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)

The early sequential development of gastric cancer was studied with experimental animals and examined with respect to what conclusions can be drawn for understanding carcinogenesis in man. After limited oral administration of N-methyl-N'nitro-N-nitrosoguanidine to 174 rats carcinomas developed in most cases directly from the otherwise unchanged mucosa through various successive stages of transformation, without passing through a benign-appearing proliferative or neoplastic epithelial lesion. Focal dysplasia grade I was the first recognizable change observed by light microscopy, followed by dysplasia grade II, and subsequently dysplasia grade III. In spite of very similar morphological characteristics, the experimentally induced dysplasias cannot be simply equated in their etiology and biological behavior with the dysplasias of the human stomach. Dysplasias of grade I and II commonly found in man are usually associated with a chronic gastritis; they are located in the upper third of the mucosa and are for the most part reversible. The experimental dysplasias occuring in the proliferative zone of an otherwise undisturbed mucosa must be considered potentially premalignant, as they are irreversible and develop progressively. This finding points out that in man dysplasias grade III within the regenerative zone of non-inflammatory mucosa should be considered particularly as possible precursors of gastric carcinomas.
 ...
PMID:Early sequential lesions during development of experimental gastric cancer with special reference to dysplasias. 39 7

The paper analyses interrelationships between chronic gastritis and carcinoma of the stomach. It has been recognized that various forms of chronic gastritis preceed carcinoma of the stomach. The source of the carcinoma origin is the epithelium of the gastric pit, intestinal and mixed epithelium. The nearest precursors of the carcinoma are foci of dysplasia of the epithelium developing in pits, intestinal cryptae and mixed glands. Proceeding from the regular emergence of the stomach carcinoma against the background of chromic gastritis, features of carcinogenesis in the stomach, and morphogenesis of chronic gastritis, the authors substantiate the pathogenetic connection between chronic gastritis and carcinoma of the stomach. Secondary changes in the gastric system have been found to develop in the III--IV stages of carcinoma. The main morphological features of carcinoma of the stomach of different histogenesis are characterized.
 ...
PMID:[Chronic gastritis and cancer of the stomach]. 42 61

The submucosal heterotopic gastric glands were found in 160 cases (10.7%) of 1500 resected stomachs; 15% in gastric ulcer, 9.9% in gastric carcinoma, 4% in duodenal ulcer and 11% in chronic gastritis. The heterotopic glands were usually found in the distal half of the stomach, diffusely or localized. Macroscopic submucosal tumor was found in 9 (5%) of 160 cases. Although the heterotopic glands were found with an intimate relation to the repeated mucosal damage and subsequent intestinal metaplasia, they had no specific relation to gastric carcinogenesis.
 ...
PMID:Heterotopic gastric glands in the submucosa of the stomach. 45 98

In children and adolescents from two areas of Costa Rica with contrasting gastric cancer risks, two factors suspected to be linked to the natural history of the disease were tested: serum antibodies to Helicobacter pylori and serum pepsinogen levels. One hundred fifty-five subjects from the high-risk area of Turrubares were compared to 127 from the low-risk area of Hojancha. No significant differences were found in the prevalence of IgG or IgA antibodies to Helicobacter pylori between the two regions. The prevalence of IgG was 65.8% in the high-risk area and 72.4 in the low-risk area, and that of IgA was 43% in both areas. The levels of pepsinogen, especially pepsinogen C, were significantly elevated in subjects with H. pylori antibodies in their serum. The mean levels of pepsinogen C in those negative, positive, and strong positive for H. pylori antibodies were 8.7, 14.3, and 21.1 ng/ml. These findings suggest that H. pylori-associated gastritis, predominantly of antral localization, is very prevalent in Costa Rican children and adolescents. Such gastritis might be associated with a high prevalence of intestinal metaplasia and a high gastric cancer risk in the inland, but not the coastal rural populations. H. pylori may therefore be an insufficient cause whose role in gastric carcinogenesis is contingent upon the presence of other factors.
 ...
PMID:Antibodies to Helicobacter pylori and pepsinogen levels in children from Costa Rica: comparison of two areas with different risks for stomach cancer. 130 56

Considerable knowledge has recently accumulated on the mechanism by which Helicobacter pylori (H. pylori) induces chronic gastritis. Although H. pylori is not an invasive bacterium, soluble surface constituents can provoke pepsinogen release from gastric chief cells or trigger local inflammation in the underlying tissue. Urease appears to be one of the prime chemoattractants for recruitment and activation of inflammatory cells. Release of cytokines, such as tumor necrosis factor alpha, interleukin 1 and 6, and oxygen radicals, leads to a further tissue inflammation accompanied by a potent systemic IgA and IgG type of immune response. Chronic inflammation and antigens on glandular epithelial cells lead to a progressive destruction with loss of the epithelial barrier function. Within the gastric mucosa, patches of intestinal metaplasia develop, which may be a risk factor for subsequent development of gastric carcinoma. Hyperacidity in duodenal ulcer patients induces gastric metaplasia in the duodenal bulb, which represents a target for H. pylori colonization and ulcer formation. H. pylori can be detected in the majority of patients with peptic ulcers and, compared to age-matched healthy people, it is also found more often in patients with dyspepsia and gastric carcinoma. Although H. pylori can be detected in healthy people, the marked reduction of the ulcer recurrence rate by eradication of H. pylori (80 percent versus 20 percent relapse within one year) suggests that H. pylori is a major risk factor for duodenal ulcer formation. The potential role of H. pylori in non-ulcer dyspepsia and carcinogenesis is under investigation. Current regimens aimed at eradicating H. pylori use a combination of several drugs that are potentially toxic. Since the risk of complications may exceed the potential benefit in most patients, eradication treatment should be limited to clinical trials and to patients with aggressive ulcer disease. New drug regimens, e.g., the combination of proton pump inhibitors with one antibiotic, may provide less toxic alternatives. Beyond ulcer treatment, effective and well-tolerated eradication regimens may have a place in prophylaxis of gastric carcinoma.
 ...
PMID:Pathophysiology and clinical relevance of Helicobacter pylori. 134 Oct 68

Evidence from pathology and epidemiology studies has been provided for a human model of gastric carcinogenesis with the following sequential stages: chronic gastritis; atrophy; intestinal metaplasia; and dysplasia. The initial stages of gastritis and atrophy have been linked to excessive salt intake and infection with Helicobacter pylori. The intermediate stages have been associated with the ingestion of ascorbic acid and nitrate, determinants of intragastric nitrosation. The final stages have been linked with the supply of beta-carotene and with excessive salt intake. Nitrosating agents are candidate carcinogens and could originate in the gastric cavity or in the inflammatory infiltrate.
 ...
PMID:Human gastric carcinogenesis: a multistep and multifactorial process--First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. 2129 57

Measurements of epithelial cell proliferation in the mucosa of the gastrointestinal tract pointed out the existence of cell kinetic abnormalities which can be involved in the first steps of carcinogenesis. In particular, an increase in the cell proliferation rate and an abnormal distribution of proliferating cells were found both in animals exposed to carcinogens and in human subjects at high risk of gastrointestinal cancer. In some diseases which predispose to cancer (i.e., chronic atropic gastritis, hereditary gastrointestinal cancer, sporadic colorectal neoplasia, chronic ulcerative colitis) we observed an expansion of the proliferative compartment even when the mucosa was not affected by morphological abnormalities. This proliferative feature seems to be associated with the presence of defects in cell differentiation. The abnormality is well detected by the histological examination of the proliferative pattern using microautoradiography after incorporation of tritiated thymidine, or using immunohistochemistry after bromodeoxyuridine uptake. The literature, and our own results, indicate that the search for abnormalities of epithelial cell proliferation can be useful in studying the earliest mechanisms leading to gastrointestinal cancer, in detecting subjects at high cancer risk, and for pilot chemoprevention studies using these abnormalities as intermediate biomarkers of gastrointestinal cancer risk.
 ...
PMID:Cell proliferation biomarkers in the gastrointestinal tract. 146 7

A systematic analysis of the cellular and structural components of intestinal metaplasia (IM) was carried out in 691 consecutive endoscopic gastric biopsies from Mexicans patients. Two-thirds of the patients (461 or 66.7%) had chronic gastritis, 27.6% (or 191 patients) had gastric ulcers and 5.6% (39 patients) gastric carcinomas. IM was found in 17.4% of the gastric biopsies. While IM was present in 27.7% of patients with gastric peptic ulcer, patients with gastric malignancy had only 18.7%, and the lowest rate (13.4%) was found in 461 biopsies from patients with chronic gastritis. IM was influenced by the age but not by the sex of the patients. Only one of 120 biopsies with IM (0.8%) had incomplete IM (a lesion claimed to be a precursor of gastric carcinoma). In a previous study it was found that 32.3% of 359 Swedish patients and 59.2% of 625 Japanese patients with chronic gastritis had IM, the proportion of incomplete IM being 23.3% and 25.1%, respectively. The low frequency of IM among Mexicans (a population with a low incidence of gastric carcinoma), contrasts with the moderate frequency of IM among Swedes (who have a moderate gastric cancer incidence) and with the high frequency of IM among Japanese (with a high incidence of gastric carcinoma). These findings recorded in disparate geographical regions strongly support the view that IM is a lesion evoked by environmental factors and associated with gastric carcinogenesis.
 ...
PMID:Low frequency of intestinal metaplasia in gastric biopsies from Mexican patients: a comparison with Japanese and Swedish patients. 161 99

One hundred and thirty partially gastrectomized subjects, who had been operated on for benign peptic ulcers, were studied to assess the histologic changes in the remaining gastric mucosa and its implications for gastric carcinogenesis. Endoscopic examination and multiple mucosal biopsies from the gastroenterostomy area and gastric body were compared histopathologically. Gastric carcinoma was found in two instances among these 130 patients, making a prevalence rate of 1.5% for carcinoma in the residual stomach. Chronic atrophic gastritis and pseudopyloric metaplasia were found to have developed more often in the gastroenterostomy mucosa than in the gastric body mucosa (p less than 0.001). The mean value of the gastritis score for gastroenterostomy mucosa (2.7 +/- 1.3) was statistically higher than that for the gastric body (2.1 +/- 1.0; p less than 0.001). The degree and types of histologic alteration in the gastric mucosa were also affected by the type of operation and by the postoperative duration. The mean value of the gastritis score and the frequency of pseudopyloric metaplasia, whether in the gastroenterostomy area and/or at the gastric body, were higher in Billroth II resections than in Billroth I resections. The gastritis score and the frequency of pseudopyloric metaplasia increased as the postoperative period increased. However, in the same postoperative period, the mean values of the gastritis score and the frequency of pseudopyloric metaplasia were higher in the gastroenterostomy mucosa than in the gastric body. Gastric dysplasia was more common in the gastroenterostomy area than in the gastric body. Patients who had received a Billroth II resection and those with a longer postoperative period had a higher frequency of gastric dysplasia.
 ...
PMID:A comparative study of gastric histopathology after partial gastrectomy between the gastroenterostomy area and gastric body. 168 78

Helicobacter pylori was implicated in gastric carcinogenesis through the induction of metaplasia of the gastric mucosa. In this experiment a co-carcinogenic effect of H. pylori on chemically induced gastric carcinogenesis was examined. Wistar WKY male rats received drinking water containing 50 mg/l of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and intragastric administration of 10(6) to 10(8) colony forming unit of H. pylori thrice a week for 40 weeks. Thus, 3 groups were assigned as Group I; MNNG alone, Group II; MNNG + vehicle, and Group III; MNNG + H. pylori (n = 30, each). At autopsy, 9 rats (30%) had 7 glandular stomach and 3 duodenal tumors in Group I, and 10 rats (33%) had 8 glandular stomach and 2 duodenal tumors in Group II, whereas in Group III 4 rats (13%) had 2 glandular stomach and 2 duodenal tumors (chi 2 = 4.257, P < 0.15 for the incidences of glandular stomach tumors among 3 groups). The finding seems to suggest that H. pylori has an ambitendency in the gastritis-metaplasia-carcinogenesis sequence as a promoter for the induction of the predisposing mucosa and as an inhibitor against certain carcinogens.
 ...
PMID:Helicobacter pylori is not a co-carcinogen in N-methyl-N'-nitro-N-nitrosoguanidine-induced rat gastric carcinogenesis. 184 54


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