Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038358 (gastric ulcer)
 5,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Helicobacter pylori is firmly established as a human pathogen; it fulfils all of Koch's postulates as the infectious agent causing chronic, active (type B) gastritis. Infection is strongly associated with duodenal and gastric ulcer. Recently, gastric mucosal-associated lymphoid tissue lymphoma has been successfully treated by curing H. pylori infection. Because of the evidence that the organism causes chronic gastritis and an increased risk of gastric cancer, it has been classified as a category 1 carcinogen by the World Health Organization. However, the overwhelming majority of people infected have no symptoms. Current eradication therapy is not ideal; there are treatment failures and substantial side effects. As a result, therapy should be reserved for people with clinical symptoms and complications. The infection, if present, should be treated in patients who have endoscopic evidence of mucosal ulcers in the stomach or duodenum. Current evidence does not support treating the infection to prevent gastric carcinogenesis or to alleviate symptoms of abdominal discomfort in the absence of peptic ulcers.
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PMID:Why guidelines are required for the treatment of Helicobacter pylori infection in children. 888 75

The development of carcinoma in cases of gastric ulcer disease during long-term H(2)-blocker treatment is slowly increasing, and ulcers that require such treatment exhibit the characteristics of intractable conditions, including linear ulcers, simultaneous gastric and duodenal ulcers, immature intestinal metaplasia of the gastric epithelium, and atrophic gastritis accompanied with multiple ulcer cicatrices. The incomplete form of intestinal metaplasia resembling Filipe's type III lesions and showing structural atypia developed in the background gastric mucosa in such cases, and the characteristics of this metaplasia included structural atypia, a residuum of gastric-type mucous cells, rapid proliferative activity, and in some areas abnormal expression of P53 protein. In addition, in rat studies it was demonstrated that prolonged administration of H(2)-blockers while gastric ulcers were present accelerated cell proliferation in the background gastric mucosa in the long term. Accordingly, it was considered possible that the development of the incomplete form of intestinal metaplasia, which was strongly suggested to have some relation to the sites where intestinal-type gastric carcinoma appeared, was accelerated by mucosal injury due to chronic ulcers and by persistent elevation in intragastric pH. The results of the present study of gastric carcinoma as a complication of peptic ulcer disease indicated the possibility that Helicobacter pylori was a major contributory factor to the development of the incomplete form of intestinal metaplasia from damage to the background mucosa, but it was unclear whether H. pylori made any direct contribution to carcinogenesis.
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PMID:Effects of medical treatment on gastric mucosal abnormalities in gastroduodenal ulcer disease. 1065 67

Most gastroduodenal ulcer disease results from a weakness in the normal gastric mucous barrier against the penetration of acid secreted by the stomach. Based on meticulous and insightful research, the distinguished physiologist Franklin Hollander hypothesized that the stomach is protected against its own acid secretion by a dynamic two-component mucus-mucosal barrier. Hollander and his co-workers defined the physical and chemical characteristics of the mucus components of this barrier, as well as the defense provided by the surface epithelial cell layer, which he viewed as the second line of defense (the second component). Barrier investigators at Mount Sinai demonstrated the effects of impairment of barrier function with resultant increased back-diffusion of acid, and they defined the consequences of this acid penetration into the gastric epithelium. The contribution of these workers included important observations on the natural impermeability of the gastric corpus and fundus as well as the normally increased permeability of the antrum. They also presented evidence on the role of bile in duodenogastric reflux in gastric ulcer disease and the presence of impaired barrier function in patients with gastric ulcer and pernicious anemia. Further studies included demonstration that stress and carcinogens could disrupt the gastric mucosal barrier. Disruption of the barrier, in turn, was shown to allow carcinogenesis to occur by permitting the absorption of certain carcinogens which otherwise are warded off by the barrier. The Hollander two-component gastric mucosal barrier hypothesis has, in recent years, been increasingly validated by experimental data coming from other laboratories.
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PMID:The gastric mucosal barrier. 1067 82

We report a case of gastric carcinoma after gastrojejunostomy (GJ-stomy) without gastrectomy. Multiple gastric carcinomas were discovered 21 years after GJ-stomy without gastrectomy which had been performed for treatment of pyloric stenosis due to severe gastric ulcer. Multiple gastric carcinomas were found in the stomach, or the esophagocardiac junction, and in the corpus and anastomotic lesion of the GJ-stomy. Under the light microscope, intestinal metaplasia was detected in the antral mucosa and the area around the anastomosis. In immunohistochemical analysis, p53-specific antibodies gave a positive reaction in every gastric carcinoma and in the noncancerous gastric glands around the carcinoma at the anastomosis and in the corpus. Cells positive for immunostaining with Ki-67-specific antibodies were more numerous in all gastric carcinomas and in the area around the anastomotic lesion than in the normal gastric mucosa. Hsp70-specific antibodies reacted with cells in the noncancerous glands around the carcinoma in the anastomotic area. Mucosal injury and the potential for carcinogenesis due to exposure to gastroduodenal reflux are discussed. The results of this study suggest that similar cases with gastroduodenal reflux should be followed carefully.
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PMID:Multiple gastric carcinomas 21 years after gastrojejunostomy without gastrectomy. Report of a case. 1112 65

The epidemiologic evidence and rodent studies suggest strongly that nonselective inhibitors of cyclooxygenase (COX) enzymes such as aspirin, inhibiting both COX-1 and COX-2 isoforms, reduce the incidence of and mortality from intestinal tumors. Genetically manipulated animals show that both Cox-1 and Cox-2 disruptions decrease the tumor yield, both in genetically predisposed and in carcinogen-treated mice. The mechanisms by which COX-1 and COX-2 deficiency decrease tumorigenesis are still unknown. Cox-2 overexpression increased the tumor yield in mammary glands of the multiparous, but not virginal female transgenic mice using the murine mammary tumor virus promoter. The Cox-2 protein was strongly induced during pregnancy and lactation. These data suggest that Cox-2 overexpression may be an important target for cancer chemoprevention. This finding was supported by the observed cancer-preventive effects of the COX-2-specific inhibitors in humans and in rodents. However, based on the available data, we cannot totally attribute the cancer preventive effects of nonsteroidal antiinflammatory drugs (NSAIDs) to COX-2 alone-even COX-1 may have an important role in cancer prevention as suggested by the Cox-1-deficient Min mice. It is likely that COX-1 plays a more important role in NSAID-induced toxicity in humans, such as in gastric ulcer formation-but inhibition of COX-2 may not be without toxic manifestations either, as suggested by the poor survival of the Cox-2-nulled mice. Combinations of COX-2 inhibitors with other agents that target other pathways in carcinogenesis may be a more efficacious and a less toxic strategy in cancer chemoprevention.
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PMID:Is COX-2 inhibition a panacea for cancer prevention? 1174 53

AIM:To study the telomerase expression in gastric carcinoma and its clinical implications.METHODS:Telomerase activity was examined in gastric cancer and corresponding normal tissues using a modified TRAP (telomeric repeat amplify-cation protocol) assay (TRAP-eze) in tissue samples from 94 gastric carcinomas and 58 normal tissues, 12 gastric adenomas and 9 gastric ulcer lesions.RESULTS:Telomerase activity was present in 81 of the 94 (86.2%) gastric cancer tissues, whereas no telomerase activity was detected in any normal tissues.The incidence of telomerase activity in gastric cancer tissues was unrelated to the tumor diameter, histological grade, tumor invasion in depth, lymph node metastasis and TNM stage.CONCLUSION:Telomerase plays an important role in carcinogenesis and progression of gastric cancer, and it is suggested to be a useful tumor marker.
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PMID:Telomerase activity in gastric cancer and its clinical implications. 1181 56

H. pylori infection is associated with major gastroduodenal diseases, i.e. peptic ulcer, cancer and MALT lymphoma in the stomach. The pathogenesis of H. pylori in these diseases has been elucidated. Non-atrophic diffuse antral gastritis is correlated with duodenal ulcer and multifocal atrophic gastritis is correlated with both gastric ulcer and cancer. It is well known that Japanese tend to have multifocal atrophic gastritis. H. pylori eradication therapy dramatically reduces the recurrence rates of gastroduodenal ulcers in humans and bacterial eradication for peptic ulcer patients has been recommended in many countries. Mongolian gerbils have provided an excellent model of gastric carcinogenesis and H. pylori enhanced (promoted) chemical carcinogen-induced carcinogenesis in the stomach using this model. H. pylori eradication reduced the incidence of gastric cancer in the Mongolian gerbil model. It was a recently discovered that a transforming clone carrying the translocation t (11;18) (q21;q21) forms a MALT lymphoma, the growth of which is independent of H. pylori and will not respond to bacterial eradication. In the early stage, the tumor can be successfully treated by eradication, but at a later stage additional genetic abnormality in the lymphoma may show no response to H. pylori eradication therapy.
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PMID:[Helicobacter pylori infection and gastric diseases--pathogenesis and effects of eradication]. 1221 59

Gastric Helicobacter pylori (Hp) infection in Mongolian gerbils is an established experimental model of gastric carcinogenesis resulting from the long-term Hp infection but functional aspects accompanying this Hp-induced progression from gastritis to the cancer, especially changes in gastric acid secretion, gastric blood flow (GBF) and gastrin-somatostatin link have been little studied. It is unclear whether Hp eradication therapy alters the functional and the histopathological changes in this animal model of Hp-infection. We examined the effects of intragastric (i.g.) inoculation of Mongolian gerbils with Hp strain (cagA+ vacA+, 5 x 10(6) CFU/ml) that had been isolated from a patient with gastric ulcer as compared to those induced by vehicle (saline) in gerbils with or without gastric fistula (GF) at 1.2, 4, 6, 9, 12 and 30 wks upon gastric inoculation with this bacteria. An attempt was made to evaluate the influence of anti-Hp triple therapy with omeprazole, amoxicillin and tinidazol on gastric Hp-infection and Hp-induced functional impairment of the gastric mucosa. Gastric mucosal biopsy specimens were taken for the assessment of the morphological changes and the presence of Hp infection using rapid urease test (CLO-test) and the density of Hp-colonization were assessed by counting of the number of bacterial colonies per plate. Gastric blood flow (GBF) was measured by H2-gas clearance technique and the venous blood and the gastric content were collected for the measurement of plasma gastrin levels and the gastric luminal somatostatin level by radioimmunoassay (RIA). The Hp in gastric mucosa was detected in all animals by culture and rapid urease test at various periods upon Hp inoculation. Basal gastric acid in non-infected conscious gerbils with GF reached the level of about 28 +/- 4 micromol/h and this was reduced by over 50% immediately upon the Hp-inoculation and persisted for time intervals tested up to 30 wk. Early lesions were seen 4 wks after the Hp-inoculation and consisted of chronic gastritis with thickened gastric mucosal foldings and elongated interfoveolar ridges. Edema and congestion as well as significant mucosal inflammatory infiltration with lymphoid infiltrate in lamina propria of the mucosa occurred in all infected gerbils. Adenomatous hyperplasia with cellular atypia was observed at 12 wk upon Hp-inoculation together with increased mitotic activity and numerous apoptotic bodies formation, while lamina propria was reduced leaving dilated atypical gastric gland situated "back-to-back". This glandular atypia failed to show lamina propria or submucosa infiltration corresponding to gastric intraepithelial neoplasia. The GBF in Hp-infected gerbils was significantly lower, and a 6-7 fold increase in plasma gastrin levels combined with a significant fall in gastric luminal somatostatin contents observed at all tested periods as compared to vehicle-controls and these effects were counteracted by anti-Hp triple therapy. We conclude that: 1). Hp-infection in Mongolian gerbils in early stages before adenocarcinoma formation results in the development of typical functional and pathological changes such as suppression of gastric secretion and impairment of both, gastric mucosal microcirculation and gastrin-somatostatin link, and 2). this deleterious influence of Hp on gastric morphology and gastric functions is greatly attenuated in gerbils treated with Hp-eradication therapy.
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PMID:Triple eradication therapy counteracts functional impairment associated with Helicobacter pylori infection in Mongolian gerbils. 1267 17

Hemigastrectomy for benign disease and Helicobacter pylori infection are risk conditions for the development of gastric cancer. Aim of the study was to compare gastric histology and precursor lesions of malignancy in these two conditions. The hemigastrectomy group included 351 consecutively endoscoped subjects operated for gastroduodenal benign disease. Six to ten biopsy specimens were routinely taken from the residual gastric mucosa. The intact stomach group included 2097 consecutively endoscoped symptomatic subjects, who did not receive eradication therapy against H. pylori. The histological findings were classified as normal mucosa (NM), chronic non atrophic gastritis (CNAG), chronic atrophic gastritis (CAG), intestinal metaplasia (IM) and dysplasia (DYS). One thousand and three intact stomachs were H. pylori negative, and 1094 showed H. pylori colonization. The age over fifty was a significant risk factor for the occurrence of IM (OR 2.52, P < or = 0.001) and DYS (OR 3.46, P < or = 0.001), while Hp-positivity was a risk factor for CNAG (OR 1.81, P < or = 0.001) and CAG (OR 3.88, P < or = 0.001). Gastroresection was associated to higher risk for CNAG (OR 1.53, P < or = 0.001) and DYS (OR 4.31, P < or = 0.001) and to a lower risk of CAG (OR 0.49, P < or = 0.001). Both in males and females the risk for CNAG was significantly higher in Hp-positive (males OR 1.92, P=0.000; females OR 1.70, P=0.000) and gastrectomized subjects (males OR 2.06, P=0.000; females OR 2.43, P=0.000). Gastrectomized males, furthermore, showed an increased risk for DYS (OR 5.82, P=0.000). The aged Hp-negative and Hp-positive subjects evidenced a significant risk for IM (respectively OR's 3.42, P=0.000 and 4.85, P=0.000); the risk for DYS was significant in aged Hp-negative subjects (OR 4.09 P < or = 0.020). The Hp-positive individuals evidenced a significant risk for metaplastic mucosal changes (OR 38.17, P=0.000). Subjects aged over forty at the time of surgery and those with a longer postoperative follow up endoscopy presented an increased risk for CNAG of the residual mucosa (respectively OR's 2.75, P=0.000 and 5.25, P=0.000). CNAG and IM were the most frequently observed mucosal lesions both in subjects operated for duodenal and gastric ulcer (respectively OR's 4.02, P=0.000 and 3.00, P=0.000). Our data support that hemigastrectomy for benign disease and H. pylori infection may induce an increased incidence for histological precursor lesions for gastric malignancy and suggest that carcinogenesis in a resected stomach may be different from that in the intact stomach.
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PMID:Cancer precursor lesions in intact stomach Helicobacter pylori gastritis and in resected stomach gastritis. 1458 93

Gastric epithelial cells were incubated with a panel of clinical isolates of Helicobacter pylori, including nonulcer dyspepsia with gastritis (HS, n = 20), gastric ulcer (HU, n = 20), duodenal ulcer (HD, n = 21), and gastric cancer (HC, n = 20). HC strains induced a higher cyclooxygenase-2 (COX-2) expression than those from HS, HD, and HU. The bacterial virulence factors and the host cellular pathways were investigated. Virulence genes of iceA, vacA, babA2, cagA 3' repeat region, and hrgA failed to show any association with the disease status and COX-2 expression. Methylation-specific polymerase chain reaction revealed HC strains not affecting the methylation status of COX-2 promoter. Nuclear factor (NF)-kappaB, NF-interleukin 6, and cAMP response element were found to be involved in COX-2 induction. We explored a novel NF-kappaB activation pathway. The mutants of TLR2 and TLR9, but not TLR4, inhibited H. pylori-induced COX-2 promoter activity, and neutralizing antibodies for TLR2 and TLR9 abolished H. pylori-induced COX-2 expression. Phosphatidylinositol-specific phospholipase C (PI-PLC), protein kinase C (PKC), and Src inhibitors inhibited COX-2 induction. The dominant-negative mutants of NIK and various IkappaB kinase complexes, including IKKbeta (Y188F), IKKbeta (Y199F), and IKKbeta (FF), inhibited the COX-2 promoter activity. Phosphorylation of GST-IKKbeta (132-206) at Tyr188 and Tyr199 by c-Src was found after H. pylori infection. In summary, H. pylori induces COX-2 expression via activations of NF-kappaB, NF-interleukin 6, the cAMP response element. In NF-kappaB activation, H. pylori acts through TLR2/TLR9 to activate both the cascade of PI-PLCgamma/PKCalpha/c-Src/IKKalpha/beta and the cascade of NIK/IKKalpha/beta, resulting in the IkappaBalpha degradation and the expression of COX-2 gene. The COX-2 overexpression may contribute to the carcinogenesis in patients colonized with these strains.
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PMID:Induction of cyclooxygenase-2 overexpression in human gastric epithelial cells by Helicobacter pylori involves TLR2/TLR9 and c-Src-dependent nuclear factor-kappaB activation. 1545 96


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