BACKGROUND Emerging evidence suggests the involvement of Reelin in chemoresistance in various cancers. However, its function in cisplatin (DDP) sensitivity of non-small cell lung cancer (NSCLC) needs to be investigated. MATERIAL AND METHODS Reelin expression in cisplatin-sensitive A549 cells and cisplatin-resistant NSCLC (A549/DDP) cells was analyzed by western blot analysis. qRT-PCR, western blotting, immunofluorescence, CCK-8 assays, Annexin V/propidium iodide apoptosis assay, and Transwell migration assays were carried out to determine the function of Reelin on DDP resistance. RESULTS Reelin was markedly increased in A549/DDP cells relative to A549 cells. Knockdown of Reelin enhanced DDP chemosensitivity of A549/DDP cells, whereas overexpression of Reelin enhanced DDP resistance of A549, H1299, and H460 cells. Reelin induced DDP resistance in NSCLC cells via facilitating epithelial-mesenchymal transition (EMT). Furthermore, Reelin modulated p38/GSK3ß signal transduction and promoted Snail (EMT-associated transcription factor) expression. Suppression of p38/Snail reversed Reelin-induced EMT and resistance of NSCLC cells to DDP. CONCLUSIONS These data indicated that Reelin induces DDP resistance of NSCLC by regulation of the p38/GSK3ß/Snail/EMT signaling pathway and provide evidence that Reelin suppression can be an effective strategy to suppress DDP resistance in NSCLC.

BACKGROUND Non-small cell lung carcinoma (NSCLC) mainly includes lung squamous cell carcinoma and adenocarcinoma. This study aimed to investigate the difference between the expression of Cbl-b in lung squamous cell carcinoma and adenocarcinoma. MATERIAL AND METHODS The clinical features and survival data of NSCLC patients and Cbl-b mRNA (FPKM) were obtained from the TCGA database. Then, lung squamous cell carcinoma and adenocarcinoma cell lines were transfected with lentivirus-mediated RNA interference vector to knockdown the expression of Cbl-b. Next, a Transwell assay was performed to study the effect of Cbl-b shRNA on migration and invasion of lung squamous cell carcinoma and adenocarcinoma cells. Finally, Western blot analysis was performed to measure the expressions of PI3K, p-PI3K, AKT, p-AKT, ERK1/2, p-ERK1/2, GSK3β, p-GSK3β, mTOR, and p-mTOR protein in lung adenocarcinoma and squamous cell carcinoma cells. RESULTS The correlation of Cbl-b expression and OS was different between NSCLC adenocarcinoma and squamous carcinoma. After transfection, the expression of Cbl-b was inhibited in A549, H1975, and SW900 cells. Cbl-b shRNA promoted the migration and invasion of lung adenocarcinoma A549 and H1975 cells, but it inhibited the invasion of lung squamous cell carcinoma SW900 cells. In addition, Cbl-b regulated the expression of PI3K and ERK1/2-GSK3β pathway proteins in A549 and SW900 cells. CONCLUSIONS The OS of Cbl-b mRNA low expression in lung adenocarcinoma and squamous cell carcinoma was different. The difference in signal pathways may be one of the reasons for the difference in the correlation between Cbl-b expression and the survival rate of these 2 pathological types of lung cancer.

BACKGROUND Because such data are scarce in northern China, the purpose of this study was to determine trends in diverticulosis over the past 5 years. MATERIAL AND METHODS A total of 26 463 patients (27 558 examinations, including 1095 repeated colonoscopies) performed between January 2011 and December 2015 were reviewed respectively. The distributions of diverticulosis were recorded, which were classified as right-sided, left-sided, and bilateral type. The trends in diverticulosis were analyzed in terms of aging and yearly increase. Additionally, associations of the occurrence of diverticulosis with age (≤39, 40-59, and ≥60 years) and sex were determined using a logistic regression model. RESULTS We identified 1045 patients with colonic diverticulosis, with an overall prevalence of 3.8% (1045/27 558). A preponderance of right-sided diverticulosis was demonstrated, accounting for 72.9% (693/951) of included subjects. The proportion of colonic diverticulosis increased significantly (P<0.001 for trend), from 2.78% (112/4028) in 2011 to 4.98% (309/6208) in 2015. The proportion of patients of all age groups with diverticulosis increased significantly (P<0.001 for trend) in correlation with yearly increase. There was a greater proportion of diverticulosis, regardless of the distribution, in patients aged ³60 than in younger age groups (P<0.001 for trend). Multivariate analysis showed older age and male sex (P<0.001) were independent risk factor for diverticulosis. CONCLUSIONS Colonic diverticulosis has been increasing in northern China, where rapid aging is ongoing.

BACKGROUND The established clinical criteria for gastric cancer prognosis are insufficient due to molecular heterogeneity. Therefore, constructing a robust prognostic model is essential to predict gastric cancer patient survival. MATERIAL AND METHODS A comprehensive method, which combined weighted gene co-expression network analysis (WGCNA) with elastic-net Cox regression, was utilized to identify prognostic long non-coding RNAs (lncRNAs) from Gene Expression Omnibus database for overall survival (OS) prediction. Methods using WGCNA or elastic-net Cox regression alone were treated as "contrast" methods. The univariate and multivariate Cox regression was used to identify independent prognostic clinical factors. We performed 3-year and 5-year area under the curve (AUC) of the time-dependent receiver operating characteristic comparison of 3 different methods in gene and clinical-gene models to explore the prediction ability of the comprehensive method. The optimal model identified in the training set were validated in the validation set. Biological information analysis for the optimal model was also explored. RESULTS The clinical-gene model containing 13 co-expression lncRNAs identified by the comprehensive method and 3 clinical factors including molecular subtype, recurrence status and operation type, was the found to be the optimal model in the study, with 0.832 and 0.830 for the 3-year and 5-year AUC in the training set, and 0.764 and 0.778 in the validation set, respectively. Biological information analysis suggested that lipid metabolism played an important role in the occurrence and development of gastric cancer. CONCLUSIONS We constructed a novel prognostic model containing 13 co-expression lncRNAs and 3 clinical factors for gastric cancer patients.

BACKGROUND Aberrant DNA methylation is an important biological regulatory mechanism in malignant tumors. However, it remains underutilized for establishing prognostic models for triple-negative breast cancer (TNBC). MATERIAL AND METHODS Methylation data and expression data downloaded from The Cancer Genome Atlas (TCGA) were used to identify differentially methylated sites (DMSs). The prognosis-related DMSs were selected by univariate Cox regression analysis. Functional enrichment was analyzed using DAVID. A protein-protein interaction (PPI) network was constructed using STRING. Finally, a methylation-based prognostic signature was constructed using LASSO method and further validated in 2 validation cohorts. RESULTS Firstly, we identified 743 DMSs corresponding to 332 genes, including 357 hypermethylated sites and 386 hypomethylated sites. Furthermore, we selected 103 prognosis-related DMSs by univariate Cox regression. Using a LASSO algorithm, we established a 5-DMSs prognostic signature in TCGA-TNBC cohort, which could classify TNBC patients with significant survival difference (log-rank p=4.97E-03). Patients in the high-risk group had shorter overall survival than patients in the low-risk group. The excellent performance was validated in GSE78754 (HR=2.42, 95%CI: 1.27-4.59, log-rank P=0.0055). Moreover, for disease-free survival, the prognostic performance was verified in GSE141441 (HR=2.09, 95%CI: 1.28-3.44, log-rank P=0.0027). Multivariate Cox regression analysis indicated that the 5-DMSs signature could serve as an independent risk factor. CONCLUSIONS We constructed a 5-DMSs signature with excellent performance for the prediction of disease-free survival and overall survival, providing a guide for clinicians in directing personalized therapeutic regimen selection of TNBC patients.

BACKGROUND The aim of this study was to evaluate the effects of 3-tetrazolyl methyl-3-hydroxy-oxindole hybrid (THOH) on cell proliferation, apoptosis, and the cell cycle in human lung cancer cell lines SK-LU-1, A549, and A-427, and the normal lung fibroblast cell line, MRC-5, in vitro. MATERIAL AND METHODS Human lung adenocarcinoma cells SK-LU-1, A549, and A-427, and the normal lung fibroblast cells, MRC-5 were cultured and treated with increasing concentrations of 10 mM of a stock solution of THOH in dimethyl sulfoxide (DMSO). An MTT cell proliferation assay was used. Cell apoptosis and the cell cycle were studied using fluorescence-activated cell sorting (FACs) with fluorescein isothiocyanate (FITC), Annexin-V, propidium iodide (PI), and nuclear staining with 4',6-diamidino-2-phenylindole (DAPI). DNA damage was measured using the comet (single-cell gel electrophoresis) assay. Cell migration was evaluated using a wound healing assay, and Western blotting was used to measure protein expression levels. RESULTS Treatment of SK-LU-1 cells with THOH inhibited cell migration. Treatment of lung cancer cells, SK-LU-1, A549, and A-427, with THOH inhibited cell proliferation, with the most marked inhibition found in the SK-LU-1 lung cancer cells (IC50, 12 µM). Treatment of lung cancer cells, SK-LU-1, A549, and A-427, with THOH increased cell apoptosis, resulted in G2/M cell cycle arrest, and inhibited both the platelet-derived growth factor D (PDGF-D) and MEK/ERK signaling pathways. CONCLUSIONS Treatment of adenocarcinoma cells, SK-LU-1, A549, and A-427, with THOH inhibited cell proliferation, apoptosis, and resulted in G2/M cell cycle arrest by targeting PDGF-D and the MEK/ERK signaling pathway.