No abstract

Our previous studies had revealed that the dysregulation of manganese superoxide dismutase (SOD2) expression was a frequent event in tongue squamous cell carcinoma (TSCC) and may be associated with enhanced metastatic potential. To further evaluate the mechanism of SOD2-mediated metastasis in TSCC, TSCC cell lines with different metastatic potential (i.e., the highly metastatic UM1 line and the UM2 line, which displays fewer metastases) were used. Compared to UM2 cells, UM1 cells exhibited significantly higher SOD2 activity and intracellular H2O2, higher protein levels of Snail, MMP-1 and pERK1/2, lower protein levels of E-cadtherin, and not difference of catalase activity. Upon knockdown of SOD2 by RNA interference, UM1 cells displayed significantly reduced migration and invasion abilities, reduced activities of SOD2, lower intracellular H2O2, decreased protein levels of Snail, MMP-1 and pERK1/2, and increased protein levels of E-cadtherin. Migration and invasion ability of UM2 and SOD2 shRNA-transfected UM1 cells were enhanced by H2O2 treatment and accompanied by increased protein levels of Snail, MMP-1 and pERK1/2, and decreased protein levels of E-cadtherin. Moreover the migration and invasion ability of UM1 cells were decreased after catalase treatment. Thus, we conclude that the SOD2-dependent production of H2O2 contributes to both the migration and invasion of TSCC via the Snail signaling pathway through increased Snail, MMP-1 and pERK1/2 protein levels, and the repression of the E-cadtherin protein.

Apatinib, regorafenib, and rilotumumab improved patient PFS and OS. When combined with chemotherapy, ramucirumab and rilotumumab had high efficacy but low tolerability, and bevacizumab had moderate efficacy and tolerability for PFS. Without chemotherapy, ramucirumab and regorafenib had relatively high therapeutic efficacy tolerability for PFS.

Studies examining the relationship between diabetes mellitus (DM) and the risk of gastric cancer incidence or gastric cancer mortality have produced inconsistent results. The purpose of this study was to evaluate the evidence regarding the relationship between DM and subsequent gastric cancer incidence or gastric cancer mortality risk on the basis of cohort studies. A systematic search of articles in PubMed, EmBase, the Cochrane Library, and reference lists was conducted to identify relevant literature. Twenty-two cohort studies reporting data on 8,559,861 participants were included in the study. Overall, participants with DM had little or no change in the risk of gastric cancer, or gastric cancer mortality. There was no evidence of difference in the RR for gastric cancer between men and women. Participants with DM had a non-significant trend towards an increased risk of gastric cancer mortality in men. There was no significant difference between men and women for this relationship. Finally, although subgroup analysis suggested DM was associated with a significant impact on gastric cancer incidence and gastric cancer mortality risk in several specific populations, a significance based on gender difference was not observed. In conclusion, DM might increase the risk of gastric cancer in men when the study used standard incidence/mortality ratio as effect estimate. Further, DM were associated with higher risk of gastric cancer mortality in men if the mean age at baseline less than 55.0 years, used RR or HR as effect estimate, the study adjusted smoking or not, and the study not adjusted alcohol drinking.

No abstract

SummaryIntestinal epithelial stem cell (IESC) fate is promoted by two major transcriptional regulators, the TCF4/β-catenin complex and ASCL2, which drive expression of IESC-specific factors, including Lgr5, Ephb2, and Rnf43. Canonical Wnt signaling via TCF4/β-catenin directly transactivates Ascl2, which in turn auto-regulates its own expression. Conversely, Let-7 microRNAs antagonize the IESC lineage by repressing specific mRNA targets. Here, we identify the zinc finger transcription factor PLAGL2 as a Let-7 target that regulates IESC fate. PLAGL2 drives an IESC expression signature, activates Wnt gene expression, and enhances a TCF/LEF reporter in intestinal organoids. In parallel, via cell-autonomous mechanisms, PLAGL2 is required for lineage clonal expansion and directly enhances expression of ASCL2. PLAGL2 also supports enteroid growth and survival in the context of Wnt ligand depletion. PLAGL2 expression is strongly associated with an IESC signature in colorectal cancer and may be responsible for contributing to the aberrant activation of an immature phenotype.

Background The brain is a common site for metastasis in non-small-cell lung cancer (NSCLC). This study was designed to evaluate the relationship between the mutational of the epidermal growth factor receptor (EGFR) and overall survival (OS) in NSCLC patients with brain metastases. Methods Searches were performed in PubMed, EmBase, and the Cochrane Library to identify studies evaluating the association of EGFR mutation with OS in NSCLC patients through September 2017. Results 4373 NSCLC patients with brain metastases in 18 studies were involved. Mutated EGFR associated with significantly improved OS compared with wild type. Subgroup analyses suggested that this relationship persisted in studies conducted in Eastern, with retrospective design, with sample size ≥500, mean age of patients ≥65.0 years, percentage male < 50.0%, percentage of patients receiving tyrosine kinase inhibitor ≥30.0%. Finally, although significant publication bias was observed using the Egger test, the results were not changed after adjustment using the trim and fill method. Conclusions This meta-analysis suggests that EGFR mutation is an important predictive factor linked to improved OS for NSCLC patients with brain metastases. It can serve as a useful index in the prognostic assessment of NSCLC patients with brain metastases. Electronic supplementary material The online version of this article (10.1186/s12885-019-5331-z) contains supplementary material, which is available to authorized users.

Tumor necrosis factor alpha-induced protein 8 (TNFAIP8) is an apoptosis regulator proven to have an important function in the proliferation, invasion, metastasis, and progression of malignancies. In this study, we investigated the clinical role of TNFAIP8 overexpression in endometrial cancer (EC) and determined the relationship of TNFAIP8 with the proliferative antigen Ki-67 and metastasis-related gene matrix metallopeptidase 9 (MMP9) in 225 tumor specimens by immunohistochemistry and western blot, in order to elucidate more information on the role of TNFAIP8 protein with regard to the pathogenesis of EC. An association was observed between TNFAIP8 overexpression and clinicopathologic factors, such as advanced International Federation of Gynecology and Obstetrics stage (P<0.001), higher histologic grade (P=0.017), deep myometrial invasion (P=0.030), lymphovascular space invasion (P=0.011), lymph node metastasis (P<0.001), and recurrence. Furthermore, TNFAIP8 overexpression was strongly correlated with MMP9 and Ki-67 expression in the progression of ECs. Patients with high expression of TNFAIP8 (P<0.001 for both) and Ki-67 (P=0.007 and P=0.008) had poor overall survival and disease-free survival (DFS) rates. MMP9 overexpression did not affect survival outcomes (P>0.05). Multivariate Cox regression analysis revealed that TNFAIP8 (P=0.029) and lymph node metastasis (P=0.022) were independent factors of DFS in patients with EC. These findings suggested that TNFAIP8 may be used as a prognostic marker for the recurrence of EC, and its promotion of the proliferation and metastasis in EC may be due to its mediation of Ki-67 and MMP9.