GFP-FF3) vector and Shi-Mei Zhuang (Sun Yat-Sen University) for kindly donating the Huh7 cell line. Additional Supporting Information may be found in the online

version of this article. “
“Aim:  Hepatocellular adenoma (HCA) represents a heterogeneous entity, and recently four major subgroups were identified based on genotype and phenotype classification from Europe. HCA is rare in Asian countries including Japan

and there has been no study regarding the subgroups of HCA in Japan. Methods:  We took advantage of the reported genotype/phenotype classification to analyze 14 HCA (seven women) in Japan. Results:  We identified one hepatocyte nuclear factor (HNF)1α-inactivated HCA (one woman), two β-catenin-activated HCA (one woman), seven inflammatory HCA (IHCA, two women); four additional cases (three women) had no known phenotypic marker (unclassified HCA). The use of oral contraceptives was found only in two unclassified HCA see more (29%) cases. Fatty change of the background liver was seen in one β-catenin-activated HCA cases, four IHCA (57%) and two unclassified HCA (50%). Hepatic fibrosis was seen in five IHCA (71%) and two unclassified HCA (50%) cases. Four IHCA patients (one woman) were alcohol drinkers and one had alcoholic steatofibrosis and three had alcoholic cirrhosis. Eight HCA (57%) were multiple; one HNF1α-inactivated

HCA (100%), four IHCA (57%) and three unclassified HCA learn more (75%). The tumor was significantly larger in β-catenin-activated HCA than in other subgroups. The association of hepatocellular carcinoma was seen only in one case of unclassified HCA. Conclusion:  This study suggests that IHCA arising in men with alcoholic liver disease may be a major subtype of HCA in Japan. “
“Alternatively polarized macrophages (Mϕ) shape the microenvironment of hepatocellular carcinoma (HCC) and temper anticancer immune responses. We investigated if sorafenib alters the HCC microenvironment by restoring classical macrophage polarization and triggering tumor-directed natural killer (NK) cell responses. In vivo experiments were conducted with sorafenib (25 mg/kg)-treated C57BL/6 wildtype as well as hepatitis B virus (HBV) and lymphotoxin transgenic mice with and without HCC. Monocyte-derived Mϕ or tumor-associated macrophages (TAM) isolated from HCC tissue were treated with sorafenib (0.07-5.0 μg/mL) and cocultured with autologous NK cells. Mϕ and NK cell activation was analyzed by flow cytometry and killing assays, respectively.