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)

Thirty-one patients with clear cell ovarian carcinoma who underwent primary surgery and postoperative therapy were retrospectively evaluated. Eighteen patients (58%) had International Federation of Gynecology and Obstetrics (FIGO) stage I disease, 3 patients (9.7%) stage II disease, and 10 patients (32.3%) stage III and IV disease. Patients with stage III and IV disease demonstrated a significantly poor prognosis compared with patients who had stage I or II disease (p < 0.01). No patients with stage III and IV disease survived 5 years. p53 protein expression and proliferative activity (PA) were studied by immunohistochemical methods using p53 molecule and antibodies to PCNA (proliferative cell nuclear antigen). Intranuclear accumulations of p53 product were observed in 15 of 31 (48.4%). On the other hand, 15 of 31 (48.4%) patients stained positively for PCNA (> or = 60% of cancer cells stained positively). Positive p53 staining and highly PA were associated with poor survival. Two patients with stage I a relapsed were positive p53 and highly PA. Accordingly, consolidation chemotherapy is necessary for patients with stage I a who are positive p53 and highly PA. Platinum-based chemotherapy for patients who had minimal residual tumor was effective, but 5 patients who had > or = 2 cm tumor burden were not effective at all. The response rate for platinum-based chemotherapy was 20% (1/5) among p53 positive, in contrast to 66.7% (4/6) among p53 negative patients. So it seems that p53 positive patients are chemoresistant.
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PMID:[Survival in patients with clear cell carcinoma of the ovary]. 946 31

A large number of oncogenes have been identified as aberrant in gliomas, but only the erbB oncogene (gene encoding the epidermal growth factor receptor [EGFR]) is amplified in an appreciable number. The loss or mutation of tumor-suppressor genes located on different autosomes may be associated with progression of malignant gliomas. The p53 tumor-suppressor gene (located on chromosome 17) is frequently associated with the loss of one allele in malignant gliomas, although a large number of malignant gliomas have no p53 mutations. Some of the latter tumors have an amplified murine double minute 2 (MDM2) gene, which suppresses p53 gene activity. Genetic material from chromosome 10 may also be lost, especially in glioblastoma multiforme. In addition to the aberrant expression of EGFR, another growth factor, platelet-derived growth factor, or PDGF (ligand and/or receptors) can be overexpressed, giving cells a selective growth advantage. The blood-brain barrier is substantially altered in malignant gliomas, resulting in cerebral edema. Therapy for malignant gliomas includes surgery, radiation therapy, and chemotherapy. Surgical resection that leaves little residual tumor produces longer survival than less vigorous surgery. Radiation therapy to a dose of at least 60 Gy is required to treat malignant gliomas. Increased survival beyond that produced by standard external radiotherapy requires much larger doses; interstitial radiotherapy permits such dosing. Radiosurgery is being tested. Chemotherapy with nitrosoureas is modestly useful but appears to benefit patients with anaplastic astrocytoma more so than those with glioblastoma.
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PMID:Biology and treatment of malignant glioma. 950 24

This study was conducted to investigate the value of p53 immunohistochemical staining of pretreatment biopsy specimens in predicting the response of rectal cancer to chemoradiation. The study group comprised 42 patients with high-risk rectal cancer treated between July 1990 and July 1995 with a preoperative chemoradiation regimen of 45 Gy of external-beam irradiation and continuous-infusion 5-fluorouracil followed by surgical resection. p53 immunohistochemical staining was performed on pretreatment biopsy specimens. p53 immunohistochemical staining pattern and standard clinical and pathological parameters were correlated with extent of residual cancer in the surgical specimen. Twenty tumors were positive for p53 on immunohistochemical staining, 19 were negative, and 3 were focally positive. Thirteen patients experienced a complete response to chemoradiation. Aberrant p53 protein accumulation, as measured by immunohistochemical staining, correlated inversely with a complete pathological response to chemoradiation (P = 0.005; correlation coefficient = -0.43) and directly with an increased likelihood of residual cancer in the lymph nodes of surgical specimens (P = 0.02; correlation coefficient = 0.39). p53 immunohistochemical staining of pretreatment biopsy specimens correlates with the extent of residual disease after chemoradiation in patients with high-risk rectal cancer.
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PMID:p53 immunohistochemical staining predicts residual disease after chemoradiation in patients with high-risk rectal cancer. 981 51

The recombinant wild-type p53 adenovirus has been proven effective against the growth of human head and neck squamous cell cancer (SCCHN) cell lines iir vitro and in a nude mouse model. The addition of a FLAG peptide sequence was used in this study, along with the p53 adenovirus vector as a marker of the site of the gene therapy activity. It provides clear evidence of the exogenous gene product within the transduced carcinoma cells. No alterations in transcription or translation of the p53 gene product were noted with the addition of the FLAG sequence to the original p53 adenovirus vector. Immunohistochemical analysis displayed simultaneous expression of the p53 and FLAG proteins in the infected cells. The p53 protein remained localized to the nucleus, whereas the FLAG protein was additionally noted in the cytoplasm. In vitro growth suppression assays and in vivo microscopic residual tumor model experiments in nude mice showed a similar tumoricidal effect with the p53-FLAG adenovirus vector to that with the previously studied p53 adenovirus vector without the addition of the FLAG sequence. We conclude that the addition of the FLAG octapeptide sequence allows identification of those cells that have been affected by the molecular therapy independent of the endogenous gene expression of the cells. This novel molecular tracer may prove useful in characterizing infection efficiency and in gene therapy trials.
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PMID:Head and neck squamous cell growth suppression using adenovirus-p53-FLAG: a potential marker for gene therapy trials. 981 71

The prognostic significance of p53 expression in 316 archival epithelial ovarian cancers was assessed using a static, computer-aided image analysis system (CAS 200). Using a 10% cut-off point, 26% of primary tumors and 35% of their metastases were positive for p53 protein. p53 positivity closely correlated with tumor grade (p < 0.001), stage (p < 0.001), residual tumor (p < 0.001), serous histologic type (p = 0.005), and tumor recurrence (p = 0.007). The overall 5-year survival was 37%. In univariate survival analysis, high grade, advanced stage, older age at diagnosis, and residual tumor > 2 cm were significant predictors of poor overall survival. In both the overall (p < 0.001) and recurrence-free (p < 0.001) survival, p53 immunopositivity predicted poor prognosis. p53 expression was a significant prognostic factor of multivariate recurrence-free survival (RR 1.93, p = 0.03), but not of overall multivariate survival. In addition, p53 positivity was a marker of poor overall survival in patients with well or moderately differentiated tumors, early stage tumors, or residual tumor. Quantitation of p53 immunoexpression by CAS may offer an objective means to identify patients who need more aggressive adjuvant therapy or new treatment strategies.
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PMID:The prognostic significance of p53 expression quantitated by computerized image analysis in epithelial ovarian cancer. 989 Dec 40

This case-control study was designed to identify factors associated with long-term survival. We examined two groups of patients with epithelial ovarian cancer, one group of long-term survivors (> 5 years) and one group of short-term survivors (< 2 years), for levels of expression of p53 and p27KIP1 proteins (as both proteins have been shown to be independent prognostic markers in tumors other than ovary) and the relationship with patient survival. Our findings show that p27KIP1 expression, in contrast to p53 expression, is positively associated with long-term survival in univariate analysis (P = 0.001), in analyses stratified by residual disease (P = 0.02) or performance status (P = 0.02), the two strongest prognostic factors for ovarian cancer, as well as multivariate analysis (P = 0.002) adjusting simultaneously for age, tumor stage, residual disease, performance status, and grade of differentiation. Therefore, immunostaining for levels of p27KIP1 expression may have potential as a new prognostic factor in the management of ovarian cancer.
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PMID:Expression of the cell cycle inhibitor p27KIP1 is a new prognostic marker associated with survival in epithelial ovarian tumors. 991 26

Induction chemoradiotherapy before esophagectomy for esophageal carcinoma seems to improve patient survival. Given the toxicity of this regimen, it would be useful to predict those patients likely to benefit. p53 is known to mediate apoptosis in response to DNA damage, but there are few data evaluating the relationship between p53 expression and chemoradiosensitivity in human tissues. We immunohistochemically evaluated p53 protein expression in 95 biopsy specimens from patients with esophageal carcinoma before chemoradiotherapy. p53 expression was correlated to the pathologic response identified in subsequent esophagectomy specimens. p53 immunoreactivity was recorded semiquantitatively using the following scale: neg, < 5%; 1+, 5-25%; 2+, 26-50%; 3+, 51-75%; 4+, > or = 76%. Pathologic response in esophagectomy specimens was categorized as overt residual tumor (ORT), minimal residual tumor, and no residual tumor. Of the 95 patients, 64 had adenocarcinoma, and 31 had squamous cell carcinoma. Of those with adenocarcinoma, 46 (72%) of 64 were positive for p53. Thirty-seven (80%) of 46 p53+ patients had ORT, compared with 4 (22%) of 18 p53- patients (P < .001). There was no correlation between the degree of p53 staining and pathologic response. Of those with squamous cell carcinoma, 13 (42%) of 18 were positive for p53. Three (23%) of 13 p53+ patients had ORT, compared with 4 (22%) of 18 p53- patients (P = .96). Our data indicate that overexpression of p53 protein is associated with decreased responsiveness to induction chemoradiotherapy in patients with esophageal adenocarcinoma but that no such association exists in patients with esophageal squamous cell carcinoma.
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PMID:Overexpression of p53 protein associates decreased response to chemoradiotherapy in patients with esophageal carcinoma. 1010 9

The DNA-repair protein O(6)-methylguanine-DNA methyltransferase (alkyltransferase; MGMT) is a major determinant of resistance of cells to various alkylating cytostatic drugs. Its expression in tissues is highly variable, indicating complex regulatory mechanisms involved. Transfection-mediated expression of wild-type p53 has been shown to negatively regulate basal promoter activity of MGMT in vitro. To elucidate whether p53 is involved in regulation of MGMT in tumor tissue, we examined MGMT expression and the p53 status of 140 primary ovarian carcinomas and analyzed the data as to the correlation between MGMT and p53, as well as the survival response of the patients after chemotherapy. We show that MGMT expression is highly variable in ovarian carcinomas, ranging from zero level up to 2500 fmol/mg protein. MGMT activity was significantly lower in tumors with wild-type p53 (p53wt) than in tumors with mutant p53 (p53mt) (p = 0.045). As expected, the percentage of tumors with p53mt increased with increasing histologic grade of the tumors. Thus, p53mt was observed in 4, 45 and 64% of grades 1, 2 and 3 tumors, respectively (p = 0.001). Increase in p53mt was accompanied by an increase in MGMT activity, which was, on average, 460 +/- 66, 624 +/- 63 and 662 +/- 60 fmol/mg protein in grades 1, 2 and 3 tumors, respectively (p = 0.047). In addition, MGMT activity as well as p53mt were associated with the FIGO stage of the tumors. Mean MGMT activity was 472 +/- 48 fmol/mg for patients with FIGO stages I and II, as compared with 675 +/- 50 fmol/mg for patients with FIGO stages III and IV, (p = 0.0179). The percentage of p53mt was 27% and 54% in ovarian tumors with FIGO stages I/II and FIGO stages III/IV, respectively (p = 0.004). Thus, progression of ovarian tumors was clearly associated with increase of both MGMT activity and the percentage of p53mt. In tumors expressing low MGMT (<100 fmol/mg), p53mt was very rarely found. No significant association was observed between MGMT level in ovarian carcinomas and the survival of patients treated with cyclophosphamide and carboplatin. On the other hand, a clear correlation was found between histological type, grading, residual tumor mass and p53wt expression and duration of the patient's survival. The finding that p53wt expression was associated with low MGMT level in primary ovarian cancer supports the view that down-regulation of basal MGMT promoter activity by p53wt is also relevant in tumor cells in vivo. Int. J. Cancer (Pred. Oncol.) 84:388-395, 1999.
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PMID:Activity of O(6)-methylguanine-DNA methyltransferase in relation to p53 status and therapeutic response in ovarian cancer. 1040 91

In adults, the TP53 tumor suppressor gene is frequently mutated in astrocytic brain tumors which is supposed to represent an early event in their development. In juvenile pilocytic and low-grade astrocytomas, however, TP53 mutations have until now been reported as rare, which has led to the suggestion that these tumors may follow a different molecular pathogenesis with an involvement of genes other than TP53. Our analysis of 20 pilocytic and two low-grade astrocytomas of childhood, based on a comprehensive denaturing gradient gel electrophoresis (DGGE) mutation detection assay of the entire coding region, including all splice site junctions of TP53, showed mutations considered as causative in 7 of the 20 (35%) pilocytic astrocytomas and in one of the two low-grade astrocytomas. Our finding is significantly different from the mutation frequency of 1.3% (2/155) previously reported for these tumor types. This may be attributed to the mutation detection system used, which also detects mutations occurring outside the evolutionary conserved region of TP53. Our results suggest that, contrary to the present notion, TP53 mutations may well play a role in the development of juvenile astrocytomas. Furthermore, no mutations were found in tumors of patients with progression of residual tumor after postoperative follow-up. This suggests that TP53 mutations may be associated with less aggressive forms of juvenile astrocytomas, analogous to the situation in adult astrocytomas.
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PMID:High frequency of TP53 mutations in juvenile pilocytic astrocytomas indicates role of TP53 in the development of these tumors. 1041 86

Primary malignant epithelial tumors of the liver (PMETL) are rare in the pediatric age group, and very little is known about their biology as compared with adult tumors. The prognostic value of the DNA contents measured by image analysis and expression of oncogene c-erb2 and tumor suppressor gene p53 were studied in 30 cases of PMETL in children, including 24 with hepatoblastomas (HB) and 6 with hepatocellular carcinomas (HCC). p53 overexpression was detected in 12 out of 26 cases (46.0%), or in 3 of 5 HCC and 9 of 21 HB cases. A relatively high concordance of staining was observed with the two antibodies used (clone DO7, Dako and clone DO1, Santa Cruz Biotechnology). c-erb-B2 did not yield the characteristic membrane staining in any of the 27 cases in which reliable staining was obtained. However, 1 out of 4 patients with HCC and 1 of 23 with HB revealed strong granular cytoplasmic staining in several neoplastic cells. Interestingly, these were two of the three aneuploid multiploid cases. DNA histograms of 13 out of 29 cases (54.8%) were classified as DNA aneuploid (5/6 HCC and 8/23 HB): nine were hyperdiploid, one was hypodiploid (1HB), and three were multiploid (2HB and 1HCC). In the HB group, DNA aneuploidy was strongly associated with embryonal histological areas, suggesting that a disturbance in the process of cell differentiation is associated with marked genetic aberrations. Only the group of HB was submitted to univariate analysis of survival by the Kaplan-Meier method for age (< 24 months vs. > or = 24 months), sex, preoperative chemotherapy (yes vs. no), residual disease (metastasis, and/or unresectable tumor), p53 expression by immunohistochemistry (positive vs. negative), and DNA ploidy (diploid vs. aneuploid). Only residual disease at the time of diagnosis (P < 0.017) and preoperative chemotherapy (0.030) were found to be negatively correlated with biological behavior, estimated as overall survival. DNA aneuploidy tumors (P < 0.125) and male patients (P = 0.123) showed a trend toward a more aggressive clinical behavior, although the difference was not statistically significant. Combining DNA ploidy and residual disease, patients were categorized into three groups: group I, patients with no adverse prognostic factors, i.e., diploid tumors without residual disease; group II, patients with only one adverse prognostic factor, i.e., aneuploid tumor or residual disease; and group III, patients with both adverse factors, aneuploid tumors and residual disease at time of diagnosis. A log-rank test comparing the three survival curves showed a statistically significant difference between them (P < 0.003). Although the series of cases is small, the results of this study highlight the importance of including DNA ploidy in the protocols designed for HB in children by international cooperative groups.
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PMID:Primary malignant epithelial tumors of the liver in children: a study of DNA content and oncogene expression. 1046 88


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