doi: 10.1038/emboj.2009.376; QNZ clinical trial Published online 24 December 2009″
“Hepatocellular carcinoma (HCC) occurs in a significant number of patients with hepatitis C virus (HCV) infection. HCV causes double-strand DNA breaks and enhances the mutation frequency of proto-oncogenes and tumor suppressors. However, the underlying mechanisms for these oncogenic events are still elusive. Here, we studied the role of c-Jun, signal transducer and activator of transcription 3 (STAT3), and nitric oxide (NO) in spontaneous and diethylnitrosamine (DEN)-initiated and/or phenobarbital (Pb)-promoted HCC development using HCV core transgenic

(Tg) mice. The viral core protein induces hepatocarcinogenesis induction as a tumor initiator under promotion by Pb treatment alone. Conditional knockout of c-jun and stat3 in hepatocytes achieves a nearly complete, additive effect on prevention of core-induced spontaneous HCC or core-enhanced

HCC incidence caused by DEN/Pb. Core protein induces hepatocyte proliferation and the expression of inflammatory cytokines (interleukin-6, tumor necrosis factor-alpha, interleukin-1) and inducible NO synthase (iNOS); the former is dependent on c-Jun and STAT3, and the latter on c-Jun. Oxidative DNA damage repair activity is impaired by the HCV core protein due to reduced DNA glycosylase activity for the excision of 8-oxo-2′-deoxyguanosine. This impairment is abrogated by iNOS inhibition or c-Jun deficiency, but aggravated by the NO donor or iNOS-inducing cytokines. The core protein also suppresses apoptosis mediated by Fas ligand because of c-Jun dependent Fas down-regulation. Conclusion: Linsitinib cell line These results indicate that the HCV core protein potentiates chemically induced HCC through c-Jun and STAT3 activation, which in turn, enhances cell

proliferation, suppresses apoptosis, and impairs oxidative DNA damage repair, leading to hepatocellular transformation. (HEPATOLOGY 2010;52:480-492)”
“This study examined the comparative efficacy of three interventions: a spouse-assisted coping skills training protocol for patients undergoing a multidisciplinary pain management programme (SA-MPMP), conventional Galunisertib research buy patient-oriented multidisciplinary pain management programme (P-MPMP) and standard medical care (SMC). Thirty-six chronic low back pain (CLBP) patients and their spouses were randomly assigned to one of the three conditions. The SA-MPMP condition consisted of seven, weekly, 2-h, group sessions of training in dyadic pain coping and couple skills, delivered by a clinical psychologist with support of a multidisciplinary team of specialists, to patients together with their spouses. P-MPMP consisted of the SA-MPMP training delivered to the patient only (i.e., no spouse participation and assistance). The SMC condition entailed continuation of routine treatment, entailing medical care only.