Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0154059 (Esophagus)
 2,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proper anastomotic healing is dependent upon many factors including adequate blood flow to healing tissue. The aim of this study was to investigate the impact of vascular endothelial growth factor (VEGF(165)) transfection on anastomotic healing in an ischemic gastrointestinal anastomosis model. Utilizing an established opossum model of esophagogastrectomy followed by esophageal-gastric anastomosis, the gastric fundus was transfected with recombinant human vascular endothelial growth factor via direct injection of a plasmid-based nonviral delivery system. Twenty-nine animals were divided into three groups: two concentrations of VEGF and a control group. Outcomes included VEGF mRNA transcript levels, neovascularization, tissue blood flow, and anastomotic bursting pressure. To determine whether local injection resulted in a systemic effect, distant tissues were evaluated for VEGF transcript levels. Successful gene transfection was demonstrated by quantitative polymerase chain reaction analysis of anastomotic tissue, with significantly higher VEGF mRNA expression in treated animals compared to controls. At the gastric side of the anastomosis, there was significantly increased neovascularization, blood flow, and bursting pressure in experimental animals compared to controls. There were no differences in outcome measures between low- and high-dose VEGF groups; however, the high-dose group demonstrated increased VEGF mRNA expression across the anastomosis. VEGF production was not increased at distant sites in treated animals. In this animal model, VEGF gene therapy increased VEGF transcription at a healing gastrointestinal anastomosis without systemic VEGF upregulation. This treatment led to improved healing and strength of the acutely ischemic anastomosis. These findings suggest that VEGF gene therapy has the potential to reduce anastomotic morbidity and improve surgical outcomes in a wide array of patients.
Dis Esophagus 2012 Jul
PMID:Recombinant vascular endothelial growth factor165 gene therapy improves anastomotic healing in an animal model of ischemic esophagogastrostomy. 2189 53

It has recently been suggested that angiotensin-I converting enzyme (ACE) inhibitors decrease the risk of cancer. However, studies to date have not investigated esophageal carcinoma. Therefore, we investigated the inhibitory effect of ACE inhibitors on growth of esophageal carcinoma xenografts. We used the EC9706 cell line, which expresses the highest vascular endothelial growth factor (VEGF) mRNA level, to establish xenografts in 21 BALB/c nude mice. The mice were then randomly allocated to receive normal saline, perindopril (4 mg/kg), or benazepril (6 mg/kg). Five weeks later, the nude mice were sacrificed and all tumors were dissected and weighed. The number of microvessels was counted by immunostaining endothelial cells for CD31 and the microvessel density was assessed. The EC9706 cell line showed the highest expression of VEGF mRNA of four esophageal squamous cell carcinoma lines. After treatment, the average tumor inhibitory rate in the benazepril group was 45.4%, which was significantly higher than that of the control group (P < 0.05). Similar findings were observed when we used tumor weight as an index for tumor growth inhibition (P < 0.05). By contrast, there was no significant difference between the perindopril group and the control group (P > 0.05). The benazepril group appeared to show less vascularization than the control group (P < 0.05), but we did not find a significant difference between the perindopril group and the control group (P > 0.05). The EC9706 cell line showed the highest expression of VEGF mRNA level of the four esophageal squamous cell carcinoma cell lines examined. Benazepril inhibited the growth of esophageal carcinoma in vivo. The potential mechanism of benazepril seems to involve suppression of new vessel formation. Therefore, benazepril could be used as an effective agent for the treatment of esophageal carcinoma.
Dis Esophagus
PMID:Angiotensin-I converting enzyme inhibitors suppress angiogenesis and growth of esophageal carcinoma xenografts. 2230 61