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)

Recognition of premalignant lesions in the oral epithelium has the potential to increase survival rates for squamous cell carcinoma of the oral cavity. It has previously been reported that cytokeratin 19 (CK19), a 40-kd epithelial cytoskeletal protein within the suprabasal squamous epithelium, is a specific marker of moderate-to-severe dysplasia and carcinoma in situ in oral cavity squamous epithelium. In contrast, normal epithelium and hyperplastic lesions reportedly express CK19 only in the basal layer if at all. The authors chose to test and extend this hypothesis by studying suprabasal CK19 expression and dysplasia of the oral cavity and upper aerodigestive tract in paraffin-embedded specimens that had been fixed in alcohol, a superior fixative for the preservation of cytokeratins. The authors examined 56 alcohol-fixed, paraffin-embedded specimens including 37 from the oral cavity, using two antibodies specific for CK19 (Ks19.1 and 4.62), an antibody to the nuclear proliferation marker, proliferating cell nuclear antigen (PCNA) (19A2), and an antibody to the putative tumor suppressor gene, p53 (pAb1801). The lesions were classified as normal, hyperplasia, mild dysplasia, moderate dysplasia, severe dysplasia/carcinoma in situ, or invasive squamous cell carcinoma, following standard histologic criteria. Immunocytochemically stained sections were scored for the presence or absence of suprabasal CK19, suprabasal PCNA, and p53 positivity, regardless of location. The immunostaining patterns of the two anti-CK19 antibodies were essentially equivalent. Except for one laryngeal specimen, normal epithelium, when positive, showed CK19 expression only in scattered cells throughout the basal layer. Proliferating cell nuclear antigen-positive nuclei were found exclusively in the basal layer. In areas of hyperplasia, CK19 immunostaining was absent or confined to the basal layer in 20 of 38 specimens and was expressed in suprabasal cells in 18 of 38 hyperplastic specimens. Proliferating cell nuclear antigen immunostaining in all cases of hyperplasia was limited to the basal layer. Severe dysplasia and carcinoma in situ showed suprabasal CK19 staining in six of nine specimens and no CK19 staining in three of nine specimens. In contrast, suprabasal PCNA immunostaining was found in all dysplasia and carcinoma in situ cases. p53 expression was detected in three of nine severe dysplasia/CIS specimens and was immunocytochemically undetectable in all normal, hyperplasia, and mild to moderate dysplasia specimens. The authors conclude that suprabasal CK19 expression is neither a sensitive nor a specific marker of premalignancy in oral epithelium and cannot be used to distinguish hyperplasia from dysplasia. In contrast, a strong correlation between suprabasal expression of PCNA, a marker for proliferating cells, and dysplasia/carcinoma in situ was evident.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Markers for dysplasia of the upper aerodigestive tract. Suprabasal expression of PCNA, p53, and CK19 in alcohol-fixed, embedded tissue. 138 38

Alterations in the p53 tumor suppressor gene are the most frequent genetic abnormalities in human cancers. The p53 protein is present in normal cells, and is assumed to induce G1 arrest or apoptosis in the presence of DNA lesion. The mutant protein lacks this property. Squamous cell carcinomas of the head and neck (SCCHN) are related to carcinogens in tobacco and alcohol, and provide a good model of multiple-step carcinogenesis in association with DNA damage and p53-related tumorigenesis. Stabilization of the mutant p53 protein allows immunohistochemical analyses (IHC) to be routinely used to demonstrate the mutant p53 protein in tissue samples, whereas normal p53 protein is undetectable. Ninety-nine squamous cell carcinomas, 8 in situ carcinomas, 31 preneoplastic lesions and 79 normal carcinogen-exposed mucosas of the head and neck from a total of 107 patients were examined for the expression of p53 tumor suppressor gene protein. Samples were collected before treatment, and stained with p53 specific mono- and polyclonal antibodies (DO-7, Pab 1801 and 240, CM1) using an indirect immunoperoxidase technique. Proliferating cell nuclear antigen (PCNA) provided semiquantitative estimates of proliferation. The main localizations were the pharynx (64/107) and the larynx (21/107). Positive IHC detection of p53 was observed in 9% of normal-appearing carcinogen-exposed mucosas, 37% of hyperplasias, 68% of dysplasias, 75% of in situ carcinomas, and 56/99 (56.5%) of primary tumor samples. Mucosas from 15 control patients under 10 years of age were negative. There was no correlation between p53 IHC and localization, differentiation or TNM staging.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Immunohistochemical detection of p53 protein in preneoplastic lesions and squamous cell carcinoma of the head and neck. 761 Aug 36

Proliferating cell nuclear antigen (PCNA), nuclear DNA content and mutant p53 overexpression were studied by means of image cytometry and immunohistochemistry respectively in normal mucosa (n = 10), in mild (n = 16), moderate (n = 9) and severe (n = 17) atypical lesions, as well as in squamous cell carcinomas (n = 36) of the cervix uteri. The results show that increasing histopathological atypia in the cervical mucosa was correlated to an initial increase of PCNA followed by distinct aneuploidy and p53 overexpression. The data are suggested to contribute to a better understanding of the genesis of cervical carcinoma, and to indicate that the coexistence of both distinct aneuploidy and p53 immunoreactivity can be used to decide if a cell population is neoplastic, whereas the absence of p53 overexpression does not necessarily exclude neoplasia. This diagnostic procedure can be suggested to improve early detection of intraepithelial squamous neoplasia.
 ...
PMID:The relationship between proliferating cell nuclear antigen (PCNA), nuclear DNA content and mutant p53 during genesis of cervical carcinoma. 771 54

Ninety-nine polypoid neoplasms and eight advanced adenocarcinomas of the colon were studied immunohistochemically for p53 protein expression. For reproducible antigen retrieval, formalin-fixed, paraffin-embedded archival sections were heated at 90 degrees C for 120 min in 0.01 mol/L phosphate-buffered saline, pH 7.2, prior to immunostaining. Proliferating cell nuclear antigen served as a positive control marker for effective antigen retrieval. The 99 polyps were categorized into 24 high-grade adenomas, 60 non-invasive cancer-in-adenomas (CIA), and 15 CIA with stromal invasion. All the polyps contained portions of low-grade adenoma. Positive nuclear staining of p53 protein was observed in none of the non-neoplastic mucosa, nine (9%) of 99 low-grade adenomas, 17 (71%) of 24 high-grade adenomas, 46 (77%) of 60 non-invasive CIA, 10 (67%) of 15 invasive CIA, and five (63%) of eight advanced carcinomas. When the antigen retrieval treatment was omitted, the positivity rates were 0, 2, 17, 35, 40, and 63%, respectively. When the antigen-retrieved staining pattern was classified into (i) 'sparse' (< 25% of the nuclei of neoplastic glands labeled), 'scattered' (25-75%) and 'dense' (> 75%); or (ii) 'focal' (the positively labeled glands occupying < 25% of the tumor area), 'intermediate' (25-75%) and 'diffuse' (> 75%), the sparse and focal patterns predominated in high-grade adenomas and non-invasive CIA with low-grade atypia, while the dense and diffuse patterns predominated in invasive CIA and all the advanced carcinomas revealed the dense and diffuse patterns. Non-invasive CIA with high-grade atypia belonged to an intermediate type between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Immunohistochemical demonstration of p53 protein in colorectal adenomas and adenocarcinomas. Reliable application of the heat-induced antigen retrieval method to formalin-fixed, paraffin-embedded material. 783 78

Expressions of proliferating cell nuclear antigen (PC10), p53 protein (CMI) and c-erbB-2 (NCL-1) were immunohistochemically analysed in 123 renal adenocarcinomas with known follow-up data. c-erbB-2 protein was weakly and focally expressed in 10% of the tumours, and the expression was not related to clinical or histological variables or survival. p53 protein was expressed in 33% of the tumours. Expression of p53 protein was independent of stage, grade and prognosis, while expressions of c-erbB-2 and p53 were weakly interrelated. Proliferating cell nuclear antigen was expressed in all tumours, and the fraction of PC10-positive nuclei was significantly related to grade, stage and prognosis. Multivariate analysis of clinical, histological and immunohistochemical prognostic factors indicated that the extent of the tumour, its histological differentiation and proliferation rate of the cancer cells are the most important prognostic factors. Recurrence-free survival was related to the fraction of PC10-positive nuclei, histological differentiation, sex and expression of p53 protein. Over-expression of p53 protein was related to a long recurrence-free survival. Our results show that PC10 immunolabelling can be used to determine the prognostic category in renal adenocarcinoma, whereas the expressions of p53 protein or c-erbB-2 are only weak prognostic indicators.
 ...
PMID:Expression of proliferating cell nuclear antigen (PC10), p53 protein and c-erbB-2 in renal adenocarcinoma. 790 98

Progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the central nervous system (CNS) caused by infection with JC papova virus (JCV), is characterized by marked atypical changes in the glial cells. The JCV T protein binds cellular p53 (a tumor suppressor gene product), which as a result loses its normal down regulating influence on the cell cycle. We hypothesized that this binding would stabilize p53 and prolong its half life, leading to its immunohistochemical detection. To prove our theory combined JCV DNA:DNA in situ hybridization (ISH) and glial fibrillary acidic protein (GFAP) immunohistochemistry (IHC) as well as p53/GFAP double IHC were performed on routinely processed sections of five brains obtained at autopsy and two cerebral biopsy specimens from seven patients with PML. All specimens showed JCV infected oligodendrocytes and bizarre looking astrocytes that immunostained strongly for p53. In addition, because loss of p53 function results in proliferating cell nuclear antigen (PCNA) overexpression PCNA/GFAP double IHC was carried out, and a positive immunoreaction was obtained in JCV infected cells in the two biopsy specimens. The evidence of p53 immunoreactivity in JCV harboring glial cells seems to indicate a link between the JCV induced stabilization/inactivation of p53 and the striking tumorlike glial changes seen in PML. Proliferating cell nuclear antigen overexpression in these cells further supports this pathogenetic construct.
 ...
PMID:p53 and proliferating cell nuclear antigen expression in JC virus-infected cells of progressive multifocal leukoencephalopathy. 762 58

Proliferating cell nuclear antigen (PCNA) expression was studied by immunohistochemistry on paraffin-embedded sections of 293 primary colorectal adenocarcinomas and 56 corresponding lymph node metastases. PCNA-positive expression was detected in <25% of tumour cells in 172 (59%) cases and in > 25% in 121 (41%) cases. PCNA accumulation was related to over-expression of c-erbB-2 and p53 and tended to be increased in cases with ras over-expression. PCNA expression was identical in primary and corresponding metastases. No significant relationship was observed between PCNA expression and prognosis and other clinico-pathological variables, including grade of differentiation, growth pattern, Dukes' stage, site, age or sex. We conclude that PCNA expression may be related to alterations of oncoproteins but that PCNA itself could not provide additional information for the development of metastasis and prognosis in colorectal adenocarcinoma.
 ...
PMID:Proliferating cell nuclear antigen (PCNA) in relation to ras, c-erbB-2,p53, clinico-pathological variables and prognosis in colorectal adenocarcinoma. 860 60

Polyomavirus large T-antigen transgenic mice develop cardiac hypertrophy characterized by an increase in atrial natriuretic factor and beta-myosin heavy chain isoform expression. The aim of this study was to examine changes in proto-oncogene expression in hypertrophied hearts from the transgenic mice. Expression of early growth response-1 (Egr-1) mRNA was detected in hearts from all 15 transgenic mice, but was not detectable in 13 control mice. Reverse transcriptase-polymerase chain reaction experiments using Egr-1-specific primers confirmed the increase in Egr-1 mRNA in enlarged hearts from the transgenic mice. Expression of c-jun, junD and Ha-ras mRNAs was increased in the transgenic hearts 3, 17 and 2.8-fold respectively. Western blots showed an increase in c-myc, c-jun and ras protein in hypertrophied transgenic hearts. Immunofluorescence analyses confirmed an increase in Egr-1 and c-jun protein in transgenic cardiomyocytes. Proliferating cell nuclear antigen, Ki-ras and HSP 90 mRNAs were decreased 22, 2.7 and 3-fold, respectively in the transgenic hearts. Not altered in most hypertrophied hearts was expression of c-fos, junB, p53, c-neu, c-myc, HSP70, HSP27, TGF-beta or IGF 1 mRNAs. Proto-oncogene and growth factor gene expression in hypertrophy induced by PVLT expression is modulated with some proto-oncogenes increased and others decreased in expression.
 ...
PMID:Molecular remodelling in hypertrophied hearts from polyomavirus large T-antigen transgenic mice. 875 Nov 59

The term "nonfunctioning" pituitary adenomas (NFPA) implies heterogeneity, since it relies on a clinical definition that is mainly related to tumor mass. The first complaint is often of impaired visual function, and despite the secretion of gonadotropins, hypogonadism is frequent. NFPA must be differentiated from prolactinomas, because of the therapeutic implications, but although prolactin (PRL) levels greater than 200 ng/mL indicate prolactinoma, PRL levels of 100 to 150 ng/mL are equivocal. An assessment of gonadotropin response to gonadotropin-releasing hormone (GnRH) is of no use, but the thyrotropin-releasing hormone (TRH) test is invaluable. NFPA are monoclonal in origin, but genetic mutations data have not clarified their etiology, which remains largely unknown. Proliferating cell nuclear antigen expression is increased in recurrent adenomas, as is abnormality and overexpression of the protein kinase C family in aggressive tumors. Mutations of tumor-suppressor genes, such as the p53 and Rb genes, and of the metastasizing suppressor gene nm23, have been found in invasive tumors. Immunohistochemistry data confirm that most NFPA originate from gonadotroph cells; many NFPA are negative for all anterior pituitary hormones tested, although isolated or clustered cells are often positive for glycoprotein hormones or their subunits. Silent gonadotroph and also silent growth hormone (GH) or corticotroph tumors can constitute the anatomical basis for clinical NFPA. The heterogeneity of the immunohistochemistry data is reflected in the receptor complex of these tumors. Dopaminergic receptors have recently been visualized in vivo and there are also receptors for TRH or GnRH, since levels of alpha or beta subunits and intact gonadotropins increase after TRH or GnRH stimulation. As a result, three second-line pharmacological approaches have been tried: dopamine agonists, octreotide, and GnRH superagonists or antagonists, with tumor shrinkage of up to 11% to 20%. However, surgery should be tried first.
 ...
PMID:Nonfunctioning adenomas of the pituitary. 876 90

Proliferating cell nuclear antigen (PCNA) is an auxiliary protein for DNA polymerase delta and epsilon involved in DNA replication and nucleotide excision repair. There are two intranuclear fractions: a detergent-extractable, soluble fraction and a tightly DNA-bound fraction. To function, PCNA forms a trimeric sliding clamp which is loaded onto DNA. To better understand the role of the p53/p21 pathway in the regulation of PCNA after irradiation, we studied three closely related human lymphoblastoid cell lines, WTK1, TK6 and TK6E6, an HPV16 E6-transfected line, that differ in p53 status, radiosensitivity and susceptibility to radiation-induced apoptosis. Time-dependent changes in PCNA levels were measured in the different nuclear fractions by Western blot analysis after protein crosslinking. The results were compared to those for human diploid fibroblasts studied under different growth conditions. There was no change in total cellular levels of PCNA after irradiation, consistent with predominantly post-translational regulation. Changes in intranuclear distribution and complex formation occurred in a p53/p21-dependent manner. The loading of PCNA onto DNA was increased in cells with low p21 levels. A disruption of PCNA trimers was observed in exponentially growing p53+ cells in the soluble fraction. Thus the p53/p21 signal transduction pathway appears to play a significant role in the regulation of the response of PCNA to radiation.
 ...
PMID:The response of proliferating cell nuclear antigen to ionizing radiation in human lymphoblastoid cell lines is dependent on p53. 942 Nov 52


1 2 3 Next >>