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Abstract: The objective of this study was to evaluate the expression of epithelial membrane protein-2 (EMP2) and its clinicopathological associations in patients with gallbladder carcinoma (GBC). A retrospective population-based cohort study was performed based on a biobank from 1986 to 2005. Biopsies of 164 GBC patients without initial distant metastasis were collected during surgical intervention. Immunoexpressions of EMP2 and Ki-67 were analyzed and the outcomes were correlated with clinicopathological features and patient survival. Results indicated that loss of EMP2 expression (50%) was correlated with female patients (p = 0.037), advanced primary tumor (p < 0.017), vascular (p < 0.001), and perineural (p < 0.027) invasions and high Ki-67 labeling index (p < 0.001).In multivariate analysis, loss of EMP2 expression, high Ki-67 labeling index, and age emerged as independent prognosticators for worse disease-specific (p < 0.001; p < 0.001; and p = 0.001, respectively) and disease-free (p = 0.002; p = 0.002; and p = 0.008, respectively) survivals, following by the American Joint Committee on Cancer stage (p < 0.001; p < 0.001; and p < 0.001, respectively). Collectively, loss of EMP2 expression is common and associated with adverse prognosticators and might confer tumor aggressiveness through hampering its interaction with specific membrane protein(s) and antiproliferative activity, and perhaps the downstream signal transduction pathway(s). [Copyright &y& Elsevier]

Objective: To elucidate the relationship of oxidative stress and specificity protein 1 (Sp1) in the process of epithelial-to-mesenchymal transdifferentiation (EMT) and also to investigate the molecular mechanism of protective effect of probucol on the pathogenesis of diabetic kidney disease (DKD). Methods: Thirty male Sprague-Dawley (SD) rats were randomly divided into control group, diabetic group, and diabetic group under probucol therapy ( n = 10 per group). The biochemical indicators including 24-h urinary total protein (24-h UTP) excretion, blood glucose (BG), lipids [triglycerides (TGs), total cholesterol (TC)], serum creatinine (Scr), creatinine clearance rate (Ccr), kidney tissue malondialdehyde (MDA) level, and glutathione peroxidase (GSH-Px) activity were assessed in all groups. The renal pathological changes were evaluated by hematoxylin and eosin (HE) and Masson staining. The protein expression of Sp1, α-smooth muscle actin ( α-SMA), and E-cadherin was also measured and analyzed by immunohistochemistry and Western blotting. Results: Compared with the control group, the BG, TC, Scr, 24-h UTP, and MDA level of renal tissue increased significantly and the Ccr reduced in the rats of diabetic group (all p < 0.01). The pathological scores and the expression of Sp1 and α-SMA in renal tissue were up-regulated ( p < 0.01) and the expression of E-cadherin was down-regulated significantly in the diabetic animals ( p < 0.01). In the diabetic animals treated with probucol, the renal injuries were alleviated ( p < 0.01). Conclusions: Oxidative stress may play an important role in the EMT process of tubular epithelial cells. Probucol could ameliorate renal disease progression in this model of diabetic nephropathy, which might be due to an antioxidant action, down-regulation of Sp1 protein expression, and inhibition of renal tubular EMT. [ABSTRACT FROM AUTHOR]