c-Met was found to be overexpressed in 73.2% of patients (186/254) and was significantly associated with overexpression of p-AKT (P = 0.0274), p-GSK3 (P = 0.0047) and Ki-67 (P = 0.0012). Interestingly, c-Met overexpression was significantly more common in the germinal center subtype of DLBCL, as compared with activated B cell subtype (P = 0.0002). Overexpression of c-Met in DLBCL was significantly associated with better survival (P = 0.0028) and remained significant in multivariate analysis with international prognostic index, thereby confirming c-Met as independent prognostic marker for better outcome in DLBCL. In vitro pharmacological c-Met inhibition and siRNA targeted against c-Met triggered caspase-dependent

apoptosis. These findings provide evidence that c-Met is an independent prognostic marker for better check details outcome in Middle Eastern DLBCL. This data also enlightens the fact that c-Met through AKT kinase has a critical role in carcinogenesis of DLBCL, and strongly suggest E7080 that targeting c-Met may have therapeutic value in treatment of DLBCL. Laboratory Investigation (2010) 90, 1346-1356; doi:10.1038/labinvest.2010.108; published online 7 June 2010″
“Morphine is a widely used analgesic in humans that is associated with multiple untoward effects, such as addiction and physical

dependence. In rodent models, morphine also induces locomotor activity. These effects www.selleck.cn/products/riociguat-bay-63-2521.html likely involve functionally selective mechanisms. Indeed, G protein-coupled receptor desensitization and adaptor protein beta-arrestin 2 (beta arr2) through its interaction with the m-opioid receptor regulates the analgesic but not the rewarding properties of morphine. However, beta arr2 is also required for morphine-induced locomotor activity in mice, but the exact cellular and molecular mechanisms that mediate this arrestin-dependent behavior are not understood. In this study, we show that beta arr2 is required for morphine-induced

locomotor activity in a dopamine D1 receptor (D1R)-dependent manner and that a beta arr2/phospho-ERK (beta arr2/pERK) signaling complex may mediate this behavior. Systemic administration of SL327, an MEK inhibitor, inhibits morphine-induced locomotion in wild-type mice in a dose-dependent manner. Acute morphine administration to mice promotes the formation of a beta arr2/pERK signaling complex. Morphine-induced locomotor activity and formation of the beta arr2/pERK signaling complex is blunted in D1R knockout (D1-KO) mice and is presumably independent of D2 dopamine receptors. However, D1Rs are not required for morphine-induced reward as D1-KO mice show the same conditioned place preference for morphine as do control mice. Taken together, these results suggest a potential role for a D1R-dependent beta arr2/pERK signaling complex in selectively mediating the locomotor-stimulating but not the rewarding properties of morphine.