Zinc oxide (ZnO) nanoparticles can exhibit toxic effect on cells and tissues, which may be involved in the excessive generation of reactive oxygen species (ROS) and the consequent mitochondria-mediated apoptotic pathway. Nevertheless, the detailed mechanism remains unclear. In this study, we explored the effects of ZnO nanoparticles on the expressions of cytochrome c, ATP level, mitochondrial membrane potential, ROS, apoptosis, total antioxidant enzyme activities and apoptotic-related protein levels in murine photoreceptor cells as well as the changes of proteomic profiling. Moreover, we also performed the bioinformatics analysis for the differentially expressed proteins. Our results show that ZnO nanoparticles induce the release of cytochorme c, decrease the intracellular ATP level, collapse the mitochondrial membrane potential, elevate the ROS level, inhibit total antioxidant enzyme activities and increase the Bax and Caspase 3 levels whereas it decrease the Bcl-2 expression, leading to cell death. Proteomic analysis reveals the differentially expressed proteins are involved in cytochrome c oxidase activity and oxidative phosphorylation. Protein-protein interaction analysis confirms the differentially expressed proteins are closely associated with the clusters related to apoptotic signaling pathway and oxidative phosphorylation-associated proteins. Our results indicate that mitochondria play a central role in ZnO nanoparticle-induced murine photoreceptor cell death.

No abstract

Non-small cell lung cancer (NSCLC) patients harboring MET exon 14 skipping or high MET amplification display a high rate of response to MET inhibitors. However, MET fusions in NSCLC have rarely been revealed. In this report, a 63-year-old woman with lung adenocarcinoma (LADC), harboring EGFR exon 18 G719D and exon 21 L861Q mutations, received first-generation, EGFR-tyrosine kinase inhibitor (TKI) icotinib therapy. Next generation sequencing (NGS) results only displayed an EGFR T790M point mutation following icotinib resistance. Thus, the patient was treated with osimertinib and achieved a stable disease (SD). However, disease progressed after 15 months and a novel MET fusion (CUX1 exon14-MET exon15) in addition to EGFR G719D/L861Q mutations were simultaneously detected in a tissue biopsy sample. After more than nine months, the patient subsequently achieved a PR with the combination of icotinib and crizotinib. To our knowledge, this is the first case of LADC patient displaying the presence of EGFR double uncommon mutations and an acquired novel CUX1-MET fusion that has benefited from icotinib plus crizotinib treatment. Following nine months of PR with icotinib plus crizotinib, the patient, until the time of publication, is exhibiting stable disease. The results suggest that the CUX1-MET fusion may be sensitive to crizotinib, although previous reports indicated that some MET fusion cases did not respond to crizotinib. Given this disparity, distinguishing MET fusion partners when crizotinib is used in LADC treatment is also very important.

No abstract

Hepatocellular carcinoma (HCC) is an aggressive liver tumor that occurs due to chronic liver disease, and it has a high mortality rate and limited treatment options. Immune checkpoint inhibitors have been successfully introduced and used in cancer therapy, among which inhibitors of programmed death ligand-1 (PD-L1) and its receptor programmed death-1 (PD-1) are commonly administered for HCC as combination therapy, including combined anti-angiogenic and immunotherapy combination therapy. We report a case of a primary massive HCC patient with portal hepatic vein tumor thrombus who had a good response to atezolizumab in combination with bevacizumab, following progression of disease on combined immunotherapy with pembrolizumab and lenvatinib. This case demonstrates for the first time that an HCC patient who is resistant to anti-PD-1 antibody immunotherapy can benefit from anti-PD-L1 antibody immunotherapy, providing a potentially promising strategy for the treatment of HCC.