Effects of Helicobacter pylori eradication on methylation status of E-cadherin gene in noncancerous stomach
ABSTRACT Promoter hypermethylation of E-cadherin plays an important role on gastric cancer development. Whereas E-cadherin methylation was frequently detected in the stomach of Helicobacter pylori-infected individuals, we tested whether eradication of H. pylori alters the methylation status of the noncancerous gastric epithelium.
Endoscopic biopsies were taken from the antrum and corpus of H. pylori-infected subjects without gastric cancer. Presence of methylated E-cadherin sequences in the gastric specimens was detected by methylation-specific PCR. Bisulfite DNA sequencing was done to determine the topographical distribution and changes in methylation profiles with H. pylori eradication.
Among the 28 H. pylori-infected subjects (median age, 44.5 years), 15 (53.6%) had E-cadherin methylation detected in stomach at baseline. Discordant methylation patterns between the antrum and corpus were noted in six patients. One year after successful H. pylori eradication, there was a significant reduction in the methylation density of the promoter region and exon 1 of the E-cadherin gene as detected by bisulfite DNA sequencing (P < 0.001).
Promoter methylation in E-cadherin was frequently detected in the stomach of H. pylori-infected individuals. Eradication of H. pylori might possibly reduce the methylation density in E-cadherin gene and the chance of subsequent neoplastic transformation.
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ABSTRACT: The importance of the extracellular matrix (ECM) has become recognised as an important component of the functioning of cells. However the roles of the ECM in the anterior pituitary gland have received little attention. The pituitary has the particular characteristics of possessing a number of endocrine cells as well as less well studied non-endocrine cells. Because each cell has specific and vital roles in the physiology being of an individual the ECM must also possess selective activities. The details of ECM behaviour have not yet been delineated in the pituitary and this review first considers general characteristics of ECM compounds and then examines the properties of peptides with regard to functioning of the cells of the pituitary. It is noted that there are variations between ECM associated with normal cells and with tumours, that there are both morphological and biochemical responses to alterations in the composition of substrate on which cells are grown, and that a development of further models of ECM will be required for continued advances in the understanding of the manner in which the pituitary behaves in normal, clinical and pathological circumstances. Overall, the observations suggest that modulation of the ECM provides opportunities for enhancing well-being of individuals.
Article: Coming unglued.Clinical Cancer Research 06/2006; 12(10):2951-4. DOI:10.1158/1078-0432.CCR-06-0460 · 8.19 Impact Factor
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ABSTRACT: Although Helicobacter pylori infection is closely associated with gastric cancer development, follow-up studies after H. pylori eradication are still scarce. To clarify the cancer preventive effect of H. pylori eradication, with special attention to differences in effect according to histology. Patients who underwent H. pylori eradication therapy and were followed-up endoscopically for at least 1 year were analysed. The incidence of gastric cancer and factors associated with cancer development were investigated. A total of 1807 patients were enrolled. Six of 1519 H. pylori eradicated and five of 288 persistent subjects developed gastric cancer. Four of the eradicated subjects developed the intestinal type and two the diffuse type, while four of the persistent subjects developed the intestinal type and one the diffuse type. Kaplan-Meier analysis indicated a significantly lower incidence in eradicated patients than in persistent patients. The incidence of intestinal type was significantly lower than in eradicated patients, while the diffuse type could not be evaluated because of the low incidence. Helicobacter pylori-eradicated patients had a reduced incidence of gastric cancer compared with H. pylori-persistent patients, particularly the intestinal type, suggesting that H. pylori is strongly associated with intestinal-type gastric cancer.Alimentary Pharmacology & Therapeutics 05/2007; 25(7):805-12. DOI:10.1111/j.1365-2036.2007.03268.x · 5.48 Impact Factor