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)

Cyclooxygenase and particularly COX-2 expression impaired survival in patients operated on for endometrial adenocarcinoma of the uterus: 5-year overall and relapse-free survival in absence of expression was 92% and 88%, respectively, while in cases of distinct expression, it fell down to 52% and 48%, respectively (p = 0.0004; 0.0005). Similar correlations were observed for COX-1, although with lower significance (p = 0.02). Particularly unfavorable prognosis is associated with high expression of combination of COX-2 and COX-1. The end-results of radiotherapy were associated with proliferative levels of squamous cell cervical carcinoma: for Ki-67--below median of < or = 50%, 5-year survival rate was 77%, mean survival--80 months; for Ki-67 above median of > or = 50%, the indices were 47% and 47 months, respectively, (p = 0.002). There were similar correlations for mutated suppressor-gene 53: 67%--for absence of expression and 53%--for its presence (p = 0/03). Immunohistochemical markers COX-2, Ki-67 and p53 can be used as sole prognosticators and their predictive significance is higher than that of either stage (II or III) or cell differentiation grading.
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PMID:[Immunohistochemical markers as prognosticators in gynecologic oncology]. 1894 1

We evaluated the occurrence of mutations in P53, K-RAS, COX-2, expression of COX-2 and hTERT and relations among clinicopathological signs. P53 mutations were identified in 34.4% of tumours, the majority of them occurring in SCC (squamous cell carcinoma, 55.6%). K-RAS was mutated in 12.2% of NSCLC tumours, the majority of the mutations being found in ADC (adenocarcinoma, 27.0%). Mutational screening detected three different COX-2 mutations and five different P53 mutations, published for the first time. With RT-PCR we observed that the expression of the tested genes, hTERT and COX-2, was highly significant for ADC (p<0.01) and SCC (p<0.05). Statistical analysis of the combined results revealed significant correlation between expression of COX-2 and hTERT (p<0.001), hTERT expression and staging (p<0.05) and survival (p<0.01). A positive correlation between COX-2 expression and K-RAS mutation (p<0.05) was also observed. This study provides insight into associations between the analysed biomarkers and the clinical-pathological data of the patients.
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PMID:K-RAS and P53 mutations in association with COX-2 and hTERT expression and clinico-pathological status of NSCLC patients. 1895 20

Epigenetic modification is one of the mechanisms leading to gene silencing in neoplastic cells. By methylation-specific PCR, we analyzed the promoter methylation of three cancer-related genes: Ras Association domain Family 1A (RASSF1A), Death Associated Protein kinase (DAP-kinase) and Retinoic Acid Receptor beta2 (RARbeta2) in two NPC xenografts (C15 and C17), 68 primary NPC tumors, and nine normal nasopharyngeal epithelia. We showed that C15 and C17 displayed a complete promoter methylation of RASSF1A, RARbeta2 and DAP-kinase genes. In primary NPC tumors, the incidence of promoter methylation was very high for all three tested genes: 91% for RASSF1A, 88% for both RARbeta2 and DAP-kinase whereas all normal nasopharyngeal epithelia were unmethylated. Interestingly, our study revealed that aberrant promoter methylation of the three genes were statistically associated with the lymph node involvement (p < 0.0001). In addition, hypermethylation of RASSF1A was correlated with age at diagnosis (p = 0.047) and T stage (p = 0.037) while the RARbeta2 hypermethylation was associated with histological type (p = 0.011). Taken together, our results demonstrate that silencing of RASSF1A and RARbeta2 expression by promoter hypermethylation is associated with highly differentiated tumors, advanced tumor stage and the presence of lymph node metastasis. To assess the functional significance of the epigenetic silencing of RARbeta2 and DAP-kinase in NPC, we analysed the expression of two downstream target genes COX-2 and p53 by reverse PCR (RT-PCR) and immunohistochemistry (IHC). We revealed a significant association between expression of COX-2 and loss of RARbeta2 through aberrant methylation (p = 0.003) in NPC biopsies. We concluded that the inactivation of RASSF1A, RARbeta2 and DAP-Kinase by hypermethylation is a key step in NPC tumorigenesis and progression.
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PMID:Inactivation of RASSF1A, RARbeta2 and DAP-kinase by promoter methylation correlates with lymph node metastasis in nasopharyngeal carcinoma. 1922 69

Somatic LKB1 serine/threonine kinase alterations are rare in sporadic cancers, with the exception lung adenocarcinoma, but no mutations in squamous cell or large cell primary carcinoma were discovered. We screened the LKB1 gene in 129 primary nonsmall cell lung carcinomas, adjacent healthy lung tissue, and control blood samples. Forty-five percent of nonsmall cell lung tumors harbored either intron or exon alterations. We identified R86G, F354L, Y272Y and three polymorphisms: 290+36G/T, 386+156G/T, and 862+145C/T (novel). R86G (novel) and F354L mutations were found in six squamous cell carcinomas and three large cell cancer carcinomas, but not in the adjacent healthy tissue or controls samples. The F354L mutation was found in advanced squamous cell carcinomas with elevated COX-2 expression, rare P53, and no K-RAS mutation. Results indicate that the LKB1 gene is changed in a certain proportion of nonsmall cell lung tumors, predominately in advanced squamous lung carcinoma. Inactivation of the gene takes place via the C-terminal domain and could be related to mechanisms influencing tumor initiation, differentiation, and metastasis.
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PMID:Somatic alterations of the serine/threonine kinase LKB1 gene in squamous cell (SCC) and large cell (LCC) lung carcinoma. 1922 1

p73 encodes multiple functionally distinct isoforms. Proapoptotic TAp73 isoforms contain a transactivation (TA) domain, and like p53, have tumor suppressor properties and are activated by chemotherapies to induce cell death. In contrast, antiapoptotic DeltaNp73 isoforms lack the TA domain and are dominant-negative inhibitors of p53 and TAp73. DeltaNp73 proteins are overexpressed in a variety of tumors including neuroblastoma. Thus, identification of drugs that upregulate TAp73 and/or downregulate DeltaNp73 represents a potential therapeutic strategy. Here, we report that cyclooxygenase (COX) inhibitors induce apoptosis independent of p53, and differentially modulate endogenous p73 isoforms in neuroblastoma and other tumors. COX inhibitor-mediated apoptosis is associated with the induction of TAp73beta and its target genes. COX inhibitors also downregulate the alternative-spliced DeltaNp73(AS) isoforms, Deltaexon2 and Deltaexon2/3. Furthermore, forced expression of DeltaNp73(AS) results in diminished apoptosis in response to the selective COX-2 inhibitor celecoxib. Celecoxib-mediated downregulation of DeltaNp73(AS) is associated with decreased E2F1 levels and diminished E2F1 activation of the p73 promoter. These results provide the first evidence that COX inhibitors differentially modulate p73 isoforms leading to enhanced apoptosis, and support the potential use of COX inhibitors as novel regulators of p73 to enhance chemosensitivity in tumors with deregulated E2F1 and in those with wild-type (wt) or mutant p53.
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PMID:Cyclooxygenase inhibitors differentially modulate p73 isoforms in neuroblastoma. 1936 20

The goal of this study was to investigate whether sub-chronic anti-oxidant treatment with ascorbic acid (Vit C) is able to protect the heart against myocardial infarction. The effects of Vit C treatment on the histopatological changes and immunohistochemistry for p53, COX-2 and iNOS were evaluated in rats submitted to acute myocardial infarction induced by isoproterenol (ISO). Male Wistar rats (n = 32) were divided into four groups: group 1, control; group 2, ISO treated; group 3, Vit C treated; group 4, ISO + Vit C treated. An amount of 150 mg/kg of isoproterenol was administered for two consecutive days. The rats were treated with Vit C once a day (150 mg/kg, orally) for seven consecutive days. In the day 5 and 6 the rats from group ISO + Vit C were submitted to acute administration of ISO third minutes after Vit C treatment. The results pointed out that treatment with Vit C showed mild degenerative changes of myocardial tissue in ISO group. Also, the antioxidant was able to decrease the iNOS expression in rats treated with Vit C. Taken together, our results suggest that chronic Vit C administration was able to prevent the myocardial infarction induced by ISO as a result of iNOS downregulation. Certainly, this finding offers new insights into the mechanisms underlying the relation between oxidative stress and cardiac mortality after myocardial infarction.
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PMID:Ascorbic acid prevents acute myocardial infarction induced by isoproterenol in rats: role of inducible nitric oxide synthase production. 1946 70

The correlation between the expression of COX-2 and p53 protein in basal cell carcinoma (BCC) of eyelid and apoptosis was investigated. Specimens of BCC were collected from 40 cases (aged 28-68 y) at the Department of Pathology, Renmin Hospital of Wuhan University, and Department of Pathology, Zhongnan Hospital of Wuhan University during from 1999 to 2006. Five specimens of paracancerous tissues served as control group. Immunohistochemical staining was performed to detect the expression of COX-2 and p53 in the tissues. The average absorbance (A) and the average positive area rate of COX-2 and p53 protein were measured by image analysis. The positive area rate of COX-2 and p53 protein was analyzed by linear correlation analysis. It was found that COX-2 and p53 proteins were highly expressed in BCC of eyelid, and weakly expressed in paracancerous tissues. Image analysis revealed that the expression of COX-2 and p53 proteins in BCC of eyelid was significantly higher than that in paracancerous tissues (P<0.01). Spearman rank correlation analysis demonstrated a positive correlation between the expression of COX-2 and p53 (r=0.113, P=0.421). It was concluded that COX-2 can increase the expression of p53 protein, therefore suppressing apoptosis.
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PMID:Correlation and expression of COX-2 and P53 protein in basal cell carcinoma of eyelid. 1951 27

The present study was undertaken to evaluate the possibility of using a panel of proteins and single nucleotide polymorphisms (SNPs) involved in apoptosis, growth control, and DNA repair as predictive markers for cisplatin sensitivity. For this purpose the intrinsic cisplatin sensitivity (ICS) was determined in 39 cell lines derived from squamous cell carcinomas of the head and neck using a colony-forming assay. In these cell lines and in normal oral keratinocytes (NOK), the expression of epidermal growth factor receptor (EGFR), Hsp70, Bax, Bcl-2, Bcl-XL, survivin, and COX-2 was determined. Moreover, the p53, MDM2, FGFR4, XPC, XPD, XRCC1, and XRCC3 genes were analyzed for the presence of specific single nucleotide polymorphisms (SNPs). Pearson's correlation test showed that EGFR was the only protein that was significantly correlated to the ICS (r=0.388, p=0.015). The combination of EGFR, Hsp70, Bax, and Bcl-2 gave the strongest correlation (r=0.566, p<or=0.001), whereas Bax alone had the second highest influence on the ICS. Furthermore, all four SNPs within genes involved in DNA repair, i.e. XPC, XPD, XRCC1, and XRCC3, tended to influence the ICS. In order to find the combination of factors, on both protein and gene levels, with the highest correlation to ICS, a multivariate statistical calculation was performed. Our results indicate that SNPs in DNA repair genes (XRCC3241 and XPD751) influence the ICS and together with the expression of EGFR, Hsp70, Bax, and Bcl-2, they could predict the cisplatin sensitivity of head and neck cancer cell lines (r=0.614, p<or=0.001).
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PMID:Proteins and single nucleotide polymorphisms involved in apoptosis, growth control, and DNA repair predict cisplatin sensitivity in head and neck cancer cell lines. 1972 96

The incidence of nonmelanoma skin cancer including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) has dramatically increased in the last decades, and chronic sun exposure was identified as a main etiologic agent. UV radiation may produce DNA damage either directly or through reactive oxygen species (ROS). As mutations caused by UV may lead to skin cancer due to oncogene activation and tumor suppressor gene inactivation, efficient safeguard mechanisms have been developed during evolution. These enclose induction of apoptosis and formation sunburn cells aiming at the removal of premalignant cells. The keratinocyte apoptotic machinery in response to UV consists of both intrinsic/mitochondrial and extrinsic/death receptor-mediated cell-death pathways, which are particularly regulated by mitogen-activated protein kinases (MAPKs, JNK and p38) and the tumor-suppressor protein p53. For development of skin cancer, it appears that critical steps in apoptosis control are dysregulated leading to resistance both to death ligand-mediated and intrinsic proapoptotic pathways. These particularly include inactivation of p53, as well as activation of EGFR, COX-2 and MAPKs, which result in specific regulation of Bcl-2 proteins, death ligands and death receptors. The final unravelling of apoptosis regulation in epithelial skin cancer may allow the development of new targeted therapeutic strategies.
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PMID:UV-induced squamous cell carcinoma--a role for antiapoptotic signalling pathways. 1977 66

Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma. We established a new human MPNST cell line (designated FMS-1) from MPNST of the right brachial plexus of a 69-year-old woman with NF1. The cell line has been maintained for >24 months with >100 passages. FMS-1 cells showed a fibrosarcoma-like or epithelioid pattern in the heterotransplanted tumor, compared with a fascicular growth pattern of short-spindle tumor cells in the primary tumor. Immunophenotypically, FMS-1 cells showed almost the same characteristics as the primary tumor. Cytogenetic and molecular analyses revealed a deletion in exons 5-8 of the p53 gene. Epidermal growth factor receptor (EGFR) and cyclooxygenase (COX)-2 were expressed in FMS-1 cells. To improve the highly aggressive course and poor prognosis and establish new therapeutic methods, molecular genetic and biological characterizations of MPNST are required. Thus, FMS-1 cells might be useful for investigating biological behaviors and developing new molecular-targeting antitumor drugs for MPNST expressing EGFR or COX-2.
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PMID:Establishment and characterization of a novel human malignant peripheral nerve sheath tumor cell line, FMS-1, that overexpresses epidermal growth factor receptor and cyclooxygenase-2. 1992 Dec 53


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