Interference of Notch 1 inhibits the proliferation and invasion of breast cancer cells: Involvement of the ß­catenin signaling pathway.

Breast cancer is one of the most common types of carcinoma in humans. The aim of the present study was to identify the role of Notch 1 in the proliferation and invasion of human breast cancer cells. Firstly, the levels of Notch 1 were determined by western blot analysis in breast cancer cell lines, and the results revealed that the expression levels of Notch 1 were markedly higher in MDA­MB­231 and MCF­7 cells, and lower in MCF­10A cells, compared with human mammary epithelial cells. An MTT assay was used to determine the viability of breast cancer cells. The optical density (OD)490 values were significantly decreased in Notch 1 short hairpin (sh)RNA­transfected MCF­7 and MDA­MB­231 cells, compared with the OD490 values in the negative control shRNA­transfected cells. The MCF­7 cells and MDA­MB­231 cells were also treated with increasing concentrations of MRK003, a Notch 1 inhibitor, for 24, 48 and 72 h, respectively. The inhibition rate was gradually increased in the MRK003­treated cells in a time­ and dose­dependent manner. The invasive ability of the cells was determined using a Transwell migration assay. The migration ability was significantly decreased in the Notch 1­transfected MCF­7 cells and MDA­MB­231 cells. The molecular mechanism was examined, and the knockdown of Notch 1 significantly decreased the expression levels of ß­catenin, matrix metalloproteinase (MMP)­2 and MMP­9, and was also correlated with the downregulation of ß­catenin in the nucleus. In conclusion, Notch 1 was key in the progression of breast cancer, and knocking down the expression of Notch 1 significantly suppressed the proliferation and invasion of breast cancer cells. This provides novel clues for cancer therapy in human breast cancer.

Risk of adverse events with bevacizumab addition to therapy in advanced non-small-cell lung cancer: a meta-analysis of randomized controlled trials.

BACKGROUND: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor ligand, has shown survival benefits in the treatment of many types of malignant tumors, including non-small-cell lung cancer (NSCLC). We conducted this systematic review and meta-analysis to investigate the risk of the most clinically relevant adverse events related to bevacizumab in advanced NSCLC. METHODS: Databases from PubMed, Web of Science, and Cochrane Library up to August 2015, were searched to identify relevant studies. We included prospective randomized controlled Phase II/III clinical trials that compared therapy with or without bevacizumab for advanced NSCLC. Summary relative risk (RR) and 95% confidence intervals were calculated using random effects or fixed effects according to the heterogeneity among included trials. RESULTS: A total of 3,745 patients from nine clinical trials were included in the meta-analysis. Summary RRs showed a statistically significant bevacizumab-associated increased risk in three of the adverse outcomes studied: proteinuria (RR =7.55), hypertension (RR =5.34), and hemorrhagic events (RR =2.61). No statistically significant differences were found for gastrointestinal perforation (P=0.60), arterial and venous thromboembolic events (P=0.35 and P=0.92, respectively), or fatal events (P=0.29). CONCLUSION: The addition of bevacizumab to therapy in advanced NSCLC did significantly increase the risk of proteinuria, hypertension, and hemorrhagic events but not arterial/venous thromboembolic events, gastrointestinal perforation, or fatal adverse events.

Therapeutic drug monitoring in voriconazole-associated hyponatremia.

Voriconazole is a second generation triazole antifungal agent and the first choice therapy for invasive aspergillosis (IA). Although voriconazole may be associated with many adverse events, hyponatremia has been rarely reported which potentially could result in death. Therapeutic drug monitoring (TDM) and individualization of therapy by measuring voriconazole plasma concentrations improved the efficacy and safety in patients. We report the effect of TDM to adjust voriconazole dosage in a voriconazole-related hyponatremia patient.