Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Altered patterns of p53 and pRB expression have been reported to be frequent events and to have prognostic significance in bladder cancer. To assess the potential adverse consequences of having altered patterns of both p53 and pRB proteins in patients with bladder neoplasms compared with having one or neither abnormality, we have studied a cohort of superficial transitional cell carcinomas of the urinary bladder by immunohistochemical analysis. The present study included 59 well-characterized superficial transitional cell carcinomas (Ta, n = 28; T1, n = 31) for which clinicopathological variables were available. Nuclear overexpression of p53 was identified in 22 cases (37%). A statistically significant association was observed between the p53-positive phenotype and disease progression (P < 0.001), as well as reduced survival (P < 0.001). Undetectable levels of pRB were observed in 11 cases (19%). Patients with a pRB-negative phenotype had a more frequent disease progression (P = 0.014) and decreased overall survival (P = 0.014). We also observed a significant association between altered p53 and undetectable pRB expression patterns (P = 0.001). Nine tumors showed both a p53-positive and a pRB-negative phenotype. There was an even more marked increase in progression (P = 0.00005) and decreased overall survival (P = 0.0004) in patients whose tumors had both alterations after controlling for tumor stage, tumor grade, and suspicion of vascular invasion. These data suggest that alterations of p53 and pRB have a cooperative negative effect on both progression and survival in primary bladder cancer. It may be postulated that aberrant p53 and pRB expression deregulates cell cycle control at the G1 checkpoint and engenders tumor cells with reduced response to programmed cell death. The imbalance produced by an enhanced proliferative activity and a decreased apoptotic rate may determine the aggressive clinical course of the bladder tumors harboring both p53 and pRB alterations.
 ...
PMID:Cooperative effects of p53 and pRB alterations in primary superficial bladder tumors. 910 1

The p21WAF1/CIP1 gene is regulated by p53 and encodes a cyclin-dependent kinase (Cdk)-inhibitor involved in senescence and cell quiescence. The role of p21 as a negative regulator of cell proliferation suggests that it may function as a tumor suppressor gene. However, only a few mutations of the p21WAF1/CIP1 gene have been reported to date. In order to assess potential p21WAF1/CIP1 gene alterations in human bladder cancer, we have examined this gene and its encoded product in a well-characterized cohort of 27 primary bladder tumors. Mobility shifts by single-strand conformation polymorphism in the p21WAF1/CIP1 gene were identified in 2 cases. Sequencing analyses revealed that one of these cases had point mutations in the 3' untranslated region, while the other case had a frame shift mutation at positions 322 (C to A) and a deletion of 8 nucleotides (323-->331; CCG-->ACG, codon 81 Arg-->Thr) that produced a stop signal at codon 83 (Gly--Stop). This tumor had a p21-negative phenotype by immunohistochemistry, but did not lose any allele. We further characterized these cases by the study of TP53 mutations using single-strand conformation polymorphism (PCR-SSCP) and sequencing, as well as immunohistochemical assays. Seven mobility shifts were identified and seven cases showed p53 nuclear accumulation. The two cases displaying mutated p21WAF1/CIP1 had wild-type TP53. It is concluded that p21WAF1/CIP1 gene aberrations are infrequent in bladder carcinoma but may be occasionally identified in primary bladder tumors.
 ...
PMID:Analysis of p21WAF1/CIP1 in primary bladder tumors. 911 33

Target genes implicated in cellular transformation and tumor progression have been divided into two categories: proto-oncogenes (that when activated become dominant events characterized by gain of function) and tumor-suppressor genes (recessive events characterized by the loss of function). Alterations in proto-oncogenes and tumor-suppressor genes seem equally prevalent among human cancers. Multiple mutations appear to be required to conform the malignant phenotype. It is therefore conceivable that cancer be viewed fundamentally as a genetic disease entailing inherited (also called germ-line) and/or acquired (also termed somatic) mutations of genes in these two categories. Molecular studies of bladder neoplasms have identified a series of nonrandom genetic alterations affecting a particular set of oncogenes and tumor-suppressor genes. Because the modality of therapy for patients with bladder neoplasms primarily depends on morphological evaluation and clinical staging, the diagnosis carries significant consequences. However, it is well known that morphologically similar tumors presenting in any assigned stage may behave in radically different fashions, which seriously hampers the physician's ability accurately to predict clinical behavior in a given case. Recent studies have shown that inactivation of certain tumor-suppressor genes, such as RB and TP53, occur in bladder tumors that have a more aggressive clinical outcome and poor prognosis. In the present paper we review the molecular abnormalities associated with these dominant and recessive genes in bladder cancer and discuss the potential clinical use of their detection. The implementation of objective predictive assays to identify these alterations in clinical material will enhance our ability to assess tumor biological activities and to design effective treatment regimens. The need now is to translate this newly developed scientific knowledge into diagnostic and therapeutic strategies, which in turn will enhance the quality of life and prolong the survival of patients with bladder cancer.
 ...
PMID:Molecular and immunopathology studies of oncogenes and tumor-suppressor genes in bladder cancer. 914 1

The relevance of p53 mutations to rat bladder cancer progression induced by a single injection of N-methyl-N-nitrosourea (MNU) and the chemopreventive effects of indomethacin (IM) were investigated in male F344 rats, initially given N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) at a dose of 500 ppm in the drinking water for 10 weeks. The animals were subsequently treated with a single intraperitoneal injection of MNU at a dose of 50 mg/kg b.w. at week 20. A subgroup was then given IM dissolved in the drinking water at a concentration of 20 ppm for 20 weeks. The experiment was terminated at week 40 when transitional cell carcinomas (TCC) were observed in all animals given BBN, regardless of the administration of MNU and/or IM (incidences ranged from 80 to 100%). The extent of invasion was significantly greater with the additional MNU treatment but no inhibitory effects of IM were noted. A low frequency of p53 mutations was detected without relation to the extent of tumor invasion. Thus, only two mutations were found, one in a Ta and the other in a T1 carcinoma. The present study thus demonstrated that p53 mutations are not involved in MNU-induced progression in rat urinary bladder cancers, suggesting that they are not critical for malignancy.
 ...
PMID:Lack of involvement of p53 gene mutations in N-methyl-N-nitrosourea-induced bladder tumor progression in N-butyl-N-(4-hydroxybutyl)nitrosamine-treated rats and no suppression by indomethacin. 914 32

Epidemiological studies suggest that bladder cancer may be caused by carcinogens in tobacco and certain occupational exposures. Molecular studies have shown that chromosome 9 alterations and TP53 mutations are the most frequent events in bladder cancer. To date, the relationships between epidemiological risk factors and genetic alterations have not been fully explored in bladder cancer. The purpose of this study was to explore the association between smoking and chromosome 9 aberrations in bladder cancer cases. Seventy-three patients with bladder cancer at Memorial Sloan-Kettering Cancer Center were evaluated for smoking history, occupational history, and chromosome 9 alterations. The epidemiological data were abstracted from medical charts. Patients' tumor tissues were analyzed using RFLP and microsatellite polymorphism assays for detection of chromosome 9 alterations. Elevated odds ratios (ORs) were found for chromosome 9 alterations in smokers compared to those in nonsmokers (OR = 4.2; 95% confidence interval, 1.02-17.0) after controlling for age, sex, race, occupational history, and stage of disease. The ORs were 3.6 for those smoking < or = 20 cigarettes per day and 5.8 for those smoking > 20 cigarettes per day. No association was found between occupational history and chromosome 9 alterations. This study supplies evidence suggestive of the link between smoking and chromosome 9 alterations in the etiology of bladder cancer and indicates that potential tumor suppressor genes on chromosome 9 may be involved in smoking-related bladder carcinogenesis.
 ...
PMID:Cigarette smoking and chromosome 9 alterations in bladder cancer. 914 91

Forty-four pathologic specimens of 39 bladder cancer patients were analyzed immunohistochemically with D07 monoclonal antibody to detect over-expression of mutant p53 gene. The findings were interpreted by correlating with patient age, sex, cigarette smoking, number and macroscopic appearance of tumour, histological tumour grade, muscular invasion, vascular invasion, necrosis and urothelial atypia or dysplasia. Mutant p53 gene was over-expressed in 8 (18.2%) specimens. Statistically significant correlation with grade, vascular invasion, necrosis and patient sex was found with p53 over-expression. Available follow-up data were insufficient to draw a conclusion about the prognostic role of p53 over-expression. Prospective studies with larger number of patients are needed to define the exact place of nuclear p53 over-expression in transitional cell bladder cancer.
 ...
PMID:Correlation of nuclear p53 over-expression with clinical and histopathological features of transitional cell bladder cancer. 920 34

We investigated the expression of androgen receptor (AR) protein in transitional cell carcinoma of human urinary bladder in paraffin-embedded sections of tumours obtained from nine patients with urinary bladder cancer treated by radical cystectomy. In addition, immunoblotting of AR was also performed on selected samples. Nuclear immunoreactivity of AR was found in seven of the nine urinary bladder cancers studied. AR showed variable staining intensity within a tumour. In the immunoblots, a 110 kDa AR signal was seen with anti-AR antibody, and faint bands of 90 and 60 kDa were also observed. Immunohistochemistry of p53 and c-erbB-2 was also carried out and compared with the distribution of AR. The high frequency of AR expression suggests a role for androgens in transitional cell carcinoma of human urinary bladder.
 ...
PMID:Immunodetection of androgen receptor in human urinary bladder cancer. 920 60

Mutations in the p53 tumour suppressor gene are found at high frequency in bladder cancer. There is strong evidence that p53 plays an important role in controlling the cell cycle after DNA damage by ionizing radiation. However, the effect of loss of p53 function on radiosensitivity is not yet clear. Radiotherapy combined with chemotherapy is the most common treatment for patients with invasive bladder cancer. Recently three bladder cancer cell lines have been established and this paper investigates the p53 status and clonogenic survival of these cell lines following irradiation. It was found that one line expresses wt p53 (UCRU-BL-13) and two lines contain a codon 72 polymorphism (UCRU-BL-17 and UCRU-BL-28). UCRU-BL-17 cells also contain a point mutation affecting codon 280. The level of p53 expression in the cell lines is clearly different, with UCRU-BL-17 expressing a higher level of p53 compared with UCRU-BL-13; UCRU-BL-28 expressed intermediate levels. The clonogenic survival of these cell lines has been determined. It was found that the line expressing a p53 mutation was more sensitive than those with wild type p53, providing support for a model in which loss of p53 function is associated with increased radiosensitivity, possibly due to reduced p53-dependent DNA repair.
 ...
PMID:Relationship between radiation response and p53 status in human bladder cancer cells. 924 90

Twenty-eight transitional cell carcinomas of the bladder, grade 2 or 3, were analyzed for the presence of p53 mutations. Thirteen tumors were found to contain 14 mutations. These were all base substitution mutations, of which nine were GC-->AT transitions (three at CpG sites). The remaining five mutations were transversions (three GC-->CG, one GC-->TA, and one AT-->TA). Four of the mutations were found at codon 280. A comparison with other studies of bladder tumors reveals that a region encompassing codons 280 and 285 represents a hot spot for p53 mutation in bladder cancer. The 280/285 hot spot lies within two purine-rich sequences that may provide some clues to the identity of potential bladder carcinogens. A comparison of mutations from bladder tumors of smokers and nonsmokers reveals no significant differences.
 ...
PMID:A hot spot for p53 mutation in transitional cell carcinoma of the bladder: clues to the etiology of bladder cancer. 926 74

Overexpression of p53 is considered to be predictive of mutations of the p53 gene. Exposure-specific mutations of the p53 gene have been described for cancers at different sites. An association between p53 mutation/overexpression and smoking has been described in early stage bladder cancer, but results were conflicting. We have conducted a study on 131 bladder cancer cases, considering p53 expression and smoking habits in an area where the use of air-cured tobacco, rich in carcinogenic arylamines, is common. The study suggests that the use of air-cured tobacco induces p53 overexpression (possibly via mutation) in early stage-low grade bladder cancer, more frequently than flue-cured tobacco (odds ratios = 3.4, 95% confidence intervals 0.9-13 in stage 1; odds ratios = 24, 95% confidence intervals 1.1-519 in stage 1, grade 1). However, all the excess associated with air-cured tobacco was concentrated in recurrences. When available, the biopsies of recurrent cases with early-stage disease were re-examined and all showed p53 expression at first diagnosis (with 10-50% of cells positive) (n = 5). It is hypothesized that exposure to tobacco-related chemicals increases the risk of recurrences via p53 overexpression/mutation. Expression of the bcl-2 gene was detected in only 2 out of 13 p53-positive smokers.
 ...
PMID:Tobacco smoke, recurrences, and p53/bcl-2 expression in bladder cancer. 927 45


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>