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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Research is asking how H. pylori causes diseases, and also why the same bacteria produces different conditions in different persons. The process involves bacterial factors and the host's response. Some bacterial factors such as urease are produced by all strains of H. pylori. This enzyme may damage the gastric epithelium by practically releasing ammonia. Other bacterial factors such as vacuolating toxin are only produced by some strains, and these strains are more likely to cause ulcers or cancer. The host's response has been studied by physiologists, immunologists, and histologists, but the separation of systems is artificial. For example, physiologists find that H. pylori stops gastric D-cells from expressing somatostatin normally, which impairs reflex inhibition of acid secretion, but the D-cell malfunction is probably due to inflammatory factors. In H. pylori gastritis, the gastric epithelial cells behave like immunocytes and express class II molecules and cytokines such as interleukin-8. The patient's histological response to H. pylori is quite closely related to the disease outcome. Patients who respond by developing gastric atrophy are more likely to get gastric ulcers or stomach cancer, but patients whose gastric corpus remains healthy tend to secrete more acid and develop duodenal ulcers, particularly if they have gastric metaplasia in their duodenum. Studies of disease mechanisms provide a valuable insight into the development of these common diseases, and may enable us to identify at-risk groups who particularly merit eradication therapy.
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PMID:Pathogenic mechanisms. 856 49

The International Agency for Research on Cancer, sponsored by the World Health Organization, has recently categorized Helicobacter pylori infection as a class I carcinogen, based on evidence that this infection increases the risk of gastric cancer. The classification was intentionally qualitative in nature and not associated with any public health recommendations. In addition, no specific causal mechanism was proposed to explain the relationship between H. pylori and gastric cancer. In this paper, the magnitude of the risk, implications of the relationship for the prevention of gastric cancer and nature of the causal mechanisms are considered. Relative risk of gastric cancer may be substantial; even with conservative assumptions, the proportion of new cases of gastric cancer worldwide attributable to H. pylori infection is approximately one third of a million annually. This figure is likely to increase with changes in the age structure of the population, and the eradication of H. pylori as a means of prevention of gastric cancer should be considered. A strategy of screening populations in middle age and treating those infected could be relatively inexpensive to administer, but the efficacy is totally unknown and requires evaluation in a randomized controlled trial. Studies designed to address this issue in the general population would need to be large and long-term if gastric cancer is used as an end-point. With respect to carcinogenic mechanisms, a number of constitutive properties of H. pylori may be of relevance to cancer without being specifically carcinogenic. Thus ammonia, which is produced in abundance as a result of urease activity, may promote cell division. Other relevant properties result from the immune response of the host to the bacterium. For example, the excessive production of reactive oxygen metabolites can lead to extensive DNA damage and molecular mutations.
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PMID:Helicobacter pylori and gastric cancer. 872 82

Adenosine deaminase activity was studied in tissue slices taken endoscopically from gastric mucosa of patients with the intestinal type of gastric carcinoma. The enzyme activity was measured in mucosal homogenates by determination of ammonia liberated from substrate during 10-min incubation. It was found that: (1) the enzyme activity of de novo gastric cancer was significantly lower than that of recurrent cancer of the gastric remnant; and (2) the enzyme activity of uninvaded gastric mucosa surrounding the neoplastic lesion of non-operated stomach was significantly lower than of the gastric mucosa of partially resected stomach due to malignancy. Since the enzyme activity in gastric cancer and surrounding uninvaded gastric mucosa correlated well with the advance of neoplastic disease estimated by ultrasonography examination, we speculate that some systemic factors associated with tumor progression might be implicated in the regulation of adenosine deaminase activity.
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PMID:Adenosine deaminase activity in patients with the intestinal type of gastric carcinoma. 902 Sep 21

The mutagenic activity of glycine upon nitrosation was studied in the Ames tester strains TA98, TA100, TA102, and TA104. The results obtained show that glycine at acidic pH values and in the presence of Cl- can react with nitrite giving rise to genotoxic compounds to the tester strains used. When these experiments were carried out in the presence of gastric juice the genotoxicity observed was associated with the Cl- concentration in the different gastric juice samples. The nature and the mechanism of genetic lesion induced by the ultimate genotoxicant arising from the nitrosation of glycine are not fully understood. Primary amines (e.g., amino acids) have been described as potential alkylating agents after nitrosation. However, in our experimental conditions these alkylating activities were not detected, suggesting that other mechanisms could be involved in the genetic lesion induced by nitrosated glycine. The influence of Cl- in the genotoxic activity of glycine and other primary amines upon nitrosation and its possible involvement in the etiology of gastric cancer are discussed.
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PMID:Mutagenic activity of glycine upon nitrosation in the presence of chloride and human gastric juice: a possible role in gastric carcinogenesis. 912 93

Helicobacter pylori (Hp) has strong urease activity and produces a large amount of ammonia in the stomach. In animal studies, ammonia was shown to accelerate cell kinetics of gastric mucosa, and long-term exposure of the stomach to ammonia leads to mucosal atrophy. To understand this process, we examined the effects of ammonia on the growth and cell cycle progression of human gastric cancer cell lines (HGC-27, MKN1, MKN45) using flow-cytometric analysis. In each cell line, ammonia inhibited the cell growth in a dose-dependent manner and caused significant accumulation of S-phase cells at a cytostatic dose. DNA synthesis of HGC-27 cells treated with ammonia was also suppressed to about 50% of that of the untreated cells. Similar effects were observed on addition of ammonium chloride at the same concentration, while adjusting the pH of the media with NaOH alone to that with the cytostatic dose of ammonia did not affect the cell cycle progression. These observations indicate that ammonia induces S-phase arrest in gastric cells independently of pH.
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PMID:Ammonia inhibits proliferation and cell cycle progression at S-phase in human gastric cells. 924 35

Helicobacter pylori can utilise amino acids as the sole carbon energy source. The present study demonstrated that H. pylori grown in continuous culture in a defined medium containing glucose and amino acids utilised alanine, arginine, asparagine, aspartate, glutamine, glutamate, proline and serine. Specific asparaginase and glutaminase enzymes deaminated asparagine and glutamine respectively to aspartate and glutamate, with the production of ammonia. The glutaminase activity was inhibited by 6-diazo-5-oxo-L-norleucine. All the 13 strains of H. pylori tested produced both glutaminase and asparaginase activities. Glutamine is important in the health of the gastric and intestinal mucosa and is a primary energy source for lymphocytes. Depletion of glutamine at the site of H. pylori infection may be of significance in the pathogenesis of H. pylori-associated diseases such as peptic ulcer and gastric cancer.
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PMID:Amino acid utilisation and deamination of glutamine and asparagine by Helicobacter pylori. 929 92

Helicobacter pylori infection increases gastric acid secretion in patients with duodenal ulcers but diminishes acid output in patients with gastric cancer and their relatives. Investigation of the basic mechanisms may show how H. pylori causes different diseases in different persons. Infection of the gastric antrum increases gastrin release. Certain cytokines released in H. pylori gastritis, such as tumor necrosis factor alpha and specific products of H. pylori, such as ammonia, release gastrin from G cells and might be responsible. The infection also diminishes mucosal expression of somatostatin. Exposure of canine D cells to tumor necrosis factor alpha in vitro reproduces this effect. These changes in gastrin and somatostatin increase acid secretion and lead to duodenal ulceration. But the acid response depends on the state of the gastric corpus mucosa. The net effect of corpus gastritis is to decrease acid secretion. Specific products of H. pylori inhibit parietal cells. Also, interleukin 1 beta, which is overexpressed in H. pylori gastritis, inhibits both parietal cells and histamine release from enterochromaffin-like cells. H. pylori also promotes gastric atrophy, leading to loss of parietal cells. Factors such as a high-salt diet and a lack of dietary antioxidants, which also increase corpus gastritis and atrophy, may protect against duodenal ulcers by decreasing acid output. However, the resulting increase of intragastric pH may predispose to gastric cancer by allowing other bacteria to persist and produce carcinogens in the stomach.
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PMID:How does Helicobacter pylori cause mucosal damage? Its effect on acid and gastrin physiology. 939 59

Many putative virulence determinants of Helicobacter pylori are believed to trigger and worsen the gastroduodenal mucosa damage observed in infected patients. H. pylori urease reacts with the gastric urea and generates ammonia; ammonia combines with water and yields ammonium hydroxide, which is cytotoxic. Ammonia may also inhibit cell proliferation and cause indirect mucosal injury by stimulating neutrophils. Phospholipases may damage the gastric mucosa by degrading phospholipids and generating precursors of ulcerogenic components. Other enzymes, such as protease, neuraminidase, fucosidase, and alcohol dehydrogenase, can contribute to damage of the gastric epithelium by destroying the integrity of mucus or by inducing lipid peroxidation. Infection by vacuolating cytotoxic (VacA+) H. pylori strains is considered to constitute increased risk for development of peptic ulcer and gastric cancer. Exploration of the vacA gene structure has shown the existence of strongly toxigenic strains, and has confirmed at the molecular level the increased ulcerogenic potential of VacA+ H. pylori strains. A pathogenicity island called cag has been recently described in Type 1 H. pylori strains (VacA+/CagA+).cag contains the cagA gene (whose expression is associated with toxigenicity) and many genes, some of which are highly homologous to virulence genes of other virulent bacteria, that account for the enhanced pathogenic potential of CagA+ organisms.
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PMID:Helicobacter pylori factors involved in the development of gastroduodenal mucosal damage and ulceration. 947 42

Helicobacter pylori appears to play a major role in the development of gastric cancer in humans. The mechanism behind the carcinogenic or co-carcinogenic effects of H. pylori has not been established. Ammonia, generated by urea from H. pylori, has been studied as a possible cause. However, the ammonia-monochloramine system has been shown to play a more important role in H. pylori-associated mucosal injury. Therefore, the effects of combined administration of monochloramine and methionine, singly or together, on the development of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in inbred Wistar rats. After receiving oral MNNG and regular chow pellet for 25 weeks, rats received regular chow pellets or chow pellets containing 20% ammonium acetate, and normal tap water or water containing 30 mM sodium hypochlorite, with or without a subcutaneous injection of methionine, until the end of the experiment (week 52). Treatment with both ammonium acetate and sodium hypochlorite, which produce monochloramine, significantly increased the incidence of gastric cancers in week 52, whereas the concomitant administration of methionine with ammonium acetate and sodium hypochlorite significantly attenuated such enhanced gastric carcinogenesis. Spectrophotometric examination revealed that methionine scavenged monochloramine. Our findings suggest that H. pylori-associated gastric carcinogenesis may be mediated by monochloramine.
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PMID:Attenuation by methionine of monochloramine-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. 953 64

Peptic ulcer disease and gastric cancer of the antrum and body have been declining in the 20th century. In contrast, a new group of diseases are increasingly rapidly in Western countries: gastroesophageal reflux disease, Barrett's esophagus, and adenocarcinoma of the distal esophagus. Recent studies suggest this phenomenon may be related to the simultaneous fall in the prevalence of Helicobacter pylori (H. pylori) colonization, especially by the virulent cagA + strains. H. pylori infection with the cagA+ strain is potentially protective against the spectrum of gastroesophageal reflux disease because it lowers intragastric acidity as the result of a pangastritis, frequently with multifocal gastric atrophy and possibly increased intragastric ammonia production. Assuming that some types of H. pylori strains are protective, our entire approach to the worldwide elimination of this organism, sometimes indiscriminately, will need critical reevaluation.
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PMID:Helicobacter pylori and gastroesophageal reflux disease: the bug may not be all bad. 1052 Aug 76


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