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)

Twenty-one invasive squamous-cell carcinomas (SCC) of the bladder from Schistosoma-hematobium-infected patients were examined immunohistochemically for the expression of p53, Rb, EGFR and c-erbB-2 proteins; and screened by single-strand conformation polymorphism and sequencing for mutations in the ras (H, N, K) codon hotspots (12, 13, 61) and p53 (exons 4-9) genes. Positive staining for p53, EGFR and c-erbB-2 was reported in 38, 67 and 28% of tumors respectively. Only one of the tumors, the only one that was poorly differentiated, displayed an absence of nuclear Rb staining. Ras alterations were detected in the H-ras gene in 3 tumors, 2 of which harbored a codon-13 (Gly-->Arg) and one a codon-12 (Gly-->Ser) point mutation. p53 mutations were recorded in 12 tumors (57%), 6 of which stained positively for p53. Four tumors had exon-7 mutations (codons 235, 241 and 249; one tumor had 2 exon-7 mutations). Eight tumors were mutated in exon 8 (codons 264, 271, 273, 285, 286, 288 and 294), 5 of which harbored multiple mutations. One tumor had an insertion/deletion event in exon 9. The frequency of detection of over-expression of EGFR and c-erbB-2 in bilharzial-bladder lesions is comparable to that reported in TCC, contrasting with the infrequent loss of Rb expression found in invasive lesions associated with schistosomiasis infection. However, the detection of multiple p53 mutations in these lesions is suggestive of the involvement of a carcinogenic agent with maintenance of preferential activation of the H-ras gene.
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PMID:Molecular events underlying schistosomiasis-related bladder cancer. 762 66

Gliosarcomas are morphologically heterogeneous tumors of the central nervous system composed of gliomatous and sarcomatous components. The histogenesis of the latter is still a matter of debate. As mutations of the p53 tumor suppressor gene represent an early event in the development of gliomas, we attempted to determine whether both components of gliosarcomas share identical alterations of the p53 gene. Using single-strand conformation analysis (SSCA) and direct DNA sequencing of the p53 gene, we analyzed dissected gliomatous and sarcomatous parts of 12 formalin-fixed, paraffin-embedded gliosarcomas. The two tumors that contained a p53 alteration were found to carry the identical mutation (exon 5; codon 151, CCC-->TCC; codon 173, GTG-->GTA) in the gliomatous and the sarcomatous components. These findings suggest a common origin of the two cellular components from neoplastic glial cells.
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PMID:Identical mutations of the p53 tumor suppressor gene in the gliomatous and the sarcomatous components of gliosarcomas suggest a common origin from glial cells. 766 53

The state of p53 tumour suppressor and the frequency of high-risk human papillomavirus (HPV) infections were studied in nine human oral cancer cell lines. Three cancer cell lines (SCC-4, Tu-177 and FaDu) had similar amounts of p53 transcripts to normal cells, but contained significantly higher levels of p53 protein than the normal control cells. Sequencing highly conserved open reading frames of the p53 gene of these cancer cells showed point mutations in the SCC-4 and Tu-177 cell lines, a base transition from CCC to TCC occurred at codon 151; and in the line FaDu, a mutation of CGG to CTG occurred at codon 248. The HEp-2 and 1483 cancer lines contained significantly lower levels of p53 protein compared to the normal counterpart. Sequencing of p53 cDNA for HEp-2 and 1483 lines showed no mutations, but northern analysis revealed that these cell lines expressed HPV-18 E6/E7 messages. Four cell lines (SCC-9, SCC-15, SCC-25, and Tu-139) expressed negligible amounts of p53 transcripts compared to the normal counterpart and undetectable levels of p53 protein. These cell lines contained mutations in the highly conserved open reading frames of the p53 gene as follows: the SCC-9 had a deletion of 32 base pairs between codons 274 and 285; the line SCC-15 had an insertion of five base pairs between codons 224 and 225; the line SCC-25 had a deletion of two base pairs in codon 209; and the Tu-139 line had a deletion of 46 base pairs between codons 171 and 186.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inactivation of the p53 gene by either mutation or HPV infection is extremely frequent in human oral squamous cell carcinoma cell lines. 770 4

An explant culture technique was used to culture normal urothelium from patients with muscle-invasive bladder cancer (transitional cell carcinoma, TCC) (n = 11) and from non-tumour-bearing patients (n = 60). Cell cultures were examined for expression of p53 using the monoclonal antibody p53-240. There was a statistically significant increase in p53 expression in normal urothelial cell cultures from patients with TCC (P < 0.0005). Normal urothelial cultures from patients with TCC also showed more rapid proliferation in vitro when compared with non-tumour-bearing patients (P < 0.0005). A subgroup of non-tumour-bearing patients (n = 14) showed > 5% of cells expressing p53. p53 expression in this subgroup was found to correlate with cell proliferation in vitro (r2 = 0.766). None of these urothelial specimens was observed to express p53 when paraffin-embedded preparations were stained with p53-D07 antibody prior to culture. The rate of cellular proliferation in this subgroup did not differ from that of normal urothelium from TCC patients. Twenty-two paraffin-embedded, muscle-invasive TCC specimens were also evaluated for p53 expression using p53-D07. The expression of p53 in these tumours did not differ from that observed in normal urothelial cell cultures from patients with TCC (P = 0.26). This study identifies an overexpression of p53 in normal urothelial cells from patients with TCC and in proliferating cultures from a significant subgroup of patients without malignant disease. Increased p53 expression in normal cultured urothelial cells from patients with bladder cancer implies a global change in the mechanisms controlling urothelial cell division. This may represent an early step in the pathway to carcinogenesis.
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PMID:Expression of p53 in urothelial cell cultures from tumour-bearing and tumour-free patients. 781 43

Mutations in the p53 gene occur frequently in bladder cancers. Better prognostic factors are needed to help select appropriate treatment for patients with TCC stage T1. Paraffin-embedded tumors from 73 patients with TCC stage T1 were processed for two-parameter flow cytometry, measuring both p53 protein and DNA. There were no statistically significant differences between the WHO grades with respect to p53 protein staining. Furthermore, there were no statistically significant differences between diploid, tetraploid and aneuploid tumors regarding content of mutant p53 protein. Neither were any statistically significant differences observed when ploidy and WHO grade were grouped together. Progression of disease was not correlated with positive p53 protein staining. These results indicate that mutant p53 protein cannot be used as a prognostic factor in TCC stage T1.
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PMID:Flow cytometric DNA and p53 analysis in superficially infiltrating bladder carcinoma. 787 10

In this paper the predictive value of molecular prognostic parameters for bladder cancer is discussed. DNA ploidy has additional prognostic value for grade 2 tumors, irrespective of stage, with aneuploid tumors having a poor prognosis. Overexpression of the epidermal growth factor receptor (EGFR) can be used as a prognostic factor for the group of superficial tumors. Both abnormal E-cadherin and retinoblastoma (RB) expression have additional prognostic value for invasive tumors. The exact predictive value for the superficial tumors needs further study. The results with respect to p53 are conflicting and its exact role especially in the progression of pT1g3 tumors has to be clarified. In view of the discordance concerning its prognostic value, c-erbB-2 overexpression also needs further study. It appears that at this moment only a few molecular markers seem to have potential prognostic value, but their precise clinical relevance has to be studied more extensively. In particular the value of progression markers in the superficial TCC needs more attention.
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PMID:Molecular prognostic factors in bladder cancer. 791 39

The tumor suppressor genes p53, Rb, and DCC were studied in five human oral cancer cell lines (FaDu, SCC-4, HEp-2, 1483, and OEC-M1) and in primary normal human oral keratinocytes (NHOK). All tested cancer lines had similar amount of p53 messages to normal cells, but the cancer lines FaDu and SCC-4 contained significantly higher p53 protein levels than did the normal counterpart. Sequencing p53 cDNA for these cancer cells showed point mutations: In the FaDu cell line, a mutation of CGG to CTG occurred at codon 248; and in the SCC-4 cell line, a mutation of CCC to TCC occurred at codon 151. The HEp-2 and 1483 cancer lines translated very low levels of p53 protein compared to the normal counterpart. Sequencing of p53 cDNA for HEp-2 and 1483 lines showed no mutations. Southern and Northern analyses revealed that these cell lines harbored HPV-18 DNA and expressed the viral E6/E7 protein. The OEC-M1 line showed different restriction fragment length polymorphism for the p53 gene compared with other cells, and did not express p53. All oral cancer cell lines except the OEC-M1 cells expressed both phosphorylated and hypophosphorylated Rb proteins. Further, the OEC-M1 line expressed smaller sized hypophosphorylated Rb proteins compared with normal cells. Unlike the other cancer lines, the HEp-2 and OEC-M1 lines also did not contain DCC mRNAs. These data indicate that "high risk" HPV infections and mutations of p53, Rb, and DCC genes are frequently found in oral cancer cells and may be associated with oral cancer.
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PMID:State of p53, Rb and DCC tumor suppressor genes in human oral cancer cell lines. 823 12

A new human pre-B acute lymphoblastic leukemia cell line (KMO-90) was established from the bone marrow sample of a 12-year-old girl with acute lymphoblastic leukemia (ALL) carrying 1;19 chromosome translocation. KMO-90 cells expressed HLA-DR, CD10, CD19, and CD22 antigens. These cells had also cytoplasmic immunoglobulin lacking surface immunoglobulin, indicating that these had a pre-B phenotype. Chromosome analysis of this cell line showed 48, XX, +8, +19, t(1;19)(q23;p13). Southern blot analysis showed the same sized rearrangements of the E2A gene in KMO-90 cells as those in the original leukemic cells. By means of reverse transcriptase-polymerase chain reaction analysis, we detected E2A/PBX1 fusion transcripts in KMO-90 cells. KMO-90 is useful when studying the role of the 1;19 translocation in the etiology of pre-B ALL. Furthermore, we studied alterations of the p53 gene in this cell line by polymerase chain reaction, single-strand conformation polymorphism analysis. KMO-90 cells were identified to have a point mutation at codon 177 (CCC-->TCC) of the p53 gene, suggesting that alterations of the p53 gene may have an important role in the establishment of this cell line.
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PMID:Establishment of a new human pre-B acute lymphoblastic leukemia cell line (KMO-90) with 1;19 translocation carrying p53 gene alterations. 841 23

The frequent change of the transitional cell carcinoma of the urinary tract accounts for the fact that cytological abnormalities in urinary specimens are often not sufficient to enable a definitive diagnosis of malignancy. The purpose of this work was to evaluate the possible use of p53 protein in increasing the diagnostic accuracy of urinary cytology. The expression of p53 was investigated by immunocytochemistry in two groups of urinary specimens, one cytologically positive and the other cytologically negative for cancer. Immunostaining was carried out using a monoclonal antibody to p53. In the positive group, in which bladder cancer was confirmed by cystoscopy and biopsy (31 cases), positive reaction for p53 was found in 55% of the cases (17 cases). In the negative group (92 cases), presence of cancer was histologically ascertained in 64 cases and in this group 15 cases (23.4%) showed positive p53 staining. In the remaining 28 cases of this group, where TCC was not present, 7 cases showed p53 positivity in non-neoplastic urothelial cells. This result shows that, while immunocytochemical detection of p53 in urinary specimens may be used for prognostic evaluation of patients with bladder cancer, it does not contribute to the diagnostic accuracy in cases with morphologically inconclusive or negative cytology. The sensitivity and specificity of the method in detecting bladder carcinoma were 23.5 and 75%, respectively.
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PMID:Does p53 immunostaining improve diagnostic accuracy in urine cytology? 940 4

Mutations of p53 gene have been found in a variety of human malignancies; however, the impact of immunohistological detection of p53 expression in the development and progression of TCC of the bladder is still uncertain. In the present study, we investigated the p53 oncoprotein expression and compared the findings to DNA ploidy and pathohistological stage and grade. The study included 147 patients with transitional cell carcinoma of the bladder investigated between February 1981 and September 1994. The average age of the 55 women and 92 men was 67 years (range: 20-71 years). A total of 76 patients (52%) had stage pTa to pT1, 35 (24%) stage pT2, 25 (17%) stage pT3, and 11 (7%) stage pT4 disease. Frozen sections of tumor biopsies obtained by transurethral resection were immunohistochemically stained using the monoclonal antibody clone D0-7 (DAKO), which recognized two different epitopes for mutant and wild-type p53 protein. Tumors expressing p53 in more than 10% of the tumor nuclei were regarded as positive. The DNA ploidy was determined by image analysis. Immunohistochemical detection of p53 expression was found in 84 (57%) of the 147 tumors examined. Positive p53 staining was seen in grade I tumors in 10 to 25%, in grade II tumors 25 to 75%, and in grade III up to 58% of the tumor nuclei. There was a positive correlation between p53 expression and pathological stage (28% in pTa, 73% in pT1-2, and 68% in pT3-4 tumors). There was no appreciable relationship between DNA Ploidy and p53. Although carcinomas with p53 expression had a slight tendency to be more prevalent among higher disease stages and poorly differentiated transitional cell carcinoma, immunohistochemical detection of p53 is not a valuable tool for predicting the outcome of patients with TCC or for identifying subgroups of patients that may be at a higher risk for tumor progression.
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PMID:Immunohistochemical detection of p53 protein in transitional cell carcinoma of the bladder in correlation to DNA ploidy and pathohistological stage and grade. 946 48


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