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Yes-associated protein (YAP) positivity indicates a poor prognosis in gastric cancer. Transcriptional co-activator with a PDZ-binding domain (TAZ), a YAP paralog, is highly expressed in gastric signet ring cell carcinoma. Verteporfin (VP), a clinical photosensitizer, was recently shown to inhibit YAP/TAZ. In the present study, the therapeutic potential of VP treatment was explored using two gastric cancer cell lines: MKN-45 (TAZ-dominant) and MKN-74 (YAP-dominant). Cell proliferation was evaluated by MTS assay. Vascular mimicry was evaluated by the tube formation assay. Gene and protein expression levels of YAP/TAZ downstream effectors [such as Survivin, Cysteine-rich angiogenic inducer 61 (CYR61), and connective tissue growth factor (CTGF)] were measured. YAP or TAZ localization was evaluated by immunofluorescence. Cell death was assessed by immunofluorescent staining of Annexin V. YAP and TAZ expression were knocked down by small interfering RNA. The current results demonstrate that MKN-45, a poorly differentiated TAZ-dominant gastric cancer cell line, was more sensitive to VP than MKN-74, a moderately differentiated YAP-dominant gastric cancer cell line. VP changed the localization of YAP/TAZ, promoted its degradation and significantly decreased the protein level of Survivin in both cell lines. Cell death was induced by VP treatment in a dose-dependent manner. Vascular mimicry was inhibited in both cell lines. Proliferation in both cell lines decreased in response to YAP/TAZ knockdown. The present study indicated that VP has potential as a therapeutic agent in YAP- and TAZ-dominant gastric cancers due to its ability to suppress the anti-apoptotic protein Survivin via inhibition of YAP and TAZ. [ABSTRACT FROM AUTHOR]

A case study of a 56-year-old Japanese man who had been taking 30 mg lansoprazole once daily for reflux oesophagitis, is presented. Topics include physical examination revealed diffuse swelling of the hands and fingers, as well as nail fold bleeding in dermoscopic observation; and Bosentan is an endothelin receptor antagonist that has been approved for treatment of systemic sclerosis (SSc)- associated pulmonary hypertension and digital ulcers.

Non-alcoholic steatohepatitis is characterized by hepatic fat accumulation, inflammation and varying degrees of fibrosis. The dipeptidyl peptidase-IV enzyme is important in glucose metabolism, as well as lipid accumulation, extracellular matrix metabolism and immune stimulation. Furthermore, the enzyme activity of dipeptidyl peptidase-IV is known to be increased in non-alcoholic steatohepatitis. Therefore, dipeptidyl peptidase-IV inhibitors are potential therapeutic agents for non-alcoholic steatohepatitis. The present study assessed the therapeutic effects of sitagliptin, a dipeptidyl peptidase-IV inhibitor, on non-alcoholic steatohepatitis using fatty liver Shionogi-ob/ob male mice. Sitagliptin (2 mg/kg/day; n=10) or placebo (control; n=10) was orally administered to fatty liver Shionogi-ob/ob mice for 12 weeks, and hepatic steatosis, fibrosis, inflammation and oxidative stress were assessed in comparison with the controls. Sitagliptin administration reduced body weight and blood glucose levels, and improved hepatic fibrosis. It also inhibited the gene expression levels of fatty acid synthase, transforming growth factor-β1, tissue inhibitor of metalloproteinases-1, procollagen-type 1, tumor necrosis factor-α, monocyte chemoattractant protein-1 and enhanced peroxisome proliferator activated receptor-α. Furthermore, a marked attenuation of hepatic stellate cell activation and Kupffer cells was observed in the sitagliptin group. A decrease in oxidative stress and apoptosis was also observed. Sitagliptin attenuated the progression of hepatic fibrosis by improving lipid metabolism, inflammation and oxidative stress in non-alcoholic steatohepatitis. [ABSTRACT FROM AUTHOR]