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Cytokine-induced killer (CIK) cells were isolated and proliferation from human peripheral blood and cultured in appropriate growth medium. The biological characteristics of CIK cells were further determined by the characterization of surface markers by flow cytometry. CIK cells inhibited the proliferation of human lung adenocarcinoma NCL-H157 cells. Vascular endothelial growth factor (VEGF) expression was down-regulated in CIK cells co-cultured with NCL-H157 cells by western blotting analysis. Furthermore, in comparison with cells untreated by CIK, the NCL-H157 had a lower proliferation capacity. We proposed that the pharmacological mechanisms of NCL-H157 promoted by CIK can be estimated possibly with different biological significance that can be ascribed to down-regulated VEGF expression in vitro. The results suggest that the VEGF pathway guides developmental inhibiting of NCL-H157, and we speculate that the function of VEGF pathways is to guide NCL-H157 to inhibition by abundant CIK. [ABSTRACT FROM AUTHOR]

miR-410 acts as an oncogene or tumor suppressor gene in some malignancies. However, its role in NSCLC is still unknown. In this study, we showed that the expression of miR-410 was up-regulated in both human NSCLC tissues and cells. Overexpression of miR-410 promoted cell proliferation, migration, and invasion of NSCLC. In addition, bromodomain-containing protein 7 (BRD7) was a direct target of miR-410. MiR-410-mediated downregulation of BRD7 led to increase Akt phosphorylation. Inhibition of Akt phosphorylation can rescue the effect of miR-410 on NSCLC cell. The expression of BRD7 was downregulated in NSCLC and was inversely expressed with miR-410 in NSCLC. Our data provided new knowledge regarding the role of miR-410 in the lung cancer progression. [ABSTRACT FROM AUTHOR]

Background Adenocarcinoma, the most common form of lung cancer, is one of main human malignant tumors. In this paper, we focus on the effect of antitumor activity of cytokine-induced killer ( CIK) cells on human lung adenocarcinoma cell line A549. Methods CIK cells were obtained by inducing peripheral blood mononuclear cells with recombinant human (rh) interferon-gamma, monoclonal anti- CD3 antibody, rh interleukin (IL)-1alpha, and rhIL-2, which were added into the culture. A549 cell viability of CIK cells was determined using MTS assay. Flow cytometry ( FCM) experiments were performed to detect cell cycle changes. The expression of P27 in A549 cells treated by CIK cells was evaluated by Western blot. Result The percentage of CD3+ CD16+ CD56+ T cells in a representative peripheral blood mononucleated cell sample was 33.7 ± 1.3%. CIK cells, in dose and time dependent manners, inhibited the proliferation of A549. FCM demonstrated that A549 cells were accumulated in G2/M and G0/G1 phases when treated with CIK cells. FCM was used to analyze whether A549 cells treated with CIK cells induced apotosis or necrosis at 10:1 or 20:1. Compared to the control group, P27 was prominently upregulated in the CIK treated group. Conclusion We propose that the pharmacological mechanisms of A549 cells inhibited by CIK cells can be estimated to possibly elicit different biological significance, which, in part, can be ascribed to a different mass transport rate in vitro. [ABSTRACT FROM AUTHOR]

Tumor mutation burden (TMB) is an independent indicator used to select patients sensitive to immunotherapy. The present study aimed to investigate the clinicopathological and molecular characteristics of patients with hypermutant lung cancer to identify an economical, simple and complementary method for predicting TMB and immunotherapy responses. In total, 1,000 patients with lung cancer were randomly selected, and their samples were submitted to next-generation sequencing, with their TMB status reviewed. The threshold of hypermutation was set to 17.24 mutations (muts)/Mb. The proportion of smokers was higher in the hypermutant cohort (n=67) compared with in the non-hypermutant cohort (n=933; 85.1 vs. 46.6%; P<0.0001). Compared with in the non-hypermutant cohort, the proportion of squamous cell carcinoma cases and small cell lung cancer cases was higher in the hypermutant cohort (22.4 vs. 13.1% and 6.0 vs. 2.6%, respectively). In addition, compared with in the non-hypermutant cohort, mutations in the low-density lipoprotein receptor-related protein 1B were more frequently observed in the hypermutant cohort (67.2 vs. 14.3%; P<0.0001). A similar trend was obtained for all genes tested, except for the EGFR gene. Furthermore, in the hypermutant cohort, the prevalence of microsatellite instability was extremely high (9.0%). The mutation frequency in DNA damage response (DDR) genes was notably higher in the hypermutant cohort, where several DDR-associated genes were enriched, compared with in the non-hypermutant cohort. The enrichment analysis revealed a strong association between mutations in Notch signaling and high TMB. To the best of our knowledge, the present study is the first to comprehensively investigate the clinical and genetic characteristics of patients with hypermutant lung cancer in a Chinese population. The results of the current study suggested that hypermutant lung cancer exerted distinctive clinical and genetic features, which may be used as complementary indicators for screening patients sensitive to immunotherapy. [ABSTRACT FROM AUTHOR]