Unexpectedly, mutations and activation of β-catenin occurred at late stage of tumor progression and were preceded by chromosomal instability in DEN-initiated/PB-fed mice. Thus, mutations and activation of the Wnt/β-catenin pathway are not involved in tumor initiation in this model of hepatocarcinogenesis. Furthermore, these findings add complexity to the previous assumption5, 6 that genomic instability and activation of β-catenin characterize two distinct and

mutually exclusive groups of liver tumors. Although numerous studies, including the one by Aleksic et al., significantly improved our knowledge of the extent and significance of genomic instability in hepatocarcinogenesis, many questions on this topic FK506 supplier remain unanswered. Indeed, while mutations of DNA repair genes are responsible for the generation of genomic instability in hereditary cancers, the molecular bases of genomic instability in sporadic tumors (including HCC) are still poorly delineated.1 Telomere shortening, changes in global DNA methylation status, oncogene-induced DNA replication stress, generation of reactive oxidative, and nitroxidative species by the tumor microenvironment and the viral etiological factors as well as inactivation of detoxification systems have been proposed as the “primum movens” of genomic instability in HCC.19, 20 It is plausible to believe that many of these mechanisms act in combination

Selleck ABC294640 to disrupt the hepatocytes genome integrity. Additional investigations are required to better elucidate the interaction of

the aforementioned mechanisms in liver carcinogenesis. Also, systematic in vivo and in vitro studies are needed to define the oncogenic and oncosuppressive roles of the genes located in the chromosomal loci affected by genomic alterations in order to identify the key genes responsible for liver cancer development and progression. “
“Aim:  MCE Transient elastography is known as a rapid, objective, and highly reliable technique for staging hepatic fibrosis caused by hepatitis C virus infection; however, the relationship between degree of fibrosis and the collagen deposition or the accumulation of myofibroblasts in non-alcoholic fatty liver disease (NAFLD) remains to be further elucidated. Methods:  The subjects were 36 patients with NAFLD who received liver biopsy and liver stiffness measurement using transient elastography. Their clinical data and laboratory values were collected. Morphometric analyses of liver fibrosis indicated by collagen deposition and the relative numbers of myofibroblasts were performed. Results:  Liver stiffness measured by transient elastography correlated with histopathological fibrosis staging of NAFLD determined by Brunt’s scoring system (P = 0.000149). The fibrosis staging correlated with the ratios of the Sirius red-positive area (P = 0.000032) and α-smooth muscle actin-positive area (P = 0.000898). Finally, liver stiffness significantly correlated with the ratios of the Sirius red-positive area (r = 0.390, P = 0.