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)

Expression of the p53, the epidermal growth factor receptor (EGFr; c-erbB-1) and c-erbB-2 proteins was studied in 82 patients with primary transitional cell carcinoma of the bladder using an immuno-histochemical method. Strong or moderate staining was found in 18% of tumours for p53 with weaker staining in a further 36% giving a total of 54% of tumours stained for p53. Strong staining was found in 15% of tumours for c-erbB-2 and in 31% for the EGFr. Tumours invading the bladder muscle were significantly more likely to be strongly stained positively for p53 and/or EGFr compared with superficial tumours: only 15% of invasive tumours were stained negatively for both p53 and EGFr. No statistical association was found between p53 and EGFr expression. Weakly positive associations were found between the expression of c-erbB-2 and p53 and between muscle invasive tumours and increased expression of c-erbB-2. Alterations in the expression of p53, c-erbB-1 and c-erbB-2 were found frequently in human transitional cell carcinoma of the urinary bladder and may be of clinical use in defining patient sub-groups of differing prognosis.
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PMID:Expression of mutant p53, c-erbB-2 and the epidermal growth factor receptor in transitional cell carcinoma of the human urinary bladder. 171 24

Using an immunohistochemical method expression of PCNA, Ki-67, 486p and p53 antigen was investigated in paraffin sections of 119 patients with primary transitional cell carcinoma of the bladder. The purpose of this study was to detect recurring G1 and G2 bladder tumours compared with non-recurrent tumours. A relative large fraction of labelled cells for PCNA and Ki-67 was found in recurring G1 and G2 carcinomas. Moreover, recurrent transitional cell carcinomas showed a more positive staining pattern for 486p and p53, in contrast to non-recurrent carcinomas. Immunohistochemistry of these four antigens seems to yield additional information about the possibility of recurrence in G1 and G2 bladder carcinomas, thus allowing early, i.e. more aggressive, therapy.
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PMID:[Monoclonal antibodies (MIB 1, PC 10, 486p and p53) as prognostic factors for recurrent urothelial carcinoma of the urinary bladder]. 751 Dec 88

Expression of p53 protein was examined in 67 cases of primary transitional cell carcinoma of the bladder and 6 normal controls using an immunohistochemical method on paraffin sections. Positive nuclear staining for p53 in malignant cells was found in 34 (51%) of the 67 cancer patients; no positive staining for p53 was detected in any of the normal controls or in the benign cells, including stromal and inflammatory cells, within the tumor tissue. There were 8 positive cases (33%) in 24 grade G1 tumors, 12 (48%) in 25 G2 tumors and 14 (78%) in 18 G3 tumors. p53 protein was detected positively in 14 (36%) of 39 superficial tumors (Tis-T1) and in 20 (71%) of 28 invasive tumors (T2-T4). Thus, positive staining for p53 was found more frequently in poorly differentiated tumors (chi-squared test: G3/G1 + G2 P < 0.01) and in invasive tumors (chi-squared test: T2-T4/Tis-T1 P < 0.01). Expression of p53 was also closely associated with recurrence of tumors. Alterations in p53 expression may be of prognostic value in cases of bladder transitional cell carcinoma.
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PMID:Expression of p53 product in Chinese human bladder carcinoma. 768 67

Surgical specimens from 30 patients with transitional cell carcinoma of the bladder were examined for the presence of mutation of the p53 tumor suppressor gene using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. All of the specimens were superficial, low grade cancer, and 10 patients had recurrences during an observation period of 24 months following the initial surgical treatment. Among the 30 patients with superficial bladder cancer, 4 were found to have the mutated p53 gene and 3 of them had recurrences, which involved either invasive or high grade tumors. Two of these recurrent tumors with the p53 gene mutation showed identical mutations with those primary tumors, whereas the other one did not have the same mutation. The data suggest that bladder cancers with a mutation of the p53 gene have a greater probability of poor prognosis than those which do not, even if the primary lesion was a superficial, low grade tumor. Therefore, the presence of the p53 gene mutation may provide important clues to the factors involved in bladder cancer.
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PMID:p53 gene mutation in recurrent superficial bladder cancer. 771 16

Epidemiological studies show an increased risk of bladder cancer associated with tobacco smoking and occupational exposures. Certain carcinogens in tobacco and occupational exposures cause DNA damage and may produce specific mutations. TP53 is considered a common target for carcinogenic agents, and mutations of this gene are reported to be the most frequent nuclear abnormalities in human cancer. In order to investigate the relationship between tobacco smoking, occupations, and altered patterns of p53 expression, we have analyzed a group of 109 incident patients with superficial transitional cell carcinoma of the bladder. We assessed p53 nuclear overexpression by the use of anti-p53 antibody PAb1801 and immunohistochemistry, and identified 45 of 109 patients (41%) displaying p53-positive phenotype. We observed a significant association between the number of cigarettes smoked per day and p53 nuclear overexpression (p = 0.02). The odds ratios were 2.3 for those smoking 1-2 packs per day and 8.4 for smoking more than 2 packs per day. Similar estimates were obtained after controlling for age, sex, and race. Elevated odds ratios were also observed for dye-/ink-related (odds ratio = 2.0; 95% CI, 0.4-9.4) and cooking-related occupations (1.8, 0.6-5.0), although those were not statistically significant. These data support the hypothesis that certain carcinogens derived from cigarette smoking and occupations may induce TP53 mutations, which in turn are involved in early steps of bladder carcinogenesis.
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PMID:Tobacco smoking, occupation, and p53 nuclear overexpression in early stage bladder cancer. 811 80

The tumors of 20 patients with multifocal primary transitional cell carcinoma of the bladder or lymph node metastases were examined for molecular genetic defects which we have previously found to be present in > 50% of invasive tumors. These included loss of heterozygosity (LOH) of chromosome 9, which occurs in superficial as well as invasive bladder tumors, and LOH of chromosome 17p and p53 mutations, which are commonly found only in invasive tumors. Analysis of multiple or recurrent primary tumors in 7 patients for these markers was generally consistent with recently published data that the tumors are monoclonal in origin and that p53 mutations occur as a late event in the generation of invasive bladder cancers. Comparison of the primary tumors and metastases to regional lymph nodes in 14 patients demonstrated a complete concordance between the molecular genetic defects present, showing that LOH of chromosomes 9 and 17p and p53 mutations occurred in the primary tumors before metastasis. Because of the importance of chromosome 9 in bladder cancer, we mapped the location of a putative tumor suppressor gene by restriction fragment length polymorphism analysis of 123 cases obtained in this and earlier studies. Most of the tumors showed LOH for more than one marker on chromosome 9. Results of mapping of 4 tumors with partial deletion of chromosome 9 suggests that the tumor suppressor gene is located between 9p12 and 9q34.1.
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PMID:Role of chromosome 9 in human bladder cancer. 835 36

p53 and Rb gene mutations are intermediate biomarkers useful for the prediction of neoplastic progression in bladder cancers. Previously, we have shown that low CYP3A activity, measured by dapsone N-hydroxylation, and high CYP2D6 activity, assessed by debrisoquine 4-hydroxylation, were significant susceptibility risk factors in developing aggressive bladder cancer. However, no information is available about the relationship between drug/xenobiotic metabolizing enzyme activities and p53/Rb mutations that may suggest mechanisms of bladder carcinogenesis. We evaluated in vivo CYP3A activity by the dapsone recovery ratio (DPRR), CYP2D6 activity by the debrisoquine recovery ratio (DBRR), CYP2C19 activity by the mephenytoin R/S ratio (RSR), N-acetyltransferase activity by the monoacetyl dapsone to dapsone ratio and glutathione-S-transferase M1 (GSTM1) genotype by PCR. In immunohistochemical studies of bladder tumor tissue, over expression of p53 protein was detected with antibody pAb1801 and loss of Rb protein expression was evaluated with antibody PMG3-245 in patients with transitional cell carcinoma of the bladder. Low CYP3A activity was significantly associated with over expression of or mutated p53 protein (P < 0.05). High CYP2D6 activity (within the extensive metabolizer group) was significantly associated with loss of expression of or mutated Rb protein (P < 0.05). Positive p53 staining also predicted aggressive bladder cancer histopathology (P < 0.05, odds ratio 2.9), and the lowest tertile of DPRR predicted p53 positivity (P < 0.01, odds ratio 3.9 comparing means of lower tertile versus upper tertile of DPRR). These selective associations are consistent with the hypothesis that an environmental pro-carcinogen fails to be detoxified by CYP3A which may preferentially induce p53 mutations, whereas, an alternative pro-carcinogen that may be activated by CYP2D6, may selectively induce Rb mutations.
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PMID:Association of low CYP3A activity with p53 mutation and CYP2D6 activity with Rb mutation in human bladder cancer. 864 Sep 13

Thrombospondin-1 (TSP) is a 450-KD glycoprotein that was initially discovered in the platelet alpha-granule. It now appears that TSP is intimately involved in the regulation of a variety of cellular functions and cell-to-cell interactions. Recently, it has been demonstrated that TSP functions as a p53-dependent inhibitor of angiogenesis in cultured fibroblasts from Li-Fraumeni patients and therefore may be an important factor involved with tumor invasion and metastasis. It has previously been demonstrated that TSP can be detected in frozen tissue sections by immunohistochemical methods. Our objective in this study was to determine the optimal antigen retrieval (AR) protocol for detection of TSP in formalin-fixed, paraffin-embedded tissue by using tissue sections from patients with invasive transitional cell carcinoma of the bladder. The optimal AR protocol was determined utilizing a variety of heating conditions and antigen retrieval buffers. Our results demonstrate that TSP can be reliably detected in paraffin-embedded tissue by immunohistochemical techniques that utilize AR with high-temperature microwave heating and a low-pH Tris-HCI buffer. The importance of this method is that it allows the reliable detection of TSP in archival tissue. This should facilitate further investigation into TSP's role in the regulation of cellular processes, including its influence on tumor angiogenesis and metastasis.
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PMID:Immunohistochemical detection of thrombospondin-1 in formalin-fixed, paraffin-embedded tissue. 867 97

The role of radiotherapy for the treatment of clinical stage T3b transitional cell carcinoma of the bladder is controversial. The options range from definitive radiotherapy alone, to preoperative radiotherapy and cystectomy, to chemotherapy and radiation for bladder preservation. Our data show that long-term local control after definitive radiotherapy is only 27% and that death attributable to local-regional failure in this setting is 43%. Thus, definitive radiotherapy is only used in patients who are considered poor candidates for surgical and chemotherapy procedures. Preoperative radiotherapy (PREOP) has been studied in a number of randomized series, all of which failed to establish an improvement in patient outcome over those treated with radical cystectomy alone (CYST). However, these studies are subject to criticism, mostly because of poor patient accrual and low numbers of patients available for the analyses. A retrospective review of patients treated at MD Anderson Cancer Center indicates that local control is superior with PREOP as compared with CYST. An analysis of the impact of local control on distant metastasis rates in patients treated with CYST showed that local control was an independent correlate of distant metastasis and survival. Thus, preoperative radiotherapy may be beneficial to patients with late-stage muscle-invasive bladder cancer by securing local control and reducing distant metastasis rates as a result. The success of bladder preservation for stage T3b patients rests with the ability to select patients with radiosensitive tumors. To this end, the immunohistochemical staining status of tumor p53 and pRB was investigated in patients treated with PREOP. Abnormal pRB expression was very strongly related to radiation response, whereas altered p53 expression was associated with high distant metastasis-free and overall survival rates. These two molecular markers were complementary and show promise in facilitating the selection of late-stage patients for bladder preservation.
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PMID:Radiotherapy for stage T3b transitional cell carcinoma of the bladder. 873 36

The choice of treatment for bladder tumors is based on pathological criteria, i.e. staging and grading mainly. It has recently been observed that genetic alterations that involve activation of oncogenes and inactivation of suppressor genes can occur during tumorigenesis. p53 protein is coded for by a genes on chromosome 17, and is able to suppress malignant transformation and proliferation; it can be important in maintaining the integrity of DNA, when damaged during neoplastic disease. We have analyzed samples of transitional cell carcinoma of the bladder of 60 patients managed by conservative treatment; all the specimens have been stained for p53 protein. We could observe that the presence of the protein p53 is correlated with staging and grading and is associated with an increased risk of relapse and progression. Patients with transitional-cell carcinoma confined to the bladder that demonstrates nuclear p53 reactivity should be considered for protocols of adjuvant treatment.
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PMID:[Gene p53 mutation and prognosis in bladder tumors]. 918 26


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