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)

Astrocytomas are the most common tumors of the central nervous system (CNS). Their malignant counterparts, anaplastic astrocytoma and glioblastoma, are lethal neoplasms with poor clinical outcome and they frequently carry mutations of TP53 tumor suppressor gene. In order to determine the frequency and type of this molecular alteration in the Polish population, we analyzed the polymerase chain reaction products corresponding to the most conservative exons 5-8 for single-strand conformation polymorphism and confirmed the presence of mutations by direct DNA sequencing. We identified mutations in one of five (20%) anaplastic astrocytomas and in eight of 28 (29%) glioblastomas; the mutations were most frequently identified in the exon 8 (six glioblastomas). The frequency of TP53 mutations is thus similar to the corresponding data from other studies, and the type of mutations suggests the participation of endogenous etiological factor.
Pol J Pathol 1997
PMID:TP53 mutations in malignant astrocytomas. 952 27

Within past few years, the investigation of molecular genetic markers has had an increasing influence on clinical decisions about initial treatment and follow-up. This review presents data concerning the most studied and interesting molecular markers in ovarian cancer. p53 tumour suppressor gene, Bcl-2 oncogene, K-ras oncogene, c-erb2 proto oncogene, c-myc oncogene are examples of currently used molecular genetic markers. Some of these markers might be useful adjuncts for monitoring response to therapy, including early detection of tumour reactivation to allow curative therapy and rapid detection of treatment failure. The study of these markers may also lead to a better understanding of the biological characteristics of ovarian cancer. The information derived from studies of these markers also represents the most promising avenue towards new treatment strategies.
Ginekol Pol 1998 Feb
PMID:[Molecular markers in ovarian cancer]. 959 89

The aim of the study was to evaluate the frequency of p53, mdm2 and Ki-67 immunopositivity in MFH, and to investigate possible associations of their expression with the grade of malignancy and predominant histological pattern--storiform, pleomorphic and myxoid subtype of MFH. A total number of 51 tumor samples from 21 primary and 30 secondary MFHs was studied using monoclonal anti-p53 (DO-78, DAKO), anti-mdm2 (1F2, NOVOCASTRA) and polyclonal anti-Ki-67 (DAKO) antibodies. The p53 immunopositivity was observed in 32.7% of all tumor samples (in 36.8% of primary and in 30% of recurrent and metastatic tumors). The mdm2 immunopositivity was noted in 34.8% of all tumor samples (in 33.3% of primary and 35.7% of secondary tumors). The mean percentage of p53, mdm2 and Ki-67 positive cells was 15.5, 8.8 and 7.05, respectively. The mean Ki-67 LI was statistically higher in grade 3 than in grade 2 of malignancy (p = 0.006). A significant correlation was found between mdm2 positivity and histological subtypes of MFH--storiform and pleomorphic types were more frequently mdm2 positive than myxoid variant (p = 0.035 and p = 0.009, respectively). No such correlation was observed for p53 positivity of tumors and subtypes, but there was a statistically significant difference in the percentage of p53 positive cells between storiform and myxoid type (p = 0.049). We also noted more tumors expressing high percentage (over 20%) of mdm2 positive cells in pleomorphic and storiform subtypes than in myxoid variant (p = 0.048). The Ki-67 LI was also higher in pleomorphic than in other types of MFH (p = 0.012). A strong positive correlation was found between p53 positivity and mdm2 positivity of tumors in primary MFHs (p = 0.00146). p53 and mdm2 positive tumors were mainly in grade 3 of malignancy, but no statistically significant correlations were noted. A positive correlation between the percentage of p53 positive cells and Ki-67 positive cells (p = 0.0028) was observed.
Pol J Pathol 1998
PMID:Immunohistochemical status of p53, mdm2 and Ki-67 in malignant fibrous histiocytoma. 964 Sep 70

Ethenobases are exocyclic adducts formed with DNA by some environmental carcinogens such as vinyl chloride or urethane. In the last few years, they have received a renewed interest due to the development of sensitive techniques of analysis that made it possible to measure their formation in vivo. This minireview summarizes the information gained recently from the work of several laboratories, including ours. Increased levels of DNA etheno adducts have been measured in target tissues from rodents exposed to vinyl chloride or urethane. Hepatic tumours caused by exposure to vinyl chloride in humans and in rats and lung tumours induced by urethane in mice exhibit base pair substitution mutations in the ras and p53 genes which seem to be exposure-specific and consistent with the promutagenic properties of ethenobases. Background levels of etheno adducts have been detected in DNA from non-exposed humans or animals, pointing to an alternative, endogenous pathway of formation. This background may be affected by dietary factors. It could arise from the reaction of trans-4-hydroxy-2-nonenal (or its epoxide 2,3-epoxy-4-hydroxynonanal), a lipid peroxidation product, with nucleic acid bases. Elevated levels of etheno adducts are found in hepatic DNA from humans and rodents with genetic predisposition to oxidative stress and lipid peroxidation in the liver, and with an associated increased risk of liver cancer. These data suggest that DNA ethenobases could serve as new biomarkers of oxidative stress/lipid peroxidation.
Acta Biochim Pol 1998
PMID:Formation of DNA etheno adducts in rodents and humans and their role in carcinogenesis. 970 7

A case of eosinophilic hyperplasia of the fallopian tube has been reported in a 71-year old woman with ovarian serous cystadenofibroma. Morphological characteristics and p53 protein expression of hyperplastic eosinophilic epithelium are then discussed.
Pol J Pathol 1998
PMID:Eosinophilic hyperplasia of fallopian tube mucosa. 979 16

DNA topoisomerases regulate the organization of DNA and are important targets for many clinically used antineoplastic agents. In addition, DNA topoisomerases modulate the cellular sensitivity toward a number of DNA damaging agents. Increased topoisomerase II activities were shown to contribute to the resistance of both nitrogen mustard- and cisplatin-resistant cells. Similarly, cells with decreased topoisomerase II levels show increased sensitivity to cisplatin, carmustine, mitomycin C and nitrogen mustard. Recent studies propose that topoisomerases may be involved in damage recognition and DNA repair at several different levels including: 1) the initial recognition of DNA lesions; 2) DNA recombination; and 3) regulation of DNA structure. The stress-activated oncogene suppressor protein p53 can modulate the activity of at least three different human topoisomerases, either directly by molecular associations or by transcriptional regulation. Since DNA topoisomerases have considerable recombinase activities, inappropriately activated topoisomerases in tumor cells lacking functional p53 may contribute to the genetic instability of these cells.
Acta Biochim Pol 1998
PMID:DNA topoisomerases as repair enzymes: mechanism(s) of action and regulation by p53. 982 82

Prognostic value of p53 gene mutation was determined in 95 radically operated non small cell lung cancer patients (78 males and 17 females, mean age 57.8 years). Study group included 62 cases of squamous cell carcinoma, 30--adenocarcinoma and 3--large cell carcinoma. There were 52 patients in stage I disease, 16--in stage II, 26--in stage IIIa and one--in stage IIIb. Paraffin-embedded samples of resected tumors were assayed for p53 mutations with the use of PCR/SSCP analysis. p53 mutation were present in 22 cases (23%). The median survival in patients with and without p53 mutations were 49 and 75 months (p = 0.46), respectively, and the five-year survival rate 53% and 50%, respectively. In stage I disease the median survival for patients with p53 mutation was 53 months and for those without mutations the median survival could not be determined as more then a half of them were alive. Median survival in stage II patients with and without mutations was 35 months and 44 months (p = 0.62), and in stage IIIA--9.5 months and 17 months, respectively (p = 0.37). The results of this study indicate that p53 gene mutation is not correlated with prognosis in non-small cell lung cancer patients.
Pneumonol Alergol Pol 1998
PMID:[Evaluation of the prognostic significance of P53 mutation in patients with non-small cell lung cancer]. 985 49

The aim of the study of 41 multiform glioblastomas was the analysis of p53-protein immunoreactivity in neoplastic cells and evaluation of relationship of this biologic marker to tumour proliferation activity. Positive p53 expression was observed in 24 (58.5%) tumours, the negative one in 17 tumours (41.5%). Proliferation indexes of PCNA, anti-Ki6 and AgNORs showed high values in the multiform glioblastoma p53 positive group, but without statistical differences in comparison with the group of p53-negative glioblastomas. Significant differences were observed in survival time of patients with p53 positive tumours in comparison with p53-negative ones. In 15 patients with p53-positive multiform glioblastomas survival time was less than 6 months (62.5%) on the contrary with only 4 patients with similar survival time in p53-negative glioblastoma group (23.5%). Our results suggest that p53 expression in multiform glioblastoma cells, generally considered as the indirect index of p53 suppressor gene, reflects aggressive stadium of neoplastic disease and significantly worsens the prognosis.
Neurol Neurochir Pol
PMID:[Expression of p53 protein and proliferative activity in multiform glioblastoma]. 986 16

Induction of the tumor suppressor protein p53 restricts cellular proliferation. Since actively growing cells require the ongoing synthesis of ribosomal RNA to sustain cellular biosynthesis, we studied the effect of p53 on ribosomal gene transcription by RNA polymerase I (Pol I). We have measured rDNA transcriptional activity in different cell lines which either lack or overexpress p53 and demonstrate that wild-type but not mutant p53 inhibits cellular pre-rRNA synthesis. Conversely, pre-rRNA levels are elevated both in cells which express mutant p53 and in fibroblasts from p53 knock-out mice. Transient transfection assays with a set of rDNA deletion mutants demonstrate that intergenic spacer sequences are dispensable and the minimal rDNA promoter is sufficient for p53-mediated repression of Pol I transcription. However, in a cell-free transcription system, recombinant p53 does not inhibit rDNA transcription, indicating that p53 does not directly interfere with the basal Pol I transcriptional machinery. Thus, repression of Pol I transcription by p53 may be a consequence of p53-induced growth arrest.
 ...
PMID:p53 represses ribosomal gene transcription. 1002 89

We investigated the frequency and mutual relationship of molecular alterations in 33 malignant astrocytomas (28 glioblastomas and 5 anaplastic astrocytomas). The genetic alterations analyzed were: deletion of CDKN2a/p16 gene, TP53 mutations, and amplification of EGFR, MDM2 and CDK4. The most common genetic alteration was EGFR amplification which was revealed in 15 cases (45%). TP53 mutation was identified in 9 cases (27%) and CDKN2/p16 deletion was detected in 13 cases (41%). Either MDM2 and CDK4 amplifications were less frequent, as they were identified in 4 (12%) and 1 (3%) case, respectively. Of the 15 cases showing the amplification of EGFR, 9 had CDKN2/p16 deletion (60%, p = 0.04). On the other hand, CDKN2/p16 deletion and EGFR amplification rarely occurred with TP53 mutations (2 of 14 cases with CDKN2/p16 deletion, 14%). These results confirm the existence of at least two different pathways leading to the formation of a glioblastoma.
Pol J Pathol 1998
PMID:Mutations of TP53, amplification of EGFR, MDM2 and CDK4, and deletions of CDKN2A in malignant astrocytomas. 1032 80


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