BackgroundThe study of cyclooxygenase-2 (COX-2) inhibitors is now mired in controversy. We performed a meta-analysis to assess the efficacy and safety profile of COX-2 inhibitors in patients with advanced non-small-cell lung cancer (NSCLC).Patients and methodsA literature search of PubMed, EMBASE, the Cochrane Central databases, and ClinicalTrials.gov, up until March 26, 2017, identified relevant randomized controlled trials. Data analysis was performed using Stata 12.0.ResultsSix eligible trials (1,794 patients) were selected from the 407 studies that were identified initially. A significant difference, favoring COX-2 inhibitors plus chemotherapy over chemotherapy alone, was observed in the overall response rate (relative risk [RR] =1.25, 95% confidence interval [CI]: 1.06–1.48). Further, we conducted two subgroup analyses according to the type of COX-2 inhibitors (celecoxib, rofecoxib, or apricoxib) and treatment line (first or second chemotherapy). The first-line treatment includes: NP (changchun red bean + cisplatin or carboplatin), GP (double fluorine cytidine + cisplatin or carboplatin), or TP (paclitaxel + cisplatin or carboplatin, docetaxel + cisplatin or carboplatin). The second-line treatment includes two internationally recognized compounds, one is docetaxel and the other is the pemetrexed, both of which are individually selected. In subgroup analysis, significantly increased overall response rate (ORR) results were found for rofecoxib plus chemotherapy (RR =1.56, 95% CI: 1.08–2.25) and COX-2 inhibitor given with first-line chemotherapy (RR =1.27, 95% CI: 1.07–1.50). However, there was no difference between COX-2 inhibitors plus chemotherapy and chemotherapy alone in overall survival (hazard ratio [HR] =1.04, 95% CI: 0.91–1.18), progression-free survival (HR =0.97, 95% CI: 0.86–1.10), and 1-year survival rate (RR =1.03, 95% CI: 0.89–1.20). Toxicity did not differ significantly between COX-2 inhibitors plus chemotherapy and chemotherapy alone with the exception of leukopenia (RR =1.21, 95% CI: 1.03–1.42), thrombocytopenia (RR =1.32, 95% CI: 1.04–1.67), and cardiovascular events (RR =2.39, 95% CI: 1.06–5.42). The results of the Egger’s test indicated no significant difference in primary outcomes.ConclusionCOX-2 inhibitors improved ORR of advanced NSCLC with chemotherapy, but had no effect on survival indices. Moreover, COX-2 inhibitors may lead to higher rates of hematologic toxicities and cardiovascular events.

Background SMC1A (Structural maintenance of chromosomes 1) is overexpressed in various cancers and acts as an oncogene which has been implicated in critical biological functions (cell-cycle checkpoints regulation, cell division, and DNA repair). However, the mechanism and role of SMC1A in breast cancer are poorly understood. Methods TCGA database was utilized to explore the expression of SMC1A and the relationship between SMC1A and FOXM1 and STMN1. Subsequently, short hairpin RNA (shRNA) targeting SMC1A was used to examined the biological functions of it in MDA-MB-231 and MDA-MB-468 cells. Finally, subcutaneous xenograft model to verify the roles of SMC1A in vivo. Results In the present study, we demonstrated that SMC1A was significantly increased in breast cancer (BC) via TCGA database. Then loss and gain of function studies revealed that SMC1A contributed to BC cell survival, apoptosis, and invasion. Interestingly, we found that SMC1A triggered the AKT/FOXM1 cascade, which promoted BC cell proliferation. Furthermore, overexpression of FOXM1 abolished the inhibition of cell growth induced by SMC1A silencing in vitro. Clinically, the expression of SMC1A in BC tumor tissues is positively correlated with the expression of FOXM1. Conclusion Taken together, our findings not only enhanced our understanding of molecular mechanisms of SMC1A in BC, but also might provide a novel target for the development of therapeutic strategies.