PMO-135 Zinc finger e-box binding homeobox 1 (ZEB1) induces epithelial to mesenchymal transition (EMT) and promotes tumour progression in hepatocellular carcinoma (HCC): Abstract PMO-135 Figure 1

Abstract

Introduction There has been increasing interest in the possibility of using spontaneous canine hepatic disease as a model for those in human beings.1 Dogs with congenital portosystemic shunts (CPSS) have hypoplasia of the liver and intrahepatic portal veins. While the condition is extremely rare in people, it is more common in dogs. Surgical CPSS attenuation results in liver growth and development of the intrahepatic portal vasculature, associated with clinical improvement. 2 The precise mechanism of this hepatic response is unknown; we hypothesised that it is due to hepatic regeneration and angiogenesis. The study aimed to measure the mRNA expression of growth factors and receptors involved in liver regeneration and angiogenesis in liver biopsies from dogs with CPSS before and after partial attenuation. Methods Dogs treated for CPSS were prospectively recruited to the study and liver biopsy samples were collected and placed in RNAlater. The expression of nine genes related to liver regeneration and angiogenesis were evaluated using quantitative polymerase chain reaction (qPCR). Differences in gene expression were assessed using independent or paired T tests. Significance was set at the 5% level (p¼0.05). Results Liver biopsies were collected from 49 CPSS dogs to seven control dogs. 24 dogs tolerated complete attenuation of their CPSS and 25 tolerated partial attenuation. A second surgery was performed in all partial attenuation dogs to achieve complete attenuation and a follow-up biopsy was taken. HGF mRNA expression was significantly decreased in CPSS dogs compared with controls. There were significant increases in mRNA expression of HGF, MAT2a andVEGFR2 following partial CPSS attenuation. In addition, dogs that could tolerate complete attenuation had significantly greater MAT2a, VEGFR2 and TGFbR2 mRNA expression. Conclusion The results of this study indicate that the liver regeneration and angiogenesis are involved in the hepatic response to surgery in dogs with CPSS. This suggests that canine CPSS could be a useful, naturally occurring model of liver regeneration.Competing interests None declared. Introduction Cellular transplantation is an alternative to liver transplantation, however provision of primary human hepatocytes is limited. Human embryonic stem cell-derived hepatocyte-like cells (ES-HLCs) represent a renewable source of functional hepatocytes. However, engraftment levels of these cells in the liver is low. The mechanisms regulating interactions between transplanted hepatocytes and the host liver remain unclear. Elucidation of these mechanisms may provide a means to enhance recruitment and engraftment in vivo. Methods ES-HLCs were generated using our previously published protocol.1 Functionality of cells was demonstrated biochemically and by transplantation into immunocompromised fumaryl acetoacetate hydrolase knock-out (FAH À/À ) mice. Microarray analysis of adhesion molecule expression was undertaken and compared with primary human hepatocytes. Adhesion molecule expression of ESHLCs was assesse...

miR-128 modulates chemosensitivity and invasion of prostate cancer cells through targeting ZEB1

“…Data also indicated that it emerged as a key player in cancer progression. Aberrant expression of ZEB1 in endometrial cancers, pancreatic head cancer and hepatocellular carcinoma had been associated with aggressive disease, poor differentiation, development of metastasis and poor clinical prognosis (12)(13)(14)(15). Previous study had showed that ZEB1 was regulated by miR-200 family miRNAs in several tumors, yet expression of ZEB1 by miRNAs in PCa was rarely reported (16)(17)(18).…”