Mo2018 Cytokeratin 19 Staining Is a Novel, Predictive Biomarker for Extra-Hepatic Metastasis in Hepatocellular Carcinoma

3-methyladenine(3-MA).Results In vivo: Many vacuoles in the mucosal epithelial cells surrounding the ulcers were observed since 3h after IM administration.TEM demonstrated many lipid-containing autophagosomes in the epithelial cells, as well as autophagy of lipid droplets (lipophagy).Immunoelectron microscopy showed them to be LC3-positive.Immunostaining(IHC) showed a significant increase in the numbers of LC3-and cathepsin-positive cells, but a small number of autolysosomes.In vitro: Following IM administration, GADD153 expression was observed by WB.IHC showed an increase in the number of positive cells over time, confirming ER stress.WB and IHC revealed that IM administration resulted in reduced expression of p-mTOR and increased expression of LC3-II, confirming increased autophagy.Moreover, the administration of 3-MA restored cell viability.However, neither WB nor IHC demonstrated any change in the expression of lamp2.Conclusion Autophagy appears to contribute to NSAID-induced small intestinal injury, as evidenced by increased levels of LC3-II in vivo and in vitro, and by inhibition of cell death by 3-MA.Regarding the underlying mechanism, IM-induced ER stress may cause accumulation of lipids in the ER as well as increased autophagy (lipophagy) required for their processing.However, IM inhibits lysosome enzyme synthesis, which in turn causes autophagosome accumulation without lipid processing, thereby probably increasing cell death and causing mucosal injury.