Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the effect of Helicobacter Pylori (Hp) on the process of gastric carcinogenesis, 35 cases of chronic gastritis, 20 cases of gastric adenocarcinoma were studied by use of transmission electron microscopy, immunohistochemical and molecular biological technique. The results showed that 24 of 35 cases of chronic gastritis were positive for Hp, 11/20 cases of gastric adenocarcinoma were Hp positive. PCNA positive cell labeling index (LI) in Hp-associated chronic gastritis (LI = 20.6 +/- 4.7) was higher than that in Hp negative chronic gastritis (LI = 11.3 +/- 5.2) (P < 0.05). HSP70 expression of gastric adenocarcinoma tissues in Hp-infected patients were lower than that of non-Hp-infected gastric cancer. p53 gene mutation was found in gastric adenocarcinoma with positive Hp. It was suggested that Hp may enhance gastric cell proliferation, decrease the expression of HSP70 which induces p53 mutation.
 ...
PMID:Role of Helicobacter pylori infection in pathogenesis of gastric adenocarcinoma. 1284 Aug 56

To determine the prevalence of gastric precancerous lesions and mucosal genetic alterations in relatives of a cluster of familial gastric cancer (FGC), we studied a kindred spanning two generations. The founder, daughter and niece underwent surgery for gastric cancer (GC); a son and other two daughters of the founder, presented with chronic dyspepsia. In all subjects, gastric mucosa samples were analysed for pathological features, Helicobacter pylori infection, microsatellite (MIN) and chromosomal (CIN) instability. The overexpression of mp53 and c-myc, and cytoplasmic beta-catenin delocalisation were found in the 2 younger cancer patients. All GC and gastritis patients had normal E-cadherin expression and were MIN-negative. Aneuploidy characterised all GC cases, and mixed euploid and aneuploid cell populations were present in the gastric biopsies from two of three 'at-risk' relatives. These two subjects, one of whom had severe active gastritis, and gastric mp53 and c-myc expression, were CagA-positive H. pylori-infected. DNA aneuploidy, p53 and c-myc expression disappeared after H. pylori eradication. In this FGC cluster, genetic abnormalities were found in first-degree relatives (3 patients) only in presence of H. pylori infection (2 cases H. pylori-positive versus 1 case H. pylori-negative) supporting the hypothesis that, besides the influence of a genetic profile, FGC may be, at least partly, mediated by intrafamilial clustering of H. pylori infection.
 ...
PMID:Is there a link between environmental factors and a genetic predisposition to cancer? A lesson from a familial cluster of gastric cancers. 1285 70

Intestinal-type gastric cancer is preceded by gastritis and intestinal metaplasia. There is uncertainty regarding the stage at which genetic alterations in the p53 gene occur. Reactive oxygen species (ROS) may participate in the production of mutations and the inactivation of p53 is due to infection by the bacterium Helicobacter pylori. We have investigated whether alterations of the p53 gene can be detected in gastritis and intestinal metaplasia using the restriction site mutation assay. We also assessed the potential contribution of ROS to p53 inactivation using electron spin resonance spectroscopy (ESR) and correlated with the presence of H. pylori. In all, 35% of the gastritis samples and 45% of the intestinal metaplasia samples were found to contain mutations in exons 5-8 of the p53 gene. Electron spin resonance spectroscopy analysis showed a significant increase in free radical levels in gastritis samples compared with normal, intestinal metaplasia and cancer samples, suggesting that free radicals present in gastritis may contribute to p53 mutations. There was no significant difference in free radical levels between the H. pylori-positive and -negative groups. However, a small subpopulation of the H. pylori-negative patients had much higher levels of free radicals. This suggests a more prominent role for other factors in ROS production.
 ...
PMID:Detection of p53 mutations in precancerous gastric tissue. 1452 Apr 66

Gastric ulcer is positively, and duodenal ulcer negatively, associated with the risk of gastric cancer. The relationship between a common p53 polymorphism at codon 72 and gastric cancer risk in patients with gastric and duodenal ulcer was examined in 397 Caucasian patients using PCR-RFLP. Noncardiac cancer patients had a distribution pattern of codon 72 genotypes similar to that of other non-cancer patient groups, though the frequency of the Pro/Pro genotype looks higher in duodenal ulcer. However, patients with cancer of the cardiac region had a significantly higher frequency of the Arg/Arg genotype than patients with chronic gastritis, duodenal ulcer, and noncardiac cancer. There was no significant difference in the distribution patterns between gastric ulcer and noncardiac or cardiac cancer or between gastric and duodenal ulcer. These findings may be a reflection of differences in the interaction between p53 codon 72 polymorphism and local factors in the stomach.
 ...
PMID:A comparison study of gastric cancer risk in patients with duodenal and gastric ulcer: roles of gastric mucosal histology and p53 codon 72 polymorphism. 1510 66

Gastritis and peptic ulcers result from Helicobacter pylori (H. pylori) infection. To analyze the influence of Helicobacter on inflammatory responses and cell proliferation, we used an animal model of H. pylori-induced gastritis in p53-knockout mice. H. pylori were introduced by gastric intubation into p53-knockout C57BL/6 mice. The animals were then followed-up for 1 year and compared with uninfected controls of the same genotype. Serum levels of anti-H. pylori antibody and histopathological changes were analyzed according to the updated Sydney System. Immunohistochemistry for proliferating cell nuclear antigen (PCNA) and TUNEL staining were also performed. The infected mice showed significantly increased levels of anti-H. pylori antibody in serum. Histologically, p53-knockout mice exhibited increased scores of chronic and active inflammation compared with uninfected controls. The PCNA and TUNEL indices were 25.5% and 10/mm, respectively, in the inflammatory foci of infected mice, and were increased compared with the controls. In the p53-knockout mice, H. pylori infection caused severe inflammatory reactions. The p53 gene may play an important role in inflammatory responses including cell proliferation and apoptosis.
 ...
PMID:Helicobacter pylori induces chronic active gastritis in p53-knockout mice. 1513 11

p53 mutations have been implicated in the development of esophageal malignancies. The purpose of this study was to assess more accurately the incidence and types of p53 mutations in Barrett's esophagus (BE) with and without dysplasia and in esophageal adenocarcinoma, using pure preparations of epithelial cells obtained by laser capture microdissection (LCM). Assays were performed on paraffin-embedded tissue samples of normal antrum and premalignant and malignant esophageal samples from 57 patients, including 16 controls, 10 with BE metaplasia alone, 20 with BE-associated dysplasia, and 11 with BE-associated adenocarcinoma. All tissues were processed for LCM. DNA was extracted from isolated cells, and polymerase chain reaction (PCR) was performed using oligonucleutide primers for exons 5-8 of p53. PCR products were processed for DNA sequencing. p53 sequence abnormalities were identified in 2/16 cases of normal antrum and regenerative/chemical gastritis, 1/10 cases of BE, 1/20 cases of BE with dysplasia, and 2/11 cases of adenocarcinomas. The abnormalities occurred in exons 7 and 8 in the form of point mutations. Our results, using LCM, show that p53 gene mutations are relatively rare in esophageal preneoplastic and neoplastic conditions. Only point mutations were detected, but no deletions/insertions were identified.
 ...
PMID:Evaluation of p53 mutations in premalignant esophageal lesions and esophageal adenocarcinoma using laser capture microdissection. 1525 14

In the progression of chronic gastritis, gastric mucosal cells deviate from the normal pathway of gastric differentiation to an intestinal phenotype. Many epidemiologic studies have found an association between the formation of intestinal metaplasia and the development of gastric carcinoma. However, there is no direct evidence that shows intestinal metaplasia is a precursor lesion of gastric carcinoma, to date. We periodically examined the intestinal metaplastic mucosa of Cdx2-transgenic mice we have previously generated. Gastric polyps developed from intestinal metaplastic mucosa in all stomachs of Cdx2-transgenic mice examined. These gastric polyps consisted of intestinal-type adenocarcinoma that invaded the submucosa and muscularis propria and occasionally spread into the subserosa. p53 and APC gene mutations were recognized in the adenocarcinomas. The participation of APC and p53 gene mutations in gastric carcinogenesis from the intestinal metaplasia was verified by the Cdx2-transgenic mice, carrying Apc(Min) mutation or p53 deficiency, that developed gastric polyps much earlier than Cdx2 alone. We successfully showed that long-term intestinal metaplasia induces invasive gastric carcinoma. These results indicate that intestinal metaplasia itself plays a significant role in the genesis and progression of gastric carcinoma.
 ...
PMID:Development of gastric carcinoma from intestinal metaplasia in Cdx2-transgenic mice. 1552 Jan 78

While the hyperplasia-neoplasia sequence of enterochromaffin-like (ECL) cells has been proposed in the pathogenesis of type I gastric carcinoids, the criteria for distinction between hyperplastic endocrine cell micronest (ECM) and neoplastic ECM have not been established. The aims of this study were to clarify differences between the hyperplasia and neoplasia of ECL cells and determine the optimal classification system for gastric ECL cell proliferations in type A gastritis. Endocrine cell lesions (n=531) from 8 surgically-resected stomachs with type A gastritis were reclassified as either atrophic ECM (n=333), hyperplastic ECM (n=168), neoplastic ECM (all ECM > or =0.1 mm in size, n=15), or typical carcinoid (n=15). Hematoxylin and eosin-stained sections were semiautomatically analyzed by nuclear morphometry. Immunohistochemical expression of bcl-2, p53 and Ki-67 was also investigated. As the histologic grade of histology advanced, the morphometric values of area, circumference and largest diameter of the nuclei significantly increased (p<0.0005), while the frequency of diffuse expression of bcl-2 significantly decreased (p<0.0001). Significant differences were also observed in all morphometric parameters and in bcl-2 positivity between the hyperplastic ECM and neoplastic ECM group. There was no expression of p53 in any of the lesions. The Ki-67 index did not differ between the neoplastic ECM and typical carcinoid groups. These results suggest that our system of classification for gastric endocrine cell proliferations in type A gastritis is appropriate. Nuclear morphometry and bcl-2 immunoexpression are useful parameters for the distinction of neoplastic ECMs from hyperplastic ECMs.
 ...
PMID:Multiple gastric carcinoids and endocrine cell micronests in type A gastritis: Nuclear morphometric and immunohistochemical analysis. 1570 7

In this series of experiments, a novel protocol was developed whereby gastric cells were collected using endoscopic cytology brush techniques, and prepared, such that interphase fluorescence in situ hybridization (FISH) could be performed. In total, 80 distinct histological samples from 37 patients were studied using four chromosome probes (over 32,000 cells analysed). Studies have previously identified abnormalities of these four chromosomes in upper GI tumours. Using premalignant tissues, we aimed to determine how early in Correa's pathway to gastric cancer these chromosome abnormalities occurred. Aneuploidy of chromosomes 4, 8, 20 and 17(p53) was detected in histologically normal gastric mucosa, as well as in gastritis, intestinal metaplasia, dysplasia and cancer samples. The levels of aneuploidy increased as disease severity increased. Amplification of chromosome 4 and chromosome 20, and deletion of chromosome 17(p53) were the more common findings. Hence, a role for these abnormalities may exist in the initiation of, and the progression to, gastric cancer. Helicobacter pylori infection was determined in premalignant tissue using histological analysis and PCR technology. Detection rates were comparable. PCR was used to subtype H. pylori for CagA status. The amplification of chromosome 4 in gastric tissue was significantly more prevalent in H. pylori-positive patients (n=7) compared to H. pylori-negative patients (n=11), possibly reflecting a role for chromosome 4 amplification in H. pylori-induced gastric cancer. The more virulent CagA strain of H. pylori was associated with increased disease pathology and chromosomal abnormalities, although numbers were small (CagA+ n=3, CagA- n=4). Finally, in vitro work demonstrated that the aneuploidy induced in a human cell line after exposure to the reactive oxygen species (ROS) hydrogen peroxide was similar to that already shown in the gastric cancer pathway, and may further strengthen the hypothesis that H. pylori causes gastric cancer progression via an ROS-mediated mechanism.
 ...
PMID:Fluorescence in situ hybridisation analysis of chromosomal aberrations in gastric tissue: the potential involvement of Helicobacter pylori. 1582 59

Gastric endocrine tumours (gastric carcinoids) usually grow from enterochromaffin-like (ECL) cells. Three types of tumour may be distinguished on the basis of the background gastric pathology: type I, which develops in atrophic body gastritis (ABG); type II, which is associated with multiple endocrine neoplasia and Zollinger-Ellison syndrome; and the sporadic type III, which is not associated with any background pathology. This classification plays a major role in determining the optimal approach to these diseases. In fact, type I carcinoids can be considered to be benign lesions, with exceptional risk of metastases. Type II, in contrast, may be associated with distant metastases, which are also common in type III carcinoids. The therapeutic approach is based mainly on endoscopic excision and somatostatin analogues in types I and II, or on surgical resection in type III. Both types I and II grow under the stimulus of hypergastrinaemia through a well-described sequence. However, gastrin is sufficient to cause ECL cell hyperplasia and dysplasia, but not transformation, which is due to menin defects in MEN-I patients, or to other unknown alterations in ABG. Several other candidates--including Bcl2, p53 and MMP9--have been linked with carcinoid initiation and progression. The biology of type III tumours which are not associated with hypergastrinaemia is still poorly understood.
 ...
PMID:Endocrine tumours of the stomach. 1625 92


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