After the withdrawal of the embryonic microenvironment, the reprogrammed ES-Hepa hybrids regained malignant characteristics in terms Trichostatin A (TSA) of epigenetic inactivation of p16INK4a, activation of oncogenes, and tumorigenic potential in vivo. These results suggested the possibility of the role of microenvironment alteration such as gastric acid reflux, inflammation, and other factors in tumorigenesis from stem cells with intrinsic mutation. This might also be the reason why medicines such as 5-Aza-2��-deoxytidine and procanamide do not work after withdrawal (39, 40). Although we cannot determine the cause of the malignant ��program�� in differentiated ES-Hepa hybrids, it results in the repression of tumor suppressors and activation oncogenes by triggering DNA methyltransferases, histone-modification enzymes such as lysine acetyltransferases, lysine deacetylases, and lysine methyltransferases in the differentiated environment.

The ES-Hepa hybrids in this study may represent a ��transition�� state that p16INK4a was affected by both H3K4 and H3K27 methylation, which may predict either active or repressive states in the differentiation course. When the differentiation-related malignant program started, trimethylation of H3K27 was the first to modulate the promoter region of p16INK4a, which was much before the dimethylation of H3K9. However, although the di- and trimethylation of H3K4 were considered as markers of gene-activation chromatin structure, our ChIP results showed that, in the p16INK4a inactivation course, both methylation of H
Approximately 5 to 10% of individuals with HIV are coinfected with hepatitis B virus (HBV) but this may be as high as 20% in parts of Africa.

The natural history of HBV infection AV-951 is altered in HIV-HBV coinfection, and liver-related mortality is significantly higher in HIV-HBV-coinfected individuals than in those infected with either HIV or HBV alone (28). How HIV infection accelerates the progression of HBV-related liver disease is not known but is likely to be multifactorial. HIV-HBV coinfection is associated with higher levels of HBV DNA and lower alanine aminotransferase (ALT) levels (11). The lower ALT levels are indicative of less hepatocyte destruction, possibly due to a depressed HBV-specific T-cell response (9), suggesting that other factors may be involved in driving liver disease progression. HBV is a noncytopathic virus that directly infects hepatocytes. Hepatitis B surface antigen (HBsAg), the viral envelope, comprises large (L), medium (M), and small (S) HBsAg.