Xuzhou Medical College

About: Xuzhou Medical College is a education organization based out in Xuzhou, China. It is known for research contribution in the topics: Cancer & Cell growth. The organization has 12721 authors who have published 7802 publications receiving 102970 citations.

Ischemia/Reperfusion-Induced CHOP Expression Promotes Apoptosis and Impairs Renal Function Recovery: The Role of Acidosis and GPR4

Abstract: Endoplasmic reticulum (ER) stress-induced apoptosis is implicated in a wide range of diseases, including ischemia/reperfusion injury (IRI). As a common feature of ER stress, the role of CCAT/enhancer-binding protein homologous protein (CHOP) in renal IRI has not been thoroughly investigated. We found that IR led to renal CHOP expression, accompanied by apoptosis induction. Renal IRI was markedly alleviated in CHOP−/− mice. Observations from bone marrow chimeras showed that this was based on CHOP inactivation in renal parenchymal cells rather than inflammatory cells. In vivo and in vitro studies demonstrated that IRI induced CHOP expression in both endothelial and epithelial cells, which was responsible for apoptosis induction. These results were reinforced by the observation that CHOP knockout led to improvement of the postischemic microcirculatory recovery. In vitro studies revealed hypoxia-induced acidosis to be a major inducer of CHOP in endothelial cells, and neutralizing acidosis not only diminished CHOP protein, but also reduced apoptosis. Finally, knockdown of a proton-sensing G protein-coupled receptor GPR4 markedly reduced CHOP expression and endothelial cell apoptosis after hypoxia exposure. These results highlight the importance of hypoxia-acidosis in ER stress signaling regulation in ischemic kidneys and suggest that GPR4 inhibitors or agents targeting CHOP expression may be promising in the treatment of renal IRI.

Impact of smoking on efficacy of PD-1/PD-L1 inhibitors in non-small cell lung cancer patients: a meta-analysis

Abstract: Background Smoking status is associated with the efficacy of non-small cell lung cancer (NSCLC) treatment. Latest clinical trials have depicted the difference in the effectiveness of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors in smokers and nonsmokers. However, the lack of statistical power in these trials prevented a final conclusion. The authors postulated that the efficacy of PD-1/PD-L1 inhibitors correlated with smoking status. Materials and methods Clinical trials evaluating PD-1 inhibitors versus chemotherapies in smokers and nonsmokers were included. The hazard ratios (HRs) and 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) were used. Results A total of 1,981 patients from three Phase III randomized controlled trials (RCTs) were included. PD-1/PD-L1 inhibitors significantly prolonged the OS (HR, 0.69; 95% CI, 0.60-0.78) and PFS (HR, 0.55; 95% CI, 0.43-0.67; P = 0.027) in smoking patients versus chemotherapy. However, among nonsmoking patients, no significant improved OS and PFS were observed compared with chemotherapy. Conclusion PD-1 inhibitors were more efficacious in smoking NSCLC patients compared with chemotherapy. No better survival of nonsmoking patients was observed in the treatment of PD-1 inhibitors than chemotherapy. Difference in the efficacy of PD-1 treatment should be taken into consideration in the future guidelines and clinical practice.