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Expression Of Inducible Nitric Oxide Synthase And Nitrotyrosine In Gastric Adenocarcinomas And Their Correlation With Apoptosis

Posted on:2005-09-15Degree:MasterType:Thesis
Country:ChinaCandidate:L G LiFull Text:PDF
GTID:2144360122990778Subject:Oncology
Abstract/Summary:PDF Full Text Request
Gastric carcinoma is one of the most common malignant diseases in the world, leading to the first cause of gastrointestinal cancer - related mortality. Recent studies showed that inducible nitric oxide synthase (iNOS) might play an important role in the growth of gastric cancer.NO is derived from the oxidation of L - arginine catalyzed by Nitric Oxide Synthase ( NOS). In tissues NOS exisis mainly as a family of related but distinct isoforms, including endothelial ( eNOS) , neural ( nNOS) and inducible ( iNOS) isoforms. NO produced by eNOS and nNOS under normal physiology con-dictions is present at relatively low levels. In contrast, iNOS is widely distributed in a variety of cell types and upon induction can produce a high output of NO. Thus, excessive NO generation is important not only for its local destructive effect to tissues and cytotoxic to host cells, but also for the regulation of cell growth and programmed cell death ( apotosis). Epidemiological studies show that gastric cancer is closely linked to Helicobacter pylori ( Hp ) infection, because the incidence of gastric cancer increases 4-9 times after H. pylori infection , and more than 60% patients with gastric cancer had been infected with H. pylori , and H. pylori infection possesses a high risk for causing gastric cancer.Previous studies indicate that effects of NO synthesized by iNOS can be either tumor suppressing or tumor promoting. The tumor suppressing role has been identified by the typical findings in NO - mediated apoptosis, while the tumor promoting role has been demonstrated by the evidence that NO produced by iNOS may promote tumor angiogenesis and blood flow in tumor neovaculature, and enhance tumor growth, invasion, and metastasis. The conflicting dual roles of iNOS might work together to influence the clinical pathology and pathophysiologyof tumor.However, when there is iNOS expression in gastric adenocarcinoma, the direction and condition in which the tumor may develop ( promoted or suppressed) , remain to be defined. Our study was designed to determine whether: (1) gastric adenocarcinoma cells express iNOS and NT; (2) the distribution of NT in gastric adenocarcinoma is related to the apoptosis; (3 ) presence of iNOS , NT and apoptosis correlate with clinical features of gastric adenocarcinoma. (4) H. pylori infection is associcated with the expression of iNOS.MethodsSixty - six Specimens of gastric adenocarcinoma and ten corresponding adjacent normal gastric tissues were obtained from surgically treated patients with gastric adenocarcinoma. Of them, 36 were male and 30 were female. The mean age was 57 years ( range, 29-78 years). All the selected adjacent control gastric tissues were identified as normal by gross and microscope study. As to the grade of tumor, 36 cases were classified as poorly differentiated adenocarcinoma, with 30 cases well and moderately differentiated. None of the 66 patients had received preoperative radiotherapy or chemotherapy, and all underwent curative surgical resection of the tumor along with regional lymph node dissection at least five years ago. Clinicopathologic characteristics of these patients were investigated based on the TNM classification of malignant tumors. A modified Mc-Mullen' s staining was used for the histological assessment of H. pylori infection. Immunohistochemistry was employed to localize iNOS and NT protein in normal and tumor tissues. The occurrence of apoptotic cell death ( apoptotic index [ AI ] ) was analyzed by the terminal deoxynucleotidyl transferase - mediated deoxyuridine triphosphate biotin nick - end labeling ( TUNEL) method.ResultResults showed that H. pylori infection was observed in 68. 18% of these specimens, the rate of H. pylori infection was there were significant positive cor-relations between iNOS expression and H. pylori infection. iNOS expression was detected at an intermediate or high level in 41 of 66 (62% ) specimens of gastric adenocarcinoma; similarly, NT expression was 58% ; neither of them was found in the normal gastri...
Keywords/Search Tags:Inducible Nitric Oxide Synthase, Nitrotyrosine, Apoptosis, Helicobator pylori, Gastric Adenocarcinomas
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