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)

Transitional-cell carcinoma of the bladder is believed to arise through a series of genetic changes affecting cell growth and proliferation. Two basic types of such genes have been described: protooncogenes and tumor suppressor genes. The former have not been studied extensively in bladder cancer, although there is evidence that c-erb B-2/neu is overexpressed. Loss of specific chromosomal regions, which is common in bladder tumors, may inactivate tumor suppressor genes, of which p53 has received the most attention. Work also has been done on epidermal growth factor and its receptor, yielding evidence that malignant and normal urothelium have different sensitivities to its action. Although several advances must be made before genetic changes come to the clinical forefront, the information now being gained with such speed holds considerable promise for diagnosis and treatment.
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PMID:Molecular genetics and biochemical mechanisms in bladder cancer. Oncogenes, tumor suppressor genes, and growth factors. 144 Oct 21

For a variety of human malignancies such as breast cancer and cancer of the prostate, p53 oncoprotein overexpression indicating an alteration of the p53 tumor-suppressor gene has been described as a prognostic factor for a poor clinical outcome. To investigate the overexpression of p53 oncoprotein in transitional-cell carcinoma of the bladder, 58 bladder cancer specimens of different clinical stages and histological grades were investigated using an immunohistochemical approach. A correlation between p53 positivity and tumor stage was observed, with an increase from 38.5% of superficial (Ta) tumors to 83.3% of muscle-invasive (T3/T4) tumors staining positively for p53 oncoprotein. Furthermore, an increase from 46.7% of G1 tumors to 75% of G3 tumors was observed. In 22 of 25 (87%) informative patients the results of the immunohistochemical staining could be verified by the determination of p53 mutations as detected by polymerase chain reaction (PCR)-directed analysis of restriction-fragment-length polymorphisms (RFLP). To determine the prognostic value of p53 immunohistochemistry for the clinical course of superficial bladder cancer, the overexpression of p53 oncoprotein was investigated in 41 patients with superficial bladder tumors (T1) undergoing complete transurethral tumor resection. The detection of p53 protein was correlated with further clinically important variables such as sex, age, histological grading, former instillation therapy, and immunohistochemical determination of the proliferation rate by staining for PCNA (proliferating-cell nuclear antigen; monoclonal antibody PC10).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection of P53 tumor-suppressor-gene protein in bladder tumors and prostate cancer: possible clinical implications. 788 74

Chromosome studies on a highly malignant tumor, a small cell carcinoma of the bladder (the first to be studied cytogenetically), showed a hypertriploid mainline and a hypertetraploid minor line. Extensive chromosomal rearrangements were present in both lines, some rearranged chromosomes being seen in only one of the lines, while others, derived from chromosomes 6, 9, 11, 13, and 18, were seen in both. Although different giant chromosomes were present in the two lines, they shared a possibly significant common feature: multiple copies of 2q. DNA flow cytometry confirmed that the tumor had a hypertriploid main mode and showed that dysplastic surface epithelium present in the histologic material also had a hypertriploid DNA index. p53 expression in the tumor was demonstrated by flow cytometry.
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PMID:Chromosome abnormalities and p53 expression in a small cell carcinoma of the bladder. 788 99

A pelvic lymph node dissection, using continent urinary diversion and lower urinary tract reconstruction can significantly improve the patient's quality of life After almost 25 years of experience in treating 930 patients with carcinoma of the bladder, the Author concludes that most patients with superficial bladder cancer (grade 1 or grade 2) can be managed conservatively. Patients in the Urology Department at University of Southern California, who had grade 3 T1 tumours showing a mutation of P53 received early aggressive therapy, namely, cystectomy. The probability of recurrence for such patients was just 14% and the survival rate among all 930 patients (including grades 1-3) was over 75%. Lower urinary tract reconstruction using the Kock neobladder was found to give highly functional results, with few complications and a high satisfaction rate among patients (62% very happy, 20% happy and 18% satisfied with the results).
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PMID:[Carcinoma of the bladder: experience of the USC Los Angeles (antireflux nipple according to Ghoneim)]. 942 20

The Mdm2 protein is frequently overexpressed in human non-seminomatous germ cell tumours and transitional carcinoma of the bladder where it may contribute to tolerance of wtp53. Mdm2 forms an autoregulatory feedback loop with p53; the Mdm2 gene is responsive to transactivation by p53 and once synthesized the Mdm2 protein terminates the p53 response. We show here that the topoisomerase poison etoposide, like ultra violet irradiation, inhibits Mdm2 synthesis. Cytotoxic concentrations of etoposide (IC90 for > 3 h) result in inhibition of Mdm2 induction at both the RNA and protein level. Rapid apoptosis ensues. Global transcription is not inhibited: p21waf-1/cip1 and GADD45 expression increase in a dose dependent manner. Inhibition of Mdm2 synthesis depends on the continuous presence of etoposide, suggesting the DNA damage may prevent transcription. Downregulation of Mdm2 transcript occurs in cells expressing HPV16-E6 suggesting that inhibition of Mdm2 transcription is p53-independent. When cells are -treated with a pulse (1 h) of etoposide and reincubated in drug free medium, Mdm2 synthesis commences immediately after damage is repaired (3 h) and the p53 response is attenuated. Induction of apoptosis and loss of clonogenicity are 3-5-fold lower under pulse treatment conditions. This is the first observation of inhibition of Mdm2 transcription following treatment with topoisomerase (topo II) poisons, a feature that may be useful in tumour types where p53 is tolerated by overexpression of Mdm2.
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PMID:Differential regulation of p21waf-1/cip-1 and Mdm2 by etoposide: etoposide inhibits the p53-Mdm2 autoregulatory feedback loop. 1002 85

We present a rare case of advanced bladder cancer in a young female. A 27-year-old woman had the chief complaint of proteinuria. A clinical examination revealed a papillary, broad-based bladder tumor with a clinical stage of T3, N3, M0. Preoperatively, 3 courses of neoadjuvant chemotherapy with methotrexate, adriamycin, and cisplatin were performed, and proved to be effective. Radical cystectomy was done and the histopathologically it was diagnosis as Grade 2 transitional cell carcinoma, which did not show any p53 gene mutation. The patient's postoperative clinical course was uneventful, and she remained disease free for 27 months. Bladder carcinoma in patients under 30 years of age tends to have a early stage and a low grade. However, the above described 27-year-old female patient demonstrated the advanced stage bladder tumor. Therefore, it should be kept in mind to accurately evaluate young patients with transitional cell carcinoma of the bladder and not to rule out the possibility of advanced disease even though a patient is young.
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PMID:Advanced bladder cancer in a young female: a case report. 1180 41

The purpose of this study is to evaluate the expression of p53 and mdm2 and to determine whether they may be used as additional predictors of recurrence in superficial transitional cell carcinoma of the bladder. Paraffin sections of 80 patients with superficial transitional cell carcinoma of the bladder, who were treated with transurethral resection, were stained with p53 and mdm2 antibodies using the standard avidin biotin immunoperoxidase method. Nuclear staining for both p53 and mdm2 was calculated as the percentage of labeled nuclei out of a total number of tumor cells counted. The percentage of p53- and mdm2-positive cells showed a significant relationship with tumor grade and recurrence (p = 0.002 and p = 0.016; p = 0.01 and p = 0.003, respectively). In addition, a weak inverse relationship was found between p53 and mdm2 values (r = -0.184). p53 and mdm2 reactivities are valuable parameters in predicting recurrence in superficial bladder cancer. Thus, mdm2 expression appears to play a role in predicting biologic behavior in superficial transitional carcinoma of the bladder.
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PMID:Expression of p53 and mdm2 and their significance in recurrence of superficial bladder cancer. 1290 22

Smoking is a major risk factor for urothelial cell carcinoma of the bladder (UCC). Mutations in the FGFR3 and TP53 genes have been shown to define two distinct pathways in superficial papillary and invasive UCC disease, respectively. We investigated the relationship between smoking and these mutations by means of denaturing high performance liquid chromatography and sequencing for 110 primary UCC of the bladder. This study included 48 current smokers, 31 ex-smokers and 31 non-smokers. Thirty-five of the tumors were stage pTa, 40 pT1 and 35 > or =pT2. Fourteen of the tumors were grade 1, 37 were grade 2 and 59 grade 3. Smoking was associated with high stage (P = 0.03) and high grade tumors (P = 0.006). Twenty-two of the 110 tumors studied harbored TP53 mutations (20%) and 43 harbored FGFR3 mutations (39%). Odds ratios (OR) were higher for TP53 mutations in current smokers [OR, 2.25; 95% confidence interval (95% CI), 0.65-7.75] and ex-smokers (OR, 1.62; 95% CI, 0.41-6.42) than in non-smokers. Double TP53 mutations and the A:T-->G:C TP53 mutation pattern was found only in current smokers. Patients with the FGFR3(wild-type)/TP53(mutated) genotype had significantly higher levels of tobacco consumption, as measured in pack-years (P = 0.01). Smoking influenced neither the frequency nor the pattern of FGFR3 mutations. Our results suggest that smoking is associated with invasive and high grade UCCs, at initial presentation, and influenced TP53 or the molecular pathway defined by these mutations. In contrast, FGFR3 mutations are not affected by smoking and probably result from endogenous alterations. These data have potential implications for clinical management and prevention strategies.
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PMID:Mutations in TP53, but not FGFR3, in urothelial cell carcinoma of the bladder are influenced by smoking: contribution of exogenous versus endogenous carcinogens. 1534 1

The aim of this study was to find the correlation between serum p53 and carcinoma of the bladder and to investigate whether serum p53 protein can be used as a tumor marker for p53 gene alteration. The study included patients with carcinoma of the bladder and controls. Serum p53 protein estimation was done with an ELISA kit. There were 23 patients with superficial and 17 with invasive carcinoma. The median serum p53 was 31.5 U/ml in superficial and 41 U/ml in invasive cancer. This was significantly higher than the mean value (16.4 U/ml) of controls. Serum p53 rises in patients with carcinoma of the bladder and correlates with the grade of the disease . It can therefore be used as a tumor marker for bladder cancer.
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PMID:Serum p53 and bladder cancer: can serum p53 be used as a tumor marker? 1550

The aim of this study was to evaluate the association between p53, p21, p27 and Rb expression, alone or in combination, with pathological features and clinical outcomes of urothelial carcinoma of the bladder. Immunohistochemical staining for p53, p21, p27 and pRB was performed on tissue microarrays comprising normal urothelium from nine controls, transurethral resection specimens from 74 patients with Ta, Tis and/or T1 bladder urothelial carcinoma, radical cystectomy specimens from 226 consecutive urothelial carcinoma patients, and lymph nodes with tumor invasion from 50 of the 226 cystectomy patients. All nine controls had normal status of biomarkers. The proportion of biomarkers alterations was highest in lymph node metastases. p53, pRB and p27 were associated with pathologic stage, lymphovascular invasion and lymph node metastases (P-values<or=0.050). Each biomarker alone, each combination of two biomarkers and the number of altered biomarkers were all independently associated with disease recurrence and bladder cancer-specific death (P-values<or=0.046). In patients with organ-confined disease, p53, p21 and p27 were independently associated with disease recurrence and bladder cancer-specific death (P-values<or=0.046). There was a good but not perfect concordance in the expression of biomarkers between matched transurethral resection and cystectomy specimens (n=22; concordance rates: 77-86%) and between matched lymph node and cystectomy specimens (n=50, 70-92%). In conclusion, p53, p21, p27 and pRB have a cooperative/synergistic role in the biologic behavior of bladder urothelial carcinoma. In contrast to the use of single biological markers, evaluation of their combined status may improve prognostic models and help identify patients who might benefit from adjuvant therapies and in decision-making.
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PMID:Cooperative effect of cell-cycle regulators expression on bladder cancer development and biologic aggressiveness. 1738 51


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