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ABSTRACT: Imbalance between apoptosis and proliferation may be one of the mechanisms underlying H. pylori associated gastric carcinogenesis.
To examine the cell kinetics of gastric intestinal metaplasia and the effect of H. pylori eradication.
Endoscopic gastric biopsies were obtained from 100 H. pylori-infected patients. Apoptosis was determined by triphosphate nick-end labelling (TUNEL) and apoptotic nuclei counting, whereas proliferation was assessed by Ki67 immunostaining. Gastric biopsies were repeated in a sub-group of intestinal metaplasia patients after H. pylori eradication.
Antral apoptotic index was significantly lower in intestinal metaplasia than in non-intestinal metaplasia (0.19% vs. 0.51%; P < 0.0001) whereas the level of proliferation was comparable (28% vs. 22%, P=0.15). Serial antral biopsies taken from 14 intestinal metaplasia patients before and 1 year after H. pylori eradication showed a significant drop in proliferation in both intestinal metaplasia (50% vs. 12%, P < 0.001) and non-intestinal metaplasia area (47% vs. 9%, P < 0.001). A similar fall in apoptosis was detected in non-metaplastic region (0.58% vs. 0.38%, P < 0.001) but not in intestinal metaplasia (0.24% vs. 0.27%, P=0.56), resulting in a significant increase in the apoptosis/proliferation ratio (0.005-0.021; P=0.03).
Dysregulation in apoptosis control of gastric intestinal metaplasia may contribute to gastric carcinogenesis, which may be retarded by clearance of H. pylori.
Alimentary Pharmacology & Therapeutics 09/2001; 15(9):1467-72. · 3.77 Impact Factor
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ABSTRACT: Epidemiological studies have suggested a link between chronic Helicobacter pylori infection and ischemic heart disease but the underlying mechanism remains elusive. We hypothesized that H. pylori-associated chronic gastritis causes impairment of absorption of vitamin cofactors that are essential in the metabolism of homocysteine and results in hyperhomocysteinemia.
Forty-nine dyspeptic patients were studied. H. pylori infection was defined by rapid urease test and histology. Fasting serum homocysteine level, which was measured by a validated commercial fluorescence polarization immunoassay, was correlated with H. pylori infection statuses and gastric histology. H. pylori-infected patients were followed up for 24 weeks post eradication for changes in serum homocysteine concentration.
Univariate analyses showed that serum homocysteine level correlated with increasing age (p <.001), male sex (p =.003) and smoking habit (p =.025). There was no significant difference in serum homocysteine levels between H. pylori infected and uninfected subjects (median 10.5 vs. 10.2 micromol/l). After successful eradication of the bacterium, there was no significant reduction in homocysteine level. Moreover, there was no correlation between homocysteine level and gastric histology including H. pylori density, activity and inflammation scores, presence of atrophy or intestinal metaplasia.
The postulated link between H. pylori infection and ischemic heart disease, if it actually exists, is unlikely to be mediated through hyperhomocysteinemia.
Helicobacter 07/2001; 6(2):146-50. · 3.15 Impact Factor
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ABSTRACT: Transcriptional silencing by CpG-island hypermethylation now is believed to be an important mechanism of tumorigenesis. To date, studies on CpG-island hypermethylation in gastric carcinoma and adjacent normal tissues are few.
The authors examined 5 gastric carcinoma cell lines, 26 frozen gastric carcinoma tissues and their adjacent nontumor area for concurrent CpG-island hypermethylation in 6 tumor-related genes (p15, p16, E-cadherin, GST-pi, hMLH1, and VHL) by methylation-specific polymerase chain reaction. Nontumorous gastric tissues from 10 gastritis patients were used as controls.
Hypermethylation was not detected in any tissue taken from gastritis patients but was identified in all 5 cell lines and in 24 (92.3%) gastric carcinoma patients. CpG-island methylation in tumor-related genes also was detected in 7 out of the 25 adjacent normal tissues from cancer patients. Hypermethylation of E-cadherin, p15, and p16 were detected more frequently than GST-pi and hMLH1, whereas aberrant methylation of VHL was not detected. Concurrent hypermethylation in 2 or more tumor-related genes was detected in 3 out of the 5 gastric carcinoma cell lines, 22 (84.6%) tumor samples, and 5 (20%) adjacent gastric tissues. Eighteen (69.2%) tumor samples showed hypermethylation in >or= 3 genes.
The current study showed that concurrent hypermethylation of multiple tumor-related genes is detected frequently in gastric carcinoma and adjacent normal tissues. Study findings suggested that a mechanism that leads to dysregulation in CpG-island methylation is likely to be involved in the early gastric carcinogenesis process.
Cancer 06/2001; 91(12):2294-301. · 4.77 Impact Factor
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ABSTRACT: Background. Epidemiological studies have suggested a link between chronic Helicobacter pylori infection and ischemic heart disease but the underlying mechanism remains elusive. We hypothesized that H. pylori-associated chronic gastritis causes impairment of absorption of vitamin cofactors that are essential in the metabolism of homocysteine and results in hyperhomocysteinemia.Materials and Methods. Forty-nine dyspeptic patients were studied. H. pylori infection was defined by rapid urease test and histology. Fasting serum homocysteine level, which was measured by a validated commercial fluorescence polarization immunoassay, was correlated with H. pylori infection statuses and gastric histology. H. pylori-infected patients were followed up for 24 weeks post eradication for changes in serum homocysteine concentration.Results. Univariate analyses showed that serum homocysteine level correlated with increasing age (p < .001), male sex (p = .003) and smoking habit (p = .025). There was no significant difference in serum homocysteine levels between H. pylori infected and uninfected subjects (median 10.5 vs. 10.2 µmol/l). After successful eradication of the bacterium, there was no significant reduction in homocysteine level. Moreover, there was no correlation between homocysteine level and gastric histology including H. pylori density, activity and inflammation scores, presence of atrophy or intestinal metaplasia.Conclusions. The postulated link between H. pylori infection and ischemic heart disease, if it actually exists, is unlikely to be mediated through hyper-homocysteinemia.
Helicobacter 05/2001; 6(2):146 - 150. · 3.15 Impact Factor
