Gastric cancer remains the second leading cause of cancer-related death in the world. H. pylori infection, a major risk factor for gastric cancer, generates high levels of reactive oxygen species (ROS). Glutathione peroxidase 3 (GPX3), a plasma GPX member and a major scavenger of ROS, catalyzes the reduction of hydrogen peroxide and lipid peroxides by reduced glutathione. To study the expression and gene regulation of GPX3, we examined GPX3 gene expression in 9 gastric cancer cell lines, 108 primary gastric cancer samples and 45 normal gastric mucosa adjacent to cancers using quantitative real-time RT-PCR. Downregulation or silencing of GPX3 was detected in 8 of 9 cancer cell lines, 83% (90/108) gastric cancers samples, as compared to non-tumor adjacent normal gastric samples (P<0.0001). Examination of GPX3 promoter demonstrated DNA hypermethylation (≥10% methylation level determined by Bisulfite Pyrosequencing) in 6 of 9 cancer cell lines and 60% of gastric cancer samples (P = 0.007). We also detected a significant loss of DNA copy number of GPX3 in gastric cancers (P<0.001). Treatment of SNU1 and MKN28 cells with 5-Aza-2′ Deoxycytidine restored the GPX3 gene expression with a significant demethylation of GPX3 promoter. The downregulation of GPX3 expression and GPX3 promoter hypermethylation were significantly associated with gastric cancer lymph node metastasis (P = 0.018 and P = 0.029, respectively). We also observed downregulation, DNA copy number losses, and promoter hypermethylation of GPX3 in approximately one-third of tumor-adjacent normal gastric tissue samples, suggesting the presence of a field defect in areas near tumor samples. Reconstitution of GPX3 in AGS cells reduced the capacity of cell migration, as measured by scratch wound healing assay. Taken together, the dysfunction of GPX3 in gastric cancer is mediated by genetic and epigenetic alterations, suggesting impairment of mechanisms that regulate ROS and its possible involvement in gastric tumorigenesis and metastasis.
Bariatric surgery is now widely accepted for treatment of morbid obesity. This study compared the effects of laparoscopic sleeve gastrectomy (LSG) and laparoscopic adjustable gastric banding (LAGB) on excess weight loss (EWL) and type 2 diabetes mellitus (T2DM). PubMed and Embase were searched for publications concerning LAGB and LSG from 2000 to 2012, with the last search on August 17, 2012. EWL and T2DM improvement over 6 and 12 months were pooled and compared by meta-analysis. Odds ratios (ORs) and mean differences were calculated with 95 % confidence intervals (CIs). Eleven studies involving 1,004 patients met the inclusion criteria. Compared with LAGB, LSG achieved greater EWL. The mean percentage EWL for LAGB was 33.9 % after 6 months in six studies and 37.8 % after 12 months in four studies; for LSG, EWL was 50.6 % after 6 months and 51.8 % after 12 months in the same studies. LSG was also superior to LAGB in treating T2DM. In five studies, T2DM was improved in 42 of 68 (61.8 %) patients after LAGB and 66 of 80 (82.5 %) after LSG, representing a pooled OR of 0.34 (95 % CI 0.16–0.73) and pooled mean differences of −12.55 (95 % CI −15.66 to −9.43) and −4.97 (95 % CI −7.58 to −8.36), respectively. LSG is more effective than LAGB in morbid obesity, with higher percentage EWL and greater improvement in T2DM.
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