Expression of multidrug resistance ABC transporters has been suggested as a functional marker and chemoprotective element in early human progenitor cell types. In this study we examined the expression and function of the key multidrug-ABC transporters, ABCB1, ABCC1 and ABCG2 in two human embryonic stem (HuES) cell lines. We detected a high level ABCG2 expression in the undifferentiated HuES cells, while the expression of this protein significantly decreased during early cell differentiation. ABCG2 in HuES cells provided protection against mitoxantrone toxicity, with a drug-stimulated overexpression of the transporter. No significant expression of ABCB1/ABCC1 was found either in the undifferentiated or partially differentiated HuES cells. Examination of the ABCG2 mRNA in HuES cells indicated the use of selected promoter sites and a truncated 3' untranslated region, suggesting a functionally distinct regulation of this transporter in undifferentiated stem cells. The selective expression of the ABCG2 multidrug transporter indicates that ABCG2 can be applied as a marker for undifferentiated HuES cells. Moreover, protection of embryonic stem cells against xenobiotics and endobiotics may depend on ABCG2 expression and regulation.

Although dogs' life expectancies are six to twelve times shorter than that of humans, the demographics (e. g., living conditions) of dogs can still change considerably with aging, similarly to humans. Despite the fact that the dog is a particularly good model for human healthspan, and the number of aged dogs in the population is growing in parallel with aged humans, there has been few previous attempts to describe demographic changes statistically. We utilized an on-line questionnaire to examine the link between the age and health of the dog, and owner and dog demographics in a cross-sectional Hungarian sample. Results from univariate analyses revealed that 20 of the 27 demographic variables measured differed significantly between six dog age groups. Our results revealed that pure breed dogs suffered from health problems at a younger age, and may die at an earlier age than mixed breeds. The oldest dog group (>12 years) consisted of fewer pure breeds than mixed breeds and the mixed breeds sample was on average older than the pure breed sample. Old dogs were classified more frequently as unhealthy, less often had a “normal” body condition score, and more often received medication and supplements. They were also more often male, neutered, suffered health problems (such as sensory, joint, and/or tooth problems), received less activity/interaction/training with the owner, and were more likely to have experienced one or more traumatic events. Surprisingly, the youngest age group contained more pure breeds, were more often fed raw meat, and had owners aged under 29 years, reflecting new trends among younger owners. The high prevalence of dogs that had experienced one or more traumatic events in their lifetime (over 40% of the sample), indicates that welfare and health could be improved by informing owners of the greatest risk factors of trauma, and providing interventions to reduce their impact. Experiencing multiple life events such as spending time in a shelter, changing owners, traumatic injury/prolonged disease/surgery, getting lost, and changes in family structure increased the likelihood that owners reported that their dogs currently show behavioral signs that they attribute to the previous trauma.

This is the first report to describe the tricellulin expression profile in normal and neoplastic human pancreas. Both normal and neoplastic pancreatic exocrine tissues expressed tricellulin, whereas no expression was seen in normal or neoplastic endocrine cells. Tricellulin expression in pancreatic ductal adenocarcinomas showed a significant negative correlation with the degree of differentiation.

Fibrolamellar hepatocellular carcinoma is a subtype of hepatocellular carcinoma occurring in non-cirrhotic liver at a younger age. The tumor expresses both hepatocellular and cholangiocellular markers. Previously, our group described overexpression of tight junction protein claudin 4 in cholangiocellular carcinoma in contrast to hepatocellular carcinoma. In the present study, tight junction protein expressions were studied to possibly clarify bipotential lineage of fibrolamellar hepatocellular carcinoma. Eleven fibrolamellar hepatocellular carcinomas were compared with seven "conventional" hepatocellular carcinomas, seven cholangiocellular carcinomas, and five normal liver samples. By immunohistochemistry, all fibrolamellar hepatocellular carcinomas were positive for HepPar1 and cytokeratins 7, 8, and 18, but negative for cytokeratin 19. Glypican-3 gave weak staining in two cases. Expression of claudin 1 was lower, while that of claudin 2 was higher in fibrolamellar hepatocellular carcinomas than in other tumors. Claudins 3, 4, and 7 were not detectable in fibrolamellar hepatocellular carcinomas as in the majority of "conventional" hepatocellular carcinomas, contrary to high expression observed in cholangiocellular carcinomas. Focal or diffuse claudin 5 expression was detected in nine of 11 fibrolamellar hepatocellular carcinomas contrary to other tumors. Tricellulin was significantly downregulated in all tumors compared with normal liver. Our findings showed claudins to exhibit specific expression patterns in fibrolamellar hepatocellular carcinomas not observed in other primary liver tumors, with unique claudin 5 expression and pattern features similar to common hepatocellular carcinoma, but different from cholangiocellular carcinoma. This is the first report describing the loss of tricellulin expression in human hepatic tumors.