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)

The purpose of the present study was to carry out multivariate analysis of the effect of the expression of estrogen and progesterone receptors, p53, proliferative antigen (Ki67) and c-erbB-2 on 5-year survival in patients with invasive breast carcinoma concomitant with ductal carcinoma in situ. Material for study consisted of tissue specimens obtained from 48 patients undergoing modified Patey's mastectomy between 1991 and 1998. Univariate analysis revealed that the variables significantly affecting survival were tumour size on gross examination and the level of estrogen and progesterone receptors in the cells of invasive ductal carcinoma of the breast (for the level of significance p = 0.05). The Cox regression model revealed that the only independent variable having a significant effect on survival was the level of estrogen receptors in invasive cancer cells.
Pol J Pathol 2002
PMID:Prognostic significance of selected immunohistochemical parameters in patients with invasive breast carcinoma concomitant with ductal carcinoma in situ. 1201 22

We here report the influence of the cell cycle abrogator UCN-01 on RKO human colon carcinoma cells differing in p53 status following exposure to two DNA damaging agents, the topoisomerase inhibitors etoposide and camptothecin. Cells were treated with the two drugs at the IC90 concentration for 24 h followed by post-incubation in drug-free medium. RKO cells expressing wild-type, functional p53 arrested the cell cycle progression in both the G1 and G2 phases of the cell cycle whereas the RKO/E6 cells, which lack functional p53, only arrested in the G2 phase. Growth-arrested cells did not resume proliferation even after prolonged incubation in drug-free medium (up to 96 h). To evaluate the importance of the cell cycle arrest on cellular survival, a non-toxic dose of UCN-01 (100 nM) was added to the growth-arrested cells. The addition of UCN-01 was accompanied by mitotic entry as revealed by the appearance of condensed chromatin and the MPM-2 phosphoepitope, which is characteristic for mitotic cells. G2 exit and mitotic transit was accompanied by a rapid activation of caspase-3 and apoptotic cell death. The influence of UCN-01 on the long-term cytotoxic effects of the two drugs was also determined. Unexpectedly, abrogation of the G2 arrest had no influence on the overall cytotoxicity of either drug. In contrast, addition of UCN-01 to cisplatin-treated RKO and RKO/E6 cells greatly increased the cytotoxic effects of the alkylating agent. These results strongly suggest that even prolonged cell cycle arrest in the G2 phase of the cell cycle is not necessarily coupled to efficient DNA repair and enhanced cellular survival as generally believed.
Acta Biochim Pol 2002
PMID:Influence of G2 arrest on the cytotoxicity of DNA topoisomerase inhibitors toward human carcinoma cells with different p53 status. 1213 30

The aim of this study was to assess prospectively the occurrence of p53 and p16 mutations (considered separately and together) in NSCLC in terms of their clinical and prognostic relevance. Study group included 87 patients who underwent pulmonary resection for cure. p53 and p16 mutations were found in 22 (25%) and 14 (16%) cases, respectively. In eight patients (9%) both mutations were present, and the tendency for their common occurrence was significant (p = 0.02). There was no relation between mutation and clinical characteristics. Median survival in the entire group was 17 months and the 3-year survival probability--41%. There was no correlation between the occurrence of any mutation (considered separately or together) and survival. These results indicate that p53 and p16 gene mutations tend to occur together in NSCLC, however these alterations seem not to have noteworthy clinical and prognostic significance.
Pneumonol Alergol Pol 2002
PMID:[P53 and P16 gene mutations in non-small cell lung cancer]. 1214 79

The development and progression of astrocytic tumours is associated with acquisition and accumulation of genetic alternations. Loss of heterozygosity (LOH) on chromosome 17p., p53 mutations and overexpression of the platelet-derived growth factor (PDGF) receptor (chromosome 22q), are the most common detectable changes in astrocytomas (WHO grade II). Anaplastic astrocytomas (WHO grade III) involve LOH on chromosome 19q, deletion of p16 tumor suppressor gene on chromosome 9p and disturbed expression of gene RB on chromosome 13q. LOH on chromosome 10 is restricted largely to glioblastomas (WHO grade IV). This tumour also is characterized by amplification and/or overexpression of gene coding Epidermal Growth Factor Receptor (EGFR) on chromosome 7p. There is growing evidence that two genes encoding triiodothyronine receptors TR alpha [17q21] and TR beta [3p21-p25]) belong also to the group of genes involved in tumorigenesis. Mutations of these genes as well as markedly disturbed expression and function of the encoded proteins were found in tumour tissue. This is supported by facts. that T3 via TRs regulate proliferation, growth, differentiation and apoptosis, the processes that are deeply disturbed in tumour tissue. TRs affects also the action of certain protooncogenes (Mdm2) and tumor suppressors (p53, Rb).
Neurol Neurochir Pol
PMID:[The molecular basis of glia-derived tumours of the brain. Part I]. 1218 11

Ultraviolet (UV) irradiation produces DNA photoproducts that are blocks to DNA replication by normal replicative polymerases. A specialized, damage-specific, distributive polymerase, Pol H or Pol h, that is the product of the hRad30A gene, is required for replication past these photoproducts. This polymerase is absent from XP variant (XP-V) cells that must employ other mechanisms to negotiate blocks to DNA replication. These mechanisms include the use of alternative polymerases or recombination between sister chromatids. Replication forks arrested by UV damage in virus transformed XP-V cells degrade into DNA double strand breaks that are sites for recombination, but in normal cells arrested forks may be protected from degradation by p53 protein. These breaks are sites for binding a protein complex, hMre11/hRad50/Nbs1, that colocalizes with H2AX and PCNA, and can be visualized as immunofluorescent foci. The protein complexes need phosphorylation to activate their DNA binding capacity. Incubation of UV irradiated XP-V cells with the irreversible kinase inhibitor wortmannin, however, increased the yield of Mre11 focus-positive cells. One interpretation of this observation is that two classes of kinases are involved after UV irradiation. One would be a wortmannin-resistant kinase that phosphorylates the Mre11 complex. The other would be a wortmannin-sensitive kinase that phosphorylates and activates the p53/large T in SV40 transformed XP-V cells. The sensitive class corresponds to the PI3-kinases of ATM, ATR, and DNA-PK, but the resistant class remains to be identified. Alternatively, the elevated yield of Mre11 foci positive cells following wortmannin treatment may reflect an overall perturbation to the signaling cascades regulated by wortmannin-sensitive PI3 related kinases. In this scenario, wortmannin could compromise damage inducible-signaling pathways that maintain the stability of stalled forks, resulting in a further destabilization of stalled forks that then degrade, with the formation of DNA double strand breaks.
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PMID:DNA replication arrest in XP variant cells after UV exposure is diverted into an Mre11-dependent recombination pathway by the kinase inhibitor wortmannin. 1245 48

Oral papilloma is the most frequent benign tumor of the oral cavity but its biological potential for malignant transformation is still to be evaluated. The alteration of apoptosis and uncontrolled cell proliferation is considered to be an important factor in oral tumorigenesis. The aim of our study was to evaluate by immunohistochemistry P53, Bcl-2, CD44 and PCNA expression in oral papillomas with and without dysplasia. We examined a series of 55 oral papillomas, including 12(21.8%) cases of papillomas with epithelial dysplasia. Staining patterns were correlated with sex, age, tumor location, size and presence or absence of epithelial dysplasia. P53 showed positive reaction in 70.9%, PCNA in 80%, CD44 in 50.9% and Bcl-2 in 21.8% of papillomas. There was no correlation between sex, age, tumor size, location and presence of dysplastic epithelium in papillomas. We observed a statistically significant correlation between Bcl-2, CD44 expression and presence of epithelial dysplasia in papillomas. Coexistence of PCNA and P53 positive immunostaining was observed. Papillomas with overexpression of P53 and PCNA showed negative reaction for CD44 protein. The results of our study suggest that overexpression of P53 and PCNA might be an early event in oral tumorigenesis, whereas CD44 and Bcl-2 are potential markers of epithelial dysplasia in oral papillomas.
Pol J Pathol 2002
PMID:The expression of tumorigenesis markers in oral papilloma. 1259 36

Chronic-degenerative diseases (CDD) recognise a variety of exogenous and endogenous risk factors interacting with the organism for many years before disease onset. We applied genomic and postgenomic molecular analyses in experimental models characterised by different contribution of exogenous and endogenous CDD risk factors. Exposure of mice to halogen light for 28 days resulted in induction of cyclobutane dimers and oxidative DNA damage in the skin. Evaluation of postgenomic alterations by cDNA arrays revealed upregulation of DNA repair pathways, increased cell division rate and protooncogenes transcription, resulting in skin tumors, 1 year later. Exposure of p53-/+ mutant mice to cigarette smoke (CS) for 28 days induced DNA adducts formation in the lung. Postgenomic alterations included decreased apoptosis and increased cell division, as compared to CS-exposed wild type mice. These phenomena resulted in lung tumors, 9 months later. Transplacental exposure of mouse foetuses to cigarette smoke induced DNA adduct formation in the liver. cDNA arrays analyses demonstrated decreased cell division, apoptosis increase, and tissue hypoxia. These phenomena resulted in growth retardation of the whole organism. Molecular alterations were investigated in human trabecular meshwork, the non-replicating ocular epithelia involved in the pathogenesis of chronic degenerative glaucoma. Results indicate increased oxidative DNA damage in glaucoma patients as compared to unaffected controls. These four experimental studies suggest that DNA damage may result in different CDD (cancer, growth retardation, glaucoma) depending on the replication rate of the target cell population.
Acta Biochim Pol 2003
PMID:DNA damage and alterations of gene expression in chronic-degenerative diseases. 1267 55

TP53 is the most frequently mutated gene in human cancer, with a predominance of missense mutations scattered over 200 codons. In many cancers, specific mutation patterns can be identified, which are shaped by site-specific mutagenesis and by biological selection. In tobacco-related cancers (lung, head and neck), organ-specific patterns are observed, with many mutations compatible with the ones experimentally induced by tobacco carcinogens. In several other cancers, such as squamous cell carcinoma of the oesophagus or hepatocellular carcinoma (HCC), mutation patterns show geographic variations between regions of high and low incidence, suggesting a role for region-specific risk factors. HCC from high-incidence regions showing also a high prevalence of a specific Ser-249 TP53 mutation is one of the most striking examples of a mutagen fingerprint. All such assessments are useful to generate clues on the mutagenic mechanisms involved in human cancer. Moreover, it has been shown that DNA retrieved from plasma can be successfully used for detection of TP53 mutations, which gives hope for earlier more accurate detection of human cancers.
Acta Biochim Pol 2003
PMID:TP53 and mutations in human cancer. 1267 64

The aim of the study was to assess the frequency of serum Ab-anti-p53 in 39 patients with advanced NSCLC and to evaluate the predictive value of the test. Antibodies were present in 10 (25.6%) of patients. There was no correlation between Ab-anti-p53 and clinical characteristics including age, gender, and histological type of tumor. In 17 patients response to chemotherapy (CT) was obtained (in one patient--complete, and in 16--partial response). The percentage of patients responding to CT in group with and without serum antibodies did not differ significantly (33% and 48%, respectively; p = 0.48). The results of the study indicate that serum Ab-anti-p53 are relatively often present in advanced NSCLC patients, however the clinical value of this test needs further evaluation.
Pneumonol Alergol Pol 2002
PMID:[Serum anti-P53 antibodies (AB-anti-P53) in patients with advanced non-small cell lung cancer (NSCLC)]. 1270 76

The replication of damaged DNA involves cascading mechanisms of increasing complexity but decreasing accuracy. The most accurate mechanism uses low-fidelity DNA polymerases, Pol H and Pol I, which have active sites sufficiently large to accommodate a pyrimidine dimer. Replicative bypass of DNA damage by these polymerases produces an accurately replicated, newly synthesized strand. Pol H negative cells (XP-V cell lines) either adopt a proposed secondary bypass mechanism or a recombinational mode. The mechanism of the secondary bypass is unclear, but a number of experiments suggests roles for excision repair to remove damage ahead of replication forks, hRad6/18 proteolysis to clear the blocked forks, and the Rad17-RFC and 9-1-1 complexes to establish a new replication apparatus. This alternative pathway requires functional p53. In Pol H negative cells in which p53 is also inactive, the arrested fork fragments into DNA double strand breaks. Foci containing PCNA, Mre11/Rad50/Nbs1, and gamma-H2Ax can then be detected, along with chromosomal rearrangement and high frequencies of sister chromatid exchanges. The recruitment of recombination components to the arrested forks represents the ultimate failure of replication machinery to relieve the arrested state and bypass the damage. The resulting chromosomal instability in surviving cells will contribute to malignant transformation.
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PMID:Mechanisms by which human cells bypass damaged bases during DNA replication after ultraviolet irradiation. 1280 12


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