Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastritis caused by infection with Helicobacter pylori is one of the most common infectious diseases worldwide. There are data on the epidemiology, pathophysiology and histology of this disease that show that Helicobacter pylori gastritis plays an important role in gastric carcinogenesis. However, we must remember that only a very few among those infected with Helicobacter pylori will develop gastric cancer. Hence, one of the main targets of future research will be to identify individuals who carry a greater risk for developing gastric cancer and may therefore benefit from eradication of Helicobacter pylori in terms of gastric cancer prevention.
 ...
PMID:[Helicobacter '98--epidemiology and significance in carcinogenesis]. 957 32

Humans infected with Helicobacter pylori have abnormally low levels of the antioxidant vitamin C, which protects against the formation of carcinogenic nitrosamines, in gastric juice. Guinea pigs, like humans and nonhuman primates, have a dietary requirement for vitamin C. As such, these species have gastrointestinal vitamin C transport systems not found in other animals. We have developed and characterized a guinea pig model of chronic gastric H. pylori infection with the rodent-adapted Sydney strain of H. pylori. At 4 weeks postinfection, five of six animals of the infected group and zero of two animals of the control group were positive for H. pylori as determined by culture or PCR. At 15 weeks, six of six animals of the infected group and zero of two animals of the control group were positive. H. pylori-specific seroconversion was observed among infected animals. There were no histologic abnormalities in the gastric antra or fundi of control guinea pigs. In contrast, there was multifocal, mild to moderate lymphohistiocytic antral gastritis and formation of antral lymphoid follicles in H. pylori-infected animals. The lesion distribution in the gastric antra paralleled that observed in H. pylori-infected humans. The H. pylori-infected guinea pig should prove useful in modeling the interaction of helicobacter and vitamin C in gastric carcinogenesis.
 ...
PMID:Experimental Helicobacter pylori infection induces antral gastritis and gastric mucosa-associated lymphoid tissue in guinea pigs. 959 24

We described the localization of human telomerase RNA (hTR) expression in human gastric precancerous and cancerous lesions by using in situ mRNA hybridization. Diffusely high hTR expression was found in all carcinoma and adenoma tissues. Partially high hTR expression was seen in 75% hyperplastic polyps, 47% complete-type intestinal metaplasia and 21% incomplete-type intestinal metaplasia. All chronic gastritis without intestinal metaplasia possessed normal levels of hTR expression. The expression of hTR was heterogeneous and infiltrating lymphoid cells also expressed high levels of hTR expression. Taken together, overexpression of hTR due to stem cell hyperplasia is an early event of carcinogenesis of the stomach.
 ...
PMID:[Analysis of expression of human telomerase RNA in gastric precancerous and cancerous lesions by using in situ mRNA hybridization]. 961 20

The accumulation of wild-type p53 protein results in two pathways, cell cycle G1 arrest by p21WAF1/CIP1/SDI1 and apoptosis inhibited by bcl2, which together carry out the tumor suppressor function. Since genetic alterations of p53 are frequently observed in gastric cancers, the expression of p21 and bcl2 may be altered in gastric carcinogenesis. We therefore analyzed normal mucosa, nondysplastic lesions, hyperplastic polyps, adenomas and carcinomas of the human stomach using immuno-histochemistry, polymerase chain reaction-single-strand conformation polymorphism and DNA sequencing. In normal gastric mucosa, the expression of p21, bcl2 and p53 was topographically restricted: a) p21 expression was limited to foveolar epithelial cells; b) bcl2 and p53 expression was confined to only a few regenerative epithelial cells of the mucous neck region. In chronic gastritis or intestinal metaplasia, topographic expression became more obvious. This topographic expression was altered in hyperplastic polyps and adenomas. Hyper-plastic polyp showed an increased p21 and p53 expression with no bcl2 expression. Where as bcl2 expression increased and extended up parabasal and superficial dysplastic epithelium, p21 expression increased and was limited to surface dysplastic epithelium. Weak p53 expression was in full thickness of dysplastic epithelium. p21 and bcl2 expression in adenoma was higher than in intestinal type of carcinoma. In carcinomas, this topography was abrogated, but p53 mutation (36%) was present. There was no relationship between p53, p21 and bcl2 expression. As a result, in normal gastric epithelial cells, there was a precisely ordered topographic pattern of p21, bcl2 and wild-type p53 expression that becomes disordered during neoplasia. These results suggest that altered cell cycle and apoptosis control by wild-type p53 and its mediators appears to be an early event in gastric carcinogenesis that may facilitate tumor progression.
 ...
PMID:Altered topographic expression of p21WAF1/CIP1/SDI1, bcl2 and p53 during gastric carcinogenesis. 965 43

Gastric cancer is the end result of a chronic process, which usually starts as Helicobacter pylori-associated chronic gastritis. Although some differences exist in the histological intermediary stages and in the frequency and timing of certain molecular alterations, both diffuse and intestinal cancer are accompanied by some important common cellular changes. These include an increase in cell proliferation, and an alteration in apoptosis, which may be secondary to loss of function of p53 and loss of growth inhibition by growth factor (TGF)-beta, due to mutation of the TGF-beta receptor type II. This review examines the potential role of H. pylori in the aetiology of the molecular changes during the progression to gastric cancer, and explores the usefulness of these changes as biomarkers of increased risk of neoplasia in the intermediate steps of gastric carcinogenesis.
 ...
PMID:Review article: Cellular markers in the gastric precancerous process. 970 Oct 7

The expression and coexpression of EGFR, c-erbB-2 and c-erbB-3 in 21 gastric cancers and 20 chronic gastritis was examined using immunohistochemistry on fresh frozen tissues considering clinicopathological variables. Generally, gastric cancer patients showed a higher incidence of EGFR, c-erbB-2 and d-erbB-3 overexpression than the group with chronic gastritis (81% and 43%; 38% and 45%; 35% and 20%, respectively), however, statistically significant differences were found only for EGFR expression (p = 0.01). No association between immunoreactivity of all growth factor receptors and the histopathological structure of gastric cancer was observed. EGFR and c-erbB-3 proteins were detected more frequently in patients with III/IV than in I/II of TNM stages, while c-erbB-2 overexpression was higher in I/II vs. III/IV stages. In chronic gastritis with intestinal metaplasia and or coexisting carcinoma lesions, a higher frequency of the expression of studied proteins was observed in comparison with chronic gastritis without those alternations; however, these differences were statistically insignificant. The percentage of positive cases with coexpression of two proteins was comparable in gastric cancer and chronic gastritis (33% and 35%) but the simultaneous expression of all three receptors was evident only in gastric cancer (19%). Our results indicate that at least one or two members of EGFR related receptors could appear in the early stages of gastric tumorigenesis. The enhancement of c-erbB-2 and c-erbB-3 reactivity seems to cooperate with EGFR activation in the gastric cancer development. Our results indicate the promotional rather than direct transformational role for EGFR supergene family in gastric carcinogenesis.
 ...
PMID:Expression of epidermal growth factor receptor family proteins (EGFR, c-erbB-2 and c-erbB-3) in gastric cancer and chronic gastritis. 970 36

The gastric remnant can be regarded as a model to investigate the events of gastric carcinogenesis of intestinal type. Histologic changes precursor of the malignancy develop in higher incidence in the postoperative stomachs than in non-resected ones. 316 patients hemi-gastrectomized for peptic ulcer were assessed by an endoscopic-histologic study to provide further informations on the sequential chain of histologic lesions that precede the development of cancer. The anastomosis was by far the commonest diseased area at endoscopy, particularly in the patients with a Billroth II resection (p < 0.0004). The 10% of the 233 patients biopsied evidenced a normal gastric mucosa, in the others Superficial Gastritis 74%, Chronic Atrophic Gastritis 36%, Cystic Dilatation 52%, Foveolar Hyperplasia 29%, Intestinal Metaplasia 39%, moderate-severe Dysplasia 6% as single abnormality or variously associated were observed. The stoma was the most damaged area at histology. The occurrence of the DC, the FI and the IM at the anastomotic site was significative (p values between 0.02 and 0.001). The earliest postoperative histologic lesion was the CAG, evidenced, in mean 13 years after operation, the latest the DC observed in mean 18 years after surgery (p < 0.004). The IM, the IF, the CD, and the dysplasia in association with the CAG were observed at postoperative intervals shorter when non-associated with CAG (respective p value: NS, < 0.03, < 0.0002, NS). The probability of transition from an histologic lesions to a more advanced one in our patients was similar to that of a non resected population at medium--high risk of gastric cancer.
 ...
PMID:[Residual gastric mucosa after gastrectomy: development of precancerous lesions]. 971 85

Inactivation of wild-type p53 during gastric carcinogenesis is usually caused by mutations within exons 5-8 of the p53 gene leading to mutated, usually immunohistochemically detectable p53 proteins. However, functional inactivation of wild-type p53, mimicking mutational inactivation, may also result from binding to overexpressed MDM2 protein. While these two mechanisms of p53 inactivation are considered to be mutually exclusive, no data exist as to whether MDM2 overexpression occurs during gastric carcinogenesis. MDM2 protein overexpression was therefore studied in relation to p53 protein accumulation in gastric carcinogenesis. Forty-five paraffin-embedded gastrectomy specimens from early gastric carcinomas were examined for the presence of chronic active gastritis, chronic atrophic gastritis, subtypes of intestinal metaplasia, and dysplasia. The Lauren type was reassessed for all early carcinomas. p53 protein accumulation was examined using the monoclonal antibody DO-7. MDM2 protein overexpression was assessed with the monoclonal antibody SMP-14. Complete absence of nuclear p53 protein accumulation was observed in chronic active gastritis, chronic atrophic gastritis, and intestinal metaplasia, irrespective of the subtype. In gastric dysplasia (one mild, two moderate, one severe), only severe dysplasia was p53-positive. Intestinal-type (n = 20) and diffuse-type early gastric carcinoma (n = 25) were p53-positive in 70 and 52 per cent of the cases, respectively. MDM2 protein overexpression was not observed during gastric carcinogenesis, either in the p53-positive or in the p53-negative cases. In conclusion, it appears that functional inactivation of wild-type p53 by MDM2 protein overexpression plays no role in (early) gastric carcinogenesis.
 ...
PMID:No evidence for functional inactivation of wild-type p53 protein by MDM2 overexpression in gastric carcinogenesis. 987 38

Chronic inflammation induced by Helicobacter pylori infection has been associated with an increased risk of stomach cancer. We have analysed 167 stomach biopsies from 99 patients for H. pylori infection and immunohistochemically for the expression of inducible nitric oxide synthase (iNOS), catalase and superoxide dismutases (SODs) as markers of oxidative stress. Biopsies were graded as follows on the basis of histology: normal, superficial gastritis, variable severity of atrophic gastritis with or without intestinal metaplasia, and dysplasia. iNOS was detected in inflammatory cells in all types of gastritis with or without H. pylori infection and independently of its severity. In foveolar cells, iNOS was observed in approximately 25% of all biopsies showing any type of gastritis, but in a markedly higher proportion of dysplastic samples. Catalase and Mn-type SOD in inflammatory cells and catalase in foveolar cells were more frequently observed in marked atrophic gastritis biopsies than in less severe gastritis. Individual differences were found in the expression of these enzymes within groups with the same severity of gastritis. Prolonged oxidative stress in severe gastritis and dysplasia may play an important role in gastric carcinogenesis, through increased damage of DNA and tissue by reactive oxygen and nitrogen species.
 ...
PMID:Inducible nitric oxide synthase, anti-oxidant enzymes and Helicobacter pylori infection in gastritis and gastric precancerous lesions in humans. 992 91

Low gastric juice total vitamin C concentration in the presence of Helicobacter pylori (H. pylori) infection probably plays a role in gastric carcinogenesis. In vitro vitamin C has been shown to inhibit the growth of H. pylori. The aims of this study were to determine the effect of high dose vitamin C administration on H. pylori infection and on gastric juice total vitamin C concentration in patients with H. pylori related chronic gastritis. Sixty patients with dyspeptic symptoms and proven chronic gastritis and H. pylori infection, who were undergoing routine endoscopy, entered the study after giving informed consent. They were randomly coded into two treatment groups. Group 1 (controls, n = 28) were treated with antacids for 4 weeks and Group 2 (n = 32) received vitamin C 5g daily also for 4 weeks. Nine patients did not complete the study and were excluded. Plasma and gastric juice total vitamin C levels were measured at baseline, at the end of 4 weeks treatment and again 4 weeks after treatment cessation. In the control group H. pylori infection remained unchanged in all 24 patients throughout as did the mean gastric juice total vitamin C concentration. However, in the vitamin C treated group eight of 27 patients (30%) who completed the treatment course the H. pylori infection was eradicated (P = 0.01). In these patients the mean gastric juice total vitamin C concentration rose significantly from 7.2 +/- 1.6 micrograms/ml after 4 weeks treatment (P < M 0.001) and 19.8 micrograms/ml 4 weeks after treatment was discontinued (P < 0.001). In the remaining 19 patients with persistent H. pylori infection, the mean gastric juice total vitamin C concentration rose less than in those with successful H. pylori eradication; 6.3 +/- 1.7 micrograms/ml before treatment, 10.8 +/- 1.5 micrograms/ml after 4 weeks treatment (P < 0.05) and a return to pre-treatment levels (7.1 +/- 2.7 micrograms/ml) 4 weeks after vitamin C intake stopped. There were no side effects of vitamin C treatment. This study has shown that 4 weeks daily high dose vitamin C treatment in H. pylori infected patients with chronic gastritis resulted in apparent H. pylori eradication in 30% of those treated. In those patients there was also a highly significant rise in gastric juice total vitamin C concentration which persisted for at least 4 weeks after the treatment ceased. A significant, though less marked, gastric juice total vitamin C concentration increase was observed during vitamin C treatment even in subjects with persistent H. pylori infection, though this was not maintained after treatment ended. The mechanism whereby vitamin C treatment appeared to result in H. pylori eradication is unclear. Further confirmatory studies are indicated.
 ...
PMID:Effects of high dose vitamin C treatment on Helicobacter pylori infection and total vitamin C concentration in gastric juice. 992 92


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>