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)

K1 is a murine monoclonal antibody (MAb) derived from a hybridoma generated by the fusion of splenocytes of BALB/c mice immunized with a human ovarian tumor cell line, OVCAR-3. This antibody reacts strongly with epithelial ovarian tumors and mesotheliomas. The antigen recognized by MAb K1, designated CAK1, has recently been characterized as a 40-kDa protein probably anchored to the cell surface by glycosyl-phosphatidylinositol. Using immunoperoxidase histochemical methods, we examined 37 squamous-cell carcinoma (SqCC) samples from cervix, lung, esophagus and other origins, and 12 normal squamous epithelia of the cervix and esophagus for their reactivity with MAb K1. Of the SqCC specimens, 81% showed K1 reactivity with variable intensity, but none of 12 normal tissue samples of squamous epithelia did so. Two patterns of CAK1 expression in tumor samples were found, i.e., a heterogeneous pattern with strong intensity, and a homogeneous pattern with weak intensity. Three carcinomas in situ of the larynx, vulva and esophagus were moderately positive with K1, suggesting that CAK1 antigen may occur in the early stage of carcinogenesis of SqCC. The expression of CAK1 was also compared with expression of CA125, HER-2/neu, p53 and P-glycoprotein, and MAb K1 was found to react most consistently with SqCC. Since K1 reacts with a majority of cervical and esophageal carcinomas but has no detectable reactivity in normal epithelia of the cervix uteri and esophagus, MAb K1 could be of value as a reagent to help distinguish between normal and neoplastic cells on sections as well as in cytological samples.
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PMID:Frequent expression of the tumor antigen CAK1 in squamous-cell carcinomas. 135 Oct 45

The effects of treatment in a hydrated autoclave (121 degrees C, 2 atm for 20 min), microwave oven (in water), and simple heating (60 degrees C overnight in distilled water or 90 degrees C for 10 min in ZnSO4) on the stainability of 56 antigens by commercially available antibodies in formalin-fixed paraffin-embedded tissue sections were evaluated. The detectability of nuclear antigens, glycoprotein, lymphocytic surface markers, and chromogranin A was significantly and reproducibly improved by these treatments, whereas the detectability of viral antigens and peptide hormones was attenuated or unchanged. This enhancement includes not only the distinctiveness of the positive staining, but also the number of positive cells, as revealed by comparing serial sections. Among these four heating procedures, microwave heating and autoclaving were more effective than the others on p53, c-erbB-2, and CA125, whereas simple heating was best for smooth-muscle actin (HHF35 and CGA7). Generally the effects of the heating procedures for these antigens were consistent among the cases, but the effects on GFAP varied with the case. The alterations we observed could significantly influence the interpretation of immunohistochemical staining of currently popular tumor markers such as p53 in terms of their prevalence (28% vs 64% in gastric cancer; 36% vs 82% in metastatic liver cancer) and other diagnostically important markers.
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PMID:Alteration of immunoreactivity by hydrated autoclaving, microwave treatment, and simple heating of paraffin-embedded tissue sections. 751 73

To determine the prevalence of p53 abnormal protein expression in transitional cell carcinoma of the ovary in Peking Union Medical College hospital, and to analyse the correlation between the overexpression of p53 protein and prognostic parameters of transitional cell carcinoma of the ovary, thirty-two transitional cell carcinoma of the ovary and 20 normal ovaries were analysed. Detection of overexpression of p53 protein was carried out by immunohistochemical staining (IHS) using the monoclonal antibody DO-1 on paraffin sections. 41% of 32 samples of transitional cell carcinoma of the ovary showed positive IHS with DO-1, whereas only 5% of 20 normal ovaries showed weakly positive cytoplasmic staining (P < 0.01). p53 overexpression did not correlate with age, CA125 levels, histological grade and lymph node metastasis, but patients with overexpression of p53 had a poor prognosis. Overexpression of p53 is a more common event in transitional cell carcinoma of the ovary. Further studies are warranted to clarify the role of p53 in transitional cell carcinoma of the ovary.
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PMID:[Overexpression of p53 in transitional cell carcinoma of the ovary]. 779 48

An epithelial ovarian cancer cell line is established from a patient with recurrent familial ovarian cancer. Two of the patient's sisters and her mother have also had ovarian cancer. The histological resemblance of the cell line to the patient's Stage IV, Grade 3 papillary serous ovarian primary cancer is striking. The cell line does not secrete CA125 and is estrogen and progesterone receptor negative. Overexpression of the p53 tumor suppressor gene but not the HER-2/neu oncogene was detected by immunohistochemical analysis. An unusual chemosensitivity to cisplatin, doxorubicin, etoposide, and taxol is demonstrated, suggesting that a chemosensitivity mechanism might explain prolonged survival of some patients with familial ovarian cancers. This truly unique cell line should prove invaluable in the further evaluation of molecular genetic changes associated with familial ovarian cancers.
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PMID:Isolation and preliminary characterization of an ovarian carcinoma cell line from a patient with familial ovarian cancer. 782 46

A new cell line, SR8, and xenograft model of ovarian carcinoma has been established in this laboratory over the past 20 months from a patient with advanced ovarian cancer. Electron microscopic examination of SR8 cells demonstrated the presence of desmosomes and tonofilaments; SR8 cells expressed epithelial membrane antigen (EMA) and glandular associated cytokeratin, all of these confirmed the epithelial origin of this cell line. In addition, SR8 cells expressed CA125, as did the original ovarian tumour. EGF-R and TP53 expression was identified by immunocytochemistry (ICC) in this line. Nearly all the SR8 cells (93%) expressed HLA-class I antigen while 13.5% expressed HLA-DR. SR8 cells showed near-diploid and -triploid chromosome populations with several clonal and non-clonal rearrangements. Subcutaneous and intraperitoneal xenografting of SR8 cells resulted in invasive tumour production at both sites in 3/4 and 4/4 female nude mice, respectively. These xenografts exhibited similar morphology as that of original tumour and were found to express EMA, cytokeratin, CA125 and TP53. The potential research applications of this cell line are discussed.
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PMID:SR8--the establishment and characterisation of a new ovarian carcinoma cell line and xenograft model. 869 26

The immunophenotype of HT29 human colon cancer cells implanted into severe combined immunodeficient mice was assessed in primary tumours and their metastases in the lungs using an indirect immunohistochemical method. After primary tumours were surgically removed, the metastases were given time to develop, thus paralleling the clinical situation. While vimentin was negative in both primary and secondary tumours, E-cadherin was present as membrane-bound labelling in the primary tumours only. Whereas the markers p53, MIB1, PCNA and CEA were consistently positive in both primary and metastatic tumours, CD44 variant 6 and CA125 were negative in metastases but positive in the primary tumours. There was a significant increase in the percentage of cells labelled for p53 in the primary tumours compared with the metastases. For the proliferation markers, there was no significant difference in labelling between primary tumours and metastases for MIB1. Of the cytokeratins examined, CK 20 gave the strongest and most consistent reaction in both primary and secondary tumours. The results indicate that, for certain immunohistochemical markers, results are the same in both primary tumours and metastases. Hence, in these cases, antigens that are expressed on the primary tumour as well as on the metastases can serve as target molecules for immunologically based forms of treatment of metastases.
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PMID:Immunophenotyping of human HT29 colon cancer cell primary tumours and their metastases in severe combined immunodeficient mice. 918 53

Five human ovarian carcinoma cell lines cultured from primary and metastatic tumors of Korean patients were characterized. These lines were isolated from two papillary serous cystadenocarcinomas, two endometrioid carcinomas, and one malignant Brenner tumor. It was shown that the growth of these cell lines was stable when cultured after at least 20 passages. Population doubling times varied from 40 to 67 hr. All lines showed high viability and were proven by DNA fingerprinting analysis to be unique. Contamination by mycoplasma or bacteria was excluded. In two lines, SNU-8 and SNU-840, an elevated level of CA125 antigen secretion could be detected, whereas CEA was undetectable in all five lines. Four different mutations in functional and highly conserved regions of the p53 gene were identified in three of our five lines (60%), namely in SNU-119, SNU-251, and SNU-563. Included were two missense mutations, one in-frame 3-base-pair deletion, and one out-of-frame 1-base-pair deletion. It is interesting to note that one of these three lines, SNU-251, presented an additional simultaneous nonsense mutation of the BRCA1 gene and missense mutation of the hMLH1 gene. In its lacking both wild-type alleles of the BRCA1 gene, SNU-251 might serve as an unusual and important in vitro model for studies related to ovarian carcinoma and the BRCA1 gene. It is thus likely that the establishment and characterization of these permanent human ovarian carcinoma cell lines in continuous cultures can provide useful tools for in vitro studies related to human ovarian carcinomas.
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PMID:Establishment and characterization of human ovarian carcinoma cell lines. 929 49

The aim of this study was to compare the immunophenotype of the human colon cancer cell line HT29 tumour deposits in the lung which occurred spontaneously after subcutaneous implantation with those which arose after intravenous injection into severe combined immunodeficient (scid) mice. Irrespective of the route of implantation the colon cancer cells were readily observed in the lungs of the scid mice. Similar patterns of immunoreactivity for the proliferative markers (MiB-1, PCNA), and for the tumour suppressor gene (p53) were detected in both groups, and for carcinoembryonic antigen, with only minor quantitative differences in levels of marker expression. Whereas the marker CD44 variant 6 gave very little reaction after either route, cytokeratin expression varied amongst the different cytokeratins (CK 7, 18 or 20), and with the route of implantation. CA125 and E-cadherin were weakly expressed after intravenous injection, but generally not after subcutaneous implantation. Vimentin was not demonstrated in any of the specimens examined. In general, the expression of proliferative markers, and of oncogenes, appears to be independent of the implantation route, whilst expression of cell adhesion molecules can be dependent on the route of implantation.
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PMID:Immunophenotype of human HT29 colon cancer cell metastases in the lungs of scid mice: spontaneous versus artificial metastases. 956 Oct 26

An autopsy case of a malignant pericardial mesothelioma in a 27-year-old man with no history of exposure to asbestos is reported. He was admitted for heart failure due to pericardial effusion of unknown origin and surgically drained, but later died. The diagnosis of a malignant pericardial mesothelioma was made on the basis of histologic, immunohistochemical and ultrastructural findings. The tumor was located on the pericardium, but autopsy revealed that it had spread extensively in the mediastinum and the lungs. Microscopically, the tumor cells were epithelial like and contained histochemically demonstrable glycogen and hyaluronic acid. Immunohistochemical studies of the tumor demonstrated positive immunoreactivity for cytokeratin 19, muscle actin HHF35, epithelial membrane antigen, CA125, p53 and p21WAF1/CIP1 whereas the tumor was negative for cytokeratins 10 and 17, carcinoembryonic antigen, vimentin, epithelial antigen BerEP4, S-100, c-erbB2 and bcl-2. A high MIB-1 labeling index was noted. Under the electron microscope the tumor cells exhibited long, thin villi. The operation and autopsy findings thus revealed this to be a very rare case of malignant pericardial mesothelioma in a young man.
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PMID:An autopsy case of a malignant pericardial mesothelioma in a Japanese young man. 1050 29

The prognostic values of p53 and of its downstream mediator p21WAF1/Cip1 in patients receiving adjuvant chemotherapy for epithelial ovarian cancer have not been clearly established. Tumor extracts from a series of 120 patients treated postsurgically with cisplatin or carboplatin alone or together with other chemotherapeutics for primary ovarian carcinoma were assayed both for p53 protein by an immunofluorometric assay developed by us and for p21 protein by a commercially available immunoassay. Relative risks (RRs) for cancer relapse and death after 24 months of follow-up were determined by multivariate Cox regression analysis. Disease-free (DFS) and overall survival (OS) probabilities were also examined by the Kaplan-Meier method and log-rank tests. All other procedures were similarly nonparametric and based on two-sided tests of significance. Concentrations of p53 were elevated in patients with advanced stage disease (P = 0.02) or poorly differentiated (P = 0.03), suboptimally debulked tumors (P = 0.02), as well as in patients who failed to respond to chemotherapy (P = 0.03), as assessed by computed tomography scanning, serum CA125 determination, and second-look laparotomy. Statistically significant associations between concentrations of p53 and p21 were not found, nor were relationships demonstrated between concentrations of p21 and other clinicopathological variables or treatment response. Univariate analysis showed that p53 concentrations above the median indicated significantly higher risks for relapse (P = 0.04) and death (P < 0.01) and showed trends for increasing risks for relapse (P = 0.04) and death (P < 0.01) when p53 was considered as a four-level categorical variable. Multivariate analyses adjusted for age, stage, grade, and residual tumor size confirmed these observations (RR = 1.50; P = 0.05 for DFS and RR = 1.92; P = 0.03 for OS) for median-dichotomized p53, but the trends were of borderline significance (P = 0.09 for DFS and P = 0.07 for OS). In contrast, p21 positivity was not a significant predictor of favorable outcome in univariate survival analysis, and use of a three-level variable combining positivity or negativity status for both p53 and p21 did not yield greater separation of patients into risk groups (P = 0.07 for DFS and P = 0.06 for OS) than the use of p53 alone. Assessment of p53 expression may be an independent indicator of poor prognosis in ovarian cancer patients treated with adjuvant chemotherapy. The prognostic value of p21 expression, however, could not be demonstrated in our series of ovarian cancer patients.
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PMID:Evidence for a dose-response effect between p53 (but not p21WAF1/Cip1) protein concentrations, survival, and responsiveness in patients with epithelial ovarian cancer treated with platinum-based chemotherapy. 1095 12


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