No abstract

Breast cancer (BC) is a highly heterogeneous disease and presents a great threat to female health worldwide. Chemotherapy is one of the predominant strategies for the treatment of BC; however, multidrug resistance (MDR) has seriously affected or hindered the effect of chemotherapy. Recently, a growing number of studies have indicated that lncRNAs play vital and varied roles in BC chemoresistance, including apoptosis, autophagy, DNA repair, cell cycle, drug efflux, epithelial-mesenchymal transition (EMT), epigenetic modification and the tumor microenvironment (TME). Although thousands of lncRNAs have been implicated in the chemoresistance of BC, a systematic review of their regulatory mechanisms remains to be performed. In this review, we systematically summarized the mechanisms of MDR and the functions of lncRNAs mediated in the chemoresistance of BC from the latest literature. These findings significantly enhance the current understanding of lncRNAs and suggest that they may be promising prognostic biomarkers for BC patients receiving chemotherapy, as well as therapeutic targets to prevent or reverse chemoresistance.

IntroductionFor patients with limited-stage small-cell lung cancer (LS-SCLC), effective treatment methods still remain a clinical challenge. The aim of this study is to evaluate the survival outcome of surgery plus chemotherapy vs. surgery alone in patients with LS-SCLC.MethodsLS-SCLC patients selected from the Surveillance, Epidemiology and End Results (SEER) database diagnosed between January 1, 2004, and December 31, 2015. Comparison of overall survival (OS) and cancer-specific survival (CSS) between two groups performed propensity score matching (PSM), inverse probability of treatment weight (IPTW), and overlap weighting analysis.ResultsOf the 477 LS-SCLC patients identified from the SEER database between 2004 and 2015, 262 (54.9%) received surgery-plus-chemotherapy treatment and the others received surgery-alone treatment. Univariate and multivariate analyses showed that treatment option (P< 0.001), tumor location (P= 0.02) and AJCC stage (P< 0.001) were independent prognostic predictors of OS in LS-SCLC patients. Median OS was 35 months in surgery-plus-chemotherapy group vs. 23 months in surgery-alone group. Survival analysis showed that surgery plus chemotherapy offered significantly improved OS as compared with surgery-alone treatment before and after IPTW, PSM and overlap weighting method (all P< 0.05). According to AJCC stage stratification, OS of the unmatched patients with stage I (P= 0.049) and II (P= 0.001) SCLC who received surgery-plus-chemotherapy treatment was significantly better than that of surgery-alone patients.ConclusionsThis cohort study showed that surgery plus chemotherapy was associated with longer survival time than surgery alone in LS-SCLC patients, especially in those with stage I and II SCLC. Further prospective studies are required to confirm our conclusions.

Human bone marrow-derived mesenchymal stem cells (hBMSCs) are promising candidates for stem cell therapy in clinical trials. Applications of hBMSCs in clinical therapy are limited by cellular senescence due to long-term ex vivo expansion. Metformin, an oral hypoglycemic drug for type 2 diabetes, has been shown to have antiaging effects. However, the mechanisms of metformin in antiaging treatment remain controversial. Here, we used D-galactose (D-gal) to establish an appropriate model of senescent hBMSCs to explore the antiaging effects of metformin. Following metformin treatment with a low concentration range, senescence phenotypes induced by D-gal significantly changed, including generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential (MMP), and cell cycle arrest. In contrast, no apparent change was found in unsenescent hBMSCs. Furthermore, the results show that activation of 5 ′ AMP-activated protein kinase (AMPK) by metformin enhances cell autophagy in senescent hBMSCs. These findings suggest that metformin exerts antiaging function within the low concentration range by enhancing autophagy and exhibits potential benefits for clinical stem cell therapy by ameliorating the ex vivo replicative senescence of hBMSCs.