Cyclooxygenase-2 (COX-2) is an inducible enzyme important in inflammation and which is overexpressed in a variety of cancers. This study investigated its role in angiogenesis of gastric carcinoma (GC). Immunohistochemical examination of surgical specimens showed a positive correlation among COX-2, vascular endothelial growth factor (VEGF), and vasculature in GC. After transfection with a COX-2-expressing vector, the AGS GC cell line showed increases in both proliferation and tube formation of human umbilical vein endothelial cells (HUVECs). These in vitro angiogenic effects on HUVECs were reduced either by blocking VEGF or NS-398, a COX-2 inhibitor. To elucidate the mechanism by which COX-2 increases angiogenesis, we established a COX-2-expressing clone, AGS/COX-2, and its vector control clone, AGS/pcDNA3, and verified their functions by determining prostaglandin E2 (PGE2). Among 6 angiogenesis-associated factors, VEGF was considerably expressed in AGS/COX-2. After reducing hypoxia-inducible factor-1alpha (HIF-1alpha) protein by antisense HIF-1alpha transfection, VEGF production was reduced in AGS/COX-2 cells in a dose-dependent manner. We found that HIF-1alpha increased concomitantly with VEGF after exogenous PGE2 stimulation to wild-type AGS cells, but this effect was blocked by SC19220, a PGE2 receptor antagonist. In addition, pretreatment with NS-398 to reduce PGE2 also effectively suppressed HIF-1alpha protein accumulation and achieved a similar inhibitory effect on VEGF production as did antisense HIF-1alpha transfection. Our work supports the COX-2/PGE2/HIF-1alpha/VEGF pathway possibly contributing to tumor angiogenesis in GC.

The prevalence of BE in a Chinese general population was lower than that in other reported studies, particularly in comparison with the studies originating from Western countries. Patients with advanced age and metabolic disorders are risk factors for developing BE.

Interleukin-6 (IL-6) is a proinflammatory cytokine associated with the disease status of gastric carcinoma (GC). Vascular endothelial growth factor (VEGF) is a potent tumor angiogenic factor in GC. In this study, we attempted to clarify whether IL-6 can regulate VEGF and angiogenesis in GC. GC samples from 54 surgical specimens were subjected to immunohistochemical examination of IL-6, VEGF, and tumor microvessels, and results showed that IL-6 was positively correlated with VEGF expression and tumor vasculature. We determined VEGF expression in four GC cell lines by ELISA, revealing that GC cells can produce significant amount of VEGF with increasing dose and duration of IL-6 stimulation. Next, a luciferase reporter gene assay was employed to determine the signaling pathway driving the VEGF promoter by IL-6, which showed that the JAK/STAT pathway is involved in the stimulation of VEGF gene expression. The effects of IL-6 on angiogenesis in vitro and in vivo were evaluated by HUVEC studies and the Matrigel plug assay, respectively. Results showed that IL-6 effectively promoted HUVEC proliferation and tube formation in vitro and Matrigel plug vascularization in vivo, primarily by inducing VEGF in GC. This study provides evidence that the multifunctional cytokine, IL-6, may induce VEGF expression which increases angiogenesis in gastric carcinogenesis.

To investigate whether genetic differences in cytokine promoter polymorphisms effect various outcomes after exposure to Epstein-Barr virus (EBV) infection, 30 patients with EBV-positive gastric carcinoma (GC), 120 patients with EBV-negative GC, and 220 control subjects were enrolled. Promoter polymorphisms of tumor necrosis factor (TNF)-alpha at positions -238 and -308 and of interleukin (IL)-10 at position -1082 were determined. The frequency of the high-producer allele (-308A) in the TNF-alpha gene was significantly higher among EBV-positive GC patients compared with control subjects (23.3% vs. 12.0%, P<.05), whereas the frequency of the high-producer allele (-1082G) in the IL-10 gene was significantly higher among EBV-negative GC patients compared with control subjects (6.3% vs. 3.0%, P<.05). These data support the notion that genetic factors may modify the outcomes of infectious diseases through different TNF-alpha- or IL-10-producing capabilities.

Psychological characteristics predict likelihood of GERD symptoms but not structural state of esophagus. Male gender and obesity are risk factors for erosive esophagitis; whereas female gender and neuroticism are more likely to be associated with GERD symptoms.

No abstract

No abstract

Genes involved in regulating antimicrobial immunity and inflammation may modulate the risk of Helicobacter pyloriassociated diseases. IL-1 and TNF-␣ are major cytokines detected in H. pylori-infected tissues. We aimed to determine the role of gene polymorphisms for these cytokines and their receptors in 2 distinct H. pylori-related gastric malignancies, adenocarcinoma (GAC) and maltoma. Genotyping for IL-1␤ (-31 C/T, -511 C/T), TNF-␣ (-238 G/A, -308 G/A, -857 C/T, -863 C/A, -1031 T/C), TNFR1 (-383 A/C) and TNFR2 (196 G/T) was undertaken for 70 patients with maltoma and 204 patients with noncardia GAC and compared to 210 unrelated healthy controls. Genotype frequencies showed no differences among patients with GAC or maltoma and controls for IL-1␤, TNFR1 or TNFR2. The TNF-␣ -857 T variant was significantly underrepresented in maltoma compared to controls (6.4% vs. 14.3%, p ‫؍‬ 0.018), conferring a 3-fold decrease in risk (OR ‫؍‬ 0.33, 95% CI 0.15-0.75). Comparison of allele frequencies between GAC and controls failed to show any statistical significance for TNF-␣ polymorphisms. We concluded that TNF-␣ -857 T itself or a neighboring gene may modify the risk of maltoma. The differences in genetic background as well as divergent clinicopathologic features between GAC and maltoma support the notion that fundamental mechanistic differences exist in these 2 welldefined H. pylori-related malignancies.