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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urokinase plasminogen activator (uPA) is a serine protease involved in cancer invasion and metastasis. uPA mediates its action while attached to a membrane-bound receptor (uPAR). In this investigation we show that uPAR levels correlate with uPA levels in human breast cancers. uPAR levels, however, do not correlate with other components of the plasminogen activator system such as tissue-type plasminogen activator (t-PA), PAI-I or PAI-2. In addition, uPAR levels showed no correlation with tumor size, axillary-node status or estrogen-receptor status. On the basis of an optimum cut-off point, patients with breast cancers containing high levels of uPAR had a worse prognosis than patients with low levels of the receptor. However, as a prognostic marker in breast cancer, uPAR was not as strong as uPA. Our results are consistent with data from model systems suggesting that both uPA and uPAR are necessary for metastasis.
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PMID:Urokinase plasminogen activator and urokinase plasminogen activator receptor in breast cancer. 776 29

A fifty-four-year-old woman was admitted to the hospital for a sensation of tightness in the chest of one hour's duration. She had undergone surgery for breast cancer two years previously and had been taking 30 mg of tamoxifen and 1200 mg of medroxyprogesterone daily after surgery. Emergency coronary angiography on admission revealed thrombi in both the right coronary artery and the left anterior descending coronary artery. Tissue-type plasminogen activator was injected into both coronary arteries, resulting in diminution of thrombus size. Repeat coronary angiography on the next day disclosed no thrombus in either artery and no significant stenosis. Electrocardiographic and laboratory data indicated myocardial infarction. These findings strongly suggest that the combination hormone therapy altered the patient's blood coagulability and played an important role in the formation of the intracoronary thrombi and subsequent acute myocardial infarction.
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PMID:A case of acute myocardial infarction. Intracoronary thrombosis in two major coronary arteries due to hormone therapy. 817 79

The relationship between tissue-type plasminogen activator (t-PA) antigen content and receptor status was investigated in 200 human breast cancer cytosols to evaluate the efficacy of t-PA as a marker of functional steroid receptors. t-PA level was measured by an enzyme-linked immunoassay (ELISA) and estrogen (ER) and progesterone (PgR) receptors were assayed by the DCC method. A highly significant correlation was found between t-PA levels and receptor status. The mean +/- SE enzyme content was 13.5 +/- 2.9 in ER+ tumors and 1.8 +/- 0.3 ng/mg protein in ER- tumors; the enzyme content in PgR+ tumors was 14.2 +/- 3.3 and 3.4 +/- 1.4 ng/mg protein in PgR- tumors. When tumors were divided into four subgroups according to receptor content (ER+PgR+, ER+PgR-, ER-PgR+, and ER-PgR-), t-PA concentration was able to differentiate these groups. Also, t-PA level was compared to several clinical variables; it was not correlated with menopausal status or lymph node involvement. However, t-PA content varied according to tumor size. Our data shows that t-PA content in tumor cytosols is statistically related to receptor status and that determination of t-PA levels in breast cancer might furnish additional information as to the functional state of the receptors which may be necessary for planning hormone therapy.
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PMID:Tissue-type plasminogen activator as marker of functional steroid receptors in human breast cancer. 838 64

Plasminogen activator (PA) is a serine protease existing in two forms known as tissue-type (t-PA) and urokinase-type (u-PA). To examine whether PA is related to the postoperative clinical course of human breast cancer, total PA activity, t-PA activity, u-PA activity, and immunoreactive t-PA were determined in tissue extracts from 144 breast cancer specimens. The patients were initially divided into four groups according to the postoperative clinical course: Group I (83 patients who are disease-free), Group II (20 patients whose first metastases were found only in bone), Group III (19 patients whose first metastases were found in both bone and lung), and Group IV (22 patients whose first metastases were found only in lung). Total PA activity was significantly lower in Groups, II, III and IV than in Group I. Both t-PA activity and t-PA antigen levels were also significantly lower in Groups II, III and IV than in Group I, while no significant difference was found in u-PA activity among these groups, indicating that low activity of total PA in Groups II, III and IV was due to a decrease in t-PA but not in u-PA. In the multivariate analyses, t-PA activity was found to be an independent prognostic factor for relapse-free survival. When four groups of patients were further analysed in terms of nodal status, both t-PA activity and antigen levels were markedly decreased in the node-negative Group II compared with the node-negative Groups III and IV or with the node-positive Groups II, III and IV. Of additional interest, u-PA activity was significantly higher in node-positive patients than in node-negative patients with any group. The clinico-pathologic analyses of the patients in this series showed that node involvement and lymphatic invasion were more frequently positive in Groups III and IV than in Groups I and II. When 144 breast cancers were categorised in terms of combinations of oestrogen receptor (ER) and progesterone receptor (PgR) status, breast cancers which were positive for both receptors were found to contain the highest t-PA activity and antigen. This study provides provocative evidence suggesting a possible differential significance of t-PA and u-PA expression in human breast cancer.
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PMID:Differential biological significance of tissue-type and urokinase-type plasminogen activator in human breast cancer. 839 31

Plasminogen activator (PA) is a serine protease which exists in two forms: tissue-type (t-PA) and urokinase-type (u-PA). The total PA activity was measured in tumour extracts of 235 breast cancer patients who were followed for a median of 8.5 years after surgery. Patients were initially divided into three groups with low (< 60 units mg-1 protein), intermediate (60-300 unit mg-1 protein), or high (> 300 unit mg-1 protein) total PA activity in tumour extracts. The PA activity was not significantly associated with the recognised prognostic factors of age, menstrual status, tumour size, lymph node involvement, histologic type, grade of anaplasia, and/or vessel involvement. A significant association was found between total PA activity and the oestrogen receptor (ER) or progesterone receptor (PgR) status. Among receptor-positive tumours, a significantly greater proportion of patients had high PA activity in their tumour extracts. Breast cancer patients with low total PA activity had a significantly shorter disease-free and overall survival rate when compared to those with intermediate or high PA activity. In univariate and multivariate analyses, total PA activity (< 60 unit mg-1 vs > or = 60 unit mg-1 protein) was found to be a significant prognostic factor for disease-free and overall survival of about the same import as lymph node involvement. Furthermore, the combination of total PA activity and nodal status could be even more precise in predicting survival times and probabilities in individual patients. This retrospective study demonstrates the total PA activity is a valuable prognostic factor in determining prognosis in human breast cancer.
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PMID:Breast cancer prognosis is poor when total plasminogen activator activity is low. 843 69

In order to predict a hypercoagulable state in patients with advanced breast cancer receiving medical treatment, the effects of chemoendocrine therapy on the coagulation-fibrinolytic systems were investigated prospectively. The patients were randomly divided into two groups. The ACT group had 38 patients, who received 20 mg/m2 adriamycin (ADM) i.v. on days 1 and 8, 100 mg cyclophosphamide (CPA) p.o. on days 1-14, and 20 mg tamoxifen (TAM) p.o. daily. The ACM group had 44 patients, who received 20 mg/m2 ADM i.v. on days 1 and 8, 100 mg CPA p.o. on days 1-14 and 1200 mg medroxyprogesterone acetate (MPA) p.o. daily. The treatment was repeated every 28 days until there was evidence of progressive disease or until the full ADM dose (550 mg/m2) had been given. The following 9 hematologic parameters were measured every 4 weeks: alpha 2-plasmin inhibitor plasmin complex (PIC), anti-thrombin-III (AT-III), D-dimer (Dd), fibrinogen (Fg), plasminogen (Pg), protein C (PC), thrombin-antithrombin-III complex (TAT-III), tissue plasminogen activator (t-PA), and factor X (FX). Compared to the ACT group, patients in the ACM group showed significantly higher values of AT-III and PC, which exceeded the normal ranges. The levels of Pg, t-PA and FX were significantly higher in the ACM group than in the ACT group, but were still within the normal ranges. The levels of TAT-III, Dd and PIC decreased in the ACT group and were unchanged in the ACM group after the start of treatment. Fg remained unchanged in both groups after the start of treatment. One patient in the ACM group had thrombophlebitis of the lower extremities with high levels of TAT-III, Dd and PIC and a decrease of Fg, but her condition returned to normal after reduction of the MPA dose. Although these data are not directly indicative of a hypercoagulable state in patients receiving chemoendocrine therapy, changes in AT-III, TAT-III, Dd and PIC should be monitored carefully when this type of treatment is given.
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PMID:Effects of chemoendocrine therapy on the coagulation-fibrinolytic systems in patients with advanced breast cancer. Japan Advanced Breast Cancer Study Group and Japan Clinical Oncology Group. 851 13

The urokinase type plasminogen activator (u-PA) and the plasminogen activator inhibitor-1 (PAI-1) are among the best second-generation prognostic tissue factors in breast cancer. However, different extraction procedures and assay kits are used in different laboratories. A total of 79 breast tumour tissues stored in liquid nitrogen were analysed in this study. We compared u-PA and PAI-1 levels determined with the American Diagnostics (AD) kit after various extraction procedures. The median cytosolic extraction yield in the presence of 0.4 mol/l KCl, calculated relative to extraction in the presence of 10 ml/l Triton X100 when adapted to standard laboratory working hours (incubation for 2 h instead of 12 h) was 74.4% for u-PA and 85.8% for PAI-1. In addition, the correlations were acceptable. Cytosolic extracts prepared with KCl could permit optimal u-PA and PAI-1 assays while also enabling hormone receptors to be determined with the same specimens. Further studies with clinical data are now necessary to determine the prognostic relevance of this extraction procedure.
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PMID:Comparative study of four extraction procedures for urokinase type plasminogen activator and plasminogen activator inhibitor-1 in breast cancer tissues. 861 70

Cell-surface activation of plasminogen may be important in diseases that involve cellular migration, including atherosclerosis and tumour invasion/metastasis. Cytokeratin 8 (CK 8) has been identified as a plasminogen-binding protein expressed on the external surfaces of hepatocytes and breast carcinoma cells [Hembrough, Vasudevan, Allietta, Glass and Gonias (1995) J. Cell Sci. 108, 1071-1082]. In this investigation, we demonstrate that a soluble form of CK 8 is released into the culture medium of breast cancer cell lines. The released CK 8 is in the form of variably sized polymers that bind plasminogen and promote the activation of [Glu1]plasminogen and [Lys78]plasminogen by single-chain tissue-type plasminogen activator (sct-PA). To assess the mechanism by which CK 8 promotes plasminogen activation, CK 8 was purified from rat hepatocytes and immobilized in microtitre plates. Immobilized CK 8 bound 125I-plasminogen and 125I-sct-PA in a specific and saturable manner. The KDs were 160 +/- 40 nM and 250 +/- 48 nM, respectively. Activation of plasminogen bound to immobilized CK 8 was accelerated compared with plasminogen in solution, as determined using a coupled-substrate fluorescence assay and SDS/PAGE. The ability of CK 8 to promote plasminogen activation may be important in the pericellular spaces surrounding breast cancer cells and at the cell surface.
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PMID:Cytokeratin 8 released by breast carcinoma cells in vitro binds plasminogen and tissue-type plasminogen activator and promotes plasminogen activation. 876 Mar 60

Cytokeratin 8 (CK 8) has been identified on the external surfaces of viable, unpermeabilized epithelial cells (Hembrough, T. A., Vasudevan, J., Allietta, M. M., Glass, W. F., and Gonias, S. L. (1995) J. Cell Sci. 108, 1071-1082). In this study, we demonstrated that CK 8 is the major plasminogen-binding protein in plasma membrane fractions isolated from three breast cancer cell lines, BT20, MCF-7, and MDA-MB-157. To assess the function of CK 8 as a plasminogen receptor, monoclonal antibody 1E8 was raised against the carboxyl-terminal 12 amino acids of CK 8. The 1E8 epitope was present on the external surfaces of breast cancer cells, as determined by immunofluorescence microscopy. 125I-1E8 bound to MCF-7 cells; the maximum binding capacity (1.5 x 10(6) sites per cell) was comparable with that determined for plasminogen. When MCF-7 cells were incubated with Fab fragments of 1E8, specific 125I-plasminogen binding was decreased up to 82%. Specific plasminogen binding was decreased up to 67%, even when the unbound 1E8 Fab was removed by washing the cells prior to adding 125I-plasminogen. Preincubation with 1E8 Fab decreased plasminogen binding to BT20 and MDA-MB-157 cells, although to a lesser extent than with MCF-7 cells. Plasminogen activation by tissue-type plasminogen activator was greatly accelerated, due to a large decrease in Km, when the plasminogen was bound to MCF-7 cells. Pretreatment with 1E8 Fab decreased the rate of plasminogen activation by up to 83%, implicating CK 8 in the MCF-7 cell-accelerated reaction. These studies identify cell-surface CK 8 as a major plasminogen receptor in breast cancer cells and as a required component for the rapid activation of cell-associated plasminogen by tissue-type plasminogen activator.
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PMID:Cell-surface cytokeratin 8 is the major plasminogen receptor on breast cancer cells and is required for the accelerated activation of cell-associated plasminogen by tissue-type plasminogen activator. 881 Mar 46

The plasminogen activator system plays a key role in the proteolysis of malignant tumours. In 155 patients with primary breast cancer levels from PAI-1 and uPA were measured in cytosol with monoclonal antibodies and by an enzyme-linked immunosorbent assay. 35 tumour tissue samples form benign breast were also examined. Malignant tumours contain higher levels of PAI-1 (8.6 ng/mg) than benign tumours (1.28 ng/mg) (p < 0.01). Also the median level of uPA was significantly higher (p < 0.01) in malignant tissue (2.38 ng/mg) in comparison to benign disease (0.54 ng/mg). No correlation was found between the proteases and the classical prognostic parameters like axillary lymph node involvement, tumour size and menopausal status. However, a significant correlation (p < 0.01) was found in tumours with lymphangiosis carcinomatosa, negative hormone receptors, grade III tumour cells and high S-phase fractions (> 5%). After a median follow-up of 46 months we found that high levels of PAI-1 correlated with short DFS (p = 0.0005) and OAS (p = 0.003). However, in the Cox multivariate regression analysis only PAI-1 was significantly independent for OAS and could therefore give additional information. We conclude that levels from PAI-1 antigen measured in cytosol of primary breast cancer is an independent prognostic parameter to identify patients with high and low risk for relapse and for individualised treatment.
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PMID:[Prognostic significance of plasminogen activator inhibitor-1 (PAI-1) in primary breast carcinoma]. 885 83


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