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MOTIVATION Next-generation sequencing technology enables an entirely new perspective for clinical research and will speed up personalized medicine. In contrast to microarray-based approaches, RNA-Seq analysis provides a much more comprehensive and unbiased view of gene expression. Although the perspective is clear and the long-term success of this new(More)
BACKGROUND & AIMS Human primary liver cancer is classified into biologically distinct subgroups based on cellular origin. Liver cancer stem cells (CSCs) have been recently described. We investigated the ability of distinct lineages of hepatic cells to become liver CSCs and the phenotypic and genetic heterogeneity of primary liver cancer. METHODS We(More)
Histone deacetylase 2 (HDAC2) is a chromatin modifier involved in epigenetic regulation of cell cycle, apoptosis, and differentiation that is upregulated commonly in human hepatocellular carcinoma (HCC). In this study, we show that specific targeting of this HDAC isoform is sufficient to inhibit HCC progression. siRNA-mediated silencing of HDAC inhibited(More)
BACKGROUND Liver cirrhosis develops as a terminal complication of chronic liver disease. The clinical course is determined by the underlying etiology and the accompanying risk factors, which are influenced by the geographic and cultural background. METHODS A total of 236 patients (159 men, 77 women, median age 57 [22-81] years) were included for(More)
Recent studies suggested that induced pluripotent stem cells (iPSCs) retain a residual donor cell gene expression, which may impact their capacity to differentiate into cell of origin. Here, we addressed a contribution of a lineage stage-specific donor cell memory in modulating the functional properties of iPSCs. iPSCs were generated from hepatic lineage(More)
Hepatocellular carcinoma is the most common and deadly cause of primary liver cancer. Although the incidence of hepatocellular carcinoma is highest in Asia and sub-Saharan Africa, the steadily increasing incidence in traditionally low-incidence regions such as northern Europe and the United States is a considerable public health problem.1 Despite(More)
Hepatocellular carcinoma ranks among the most common cancers worldwide. However, besides surgery, therapeutic strategies remain limited and a detailed analysis and characterization of the tumor biology will be essential in order to identify (novel) therapeutic targets [1]. With the development of sorafenib, a first step of successful targeting molecular(More)
Epigenomic changes such as aberrant hypermethylation and subsequent atypical gene silencing are characteristic features of human cancer. Here, we report a comprehensive characterization of epigenomic modulation caused by zebularine, an effective DNA methylation inhibitor, in human liver cancer. Using transcriptomic and epigenomic profiling, we identified a(More)
The two dominant models of carcinogenesis postulate stochastic (clonal evolution) or hierarchic organization of tumor (cancer stem cell model). According to the latter, at the germinal center of tumor evolution is a cancer stem cell (CSC) which, similar to normal adult stem cells, possesses the capacity of self-renewal and a differentiation potential. Over(More)
UNLABELLED Hepatocyte growth factor (HGF)/c-Met supports a pleiotrophic signal transduction pathway that controls stem cell homeostasis. Here, we directly addressed the role of c-Met in stem-cell-mediated liver regeneration by utilizing mice harboring c-met floxed alleles and Alb-Cre or Mx1-Cre transgenes. To activate oval cells, the hepatic stem cell (HSC)(More)