Finally, the lack of BLVRA overexpression cisplatin synthesis is associated with non-responsiveness to standard antiviral therapy. Nevertheless, larger prospective studies are needed to confirm our data. Funding Statement This study was supported by grant IGA MZ NT/13092-4/2012 from the Czech Ministry of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Wnt/��-catenin signaling pathway is a master regulator of cell fate and proliferation during embryonic development that plays a main role in the control of differentiation of embryonic and adult stem cells [1]. A key element of this pathway is ��-catenin, a multifunctional protein with important functions in intracellular adhesion, cell growth, survival and differentiation [2].

In the canonical Wnt/��-catenin pathway, nuclear ��-catenin is associated with T cell factors and lymphoid enhancer-binding factor1 leading to transcriptional activation of target genes that regulate many cellular processes, such as cell cycle control through c-myc or cellular differentiation [3]. Wnt/��-catenin is activated during mesenchymal stem cells (MSC) differentiation to osteoblasts [4] and inactivated during differentiation into adipocytes [5]. Some studies have also recently documented the inactivation of this pathway during differentiation of MSC into hepatocytes [6], [7], [8]. The aberrant activation of Wnt/��-catenin pathway in committed cells has been related with the development of several types of tumors, including hepatocellular carcinoma or hepatoblastoma [9], [10], [11].

The Wnt/��-catenin pathway could be implicated in the mechanisms that participate in the progression of functional differentiated hepatocytes into tumor cells [10], [11], [12], [13]. Stem cells and cancer are inextricable linked and emerging data suggest an association between alterations in stem cells and the generation of cancer stem cells (CSC) [14], [15], [16]. However, the mechanisms by which stem cells adopt CSC properties are presently unknown. In this context it is particularly interesting to study the consequences of the activation of Wnt/��-catenin pathway during MSC differentiation into hepatocytes and its relationship with the occurrence of a tumoral phenotype. This study examines the effects of Wnt/��-catenin activation during the differentiation of MSC into hepatocytes as well as on the association of Wnt/��-catenin pathway Entinostat activation with the generation of a tumoral phenotype. Results Immunophenotype of human mesenchymal stem cells before and after differentiation into hepatocytes Human MSCs specific markers were evaluated by flow cytometry before and after 21 days of treatment with two protocols (CM1 and CM2) of hepatocytes differentiation.