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

The objective of this study was to quantify the changes in p53 and cyclin D1 protein levels in different stages of human esophageal and gastric cardia carcinogenesis in a high-risk population in Henan, China. Immunoreactivity of p53, cyclin D1 and proliferating-cell nuclear antigen (PCNA) was observed in the cell nuclei of esophageal and gastric cardia biopsies. The number of p53-immunostaining-positive cells was low in normal epithelia, slightly increased in basal-cell hyperplasia (BCH), markedly increased in dysplasia (DYS) (10-fold), and further increased in squamous-cell carcinoma (SCC) (40-fold). This pattern of change was similar to that of cell proliferation as indicated by PCNA immunostaining. On the other hand, the number of cyclin D1-immunostaining-positive cells did not increase from BCH to DYS, although a slight increase from DYS to SCC was noted. In the gastric cardia, again, the pattern of change of p53-positive cells in different stages of lesions paralleled the pattern of cell proliferation. The number of p53-positive cells was very low, much lower than that of PCNA-positive cells, in normal, chronic superficial gastritis (CSG) and chronic atrophic gastritis (CAG); therefore, the increase of p53-positive cells from CAG to DYS was more dramatic (100-fold). From DYS to adenocarcinoma (AC), the p53-positive and the PCNA-positive cells increased 4-fold. On the other hand, the number of cyclin D1-positive cells did not increase in pre-cancerous lesions, but increased slightly in AC. This study demonstrates that p53 protein accumulation increased with the progression of pre-cancerous lesions, especially in the genesis of dysplasia, both in the esophagus and in the gastric cardia. Our approach of quantitative immunohistochemistry sheds light on the mechanisms of genesis of esophageal and gastric-cardia cancers, which frequently occur together in many high-incidence areas.
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PMID:Changes in p53 and cyclin D1 protein levels and cell proliferation in different stages of human esophageal and gastric-cardia carcinogenesis. 796 Feb 22

Two main histological variants of gastric carcinoma have been identified: intestinal and diffuse types. The former is preceded by a sequential chain of events characterized as chronic gastritis, atrophy, intestinal metaplasia, dysplasia, intramucosal carcinoma, and invasive neoplasia. The second type (diffuse) lacks well-recognized precursor changes. Genotypic events in the gastric precancerous process are described, but a clear model of their sequence and relevance is lacking. Cadherins may play a role in determining which type of carcinoma develops. Translocated promoter region-MET rearrangements have been identified since early stages of the process. p53 alterations are reported beginning with the dysplasia stage utilizing immunohistochemical techniques. Single-strand conformation polymorphism and sequencing analysis show alterations in early stages, especially G:C to A:T transitions.
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PMID:Phenotypic and genotypic events in gastric carcinogenesis. 813 16

Investigation of extensively sampled nontumor gastric mucosa from 205 early gastric cancers showed Helicobacter pylori colonization in 85% of cases, including 100% of diffuse and 78% (83% in 97 cases with Swiss rolls) of glandular or mixed cancers. Intestinal metaplasia, including its type III variant, was prominent in the mucosa associated with glandular and mixed (but not diffuse) early cancers. Both glandular (usually called "intestinal") and diffuse-type cancers showed admixtures of intestinal and gastric tumor cell phenotypes. Both p53 gene mutations and p53 protein immunostaining were essentially restricted to glandular or mixed cancers and associated dysplastic lesions. Their appearance in the advanced stage of diffuse cancer was partly due to a change of the histologic pattern from glandular to diffuse during progression of some tumors. Loss of laminin, beta I integrin, or zonula adherens junctions was a common finding in both early and advanced diffuse cancer. It is concluded that two main pathways operate in gastric carcinogenesis, both starting from H. pylori gastritis and both leading to phenotypically variable, often mixed gastric/intestinal tumor growth. However, only one of the two pathways involves intestinal metaplasia, its type III variant, p53 gene alteration, and dysplasia to end in glandular cancer. In the other pathway, diffuse cancer apparently arises directly from hyperplastic, sometimes atypical necks of mostly nonmetaplastic gastric glands, through primary involvement of genes affecting cell-cell and cell-matrix junctional proteins.
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PMID:Intestinal and diffuse gastric cancers arise in a different background of Helicobacter pylori gastritis through different gene involvement. 869 48

We examined the existence and distribution of apoptotic cells in human gastric mucosa, chronic gastritis, adenomatous dysplasias and carcinomas in 15 surgically removed stomachs in which dysplasia and carcinoma were found simultaneously. Serial sections were cut for immunohistochemistry for p53 oncoprotein and Ki-67 antigen, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labelling (TUNEL). TUNEL signal-positive apoptotic cells were rare in normal mucosa, while a few apoptotic cells were noted in gastritic mucosa and intestinal metaplasia, intermingled with Ki-67 antigen-positive cells forming a generative cell zone. This suggests the cell-cycle-dependent apoptosis of gastric mucosa. The frequency of apoptotic cells per crypt was higher in incomplete than in complete metaplasia, implying greater underlying DNA damage in the former. TUNEL indices (TI: percentage of TUNEL-positive cells in tumour cells) were slightly higher in adenomatous dysplasias (4.9 +/- 2.1) than in carcinoma (3.9 +/- 1.1), but there was no no statistical difference. Ki-67 indices (KI: percentage of Ki-67 antigen-positive cells in tumour cells) were significantly (P < 0.05) higher in carcinomas than in dysplasias. Thus, gastric adenomatous dysplasias were characterized by relatively higher TI and lower KI, which might reflect a more static growth potential. The expression of p53 oncoprotein in cancer cells is thought to be an apoptosis-suppressing event, although its precise role remains to be elucidated. Overall, these results indicate that apoptosis plays a crucial part in the morphogenesis of gastritic mucosa including intestinal metaplasia, and that the process is correlated both with tumourigenesis and with proliferative activity.
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PMID:Apoptosis in human gastric mucosa, chronic gastritis, dysplasia and carcinoma: analysis by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling. 876 31

This study evaluated whether the increased risk of development of gastric carcinoma due to chronic Helicobacter pylori infection could be linked with elevated cell proliferative activity and expression of p53 and bcl-2. Forty-eight patients undergoing therapy for H pylori-positive gastroduodenal ulcers were separated into not eradicated (NE; n = 23) and eradicated (E; n = 25) groups 6 months after the treatment. Serum pepsinogen (PG) I:II ratios and histologic changes in the gastric corpus and the antrum, assessed according to the modified Sydney System, as well as epithelial cell proliferation (mitosis, Ki67, and proliferating cell nuclear antigen [PCNA]), and expression of oncoproteins (p53 and bcl-2) were examined before and at 3 months and 6 months after treatment for H pylori. Chronic persistent H pylori infection was associated with a low PG I:II ratio, increased inflammation and activity score, and elevated cell proliferation, as evidenced by the Ki67 and PCNA labeling indexes and the mitotic index in the NE group. Scattered accumulation of p53 protein continued to be observed in the NE group after treatment but was significantly decreased in the E group. We conclude that persistent H pylori infection causes gastritis, with epithelial degeneration and regeneration that result in accentuation of epithelial cell proliferation and accumulation of p53 protein, presumably heightening the genetic instability consistent with the development of carcinoma.
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PMID:Enhanced cellular proliferation and p53 accumulation in gastric mucosa chronically infected with Helicobacter pylori. 920 75

Childhood acquisition of Helicobacter pylori is a critical risk factor for gastric cancer. Since tumorigenesis involves deregulation of proliferation and apoptosis, we examined gastric epithelial cell proliferation and apoptosis in H. pylori-infected children. Apoptosis and proliferation of gastric antral epithelial cells in biopsy specimens from patients with H. pylori-induced gastritis, secondary gastritis, and noninflamed controls were compared. p53 protein expression was examined immunohistochemically. Apoptotic cells were identified in the surface epithelium in each group. The apoptotic index was higher in specimens from patients with H. pylori gastritis (120 +/- 10) than secondary gastritis (50 +/- 10) and noninflamed controls (40 +/- 10, analysis of variance P < 0.005). Apoptosis decreased following H. pylori eradication and resolution of gastritis (P < 0.02). An expanded proliferative compartment was identified in H. pylori-induced gastritis (32.4 +/- 3.5; proliferative labeling index +/- SE) compared with secondary gastritis (18.9 +/- 2.8) and noninflamed controls (13.7 +/- 3.1, analysis of variance P < 0.01). The accelerated cell turnover was associated with p53 overexpression (analysis of variance P < 0.005). Accumulation of p53 was not associated with expression of the cyclin-dependent kinase inhibitor p21. The occurrence of altered cell turnover early in the natural history of chronic infection provides an explanation for the increased risk of gastric cancer development associated with childhood acquisition of infection.
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PMID:Increase in proliferation and apoptosis of gastric epithelial cells early in the natural history of Helicobacter pylori infection. 940 20

P53 overexpression, detected by immunohistochemical analysis, has been reported in about 50% of gastric cancers whereas scarce data are available on the p53 oncoprotein in precancerous gastric lesions. This study focused on the p53 expression in gastric cancerous and precancerous lesions. One hundred gastric specimens obtained during endoscopy were analyzed: 14 cases of normal gastric mucosa, 53 of chronic gastritis with intestinal metaplasia and/or dysplasia and 33 gastric tumors. An immunoperoxidase technique and monoclonal anti-p53 antibodies were employed. Eleven out of 31 gastric carcinomas overexpressed p53. No correlation was observed between p53-positivity and histological type and grade of tumors. All precancerous lesions were p53-negative. Our results suggest that p53 overexpression is a relatively late event in gastric carcinogenesis.
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PMID:Analysis of p53 expression in precancerous and malignant gastric mucosa. 945 3

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.
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PMID:Altered topographic expression of p21WAF1/CIP1/SDI1, bcl2 and p53 during gastric carcinogenesis. 965 43

Twenty-one Meckel's diverticula containing an adequate amount of assessable heterotopic gastric mucosa were investigated for epithelial changes. Marked or moderate foveolar hyperplasia was present in 52% and 29% of the cases, respectively. Four cases displayed an excessive epithelial proliferation indefinite for dysplasia. It is pointed out that reflux type gastritis or gastropathy, which is the most common lesion in the ectopic gastric mucosa of Meckel's diverticulum, can be associated with the same confusing epithelial proliferation as reflux gastritis in the stomach, but these lesions are best regarded as representing atypia of repair. Distinguishing features from dysplasia are maturation towards the surface, lack of hyperchromatism and abscence of atypical mitoses. Negative p53 immunostaining and localization of the Ki-67 positivity to the expanded neck region could be additive clues that can help to classify lesions indefinite for dysplasia as negative for dysplasia. On the basis of the similarities of the ectopic and ortotopic gastric mucosa, it is suggested that these additive clues previously used in other parts of the digestive tract could also apply for the stomach.
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PMID:Proliferative epithelial changes in ectopic gastric mucosa of Meckel's diverticula. 965 99

The evolution of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a multi-stage process, comprising the sequential development of chronic H. pylori-associated gastritis, low grade and high grade lymphoma. The genesis of MALT lymphoma embodies the mechanisms of both physiological immune responses and the acquisition of genetic abnormalities. The tumour probably originates from an autoreactive MALT marginal zone B cell, which is generated during H. pylori infection. As a consequence of a genotoxic insult induced by H. pylori infection, the progenitor tumour cell may become genetically unstable and develop genetic abnormalities such as the t(11;18) translocation, trisomy three, c-myc and p53 mutations during a phase of expansion, which lead to partial transformation. With the growth help from H. pylori specific T cells, this abnormal B cell clone may undergo clonal expansion and gradually form a low grade MALT lymphoma. Additional genetic abnormalities including the t(1;14) translocation and other uncharacterised events could completely transform this abnormal B cell clone and result in escape from T cell dependency. Finally, further genetic events such as complete inactivation of the tumour suppressor genes p53 and p16, and possible activation of c-myc oncogene by translocation or other undetermined abnormalities can result in high grade transformation
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PMID:Recent advances in our understanding of the biology and pathogenesis of gastric mucosa-associated lymphoid tissue (malt) lymphoma. 966 52


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