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)

Mouse monoclonal antibodies PAb 240 and PAb 1801 which specifically immunoprecipitate p53 protein, were used to examine 27 fresh ovarian tumours (16 serous adenocarcinomas, six endometrioid carcinomas, one mucinous adenocarcinoma, one mucinous borderline tumour and three benign adenomas). Eleven out of 16 (69%) serous adenocarcinomas and one endometrioid tumour showed positive staining with one or both antibodies and none of the mucinous or benign tumours stained with either antibody. DNA from tumour and peripheral blood leukocytes was used to identify allelic deletions on chromosome 17p in tumours. 11/12 positively staining tumours showed less of heterozygosity (LOH) on 17p at the nearest informative locus to the p53 gene. In this series of ovarian tumours, LOH on 17p correlates closely with the aberrant expression of the p53 protein in a high proportion of advanced stage serous adenocarcinomas. This observation suggests that the p53 tumour suppressor gene is involved in the evolution of epithelial ovarian cancer (EOC) and may have prognostic significance.
 ...
PMID:Overexpression of the p53 protein and allele loss at 17p13 in ovarian carcinoma. 131 Feb 51

Using the polymerase chain reaction and single-strand conformation polymorphism analysis, p53 gene mutations were examined in 24 cases of ovarian tumor including 14 ovarian carcinomas and 2 borderline cases of common epithelial type, 7 germ cell tumors, and one stromal tumor. Abnormal bands indicating mutations were detected in 12 (50%) of the cases examined, being present most frequently in common "epithelial" ovarian carcinoma (71%, 10/14). One case each of squamous cell carcinoma originating in a dermoid cyst and anaplastic dysgerminoma were positive for mutation. Direct sequencing confirmed 12 mutations and revealed G-->A and G-->C nucleotide changes in 5 and 3 cases (42% and 25%), respectively. The mutation was localized at the CpG site of the gene in 3 cases. Immunohistochemical examination of p53 protein in 21 cases and DNA flow-cytometrical analysis in 17 cases were also performed. Nuclear accumulation of the p53 protein and DNA aneuploidy pattern were detected in 11 (52%) and 9 (53%) cases, respectively. These were significantly correlated with p53 gene mutation (P < 0.01 and P < 0.05, respectively; Fisher's exact test). Neither mutation of the p53 gene, nuclear accumulation of p53 protein nor DNA aneuploidy was detected in borderline cases of common "epithelial" type, typical dysgerminoma and immature teratoma. These results suggest that p53 gene mutation, nuclear accumulation of the protein and the DNA aneuploidy pattern are events occurring almost simultaneously in the progression of ovarian tumors, and that p53 abnormalities seem to be correlated with a high grade of malignancy.
 ...
PMID:High incidence of p53 gene mutation in human ovarian cancer and its association with nuclear accumulation of p53 protein and tumor DNA aneuploidy. 142 9

Tumorigenesis is a multistep process involving mutations of dominantly acting proto-oncogenes and mutations and loss-of-function mutations of tumor suppressor genes. Some of these mutations may be inherited, but most of them are acquired. Models for the sequential steps of the genetic changes involved in tumor development have been proposed for certain cancers, such as colon cancer. In the case of ovarian cancer, relatively little is known about the genetic events associated with the initiation or subsequent progression and metastases of the tumor. Cytogenetic analysis has revealed a high incidence of both structural and numerical chromosome changes, and the extent of these changes seems to increase with tumor progression. Oncogene activations of the proto-oncogenes K-ras, c-myc and c-erbB-2 have been found more frequently in aggressive ovarian tumors and may be associated with poor survival. Tumor-specific allele loss involving putative tumor suppressor genes has been observed for loci at chromosomes 11p, 17p, and 17q,--loci commonly deleted in other cancers too. A relatively high incidence of allelic loss on chromosome 6q appears to be specific to ovarian carcinoma. Familial breast/ovarian cancer has been suggested to map to chromosome 8q. Recently we have found a germ-line mutation in the tumor suppressor gene p53 in a family with breast- and ovarian cancers, indicating that this is the predisposing gene in this family. Genetic changes important for the etiology of ovarian cancers seem to involve both somatic mutations of oncogenes and somatic or germ-line inactivation of tumor suppressor genes.
 ...
PMID:Oncogenesis in ovarian cancer. 150 89

We examined samples of tumors of human breast, ovary, and colon of various degrees of malignancy for the expression of p53 protein, using a panel of anti-p53 antibodies and peroxidase immunohistochemistry. Of 66 tumor cases (24 cases of ovarian carcinoma, 23 cases of colon adenocarcinoma, and 19 cases of breast carcinoma), 36 (53%) showed high levels of expression of p53 using a human-specific antibody, and 16 (24%) showed high expression of a mutant form of p53. In the mutant p53-positive breast tumor samples, six (86%) were positive for HER-2/neu reactivity, compared with colon (0/4) and ovarian tumors (1/5). The pattern of p53 intracellular localization and tissue distribution, and the relationship between the expression of mutant p53 and cell differentiation, were also examined; poorly differentiated cells showed either overexpression of p53 or higher levels of mutant p53 in comparison with more normal cells.
 ...
PMID:Immunohistochemical analysis of p53 and HER-2/neu proteins in human tumors. 168 Aug 97

Previous reports have shown that one copy of the chromosome 17 was frequently lost in human ovarian cancers (1). The position of the allelic deletion has not been mapped and involvement of p53 gene has not been determined. In this study, we have shown that in human ovarian carcinoma, the commonest region of allelic loss in chromosome 17p is 17p 13.3 (65%) and 17p13.1 (63.7%; 6 out of 9 informative cases). Allelic loss was also observed at region 17p12 - 11.1 but at a lower frequency (38.6% to 37.5%). The pattern of allelic loss of p53 gene was consistent in both primary and secondary metastatic tumors of the same patient. No gross rearrangement of p53 was however observed at the remaining allele using Southern blot analysis. Allelic loss of p53 gene was closely associated with 17p 13.3, the terminal portion of chromosome 17p. The high frequency of allelic loss of p53 gene in ovarian carcinomas conformed with recent findings in cancers of colon, breast, lung and brain suggesting inactivation of p53 gene play a rate limiting step in pathogenesis of human malignancies.
 ...
PMID:Involvement of p53 gene in the allelic deletion of chromosome 17p in human ovarian tumors. 177 30

Modulation of apoptosis may influence resistance to chemotherapy and therefore affect the outcome of cancer treatment. Ovarian cancer, one of the most fatal malignancies in women, is often associated with drug resistance but the cellular pathways contributing to this effect remain obscure. We have found that Bcl-2 and p53, two proteins implicated in the control of apoptosis, are frequently expressed in fresh biopsies of primary ovarian carcinoma. Examination of Bcl-2 and p53 protein levels in pairs of cis-platin sensitive and resistant ovarian cell lines demonstrated that the resistant variants over-express Bcl-2 and/or p53, apparently due to progressive expansion of Bcl-2 and/or p53 positive subpopulations during the in vitro development of resistance. Exogenous expression of Bcl-2 or a temperature sensitive mutant p53 (ts p53) in the ovarian cell line A2780 resulted in protection from drug-induced apoptosis and a delay in drug-mediated S-phase arrest. Interestingly, p53 accumulation in response to DNA damage induced by different agents was significantly delayed and reduced in the Bcl-2 transfectants compared to the control A2780 line, suggesting that Bcl-2 may act upstream of the p53 pathway. Similarly, the induction of Bax mRNA and protein was also found to be delayed in the presence of Bcl-2. Overall, our data provide further evidence for cross-talk between Bcl-2, p53 and Bax and suggest that these genes are important determinants of drug-induced apoptosis thereby modulating resistance to chemotherapy.
 ...
PMID:The control of apoptosis and drug resistance in ovarian cancer: influence of p53 and Bcl-2. 747 41

We performed a serologic analysis for anti-murine double minute-2 (anti-mdm2) antibodies in sera of patients with different gynaecological diseases using immunoblotting technique with recombinant mdm2 as antigen. In addition, for large scale screening we established an anti-mdm2 enzyme-linked immunosorbent assay (ELISA). Serum samples from patients with breast cancer, ovarian carcinoma, cervix carcinoma and benign gynaecological tissue alterations were tested. We detected antibodies specific for mdm2 in sera derived from cancer patients, as well as from patients with non-malignant diseases. Some of the sera with antibodies against mdm2 also contained antibodies against the growth suppressor gene product p53.
 ...
PMID:Antibodies against murine double minute-2 (mdm2) in sera of patients with various gynaecological diseases. 755 98

The genetic events involved in the development of metastases of epithelial ovarian cancer are largely unknown. One gene postulated to play a role in tumour metastasis suppression is NME1 (nm23-H1), and an inverse relationship between NME1 expression and metastatic potential has been observed for some solid tumours. In this study we have investigated the levels of mRNA expression of the 2 isoforms of the NME gene, NME1 and NME2. A maximum of 45 tumours samples from 33 patients were available for Northern blot analysis. We observed variable levels expression of NME1 and NME2 mRNA. The average level of NME1, but not NME2, mRNA expression was statistically higher in metastatic biopsies when compared with primary tumour biopsies. To examine the possible tumour suppressor gene role of NME1 in ovarian tumours, 76 patients were investigated by Southern blot analysis to determine the rate of allelic deletion. Allele loss at 5 other chromosome 17 loci (D17S5, TP53, NF1, D17S74, D17S4) was also evaluated for many of these 76 patients. Allele loss was observed in 22/30 (73%) informative patients at the NME1 locus. We also observed high rates of allele loss at the other loci evaluated. No correlations with clinical stage, histological subtype or patient survival were observed in either mRNA or DNA analyses. We have established that tumour progression in ovarian cancer is accompanied by over-expression of the NME1 gene; however, despite high rates of allele loss at the NME1 locus, the concept that NME1 may be a candidate tumour suppressor gene in ovarian cancer cannot be confirmed by this study.
 ...
PMID:Increased expression of the NME1 gene is associated with metastasis in epithelial ovarian cancer. 762 7

We introduce a new epithelial ovarian carcinoma cell line (UCI 107) from a patient with papillary adenocarcinoma of the ovary who had not been previously treated. The growth characteristics, chemosensitivity, tumorgenicity, cytogenetics, antigen expression, and receptor status were examined. A standardized photometric assay was implemented to determine the response to single drug agents including doxorubicin (ADR), cisplatin (CDDP), and Taxol. Tumorgenicity was determined utilizing female athymic mice implanted either subcutaneously (sc) or intraperitoneally (ip) with 1 x 10(7) UCI 107 cells. UCI 107 cells grow rapidly in culture with lag phase of approximately 48 hr, population doubling time of 24-36 hr, and saturation density of 4.8 x 10(5) cells/cm2. The 50% inhibitory concentration values for the chemotherapeutic agents were 0.170, 0.029, and 0.330 microM for ADR, Taxol, and CDDP, respectively. Nude mice produced ip tumors within 15 days, resulting in death from carcinomatosis 40-45 days postimplantation. Subcutaneous tumor nodules (100 mm3) were observed in nude mice 12-13 days post-tumor implantation reaching a maximum tumor volume of approximately 10,000 mm3 by Day 30. The cytogenetic composite karyotype is as follows: 46, X, der (X) t (X;7) (p11;q22), inv dup (1) (q12;q32), t (6;6;11;22) (p21.3;q16;q23.3;q13.3), del (13) (q14.1). The cell line expresses progesterone receptor, increased levels of p53 protein, and cytokeratins. It does not appear to express Her-2/neu protein, estrogen receptor, nor the CA 125 tumor marker. In conclusion, UCI 107 displays unique cellular properties which make it an attractive model for the study of ovarian cancer.
 ...
PMID:Characterization and development of UCI 107, a primary human ovarian carcinoma cell line. 767 98

Germ line mutations of the p53 gene have been described in the Li-Fraumeni Cancer Family Syndrome and occur in patients with multifocal gliomas, particularly those with a history of a metachronous cancer or a family history of cancer. p53 dysfunction is often associated with ovarian cancer. Patients with ovarian carcinoma frequently develop synchronous or metachronous cancers and may have a family history of this or related cancers. Thus, we hypothesized that germ line p53 mutations might be associated with a significant proportion of ovarian cancers. Germ line DNA isolated from peripheral leukocytes of 73 patients with ovarian carcinoma was screened for p53 sequence abnormalities utilizing single-strand conformation polymorphism analysis and direct PCR sequencing techniques. As many as 40% of this cohort of ovarian cancer patients from 67 families may represent familial phenotypes. Synchronous and metachronous cancers occurred in 19% of the cohort. Only two intron-based polymorphisms were found. Neither has been previously reported. One of these, in intron 6, occurred in three unrelated patients all of whom had a history of metachronous breast cancer. A polymorphism in intron 10 occurred in a patient with synchronous endometrial cancer. No classic germ line mutations of p53 were found.
 ...
PMID:Absence of significant germ line p53 mutations in ovarian cancer patients. 767 3


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