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)

Seven kinds of serum regulatory gene coding protein for cell growth were determined with enzyme linked immunodotting in 19 indoor coal-burning exposed patients with lung cancer (Group A), 22 exposed cases without lung cancer (Group B), and 19 nonexposed cases without lung cancer (Group C) to study pathogenesis of lung cancer patients exposed to indoor coal-burning. Results showed that serum concentrations of ras, p53 and neu protein in Group A were significantly higher than those in Groups B and C, with a statistically significant difference (P < 0.05) or a very significant difference (P < 0.01). Six cases in Group A were positive for ras protein (with two strong positive), three for p53, neu and jun each, and one for p16. Two in Group B were positive for ras protein and one for p16. It suggests that serum regulatory protein for cell growth can be regarded as biological markers for environment-related lung cancer.
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PMID:[Studies on serum regulatory protein for cell growth in patients with lung cancer exposed to indoor coal-burning]. 981 20

The introduction of adenovirus 5 E1A into the SKOV3ip1 ovarian cancer cell line was shown previously to suppress HER2/neu expression and reduce the malignant potential of these cells (Yu et al., Cancer Res., 53: 891-898, 1993). In this report, we show that reduction of p185 in cells stably expressing E1A protein was coincident with increased sensitivity to cytotoxic agents. The LD50 of cisplatin was reduced 6-fold, and the LD50 of paclitaxel and doxorubicin was reduced 10-fold in E1A-expressing cells compared with control cells. The growth of SKOV3ip1 and control cells was unchanged in the presence of 150 ng/ml of tumor necrosis factor-alpha, whereas the growth of E1A-expressing cells was reduced by 30 to 40%. When we used a physiologically obtainable concentration of paclitaxel (0.5 microM), DNA laddering consistent with apoptotic cell death was seen after a 24-h exposure in the E1A-expressing cells, whereas laddering and DNA fragmentation were only detected in DNA from control cells after longer exposure (48 h) at a 20-fold higher concentration of paclitaxel. The SKOV3ip1 cells do not express p53 protein; hence, the induction of apoptosis by paclitaxel is through a p53-independent pathway. Despite their diverse mechanisms of action, the cytotoxic effects of cisplatin, doxorubicin, paclitaxel, and tumor necrosis factor-alpha were enhanced by the expression of E1A proteins in the SKOV3ip1 ovarian cancer cells. This suggests that these agents share a common final pathway of cell killing, which may represent a potential therapeutic target in resistant ovarian cancers.
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PMID:Adenovirus E1A expression enhances the sensitivity of an ovarian cancer cell line to multiple cytotoxic agents through an apoptotic mechanism. 981 92

Amplification of chromosome 11q13 is frequently observed in human malignancies, including breast cancers. A candidate oncogene at this locus is the CCND1 gene, which encodes the cell cycle regulatory protein cyclin D1. Because published data on the relationship between 11q13 amplification and prognosis in breast cancer have been controversial, we investigated the clinical significance of CCND1 amplification and its association with established clinicopathological features of prognosis in 1014 primary breast cancer patients. Amplification of the CCND1 gene and the INT-2/FGF-3 gene, which also maps to 11q13, was 10% and 17%, respectively. There were no associations between CCND1 or INT-2 amplification and patient age, tumor size, tumor grade, axillary lymph node status, HER/neu amplification, MIB-1 monoclonal antibody to Ki67 antigen count, or p53 expression. CCND1 amplification was predominantly observed in hormone receptor-positive tumors; at a copy number >/=3, CCND1 amplification was significantly correlated with both estrogen receptor (ER; P = 0.036) and progesterone receptor (P = 0.012) positivity. After a median follow-up period of 66 months, CCND1 or INT-2 amplification was not associated with significant increases in relapse or death from breast cancer. However, in the node-negative and ER-positive subgroups, there was a trend for an increased relapse rate in patients with INT-2 or CCND1 amplification. Thus, in this study, assessment of CCND1 or INT-2 amplification at 11q13 by slot-blot hybridization was of little use in determining phenotype or disease outcome in the whole group of patients but had a potential role in identifying a subset of poor-prognosis patients within the node-negative or ER-positive, good-prognosis groups. Because the prevalence of CCND1 amplification is much lower than the reported prevalence of cyclin D1 overexpression, additional studies are required to determine the true prognostic significance of altered cyclin D1 expression in breast cancer.
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PMID:Cyclin DI amplification is not associated with reduced overall survival in primary breast cancer but may predict early relapse in patients with features of good prognosis. 981 85

The genes for p53, neu (c-erbB-2) and nm23 are all located on chromosome 17. Abnormal expression of their protein products is an important prognostic parameter. The aim of this study was to investigate if numerical aberrations of chromosome 17 are reflected in the expression of these markers. The immunohistochemical expression was analysed on histological specimens from 33 breast carcinomas. In situ hybridization (ISH) was performed on interphase cell nuclei in air-dried fine-needle aspirates from the same cases using a digoxigenin-labelled alpha-satellite probe for chromosome 17. ISH for chromosome 6, 7 and 12 was used additionally to give an estimate of ploidy. Of the carcinomas 76% were aneuploid, and numerical abnormalities of chromosome 17 were found in 34%. Abnormal p53 protein was expressed in 15% (five cases). All of these were aneuploid, but only one of them revealed aneusomy of chromosome 17. Neu overexpression was found in 18% of the tumours (six cases). Five of these were aneuploid, whereas two were aneusome for chromosome 17. Four cancers showed full (normal) expression of nm23 protein, whereas 29 had reduced expression. Reduced expression was found in 23 of 25 aneuploid tumours. Numerical aberrations of chromosome 17 were found equally in carcinomas with reduced and full nm23 protein expression. Abnormal numbers of chromosome 17 seem only to have a minor impact on these markers and are not reflected significantly in their expression.
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PMID:Numerical aberrations of chromosome 17 in interphase cell nuclei of breast carcinoma cells: lack of correlation with abnormal expression of p53, neu and nm23 protein. 983 92

The goal of our study was to develop a panel of tumor cell lines along with paired non-malignant cell lines or strains collected from breast cancers, predominantly primary tumors. From a total of 189 breast tumor samples consisting of 177 primary tumors and 12 metastatic tissues, we established 21 human breast tumor cell lines that included 18 cell lines derived from primary tumors and 3 derived from metastatic lesions. Cell lines included those from patients with germline BRCA1 and FHIT gene mutations and others with possible genetic predisposition. For 19 tumor cell lines, we also established one or more corresponding non-malignant cell strains or B lymphoblastoid (BL) lines, which included 16 BL lines and 7 breast epithelial (2) or stromal (5) cell strains. The present report describes clinical, pathological and molecular information regarding the normal and tumor tissue sources along with relevant personal information and familial medical history. Analysis of the breast tumor cell lines indicated that most of the cell lines had the following features: they were derived from large tumors with or without axillary node metastases; were aneuploid and exhibited a moderate to poorly differentiated phenotype; were estrogen receptor (ER)- and progesterone receptor (PR)-negative; and overexpressed p53 and HER2/neu proteins. Of 13 patients with primary breast cancers receiving curative intent mastectomies, 7 were dead after a mean period of 10 months. Our panel of paired tumor and non-malignant cell lines should provide important new reagents for breast cancer research.
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PMID:Characterization of paired tumor and non-tumor cell lines established from patients with breast cancer. 983 71

Epithelial cells can be detected in bone marrow or peripheral stem cell preparations of patients with various kinds of cancer and their presence in bone marrow is of prognostic significance. Characterization of these cells has been hampered by their low frequency. Here we present a method that may allow sequential immunophenotyping and genotyping of epithelial cells in bone marrow. To simulate in vivo situations, cells from the colon cancer cell line HT29 were seeded into bone marrow and were first detected by the Fab fragment of the A45-B/B3 anticytokeratin antibody. Expression of Ki67, p53, Her-2/ neu (c-erbB2), and 17-1A could be detected on A45-B/B3-stained cells by immunofluorescence using a fluorescein-labeled anti-mouse immunoglobulin specific for the Fc part of mouse immunoglobulins. Reactivity for all antigens except for Ki67 persisted after A45-B/B3 labeling even when a scoring step for the presence of epithelial cells was performed before proceeding with the immunophenotyping. After immunophenotyping, numerical chromosomal aberrations and amplifications of the Her-2/neu oncogene could be assessed by fluorescence in situ hybridization in the same A45-B/B3-stained cells. This combination of immunophenotyping and genotyping may help in establishing the role of epithelial cells in bone marrow or peripheral stem cell harvests for tumor relapse and formation of metastases.
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PMID:Sequential immunotyping and genotyping of tumor cells in bone marrow of cancer patients: a model study. 984 46

Expression of proliferation- and apoptosis-related proteins was studied by immunohistochemistry in 130 usual ductal hyperplasias of the breast, of which 39 cases (30%) had adjacent invasive cancer. Overexpression of cyclin D1 and Ki-67 was found in 6% and 29% of the cases, respectively. Only two mild ductal hyperplasias were Her-2/neu positive. Overexpression of p21 and reduced expression of p27, both cdk-inhibitors, was seen in 16% and 27% of the lesions, respectively. Reduced expression of bcl-2 was found in 16% of the cases, and p53 accumulation was present in 8%. Expression of six of the seven studied proteins showed no significant difference between mild, moderate, or florid ductal hyperplasias, indicating that there are no important cell biological differences with regard to the studied proteins between the lesions within this morphologically continuous spectrum. In addition, there were no differences between lesions with and without an invasive component. Cyclin D1 positivity was exclusively seen in lesions with 75% or more p27-positive nuclei. No significant correlations were found between other proteins. Twenty-three of 91 lesions (25%) had multiple events, of which five showed altered expressions of three or four proteins. In conclusion, altered protein expression of several proliferation- and apoptosis-related genes that are known to be involved in invasive breast cancer also may be found in usual ductal hyperplastic lesions, including several lesions with multiple events. This implies that usual ductal hyperplastic lesions may be among the earliest lesions within the breast oncogenetic spectrum.
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PMID:Expression of proliferation and apoptosis-related proteins in usual ductal hyperplasia of the breast. 986 45

Although human tumor-derived cell lines play an important role in the investigation of cancer biology and genetics, there is no comprehensive study comparing tumor cell line properties with those of the individual tumors from which they were derived. We compared the properties of a series of 18 human breast cancer cell lines that were cultured for a median period of 25 months (range, 9-60 months) and their corresponding archival tumor tissues. We compared morphological characteristics, ploidy, and immunohistochemical expression of estrogen receptors, progesterone receptors, and HER2/neu and p53 proteins. For 17 of these cases, we also tested for allelic losses at 18 chromosomal regions frequently deleted in breast tumors using 51 polymorphic microsatellite markers, and we determined the TP53 gene mutation status in exons 5 to 10. There was an excellent correlation between the breast tumor cell lines and their corresponding tumor tissues for morphological features (100%); presence of aneuploidy (87%); immunohistochemical expression of estrogen receptors (87%), progesterone receptors (73%), and HER2/neu (93%) and p53 proteins (100%); allelic loss at all of the chromosomal regions analyzed (82-100% concordance); and TP53 gene mutations (75%). The same parental allele was lost in 279 (99%) of 281 of the comparisons of allelic losses. The fractional allelic loss indices (a reflection of the total allelic loss) of the cell lines and their corresponding tumor tissues were identical or similar in 15 (88%) of 17 paired comparisons. Although our previous studies (A. Gazdar et al., Int. J. Cancer, in press) indicated that only a subset of primary breast carcinomas that have several features indicative of advanced tumors with poor prognosis can be successfully cultured, the cell lines retain the properties of their parental tumors for lengthy culture periods and, thus, provide suitable model systems for biomedical studies.
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PMID:Comparison of features of human breast cancer cell lines and their corresponding tumors. 986 3

Male breast carcinoma (MBC) accounts for only 1% of total mammary carcinomas. Controversy exists about whether MBC differs clinically and pathologically from female breast carcinoma (FBC). We compared 10 archival cases with 75 stage-matched FBCs. Clinical data, histologic details, immunostains for mammary lineage markers, and results of several putative "prognostic" analyses were addressed, including DNA ploidy and expression of c-erbB-2 (neu) oncoprotein and p53 protein. Cumulative literature data on 2,530 MBCs were contrasted with information from 135 institutional cases of FBC. A statistically significant difference in grade 3 lesions at low stage persisted when MBCs of all stages were compared with similar FBCs. For stages I and IIA, 5-year survival was 60% and 86% for MBCs and FBCs, respectively (also statistically significant). This difference disappeared when all stages were compared. A similar number of MBCs and FBCs, regardless of stage, demonstrated DNA aneuploidy with or without synthesis of S-100 protein, gross cystic disease fluid protein-15, c-erbB-2 protein, and p53 protein. Hormone receptor positivity was more common in MBC than in FBC at high tumor stages. Low-stage MBC and FBC differ biologically; MBCs tend to manifest at a higher grade with lessened 5-year survival. However, aside from distinctions in hormone receptor proteins, broader comparison of MBC and FBC at stages IIB and higher shows no significant differences in 5-year survival or expression of breast cancer-associated gene products.
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PMID:Low-stage carcinoma of the male breast. A histologic, immunohistochemical, and flow cytometric comparison with localized female breast carcinoma. 989 55

Detecting and/or monitoring changes in circulating tumor markers might assist in evaluating cancer risk, diagnosis, prognosis, or response to treatment. Several categories of circulating tumor markers have been investigated in breast cancer. These categories include classical tumor-associated antigens, such as CEA and CA 15-3, markers of tumor biology, including markers of angiogenesis, adhesion, and invasion, and antibody response to tumor-associated antigens such as HER2/neu and p53. We used a recently proposed Tumor Marker Utility Grading System to evaluate the use of several circulating tumor markers for different clinical utilities in breast cancer. While there are no tumor markers with established clinical utilities for most uses, tumor-associated antigens can be used for monitoring patients with metastatic disease. In addition, markers of tumor biology such as the circulating extracellular domain of HER2/neu might be useful in determining not only prognosis, but also response to specific treatments. However, further investigations are required to further assess the utility of individual tumor markers for specific clinical uses.
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PMID:Circulating tumor markers in breast cancer: accepted utilities and novel prospects. 1006 86


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