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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastric intestinal metaplasia, an intermediate step in Correa's cascade of gastric carcinogenesis, is generally regarded as a pre-malignant lesion. Epidemiological studies suggest that patients with intestinal metaplasia have more than a 10-fold increased risk of developing gastric cancer. Within the subclassification of intestinal metaplasia, incomplete or type III intestinal metaplasia appears to be associated with even higher malignant potential. The topographical distribution of intestinal metaplasia may also have prognostic implications. Certain genetic and epigenetic alterations have been demonstrated in gastric intestinal metaplasia which straddle into gastric cancer. These findings suggest that genetic changes occur early in the multistep gastric carcinogenesis process. Unlike Barrett's oesophagus and colonic polyp, which have well-defined surveillance guidelines, there is no widely accepted surveillance programme for gastric intestinal metaplasia. An annual surveillance programme may allow early detection of gastric cancer, which theoretically may improve survival. It remains elusive whether the treatment of Helicobacter pylori infection may reverse gastric intestinal metaplasia or reduce the subsequent risk of cancer development. Further controlled studies with longer follow-up are needed to resolve this controversy. The role of chemo-prophylactic agents, e.g. cyclo-oxygenase-2 inhibitor, should be investigated.
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PMID:Review article: intestinal metaplasia and gastric carcinogenesis. 1214 69

Helicobacter pylori infection is recognized to be a pathogen of various gastroduodenal disease. Eradication therapy of H. pylori reduces the recurrence of gastro-duodenal ulcer, improves histological gastritis, and is suggested to act a certain role in protection against gastric carcinogenesis. Although, several studies show uncomfortable results arise after H. pylori infection was cured. These studies suggest that gastro-esophageal reflux disease (GERD) and gastro-duodenal erosion may increase after successful eradication of H. pylori. Recently, adenocarcinoma of the gastric cardia and esophagus increase in incidence. Reflux esophagitis and Barrett's esophagus are recognized as precancerous lesion of esophageal adenocarcinoma. It is uncertain the association of newly occurrence of GERD after H. pylori eradication and increase of esophageal adenocarcinoma. GERD may cause adenocarcinoma development, though long term observations is necessary after H. pylori eradication.
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PMID:[Occurrence of upper gastrointestinal tract disease after Helicobacter pylori eradication]. 1218 64

Enterochromaffin-like (ECL) cells are neuroendocrine cells in the gastric mucosa that control acid secretion by releasing histamine as a paracrine stimulant. The antral hormone gastrin and the neural messenger pituitary adenylyl cyclase-activating peptide (PACAP) potently stimulate histamine synthesis, storage, and secretion by ECL cells. Histamine is stored in secretory vesicles via V-type ATPases and vesicular monoamine transporters of subtype 2 (VMAT-2). Plasmalemmal calcium entry occurs via L-type calcium channels upon stimulation with secretagogues. K(+) and Cl(-) channels maintain the membrane potential. Calcium-triggered exocytosis of histamine is mediated by interacting SNARE proteins, especially by synaptobrevin and SNAP-25. Dynamins and amphiphysins appear to play a key role in endocytosis. ECL cells are under transcriptional control of various hormones. Gastrin stimulates transcriptional activity of the histidine decarboxylase (HDC), VMAT-2, and chromogranin A promoter by activation of Sp1 elements and CREB. During chronic Helicobacter pylori infection, pro-inflammatory cytokines are released that can also affect ECL cells, thus impairing their secretory function and viability, which can predispose to hypochlorhydria and gastric carcinogenesis.
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PMID:Physiology of gastric enterochromaffin-like cells. 1222 Nov 95

Gastrin is a hormone produced by G-cells in the normal gastric antrum. However, colorectal carcinoma cells may aberrantly produce gastrin and exhibit increased expression of cholecystokinin B (CCK-B)/gastrin receptors. Gastrin is trophic for the normal gastric oxyntic mucosa and exerts a growth-promoting action on gastrointestinal malignancy. Thus, gastrin may act as an autocrine/paracrine or endocrine factor in the initiation and progression of colorectal carcinoma. The molecular mechanisms involved have not been elucidated. Hypergastrinemia induced by Helicobacter pylori infection is associated with increased cyclooxygenase-2 (COX-2) expression in gastric and colorectal tissues, suggesting the possibility that gastrin up-regulates COX-2 expression in these tissues; this has not been confirmed. We report here that gastrin significantly increases the expression of COX-2 mRNA and protein, the activity of the COX-2 promoter, and the release of prostaglandin E(2) from a rat intestinal epithelial cell line transfected with the CCK-B receptor. These actions were dependent upon the activation of multiple MAPK signal pathways, including ERK5 kinase; transactivation of the epidermal growth factor receptor; and the increased expression and activities of transcription factors ELK-1, activating transcription factor-2, c-Fos, c-Jun, activator protein-1, and myocyte enhancer factor-2. Thus, our findings identify the signaling pathways coupling the CCK-B receptor with up-regulation of COX-2 expression. This effect may contribute to this hormone-dependent gastrointestinal carcinogenesis, especially in the colon.
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PMID:Gastrin stimulates cyclooxygenase-2 expression in intestinal epithelial cells through multiple signaling pathways. Evidence for involvement of ERK5 kinase and transactivation of the epidermal growth factor receptor. 1223 23

The ingestion of probiotics is associated with various beneficial effects on human health and modifies the physiological homeostasis of the intestinal flora. Probiotics are microorganisms with some particular characteristics: human origin, safety in human use, bile and acid resistance, survival in the intestine, at least temporary colonization of the human gut, adhesion to the mucosa and bacteriocine production. Thanks to these characteristics, probiotics block the invasion of human intestinal cells by the enteroinvasive bacteria. Furthermore, they should be able to stimulate and modulate the intestinal immune response, and to protect and stabilize the mucosal barrier. Finally, the efficacy of probiotics should be evident and documented with valid studies. All their properties should be maintained during processing and storage. Probiotics are usually used to protect the host from pathogens. With regard to this, they are useful in the prevention of antibiotic and traveler's diarrhea and they may play a role in the management of gastric Helicobacter pylori infection. Furthermore, their efficacy in the treatment of infectious diarrhea, in inflammatory bowel diseases, in pouchitis and in food allergy has been shown. Probiotics can improve the symptoms of irritable bowel syndrome and of lactose malabsorption. Finally, it has been suggested that such microorganisms may play a role in the prevention of carcinogenesis and of tumor growth.
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PMID:[Probiotics: history, definition, requirements and possible therapeutic applications]. 1240 63

Probiotics are "living microorganisms which upon ingestion in certain numbers exert health benefits beyond inherent general nutrition". Since 1987, when the first publication on the properties of the Lactobacillus GG was done, overall, there have been over 200 publications in peer-reviewed scientific journals. This paper will report the status and the prospectus of probiotics research at the beginning of the Third Millennium. Probiotics have proven benefits in treatment and prevention of rotavirus diarrhoea in children and reduction of antibiotic-associated intestinal side-effects. Interesting results have recently been published regarding food allergies and atopic eczema in children. Prevention of vaginitis and of travellers' diarrhoea have also been reported. Promising results are being reported in patients with inflammatory bowel disease, cystic fibrosis, dental caries and irritable bowel syndrome. It has also been suggested that probiotics could enhance oral vaccine administration, and that they may help treatment against Helicobacter pylori infection, but further studies are needed. Future areas of research regard probiotics' role in the process of carcinogenesis, given their influence on the gut microflora, and as immune modulators in autoimmune disorders. The possibility of introducing appropriate genes to the probiotics to make them produce various compounds is also under investigation. However, there is still confusion in the minds of the authorities over whether a probiotic is a drug, a food, or a dietary supplement. The challenge is to continue research to define the appropriate uses of probiotics and discover new applications which will bring benefit to humankind.
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PMID:Probiotics in the third millennium. 1240 31

Recent studies have suggested a relationship between Helicobacter pylori infection and various important micronutrients, including iron and vitamin B12, suggesting likely biological factors in the association between Helicobacter pylori and microcytic or macrocytic anaemia. There is some evidence that direct or indirect consequences of Helicobacter pylori gastritis on acid secretion account for the role of the bacterium in the absorption process of iron and Vitamin B12. The plasma, intragastric and mucosal concentration of different antioxidant compounds such as ascorbic acid, a-tocopherol and beta-carotene is also affected by Helicobacter pylori gastritis supporting the possible role of Helicobacter pylori in the multistep cascade leading to gastric carcinogenesis. The relationship between Helicobacter pylori infection and micronutrients is, therefore, a promising and, until now, poorly investigated field of research.
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PMID:Consequences of Helicobacter pylori infection on the absorption of micronutrients. 1240 46

Intestinal metaplasia (IM) is part of a stepwise sequence of alterations of the gastric mucosa, leading ultimately to gastric cancer, and is strongly associated with chronic Helicobacter pylori infection. The molecular mechanisms underlying the onset of IM remain elusive. The aim of this study was to assess the putative involvement of two intestine-specific transcription factors, CDX1 and CDX2, in the pathogenesis of gastric IM and gastric carcinoma. Eighteen foci of IM and 46 cases of gastric carcinoma were evaluated by immunohistochemistry for CDX1 and CDX2 expression. CDX1 was expressed in all foci of IM and in 41% of gastric carcinomas; CDX2 was expressed in 17/18 foci of IM and in 54% of gastric carcinomas. In gastric carcinomas, a strong association was observed between the expression of CDX1 and CDX2, as well as between the intestinal mucin MUC2 and CDX1 and CDX2. No association was observed between the expression of CDX1 and CDX2 and the histological type of gastric carcinoma. In conclusion, these results show that aberrant expression of CDX1 and CDX2 is consistently observed in IM and in a subset of gastric carcinomas. The association of CDX1 and CDX2 with expression of the intestinal mucin MUC2, both in IM and in gastric carcinoma, indirectly implies that CDX1 and CDX2 may be involved in intestinal differentiation along the gastric carcinogenesis pathway.
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PMID:Expression of intestine-specific transcription factors, CDX1 and CDX2, in intestinal metaplasia and gastric carcinomas. 1247 24

Many epidemiological studies have shown a strong association between chronic Helicobacter pylori infection and subsequent development of gastric carcinoma in humans. To confirm this link more clearly, it is necessary to use this bacterium in experimental studies to develop gastric carcinoma in suitable experimental animals. Persistent H. pylori infection has recently been achieved in the Japanese Monkeys and Mongolian gerbil models, with results demonstrating that the sequential histopathological changes in the gastric mucosa are closely mimic the gastric mucosal changes caused by H. pylori infection in humans. Gastric mucosa infected with H. pylori exhibited significantly higher gastritis score, reduction in glandular height, increase in the number of Ki-67 positive cells and over expression of p53 protein and p53 gene mutation in the Japanese Monkey Model. In the Mongolian gerbil model, H. pylori infection enhances gastric carcinogenesis in combination with known carcinogens such as MNU and MNNG, and also demonstrated that H. pylori infection alone can result in the development of gastric carcinoma. However, diagnostic criteria of gastric carcinoma in animal models remain in the great discussion. These important results provide a starting point for further studies to clarify the mechanism of gastric carcinogenesis as a result of H. pylori infection and assist the planning of eradication therapy to prevent gastric carcinoma.
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PMID:Helicobacter pylori and gastric carcinoma--from the view point of animal model. 1252 42

Although debates still exist whether Helicobacter pylori infection is really class I carcinogen or not, H. pylori has been known to provoke precancerous lesions like gastric adenoma and chronic atrophic gastritis with intestinal metaplasia as well as gastric cancer. Chronic persistent, uncontrolled gastric inflammations are possible basis for ensuing gastric carcinogenesis and H. pylori infection increased COX-2 expressions, which might be the one of the mechanisms leading to gastric cancer. To know the implication of long-term treatment of antiinflammatory drugs, rebamipide or nimesulide, on H. pylori-associated gastric carcinogenesis, we infected C57BL/6 mice with H. pylori, especially after MNU administration to promote carcinogenesis and the effects of the long-term administration of rebamipide or nimesulide were evaluated. C57BL/6 mice were sacrificed 50 weeks after H. pylori infection. Colonization rates of H. pylori, degree of gastric inflammation and other pathological changes including atrophic gastritis and metaplasia, serum levels and mRNA transcripts of various mouse cytokines and chemokines, and NF-kappaB binding activities, and finally the presence of gastric adenocarcinoma were compared between H. pylori infected group (HP), and H. pylori infected group administered with long-term rebamipide containing pellet diets (HPR) or nimesulide mixed pellets (HPN). Gastric mucosal expressions of ICAM-1, HCAM, MMP, and transcriptional regulations of NF-kappaB binding were all significantly decreased in HPR group than in HP group. Multi-probe RNase protection assay showed the significantly decreased mRNA levels of apoptosis related genes and various cytokines genes like IFN-gamma, RANTES, TNF-alpha, TNFR p75, IL-1beta in HPR group. In the experiment designed to provoke gastric cancer through MNU treatment with H. pylori infection, the incidence of gastric carcinoma was not changed between HP and HPR group, but significantly decreased in HPN group, suggesting the chemoprevention of H. pylori-associated gastric carcinogenesis by COX-2 inhibition. Long-term administration of antiinflammatory drugs should be considered in the treatment of H. pylori since they showed the molecular and biologic advantages with possible chemopreventive effect against H. pylori-associated gastric carcinogenesis. If the final concrete proof showing the causal relationship between H. pylori infection and gastric carcinogenesis could be obtained, that will shed new light on chemoprevention of gastric cancer, that is, that gastric cancer could be prevented through either the eradication of H. pylori or lessening the inflammation provoked by H. pylori infection in high risk group.
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PMID:Chemoprevention of Helicobacter pylori-associated gastric carcinogenesis in a mouse model: is it possible? 1254 79


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