Laparoscopic Roux-en-Y gastric bypass (LRYGB) is one of the most performed bariatric procedures in treating morbid obesity. There is no consensus on which technique used for gastrojejunal anastomosis is optimal. The meta-analysis aimed to solve the issue by comparing hand-sewn with mechanical gastrojejunostomy during LRYGB for morbid obesity. PubMed, Embase, Cochrane Library, Scopus, Google Scholar and Research Gate were searched (from inception to April 2016). Primary outcome was operation time. Secondary outcomes were postoperative complications (anastomotic leak, stricture, bleeding, marginal ulcer and wound infection), percent excess weight loss during one-year follow-up, reoperation, and postoperative hospital stay. Odds ratios (OR) were calculated for dichotomous outcomes and mean differences (MD) for continuous outcomes. Twelve trials were included comprising 13,626 patients (3309 hand-sewn vs. 6791 circular vs. 3526 linear). There was no difference in operation time when hand-sewn anastomosis was compared with mechanical gastrojejunostomy (MD, -6.00; 95% confidence interval (CI), -34.85 to 22.85; P = 0.68), circular stapled anastomosis (MD, -5.24; 95% CI, -32.71 to 22.24; P = 0.71) or linear stapled anastomosis (MD, - 3.75; 95% CI, -64.81 to 57.31; P = 0.90). Hand-sewn anastomosis had significantly lower incidence rate of postoperative bleeding (OR, 0.48; 95% CI, 0.31-0.74; P = 0.001) and wound infection (OR, 0.19; 95% CI, 0.08-0.45; P = 0.0002) than circular stapled anastomosis; there were no significant differences in the other secondary outcome. And there were no significant differences in all the comparable outcomes between hand-sewn anastomosis and linear stapled anastomosis. This meta-analysis revealed no significant differences between mechanical and hand-sewn anastomosis except for greater incidence rates of postoperative bleeding and wound infection with the use of circular staplers. Besides, more trials with adequate power are required and a cost analysis also worth trying. REGISTRATION NO. CRD42015020025.

Neuropilin-1 (NRP-1) is a transmembrane glycoprotein participating in the growth and metastasis of cancer cells as multifunctional co-receptors by interacting with the signaling pathways. However, its role in gastric cancer has not yet been clarified. This study aims to investigate whether NRP-1 expression is associated with the clinicopathology of gastric cancer, and involved in the growth and metastasis of gastric cancer cells. NRP-1 expression in clinical gastric cancer specimens was examined by immunohistochemistry and its association with clinicopathology analyzed. The expression of NRP-1 in a panel of human gastric cancer cells was examined by real-time RT-PCR and immunoblotting. Stable transfectants depleted of NRP-1, termed MGC-803-NRPlow, were generated from MGC-803 cells. Cell proliferation was analyzed by the Cell Counting Kit-8 and Bromodeoxyuridine incorporation assays, and migrating ability analyzed by migration assays. The xenograft model was used to assess the effects of NRP-1 depletion on tumorigenesis, growth, metastasis and therapeutic potentials. The role of NRP-1 as co-receptors in the signaling pathways stimulated by ligands was examined. The key molecules involved in cell proliferation, migration and related signaling pathways were detected by immunoblotting. Gastric cancer tissues expressed higher levels of NRP-1 compared to normal gastric mucosa. Its expression correlated with clinical staging, tumor differentiation and pathological types. NRP-1 depletion inhibited cell proliferation by inducing cell cycle arrest in the G1/S phase by upregulating p27, and downregulating cyclin E and cyclin-dependent kinase 2. NRP-1 depletion reduced the ability of cells to migrate by inhibiting the phosphorylation of focal adhesion kinase. NRP-1 depletion suppressed tumorigenesis, tumor growth and lung metastasis by inhibiting cell proliferation and tumor angiogenesis in situ. Therapeutic NRP-1 shRNA inhibited the growth of established BGC823 tumors. Depletion of NRP-1 inhibited the activation of VEGF/VEGFR2, EGF/EGFR and HGF/c-Met pathways stimulated by respective recombinant human VEGF-165, EGF and HGF proteins. The present results indicate that NRP-1 may be a potentially valuable biomarker and therapeutic target for gastric cancer.

Colon cancer‐associated transcript‐1 (CCAT1) is a highly conserved long noncoding RNA that is deregulated in several cancers. However, its role in gastric carcinoma and its post‐transcriptional regulation remain poorly understood. In this study, we provide the first evidence that CCAT1 regulates miR‐490 in gastric cancer (GC) cells. Interestingly, miR‐490 can also repress CCAT1 expression. CCAT1 expression was significantly upregulated, and miR‐490 expression was downregulated in GC. The negative correlation between miR‐490 and CCAT1 expression was observed in GC tissues. Importantly, CCAT1 contains a putative miR‐490‐binding site, and deletion of this binding site abolishes their miR‐490 responsiveness. Post‐transcriptional CCAT1 silencing by miR‐490 significantly suppressed GC cell migration. Furthermore, miR‐490 directly bound to the hnRNPA1 mRNA 3′‐UTR to repress its translation. Inhibition of miR‐490 rescued CCAT1 siRNA‐mediated suppression of cell migration. hnRNPA1 expression was significantly upregulated in GC specimens, and there was a negative correlation between miR‐490 and hnRNPA1 expression and also a positive correlation between hnRNAP1 expression level and CCAT1 level. Taken together, we show for the first time that the CCAT1/miR‐490/hnRNPA1 axis promotes GC migration, and it may have a possible diagnostic and therapeutic potential in GC. © 2016 IUBMB Life, 68(3):201–210, 2016

Cyclooxygenase (COX)-2 is overexpressed in many types of cancers including hepatocellular carcinoma (HCC). Meloxicam, a selective COX-2 inhibitor, has shown potential therapeutic effects against HCC, but the mechanisms accounting for its anti-cancer activities remain unclear. Meloxicam inhibited the ability of human HCC cells expressing higher levels of COX-2 to migrate, invade, adhere and form colonies through upregulating the expression of E-cadherin and downregulating the expression of matrix metalloproteinase (MMP) -2. Meloxicam induced cell apoptosis by upregulating pro-apoptotic proteins including Bax and Fas-L, and downregulating anti-apoptotic proteins including survivin and myeloid cell leukemia-1 (Mcl-1), through inhibiting phosphorylation of AKT. Addition of prostaglandin E2 (PGE2), the major product of COX-2, could abrogate the effects of meloxicam on the expression of survivin and myeloid cell leukemia-1 (Mcl-1), but not Bax and Fas-L, indicating that meloxicam induces cell apoptosis via both COX-2-dependent and -independent pathways. Meloxicam also induced cell autophagy by upregulating Beclin 1 and light chain 3-II. Specific inhibition of autophagy by 3-methyladenine and chloroquine had little effect on cell apoptosis but could enhance the pro-apoptotic effects of meloxicam by further upregulating the expression of Bax. Meloxicam executes its antitumor effects by targeting the COX-2/MMP-2/E-cadherin, AKT, apoptotic and autophagic pathways in COX-2-dependent and -independent pathways, and inhibition of cell autophagy could help to overcome the resistance to meloxicam-induced apoptosis in HCC.

Background: Neuropilin-1 (NRP-1) is a non-tyrosine kinase receptor interacting with multiple signaling pathways that underpin the biological behavior and fate of cancer cells. However, in pancreatic cancer, the mechanisms underlying the function of NRP-1 in cell proliferation and metastasis and the involvement of regulatory upstream miRNAs remain unclear.Methods: Potential miRNAs were mined by using multiple bioinformatics prediction tools and validated by luciferase assays. The expression of NRP-1 and miRNA-141 (miR-141) in pancreatic tissues and cells was examined by immunohistochemistry, immunoblotting and/or real-time RT-PCR. Stable transfected cells depleted of NRP-1 were generated, and regulatory effects of miR-141 were investigated by transfecting cells with miR-141 mimics and anti-miR-141. Assays of cell viability, proliferation, cell cycle distribution, transwell migration and cell scratch were employed. Xenograft tumor models were established to assess the effects of NRP-1 depletion on tumorigenesis and liver metastasis, and therapeutic effects of miR-141 on tumor growth. The role of miR-141/NRP-1 axis in regulating epithelial–mesenchymal transition (EMT) by co-interacting the TGF-β pathway was examined.Results: In this study, of 12 candidate miRNAs identified, miR-141 showed the strongest ability to regulate NRP-1. In pancreatic cancer tissues and cells, the expression level of NRP-1 was negatively correlated with that of miR-141. NRP-1 was highly expressed in pancreatic cancer tissues compared with normal pancreatic tissues, and its expression levels were positively correlated with tumor grade, lymph metastasis and AJCC staging. NRP-1 depletion inhibited cell proliferation by inducing cell cycle arrest at the G0/G1 phase through upregulating p27 and downregulating cyclin E and cyclin-dependent kinase 2, and reduced cell migration by inhibiting EMT through upregulating E-cadherin and downregulating Snail and N-cadherin. Through downregulating NRP-1, miR-141 mimics showed a similar effect as NRP-1 depletion on cell proliferation and migration. NRP-1 depletion suppressed tumor growth and liver metastasis and miR-141 mimics inhibited the growth of established tumors in mice. NRP-1 depletion and/or miR-141 mimics inhibited the activation of the TGF-β pathway stimulated by TGF-β ligand.Conclusions: The present results indicate that NRP-1 is negatively regulated by miR-141 and the miR-141/NRP-1 axis may serve as potentially valuable biomarkers and therapeutic targets for pancreatic cancer.