UNIPROT:P04637 - FACTA Search

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Query: UNIPROT:P04637 (p53)
77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary mediastinal seminomas (MS) are rare tumors. Histologically, they are similar to their counterpart in the gonads. The survival rate has varied from 50% to 85% in different series. However, large series of these tumors primarily in the mediastinum are lacking. At the molecular level, a few reports document K-ras mutations in up to 40% of testicular seminomas (TS), localized predominantly to codon 12. Reports on TS p53 immunohistochemistry (IHC) range from negative to overexpression approaching 90% of cases, and by sequence analysis one small series showed a 23% mutation rate. To date, no analyses have been performed for either K-ras mutations or p53 immunohistochemical expression in primary MS. The authors studied 13 cases each of primary MS and TS from archival formalin-fixed, paraffin-embedded sections in which adequate tumor sampling and clinical history, including serological studies, and histological, histochemical, and IHC staining, were performed to confirm the diagnosis. p53 immunoperoxidase staining using citrate buffer/microwave antigen retrieval was performed. Topographic genotyping was performed on 5-microns-thick tissue sections up to 17 years old, in which the neoplastic cell population was sampled. Additionally, multiple sites within a given cases were sampled to determine clonality of the tumor cell population. Polymerase chain reaction and subsequent sequence analysis of the K-ras-2 exon-1 gene was used for mutation analysis. Focal weak staining with p53 IHC was observed in 4 of 13 (31%) MS and 10 of 13 (77%) TS cases, with all remaining cases being negative (P < .05). Only one MS case (8%) showed K-ras mutation (codon 13 GGC > GAC; glycine > aspartate), which is in contrast to 2 of the TS cases (15%), showing codon 12 mutations. All the remaining cases were wild type. Therefore, primary mediastinal seminomas appear to be different in their K-ras sequence and p53 immunostain profile from TS. Codon mutation type may be useful in determining primary versus metastatic origin of a mediastinal seminoma.
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PMID:Primary mediastinal and testicular seminomas: a comparison of K-ras-2 gene sequence and p53 immunoperoxidase analysis of 26 cases. 881 95

Mutation of the p53 gene plays an important role in neoplastic progression in human tumorigenesis. Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) techniques are now available for the detection of point mutations. The original method using polyacrylamide gel electrophoresis is disadvantageous, particularly for clinical tests and for analysis of large numbers of samples. Therefore, using an automated capillary electrophoresis (CE) technique with a molecular-sieving polymer solution, we have devised a completely automatic fluorescence-based PCR-SSCP system (CE-FSSCP) for the differential detection of point mutations that dose not require SSCP with radioisotopes and polyacrylamide gels. The automatic CE-FSSCP system was developed for reproducible operations in the denaturation of double-stranded DNA and electrophoresis of single-stranded DNA. The detection system consists of a 100 W I2 lamp and photomultiplier. We performed CE-FSSCP with a 2% linear polyacrylamide polymer solution containing 5% glycerol. Four tissue specimens of lung tumors with mutations in exon 7 of the p53 gene were found to have mutant alleles; six-base-pair deletion at codons 247-248, a one-base-pair deletion at codon 260, a one-base-pair deletion at codon 244 and a GGC to CGC substitution at codon 244. We expect this technique to prove useful for the clinical DNA diagnosis of human cancers, determination of the therapeutic effect of anticancer agents and for the study of the molecular aspects of the mechanisms involved in the pathogenesis of human cancers.
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PMID:Fluorescence-based polymerase chain reaction-single-strand conformation polymorphism analysis of p53 gene by capillary electrophoresis. 884 80

Long term survival is rare in patients with glioblastoma multiforme (GBM). To determine if the tumors of patients with long survivals constitute a subgroup of patients with identifiable molecular genetic characteristics, we studied the p53 gene and Epidermal Growth Factor Receptor (EGF-R) expression in long-term survivors of GBM. A review of the Tumor Registry of Memorial Hospital for Cancer and Allied Diseases documented that 521 patients were treated for GBM between 1954 and 1987 and that 12 patients had seven-year or longer survivals. Six additional long-term survivors were identified from other institutions. After pathological re-examination, the diagnosis of 8 of these 18 (44%) tumors was changed to other histologic tumor types. Using immunohistochemical analysis, 4 of 10 confirmed malignant gliomas had over-expression of p53. Polymerase chain reaction/single-strand conformational polymorphism (PCR/SSCP) analysis and sequence analysis of these 4 tumors showed no p53 mutations in exons 5-8, the region where most mutations have been reported in human malignancies. Immunohistochemical analysis for EGF-R was performed on the tumors of the 10 long-term survivors. EGF-R over-expression was identified in 4 (40%), which is consistent with previous reported studies for GBM in general. These findings suggest that there is a subset of GBM defined by the accumulation of wild-type p53 and that the over-expression of EGF-R does not preclude long-term survival. The seven-year survival rate for confirmed GBM in patients from the Memorial Hospital Tumor Registry was at least 1%.
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PMID:Long-term survivors of glioblastoma multiforme: clinical and molecular characteristics. 884 60

We investigated mutations of the p53 tumor suppressor gene in B-cell lymphoid neoplasms with reference to oncogene rearrangements associated with specific chromosomal translocations. These included 15 patients with a BCL1/PRAD1 gene rearrangement and/or PRAD1 overexpression, 45 with a BCL2 rearrangement, 2 with a BCL3 rearrangement, 24 with a BCL6 rearrangement, and 6 with both BCL2 and BCL6 rearrangements. Thirty-six patients lacked detectable oncogene rearrangements. Genomic DNA was isolated from involved tissues or leukemic cells obtained at diagnosis and/or at relapse, and established cell lines. Polymerase chain reaction-mediated single-strand conformation polymorphism analysis and direct sequencing were performed to analyze abnormalities of the p53 gene. We detected p53 gene alterations in 18 of 128 patients, representing 21 of the total 151 materials analyzed. In the total of 66 patients with an oncogene rearrangement studied at diagnosis, only one had a mutation; however, 6 of 37 patients studied at relapse showed p53 mutations. Sequential analysis revealed that the p53 mutation was closely associated with transformation from follicular lymphoma to large cell lymphoma, exclusively in BCL2-positive lymphoma cases. Two of 13 mutations observed in oncogene rearrangement-positive cases and cell lines were transitions at CpG dinucleotides. In contrast, the relationship between p53 mutations and clinical behavior in oncogene rearrangement-negative cases was variable; 5 patients including one with indolent follicular lymphoma were positive for p53 mutation at initial presentation, and 2 of the 5 showed prolonged disease-free survival. Our findings suggest that p53 alteration exhibits diverse functions in the development and progression of B-cell tumors related to the presence or absence of oncogene rearrangement, and that chemotherapy-related influences may be involved in the occurrence of progression-associated p53 mutations.
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PMID:p53 mutation in B-cell lymphoid neoplasms with reference to oncogene rearrangements associated with chromosomal translocations. 887 55

Inactivation of p53 gene products either by mutation or by complex formation with E6 oncoprotein encoded by high risk HPV appears to be a common event in cervical carcinogenesis. This study was designed to clarify this association in 41 primary cervical, 15 endometrial, 3 ovarian and one rectal carcinomas. Polymerase chain reaction analysis revealed presence of high risk HPV in 36 (88%) cervical, 5 (33%) endometrial and none of ovarian and rectal carcinomas. HPV 16 was found in 14 cervical carcinomas, HPV 18 in 19 cervical and 2 endometrial carcinomas and HPV 33 in 28 cervical and 5 endometrial carcinomas. Expression of tumor suppressor protein p53 by using polyclonal antibody CM-1, was detected in 28 (68%) cervical, 7 (47%) endometrial, 2 (66%) ovarian and one (100%) rectal carcinoma. Twenty six cervical and 3 endometrial carcinoma cases were positive for both high risk HPV and p53. We conclude that beside cervical carcinoma HPV infection is not uncommon in endometrial carcinoma and in our experimental design there is no inverse correlation between HPV infection and p53 over-expression in a variety of the tumors analysed in the present study.
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PMID:Infection of human papillomavirus (HPV) and p53 over-expression in human female genital tract carcinoma. 896 6

Distal colorectal cancers, especially those in the rectum, are more aggressive and more commonly recurrent than proximal cancers. We studied the possible relationship between p53-gene mutation type and location of the tumour, since mutations in the conserved areas of the p53 gene have been suggested to result in a poorer outcome of colorectal cancer than mutations outside these areas. Exons 5 to 8 of the p53 gene were studied in specimens from 72 colorectal-cancer patients. Polymerase-chain-reaction-amplified products of tumour DNA were analyzed by automated direct sequencing. Of the mutations detected in distal cancers, 71% were located in conserved regions of the gene, while only 42% of the mutations in proximal cancers were in these areas. In rectal cancers, 81% of the mutations were located in conserved regions. The tumours with mutations in the conserved regions were more often poorly differentiated (23%) than those with other mutations (0%). Our results indicate that mutations in the conserved regions of the p53 gene accumulate in distal but not in proximal tumours. This difference may be related to the more aggressive behaviour and to different aetiological factors associated with distal tumours.
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PMID:Conserved region mutations of the p53 gene are concentrated in distal colorectal cancers. 903 77

In the pathogenesis of cervical squamous cell carcinoma, an inverse correlation between human papillomavirus (HPV) infection and mutation of the p53 anti-oncogene has been suggested. Much less is known of a possible correlation in the case of adenocarcinoma of cervix. Twenty-five cervical adenocarcinomas and 7 adenosquamous carcinomas were analyzed for presence of HPV DNA sequences and overexpression of the p53 gene. Polymerase chain reaction revealed that 11 were positive for HPV DNA (34%). Seven were positive for HPV 16 and 5 for HPV 18. A mixed infection with HPV 16 and 18 was observed in 1 case. Patients with HPV-positive carcinoma were significantly younger than those with HPV-negative carcinoma (43 +/- 13.3 years versus 57 +/- 17.4 years, P = 0.01). Immunohistochemical staining showed that p53 was overexpressed in 11 of 32 cases (34%). Overexpression of the p53 gene was found in only 1 of 11 HPV-positive cases (9%) yet was evident in 10 of 21 HPV-negative cases (48%). This inverse association was statistically significant (P < 0.05). Prognostic analysis revealed that HPV-negative adenocarcinomas had a poorer prognosis than HPV-positive cases (P < 0.01) and that tumors with p53 overexpression also had a poorer prognosis than those without such overexpression (P < 0.01). Our observations suggest that HPV-negative or p53-positive adenocarcinomas may be a biologically distinct subset with a poorer prognosis.
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PMID:Correlation between human papillomavirus positivity and p53 gene overexpression in adenocarcinoma of the uterine cervix. 910 86

Primary squamous cell carcinoma of the endometrium (ESCC) is extremely rare. There has been no report of human papillomavirus (HPV) detected in ESCC. A 64-year-old Japanese female underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and dissection of the pelvic, para-aortic, and bilateral inguinal lymph nodes. The tumor was confined to the endometrium, without invasion of myometrium or cervix. The endometrium was seen to be replaced by moderately differentiated squamous cell carcinoma, without any adenocarcinomatous element. Polymerase chain reaction amplification produced a 244- to 256-bp DNA fragment from the L1 region of the HPV genome. The amplification products were restricted, and the restricted fragment length polymorphism patterns were analyzed. The squamous cell carcinoma DNA was amplified for each exon, 5 through 8, of the p53 gene. The amplification products were used in single-stranded conformation polymorphism analysis. The tumor described showed the presence of HPV DNA. This amplified fragment was further purified by extraction from agarose gel, and the DNA was sequenced. Comparison of the fragment DNA sequence with known PV sequences showed that it had been amplified from HPV type 31. This is the first detection of HPV DNA in ESCC. Despite previous reports, HPV cannot not be excluded as a possible factor in the development of the malignancy.
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PMID:Squamous cell carcinoma of the endometrium with human papillomavirus type 31 and without tumor suppressor gene p53 mutation. 910 11

We reported that 3'-azidothymidine-3'-deoxythymidine (AZT) plus 5-fluorouracil or methotrexate produces additive cytotoxicity in HCT-8 cells: a reflection of increased AZT metabolism when de novo thymidylate (dTMP) synthesis was inhibited. We now report that AZT plus human recombinant interferon alpha-2a (rIFN-alpha 2a) produces synergistic growth inhibition in these cells. Evaluation of the effect of rIFN-alpha 2a on dTMP metabolism revealed that exposure to rIFN-alpha 2a (+/-AZT) did not affect dTMP synthase activity significantly but increased thymidine (dThd) kinase activity significantly. Consequently, AZT nucleotide production and incorporation into DNA were increased by coexposure to rIFN-alpha 2a. This alone, however, cannot explain the observed synergism. Therefore, the effect of these agents on DNA excision/repair processes was assessed. Isotope clearance studies demonstrated that rIFN-alpha 2a did not alter the rate of [3H]AZT excision from DNA. In contrast, filter-elution studies revealed that rIFN-alpha 2a (+/-AZT) produced more DNA damage and delayed repair compared with the effects produced by AZT alone. Since DNA polymerases alpha and beta are directly involved in gap-filling repair synthesis, experiments next assessed the effect of rIFN-alpha 2a and/or 3'- azido-3'-deoxythymidine-5'-triphosphate (AZTTP) on their activities. Polymerase alpha was inhibited slightly by AZTTP but not by rIFN-alpha 2a. Polymerase beta activity, however, was inhibited dramatically by rIFN-alpha 2a + AZTTP. Finally, western analysis revealed that a 24-hr exposure to 5000 IU/mL rIFN-alpha 2a (+/-20 microM AZT) significantly reduced wild-type p53 expression compared with AZT-exposed cells. We conclude that rIFN-alpha 2a enhances AZT-induced tumor cell growth inhibition by (i) increasing AZT metabolism, and (ii) inhibiting DNA repair and p53-mediated cell cycle control processes.
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PMID:Human recombinant interferon alpha-2a plus 3'-azido-3'-deoxythymidine. Synergistic growth inhibition with evidence of impaired DNA repair in human colon adenocarcinoma cells. 910 9

Tumor specimens obtained from 136 patients with primary carcinoma of the uterine cervix were analyzed for the presence of human papillomavirus (HPV) sequences and for mutation of the TP53 gene. Polymerase chain reaction (PCR) showed that 130 of 136 (96%) tumors contained an oncogenic HPV 16 or 18 sequence. HPV 16 was the predominant type in cervical squamous cell carcinomas and HPV 18 was significantly associated with cervical adenocarcinomas (p < 0.05). The more dedifferentiated the primary tumor, the more frequent the HPV 16 infection and the more differentiated, the more frequent the HPV 18 infection (p < 0.05). Two out of 136 (1.5%) tumors demonstrated single-strand conformation polymorphism (SSCP) band shifts. One (positive for HPV 18) had a nonsense mutation of codon 101 in exon 4 from AAA to TAA transversion. Another (positive for L1 consensus primer set) showed a point mutation involving codon 179 in exon 5 changing CAT to CGT transition. The three specimens negative for HPV did not contain TP53 gene mutations. Our data show that mutation of TP53 is infrequent in primary cervical carcinoma and there is no inverse correlation between HPV infection and TP53 gene mutation. Other mechanisms independent of TP53 inactivation may also be implicated in tumorigenesis of the uterine cervix.
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PMID:Human papillomavirus infection and TP53 gene mutation in primary cervical carcinoma. 920

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