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)

We have developed a procedure for nonradioactive single strand conformation polymorphism analysis and applied it to the detection of point mutations in the human tumor suppressor gene p53. The protocol does not require any particular facilities or equipment, such as radioactive handling, large gel units for sequencing, or a semiautomated electrophoresis system. This technique consists of amplification of DNA fragments by PCR with specific oligonucleotide primers, denaturation, and electrophoresis on small neutral polyacrylamide gels, followed by silver staining. The sensitivity of this procedure is comparable to other described techniques and the method is easy to perform and applicable to a variety of tissue specimens.
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PMID:Detection of point mutations by non-isotopic single strand conformation polymorphism. 1034 69

The cellular changes leading to carcinoma of the lip are still not completely understood. This study was carried out on 44 malignant and potentially malignant lesions of the lower lip [30 squamous cell carcinomas (SCC), 7 actinic cheilitis, 3 leukoplakias, and 4 nodal metastases from lower lip SCC]. Silver-stained nucleolar organizer regions (AgNORs) and the immunohistochemical expression of proliferating cell nuclear antigen (PCNA), p53, and c-myc were evaluated on formalin-fixed, paraffin-embedded sections. The results indicate that the size and numbers of AgNORs and the percentage of PCNA-positive cells are sensitive parameters for discriminating between potentially malignant lesions and SCC, and for the prognostic sub-typing of lower lip SCC. Furthermore, while p53 positivity was found more frequently in high-grade carcinomas, p53-positive cellular clones were also found in some potentially malignant lesions, a finding probably related to ultraviolet-related cellular damage. These p53-positive lesions could be considered at higher risk of progression to malignancy than the p53-negative ones, although there is no evidence for this as yet. c-myc positivity was found only in some high-grade carcinomas and metastases, and appeared correlated with the later phases of lip carcinogenesis. The combined evaluation of the proliferation status, together with the changes in p53 and c-myc oncoproteins, might constitute useful markers for the prognostic evaluation of potentially malignant, as well as malignant, lesions of the lip.
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PMID:Potentially malignant and malignant lesions of the lip. Role of silver staining nucleolar organizer regions, proliferating cell nuclear antigen, p53, and c-myc in differentiation and prognosis. 1042 97

Although numerous studies have assessed the biologic parameters of tumors, measurement of these parameters has had, to date, little impact on histologic diagnosis. Furthermore, analysis of a single parameter is insufficient to evaluate tumor malignant potential. In the present study, cell proliferation, DNA ploidy and p53 product were analyzed to objectify the tumor malignant potential in colorectal adenomas and intramucosal carcinomas. Sixty-one adenomas and 49 intramucosal carcinomas were studied using immunohistochemical analysis of Ki-67 and p53, silver-staining nucleolar organizer region (AgNOR) stain and DNA ploidy in fresh samples. Intramucosal carcinoma exhibited a greater Ki-67-positive rate and AgNOR count than the adenomas, although these parameters varied widely among samples. The incidence of aneuploidy and p53 over-expression in colorectal intramucosal carcinomas was significantly higher than in colorectal adenomas. These results indicate that DNA aneuploidy and p53 accumulation are the most reliable parameters for distinguishing benign and malignant lesions.
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PMID:Usefulness of proliferative activity, DNA ploidy pattern and p53 products as diagnostic adjuncts in colorectal adenomas and intramucosal carcinomas. 1050 22

Cell culture, flow cytometry and silver-staining PCR-SSCP methods were used to explore the effects of sterigmatocystin(ST) (1 mg/L and 3 mg/L) on carcinogenesis and mutation of tumor suppressor gene p53 in human fetal gastric mucosal cells in vitro. Four weeks after treated with ST, the cells showed vigorous growth and malignant transformation foci. Twenty-four weeks after ST treatment, the cells could form cellular colonies in soft agar(the mean colony number was 15 and 17 perdish for ST 1 mg/L and 3 mg/L groups respectively). Flow cytometric analysis showed that both proliferation indexes (PI) and the cellular DNA contents of ST treated cells were much higher than those of normal control. The DNA contents of ST treated cells were in DNA aneuploid range. Mutant p53 protein expression was also significantly higher in ST treated cells. Silver-staining PCR-SSCP analysis showed that abnormal electrophoretic migration bands could be seen at exon 8 of p53 gene in ST-treated groups 22 weeks after ST treatment, while no abnormal bands were found in control group. Thus, the results further confirmed the carcinogenic effects of ST on human fetal gastricmucosal cells.
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PMID:[Mutation of p53 gene in human fetal gastric mucosal cells by sterigmatocystin in vitro]. 1068 99

This study was performed to examine the correlation between mutations of the p53 tumor suppressor gene, the occurrence of apoptosis, and proliferation in cholangiocellular carcinoma of the liver. The results obtained were compared with pathohistological stage (according to UICC) and grade and with disease related survival rate. In 41 curatively (R0-) resected intrahepatic cholangiocellular carcinomas, the status of the p53 gene was determined by direct sequencing of exons 4-9 and immunohistochemically. Apoptosis was assessed using the in situ end labeling (ISEL) technique in combination with morphological criteria. Proliferation was analyzed by immunohistochemistry of MIB-1 (Ki-67), Proliferating cell nuclear antigen (PCNA), and silver-stained nucleolar organizer regions (AgNOR). The results obtained were compared with pathohistological stage (according to UICC), grade, several other histopathological factors, and survival rate. Mutations of p53 were detected in 15/41 carcinomas examined (37%). The most common change was a G-->C and C-->T transition, changing the hot spot amino acid determined by exons 4-8. Of these 15 tumors, 14 were also p53-positive by immunohistochemistry. In each carcinoma examined, we could demonstrate MIB-1, PCNA, and AgNOR dots and also apoptotic cells in variable proportions. The proliferation markers showed a significant correlation among themselves. In univariate survival analysis, the extent of the primary tumor, lymph node status, grade, and p53 were significant factors influencing patient survival. Performing multivariate Cox regression survival analysis, however, only the extent of primary tumor and lymph node status had an independent prognostic impact. Apoptosis was not related to patient prognosis or to other parameters examined. In conclusion, these results indicated that p53 could serve as an additional prognostic parameter that could provide auxiliary information for patient outcome. However, tumor stage and lymph node involvement were the strongest prognostic factors. We failed to establish apoptosis or other pathological parameters as factors predicting the prognosis of patients with cholangiocellular carcinoma.
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PMID:Mutations of p53 tumor suppressor gene, apoptosis, and proliferation in intrahepatic cholangiocellular carcinoma of the liver. 1071 45

This review summarizes research advances of cytometric, proliferation, cytogenetic, and molecular "objective" measurable parameters, as additional aids to prognostic information of salivary gland tumors provided by classical clinicopathologic indicators. Flow cytometric DNA ploidy and S-phase fraction seem to be of value as predictors of tumor behavior, aneuploidy, and high S-phase identifying an unfavorable clinical evolution of salivary gland neoplasms. Cell proliferation markers assessed by immunohistochemistry (e.g., PCNA, Ki-67) also appear to have predictive significance, but some conflicting results, in part related to technical procedures, limit their routine clinical application. Silver-stained methods (AgNORs) show a scarce value in estimating prognosis of salivary gland malignancies. p53 and c-erbB-2 as well as karyotyping, are of disputable benefit for clinical use, but the biologic information they provide give a better understanding on the molecular mechanisms involved in the development and progression of tumors. Further studies, with large databases, long follow-up information, uniformized histologic classification, and standardized methodologies, are needed to establish how these "objective" parameters would be of truly beneficial for the treatment of patients with salivary gland tumors.
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PMID:Objective biologic parameters and their clinical relevance in assessing salivary gland neoplasms. 1097 8

Until recently the only way to rescue masked epitopes in routinely processed surgical pathological material was enzymatic digestion. The use of heat for antigen retrieval, first by microwave irradiation, represents an important breakthrough in immunohistochemistry. With the acceptance of microwave oven pretreatment, various modified techniques and alternative heating methods have also been proposed. Wet autoclave pretreatment for tissue proteolysis is a highly reliable alternative to the microwave antigen retrieval technique. It provides uniform heating of the slides, hence an even enhancement of staining intensity in a variety of formalin-sensitive antigens, and it also offers consistent interlaboratory results. The method has been introduced in routine diagnostic immunohistochemistry for the detection of estrogen- and progesterone receptors, L26-, Ki-67- and bcl-2 antigens and variable types of cytokeratins (1/5/10/11, 8, 13, 19). Experimentally, wet autoclaving can be used very successfully for the immunophenotyping of p53 and mdm2 expression, for the detection of adhesion molecules (CD44, integrins) and some anti-inflammatory molecules (annexins), among others. It has produced a substantial improvement in the visualisation of silver-stained nucleolar organizer regions- associated proteins (AgNORs) in routine paraffin sections and along with modified silver staining and standardized AgNOR parameters assessed by image analysis. Wet autoclaving-based AgNOR staining has been proposed by a European multicentric study group as the standardized method for AgNOR analysis in archival material.
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PMID:Significance of Wet Autoclave Pretreatment in Immunohistochemistry. 1117 90

After obtaining the results of p53 gene mutation by a silver staining method to polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis, P53 protein staining and proliferation cell nuclear antigen (PCNA) index by double-blind method, multivariate correlation analysis two by two showed that PCR-SSCP, P53 positive protein staining and PCNA index had markedly correlation not only in oral precancerous lesions (OPL) but also in primary sites and regional metastatic lymph nodes of oral squamous cell carcinomas (OSCC). This indicated that the nature of the three indexes was the same. After introducing the sex and age of patients which have been proved to be related to the initiation and development of OPL and OSCC according to other researchers and are easy to be obtained in clinics, multivariate discriminatory analysis was carried on and three groups of discriminatory equations were gotten about the pathological grading of OPL and OSCC and metastasis condition of OSCC. The accuracy of these equations was 82.5%, 78% and 80%, individually. This suggests that the equations have applicable potentiality already.
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PMID:[A study on the significance of p53 gene mutation, P53 protein positive staining and PCNA staining]. 1148 26

Heat shock protein hsp27 is a molecular chaperone and identification of hsp27-binding proteins might help to elucidate its functional role in keratinocyte biology. In the present investigation we used a human epidermal cell carcinoma cell line (A431) transfected with hsp27 (A431/16) to study interference between hsp27 protein and other proteins. Immunoprecipitation experiments with anti-hsp27 antibody revealed a multicomponent complex when analysed by silver staining. By immunoblotting analysis we could demonstrate that hsp27 associates with actin, the mutant form of p53, hsp70 and hsp90. Immunofluorescence analysis showed a co-localization between hsp27 and p53, hsp70 and hsp90. To control for the specificity of the observed interactions, immuno-precipitations with antibodies to actin, p53, hsp70 and hsp90 respectively, were performed. All of the tested proteins demonstrated a coimmunoprecipitation with hsp27. We conclude that hsp27, like the other heat shock proteins, is part of a complex system of molecular chaperones in epidermal keratinocytes.
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PMID:Characterization of proteins associated with heat shock protein hsp27 in the squamous cell carcinoma cell line A431. 1177 27

p53 and p185 expression in primary breast cancer with microsatellite instability (MSI) is still largely unexplored. To investigate the relationship between these oncoproteins and the pathways of genomic instability, we examined 52 primary invasive breast cancers stratified by the presence and absence of MSI. We determined the status of eight microsatellite loci using radioactive and silver staining methods, and evaluated the immunohistochemical expression of p53 and p185 in a consecutive series of Italian cancer patients characterized by clinical-pathological and biological parameters. Nineteen cases (36.5%) were MSI-positive in at least two loci. p53 was expressed in 15 cases (28.8%) and p185 in eight (15.4%). MSI-positive tumors were inversely correlated with p53 expression (p = 0.0007); in addition, the percent of p53-expressing cells decreased as the number of MSI-positive loci increased. MSI-positive tumors were correlated with a larger tumor size (p = 0.04), lymph-node metastasis (p = 0.001), and advanced clinical stage (p = 0.0006). These data demonstrate the existence of two subsets of primary breast cancers: one characterized by MSI, the other by p53 expression. MSI-positive patients had a more advanced and/or aggressive disease.
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PMID:p53 expression is decreased in primary breast carcinomas with microsatellite instability. 1216 Mar 31


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