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)

p53 alterations are considered as one of the most important factors responsible for drug resistance in ovarian carcinomas, although the relationship between p53 gene status and response to cisplatin-based chemotherapy in ovarian cancer patients remains unclear. The aim of the study was to evaluate the relationship between p53 protein accumulation, p53 gene mutation and response to cisplatin-based chemotherapy in patients with ovarian carcinoma considering conventional clinicopathological parameters. Tissue sections and corresponding cyst and/or ascitic fluid cells from 79 patients with epithelial ovarian cancer were analyzed immunohistochemically for p53 expression. The PCR-SSCP analysis was performed in 25 cases and the results were compared with immunohistochemical data. It was demonstrated that p53 expression reaching approximately 50% of positive cells in immunostaining was usually associated with PCR-amplified exons showing abnormal migration and suspected for mutation. p53 gene changes were not correlated with histological structure, grade of differentiation or residual tumor after cytoreductive surgery, despite being detected more frequently in III/IV than in II FIGO stages and in patients with residual disease above 2 cm. A significant correlation between p53 accumulation and p53 gene alteration and poor response to cisplatin-based chemotherapy was shown. The overall survival time of patients decreased with an increase in p53 protein expression. A strong p53 expression especially accompanied by p53 changes detectable by PCR-SSCP analysis appears to be a good indicator of the resistance to cisplatin-based chemotherapy. The association between strong p53 overexpression and shorter overall survival time was also revealed.
 ...
PMID:Expression and mutation of p53 in tumor effusion cells of patients with ovarian carcinoma: response to cisplatin-based chemotherapy. 1112 80

Ionized radiation leads to G1 arrest and apoptosis by a p53-dependent pathway and G2-M arrest through a p53-independent pathway. In this study, we evaluated the role of cell cycle-regulating molecules in the sensitivity of cancer cells for radiation therapy. Forty-seven patients with squamous cell carcinomas of the esophagus had undergone radiation therapy, followed by surgical resection. They were classified as sensitive to radiation (SR, 14 cases) with no residual tumor in the surgical specimen or as resistant to radiation (RR, 33 cases) with viable residual tumors. Their preradiation biopsy samples were immunohistochemically investigated for the expressions of cell cycle-related molecules, including p53, CDC25A, CDC25B, cyclin D1, cyclin B1, and Ki-67. p53 expression was negative in 71% (10 of 14) of SR and positive in 91% (30 of 33) of RR. The association was strong between high radiation sensitivity and negative p53 expression (P < 0.0001). CDC25B, which is not expressed in normal epithelium but is in the cytoplasm of esophageal cancers, was strongly expressed (2+) in 46% (6 of 14) of SR and in 6% (2 of 23) of RR. Thus, the sensitivity for radiation therapy was significantly correlated with CDC25B overexpression. With respect to CDC25A, cyclin D1, cyclin B1, and Ki-67, no statistically significant differences were found in their expressions between SR and RR tumors. p53 and CDC25B expressions showed no significant associations, and multivariate analysis revealed that both p53 and CDC25B are significant independent markers for predicting radiation sensitivity. CDC25B was revealed to be a novel predictor of radiation sensitivity in esophageal cancers. Because CDC25B is an oncogene, which affects G2-M progression, these results suggest the importance of a p53-independent G2-M checkpoint in radiation therapy.
 ...
PMID:CDC25B and p53 are independently implicated in radiation sensitivity for human esophageal cancers. 1115 45

The objective of this study was to determine whether the association between GSTM1 null/GSTTI null and survival in ovarian cancer is mediated by the influence of these genes on p53 expression. In 81 women with pure invasive ovarian cancer, GSTM1 null and GSTT1 null genotypes were identified using polymerase chain reaction and p53 expression was assessed using immunohistochemistry. The association of these factors with survival was examined using Cox's proportional hazards regression models. Performance status (P < 0.001), operative stage (P = 0.004), residual disease (P = 0.001), histologic subtype (P = 0.05), tumor grade (P = 0.007), and the combined GSTMI null/GSTTl null genotype (P = 0.023) were all individually associated with survival. p53 expression was not associated with survival (P = 0.45). In a multivariate analysis, the effects of GSTM1 null/GSTT1 null on survival were lost when residual disease and tumor grade were included. The effects of p53 expression on survival were unchanged when residual disease, tumor grade, operative stage, and performance score were included. GSTM1 null/GSTT1null did not influence the effects of p53 expression on survival and vice versa. The GSTM1 null/GSTT1 null genotype was associated with response to primary chemotherapy (P = 0.007) but p53 expression was not. We conclude that the association of GSTM1 null/GSTTl null with survival appears to be mediated through different mechanisms to p53 expression in ovarian cancer and in addition, may be a better predictor of outcome.
 ...
PMID:Glutathione S-transferase GSTM1 and GSTT1 genotypes in ovarian cancer: association with p53 expression and survival. 1132 8

Mutations of the p53 tumour suppressor gene have been found in most human cancers, including ovarian epithelial malignancies. This study investigated whether the presence or absence of p53 mutation was associated with outcome following platinum-based chemotherapy in patients with ovarian cancer. DNA samples from tumour tissue and blood were obtained from 73 patients with primary tumours, 50 of whom received platinum-based adjuvant chemotherapy. Single-strand conformation polymorphism analysis and direct DNA sequencing of exons 5-8 detected mutations in 44% (32 of 73) of tumours. These were more common in late-stage (III or IV) than in early-stage disease (I or II) (p=0.03). There was no association with histological type, volume of residual disease following surgery, or initial CA125 levels. No significant association was found between p53 status and overall survival or disease-free survival following chemotherapy. Likewise, there was no correlation between p53 mutation and response to chemotherapy as defined by normalization of CA125 levels. Tumours with p53 missense mutations recurred within a significantly shorter time than those with normal p53 (p=0.04). In addition, there was a tendency for tumours with missense mutations to have a shorter disease-free survival than those with non-missense mutations, although this did not reach statistical significance (p=0.07).
 ...
PMID:P53 mutation does not affect prognosis in ovarian epithelial malignancies. 1132 43

Sera from 99 ovarian cancer patients were assayed for serum autoantibodies to p53 using a newly developed enzyme-linked immunosorbent assay (ELISA). Results were compared to the investigation using the former ELISA. The incidence of autoantibodies (25%) was lower using the newly developed ELISA as compared to the previous results (41%). The results were consistent in 79% of patients (P < .001). The incidence of autoantibodies was lower in patients with complete remission (19%) as compared to that of patients with recurrence (30%) and before primary surgery (26%). No statistically significant correlation was found among p53 serum autoantibody status and tumor stage, degree of malignancy, histologic subtype, and residual tumor after primary surgery. Use of the newly developed ELISA resulted in a higher consensus between immunohistochemically negative and autoantibody negative cases. Owing to further purifying of the prepared human recombinant p53. the newly developed ELISA seems to be of higher specificity as compared to the former ELISA.
 ...
PMID:Detection of serum autoantibodies to tumor suppressor gene p53 with a new enzyme-linked immunosorbent assay in patients with ovarian cancer. 1134 46

Patients with neurofibromatosis type 1 (NF1) often have gliomas as a complication, most of which are benign pilocytic astrocytomas which have arisen in optic pathways. In the present case, a 17-year-old girl (at death) with stigmata of NF1, initially had a bulky tumor mass in the left thalamus, developing into the lateral ventricle, at 13 years of age. Partially resected tissue samples showed pleomorphic astrocytoma with abundant xanthoma cells and degenerative structures such as Rosenthal fibers (RF) and eosinophilic granular bodies. Fine eosinophilic granules identical to RF, both immunophenotypically and ultrastructurally, were also seen. The residual tumor was subtotally resected 6 months later, and the tumor histology was essentially similar as before, accompanying the regenerative structures; this was believed to be a good prognostic indicator. However, several anaplastic features such as mitosis, necrosis and vascular proliferation appeared even in areas rich in the regenerative structures. After a 2-year, disease-free interval, multiple tumor relapse occurred in June 1997. Partially resected tumor tissues were composed of monotonous small anaplastic cells with prominent proliferative activity. Surprisingly, the tumor cells had retained eosinophilic granules within the cell bodies. Postoperative chemotherapy with procarbazine, MCNU and vincristine (PCV) suppressed the residual tumor dramatically, but the regrowing tumor finally became uncontrollable, leading to the patient's death. TP53 mutation was not detected, while p27 immunopositivity was constantly high during malignant progression, suggesting acquisition of proliferative activity to overcome p53 and p27 inhibitory functions. A review of previously published reports failed to reveal any cases of this type.
 ...
PMID:Neurofibromatosis type 1-associated unusual pleomorphic astrocytoma displaying continual malignant progression. 1147 72

The prognosis in ovarian carcinoma remains poor. We need to identify patients who are less likely to respond to treatment. In order to evaluate the prognostic value of C-erb-B2, p53 and Ki 67 expression and correlate these markers with classic prognostic factors, we studied paraffin-embedded tumor tissue from 81 patients with epithelial ovarian cancer and made a quantitative evaluation of C-erb-B2, p53 and Ki 67 expression by immunohistochemistry. The results were: age 5.4 +/- 15(22-88); 66% with normal physical activity; 48.2% with residual disease < 2 cm; initial stage--42% and advanced stage--58%. Age, performance status, residual disease and stage were correlated with 2 and 5 years survival. Positive immunostaining: p53--87%, C-erb B-2--51% and Ki67--100%. P53 and C-erb B-2 were associated with residual disease and stage; patients with no C-erbB-2 staining had a significantly better survival. A direct and significant correlation was found between p53 and Ki67 and between C-erb B-2 and p53. We conclude that these markers have a high expression in ovarian carcinoma and p53 and C-er B-2 correlate with stage and residual disease. Although C-erb B-2 was associated with better survival, it was not found to be an independent prognostic factor.
 ...
PMID:[Prognosis value of p53, C-erB-2 and Ki67 proteins in ovarian carcinoma]. 1155 25

This study was undertaken to determine whether the transcription factor EGR-1 expression: (1) in the primary tumor, correlates with radiation response in terms of complete local tumor control with no evidence of disease or recurrence and no evidence of metastasis; (2) in the postirradiated biopsies correlates with residual tumor; and (3) correlates with the expression of Egr-1 target genes such as TP53, pRB, and Bax. The authors analyzed: (1) 25 pretreated surgically resected paraffin-embedded primary adenocarcinomas of the prostate for the presence of EGR-1 expression and mutation, and correlated this with clinical endpoints such as serum prostate-specific antigen levels and current clinical status; (2) 27 postirradiated biopsies of prostate for the presence of EGR-1 expression, and correlated these findings to the residual tumor status; and (3) 12 prospective prostate tumor specimens for EGR-1 expression and its target genes. EGR-1 expression was determined by immunohistochemistry and mutations were screened in two regions of the Egr-1 gene (trinucleotide AGC repeats in transactivation domain [TD] and poly A tract in 3'UTR) by polymerase chain reaction-single strand conformational polymorphism analysis. Of 25 patients, 18 patients showed expression of EGR-1. EGR-1 overexpression correlated with treatment failure. No correlation with EGR-1 overexpression and its target genes was found, which may indirectly suggest that overexpressed EGR-1 may lack transactivation function. In summary, EGR-1 overexpression in the mutant form may provide an indication of clinical failure (local recurrence or metastasis).
 ...
PMID:Early growth response-1 gene: potential radiation response gene marker in prostate cancer. 1158 4

Circulating anti-p53 antibodies have been described and used as tumoural markers in patients with various cancers and strongly correlate with the p53 mutated status of the tumours. No study has yet looked at the prevalence of such antibodies in skin carcinoma patients although these tumours have been shown to be frequently p53 mutated. Most skin carcinoma can be diagnosed by examination or biopsy, but aggressive, recurrent and/or non-surgical cases' follow up would be helped by a biological marker of residual disease. We performed a prospective study looking at the prevalence of anti-p53 antibodies using an ELISA technique in a series of 105 skin carcinoma patients in comparison with a sex- and age-matched control skin carcinoma-free group (n = 130). Additionally, p53 accumulation was studied by immunohistochemistry to confirm p53 protein altered expression in a sample of tumours. Anti-p53 antibodies were detected in 2.9% of the cases, with a higher prevalence in patients suffering from the more aggressive squamous cell type (SCC) of skin carcinoma (8%) than for the more common and slowly growing basal cell carcinoma type or BCC (1.5%). p53 protein stabilization could be confirmed in 80% of tumours studied by IHC. This low level of anti-p53 antibody detection contrasts with the high rate of p53 mutations reported in these tumours. This observation shows that the anti-p53 humoral response is a complex and tissue-specific mechanism.
 ...
PMID:Divergence between the high rate of p53 mutations in skin carcinomas and the low prevalence of anti-p53 antibodies. 1174 30

Prognostication of head and neck cancer (HNCC) involves molecular identification of residual tumor cells, prediction of recurrence, distant metastases or secondary tumors and prediction of the sensitvity to therapy. Biomarkers of HNCC are mutations of p53, p16 and amplification of Cyclin D and E2F4. One hundred and fifty-two HNCC cases have been evaluated for p53, hMLH1, Cyclin D and p16 gene alterations using PCR-SSCP and Western blot analysis. P53 mutations of HNCC have been found in 37.5% of cases. However, 11% of the cases showed p53 mutations in the normal peritumoral mucosa suggesting "field cancerization" process. Mismatch-repair gene mutations (MMR: hMHL1 and hMSH2) occurred with 17 and 8.6% frequency, respectively, while E2F4 mutations were even more frequent (21.4%) in HNCC. Our data suggest that E2F4 overexpression can be caused by the inactivation of the p16 gene in HNCC, while its mutations are most probably associated to the mutations of the MMR genes. These molecular informations can help to predict the biological potential of HNCC as well as the probability of the development of secondary HNCCs.
 ...
PMID:[Genetic marker analysis in head and neck cancer] 1205 Jul 11


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