BackgroundImmune system evasion, distance tumor metastases, and increased cell proliferation are the main reasons for the progression of non-small cell lung cancer (NSCLC) and the death of NSCLC patients. Dysregulation of circular RNAs plays a critical role in the progression of NSCLC; therefore, further understanding the biological mechanisms of abnormally expressed circRNAs is critical to discovering novel, promising therapeutic targets for NSCLC treatment.MethodsThe expression of circular RNA fibroblast growth factor receptor 1 (circFGFR1) in NSCLC tissues, paired nontumor tissues, and cell lines was detected by RT-qPCR. The role of circFGFR1 in NSCLC progression was assessed both in vitro by CCK-8, clonal formation, wound healing, and Matrigel Transwell assays and in vivo by a subcutaneous tumor mouse assay. In vivo circRNA precipitation, RNA immunoprecipitation, and luciferase reporter assays were performed to explore the interaction between circFGFR1 and miR-381-3p.ResultsHere, we report that circFGFR1 is upregulated in NSCLC tissues, and circFGFR1 expression is associated with deleterious clinicopathological characteristics and poor prognoses for NSCLC patients. Forced circFGFR1 expression promoted the migration, invasion, proliferation, and immune evasion of NSCLC cells. Mechanistically, circFGFR1 could directly interact with miR-381-3p and subsequently act as a miRNA sponge to upregulate the expression of the miR-381-3p target gene C-X-C motif chemokine receptor 4 (CXCR4), which promoted NSCLC progression and resistance to anti-programmed cell death 1 (PD-1)- based therapy.ConclusionTaken together, our results suggest the critical role of circFGFR1 in the proliferation, migration, invasion, and immune evasion abilities of NSCLC cells and provide a new perspective on circRNAs during NSCLC progression.
Capparis spionosa L. is a traditional medicinal plant in China and central Asia. In this study, an experiment was designed to investigate the optimization of the extraction of anti-tumor polysaccharides from the fruit of Capparis spionosa L. (CSPS) by response surface methodology (RSM). Four independent variables (extraction temperature, extraction time, ratio of water to sample and extraction cycles) were explored. Meanwhile, the in vivo anti-tumor activity of CSPS was investigated. The results showed that the experimental data could be fitted to a second-order polynomial equation using multiple regression analysis. The optimum extraction conditions were as follows: extraction temperature 92 °C, extraction time 140 min, ratio of water to sample 26 mL/g, and three extraction cycle. Under these conditions, the yield of polysaccharides reached 13.01%, which was comparable to the predicted yield (12.94%, p > 0.05). This indicated that the model was adequate for the extraction process. Additionally, CSPS could prolong the survival time of H22 bearing mice in vivo. The anti-tumor activities of CSPS were dose-dependent.
In this study, an experiment was designed to optimize the synthesis of seleno-Capparis spionosa L. polysaccharide (Se-CSPS) by response surface methodology. Three independent variables (reaction time, reaction temperature and ratio of Na2SeO3 to CSPS) were tested. Furthermore, the thermal stability, particle size, shape and cytotoxic activity of Se-CSPS in vitro were investigated. The optimum reaction conditions were obtained shown as follows: reaction time 7.5 h, reaction temperature 71 °C, and ratio of Na2SeO3 to CSPS 0.9 g/g. Under these conditions, the Se content in Se-CSPS reached 5.547 mg/g, which was close to the predicted value (5.518 mg/g) by the model. The thermal stability, particle size and shape of Se-CSPS were significantly different from those of CSPS. Additionally, a MTT assay indicated that the Se-CSPS could inhibit the proliferation of human gastric cancer SGC-7901 cells in a dose-dependent manner.
Backgrounds: We performed this systematic review and meta-analysis to compare the efficacy of new-generation tyrosine kinase inhibitors (NG-TKIs; including dasatinib, nilotinib, bosutinib, radotinib, and ponatinib) versus imatinib for patients with newly diagnosed chronic myeloid leukemia (CML). Summary: We identified randomized controlled trials comparing the efficacy of NG-TKIs versus imatinib as the first-line treatment for CML patients by searching the PubMed, Cochrane library, and EMBASE databases. Two reviewers independently extracted data and assessed study quality. A meta-analysis was performed to calculate risk ratios and 95% CIs using a fixed-effects model.Our study included 10 trials. Overall, treatment with NG-TKIs significantly improved the major molecular response and MR4.5 at all time points, and early molecular response at 3 months. Importantly, overall survival (OS) was significantly higher with the NG-TKIs at 12 months. Besides, NG-TKI-treated patients showed a significantly lower CML-related death and progression to the accelerated phase/blast crisis. Key Messages: In first-line treatment, NG-TKIs are superior to imatinib regarding OS at 12 months, and because molecular response rates were higher with the NG-TKIs at all time points, the NG-TKIs favor treatment-free remission.
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