Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the occurrence of type-1 inhibitor of plasminogen activators (PAI-1) in human breast tumors. PAI-1 levels, measured by enzyme-linked immunosorbent assay, were significantly higher in malignant breast carcinomas (n = 178) than in benign breast tumors (n = 25). The levels of PAI-1 were found to be correlated with those of urokinase-type plasminogen activator (u-PA). The presence of PAI-1 in tumor extracts was also demonstrated by immunoblotting analysis. Immunohistochemical investigations by the use of monoclonal and polyclonal antibodies showed that PAI-1 was mostly localized in the tumor islands, associated with the tumor cells; in addition, it was present in vessel walls and in normal duct epithelia, but absent from the stroma. Analysis of RNA extracted from tumors by polymerase chain reaction revealed the presence of PAI-1 mRNA. We conclude that PAI-1 is present in human breast carcinoma cells, and that it is--at least partially-- produced locally, either by the cancer cells or by other cells in the tumors. We have previously demonstrated that a high level of u-PA in human breast carcinomas is associated with poor prognosis. These results, combined with our present findings, present 2 possibilities: either the cancer cells need PAI-1 in order to utilize the u-PA-mediated pathway of plasminogen activation for invasion and metastasis; or PAI-1 represents a defense mechanism against tumor invasion.
Int J Cancer 1992 Jan 21
PMID:Type-1 plasminogen activator inhibitor in human breast carcinomas. 173 May 15

We measured antigen levels of 2 kinds of plasminogen activator, tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (UK), as well as those of their primary inhibitors, type-I plasminogen activator inhibitor (PAI-1) and type-2 plasminogen activator inhibitor (PAI-2), in tissue extracts from benign and malignant breast tumors. Tumor tissue samples from 40 fibroadenomas and 40 breast cancers were examined. t-PA antigen levels were the same in the 2 groups. Malignant tumors contained higher levels of UK antigen than did benign tumors. In the case of breast cancer, UK antigen levels of tumors with axillary lymph-node involvement were significantly higher than those of tumors without lymph-node involvement. PAI-1 and PAI-2 antigen levels of breast-cancer tissue samples were higher than those of fibroadenoma samples. PAI-1 antigen levels of carcinomas with lymph-node involvement were also significantly higher than those of carcinomas without node involvement. PAI-2 antigen levels, on the contrary, were higher in carcinomas without node involvement. UK, PAI-1 and PAI-2 antigen levels are potentially excellent independent factors for prediction of the metastatic potential of breast cancers.
Int J Cancer 1992 Feb 01
PMID:Plasminogen activator system in human breast cancer. 173 2

The antigen levels of plasminogen activators (PAs), tissue-type PA (t-PA) and urokinase-type PA (u-PA), were measured in extracts from 30 gastric carcinomas and corresponding normal gastric mucosa. The t-PA level was significantly higher in normal mucosa than in cancer tissue, while the u-PA level was significantly higher in cancer tissue. The u-PA level increased with increasing tumor stage, and there was a significant difference between early and advanced cancer. The u-PA level also increased with the degree of nodal involvement, and it was higher in undifferentiated tumors than in well-differentiated ones. It was higher in cases with venous invasion, liver metastasis or peritoneal dissemination than in cases without these features.
 ...
PMID:Relationship between plasminogen activators and stomach carcinoma stage. 176 72

The correlation between the production of plasminogen activators (PA), especially urokinase-type PA (u-PA), by cancer cells and their metastatic potential was studied. For this purpose, cells from the human rectal adenocarcinoma tumor line (RCM-l/nu) originally maintained by serial passage in nude mice as the solid subcutaneous tumor, were injected into the spleen. Cancer cells from liver metastatic foci were suspended and then injected into the spleen. After 10 cycles of this selection, a highly metastatic liver tumor line termed L-10 was obtained. The amount of u-PA in the supernatant of the tumor homogenate of L-10 was larger than that of RCM-l/nu. Using an in vitro culture system, the media conditioned by L-10 cells had a higher PA activity and a higher u-PA antigen level than by RCM-l/nu cells. The apparent difference in u-PA activity and antigen levels of these two lines was not due to the difference in the production of plasminogen activator inhibitor (PAI), because PAI antigen level and PAI activity in the culture media were almost equal between them. No tissue-type PA production was detectable in these tumor lines. From these results we deduce that u-PA may play an important role in tumor metastasis.
 ...
PMID:Correlation between urokinase-type plasminogen activator production and the metastatic ability of human rectal cancer cells. 176 31

In order to evaluate precisely the fibrinolytic states in clinical disorders, plasma levels of D dimer (cross-linked fibrin degradation products) were measured by a newly developed, rapid quantitative method based on the latex photometric immunoassay in patients with hematological malignancies, diabetes mellitus, collagen disease, liver disease, thrombotic disease and disseminated intravascular coagulation (DIC). Plasma levels of D dimer were elevated in a variety of diseases, especially in DIC. Patients with hematological malignancies, liver disease and thrombotic disease also had relatively high levels of D dimer. On the whole, D dimer values were positively correlated with plasmin-alpha 2-plasmin inhibitor complex and thrombin-antithrombin III complex. In addition, plasma D dimer was measured during fibrinolytic therapy with urokinase or tissue-type plasminogen activator; its elevation was detected in some patients. These findings indicate that accelerated fibrinolysis is frequently observed in a variety of diseases, and that a rapid quantitative measurement of D dimer would be valuable for the precise assessment of fibrinolysis in these disease states.
 ...
PMID:[Evaluation of clinical usefulness of a rapid quantitative measurement of D dimer (cross-linked fibrin degradation products)]. 177 52

170 patients were treated with continuous infusion of epirubicin, mitoxantrone, carboplatin or 5-fluorouracil through an implanted venous access port with a portable infusion pump. A total of 440 cycles were given on an outpatient basis. The patients were instructed how to dissolve their drugs and to change the syringes. The complication rate was low. 10 patients developed a thrombosis of the subclavian vein, resulting in cessation of therapy in 5. Pulmonary embolism occurred twice, in 1 patient during a period of subclavian vein thrombosis. Needle dislocation occurred 6 times and catheter occlusion 20 times. Patency was restored with saline or urokinase. Local infection occurred 3 times and systemic infection only once. This technique is suitable for continuous infusion of different cytostatic drugs on an outpatient basis. Patients were able to prepare their drugs at home and the system can remain in situ for 3 weeks without increasing the complication rate.
Eur J Cancer 1991
PMID:Continuous infusion of chemotherapy on an outpatient basis via a totally implanted venous access port. 182 78

The occurrence and distribution of components of fibrinolysis pathways were determined using immunohistochemical techniques applied to 10 cases of primary carcinoma of the breast, normal breast tissue obtained from two patients undergoing reductive mammoplasty, and three cases of benign breast tumors. Tumor cells stained for urokinase- and tissue-type plasminogen activators, plasminogen activation inhibitor-1, plasminogen, and plasmin-antiplasmin complex neoantigen. The tumor connective tissue stained for fibrinogen and its D fragment plasmin digestion product. By contrast, only occasional nonneoplastic duct epithelial cells stained for urokinase- and tissue-type plasminogen activators and there was little or no staining for the other antigens tested. These results are consistent with the existence of local amplification of expression of enzymatically active plasminogen activators, and particularly of urokinase-type plasminogen activator, in situ in primary breast cancer tissue. These features distinguish malignant from benign breast tissue and may modulate neoplastic progression through an effect on tumor cell proliferation, invasion, and metastatic dissemination.
Cancer Res 1991 Jan 01
PMID:Occurrence of components of fibrinolysis pathways in situ in neoplastic and nonneoplastic human breast tissue. 184 11

To determine whether a relationship exists among urokinase plasminogen activator (u-PA) activity, tissue plasminogen activator (t-PA) activity, and the malignant transformation of human fibroblasts, we measured receptor-bound and secreted u-PAs and t-PA activity in fibroblast cell strains of a unique cell lineage and compared the results with the values obtained in human fibrosarcoma-derived cell lines and control cell lines. The lineage consists of four nonmalignant, infinite life span cell strains, clonally derived from a finite life span, neonatal foreskin-derived cell line or one of its derivatives and 10 malignant cell strains clonally derived from that same derivative. Seven of the latter were malignantly transformed by K-, H-, or N-ras oncogene transfection, two were obtained following carcinogen treatment, and one arose spontaneously. All 10 malignant strains in this lineage exhibited significantly higher levels of activity of receptor-bound u-PA than was found in the cell strain from which they arose or the nonmalignant cell strains derived from it. The ras oncogene-transformed malignant strains also exhibited significantly higher levels of activity of receptor-bound t-PA than their cell strain of origin. The other three malignant strains showed undetectable levels, consistent with their attaining the malignant state by an alternate process. The five fully malignant fibrosarcoma-derived cell lines tested also showed high levels of receptor-bound u-PA and t-PA. The majority (greater than or equal to 80%) of the nonmalignant control cell lines did not do so. The 10 malignant cell strains in the lineage also exhibited higher levels of activity of secreted high molecular weight u-PA or t-PA than did their cell strain of origin and the nonmalignant cell strains derived from it, as did the malignant fibrosarcoma-derived cell lines. The data suggest that the malignant state of human fibroblasts is always associated with high levels of activity of receptor-bound u-PA, and in addition cells transformed to the malignant state are very likely to exhibit high levels of receptor-bound t-PA and secreted forms of plasminogen activators.
Cancer Res 1991 Feb 15
PMID:Malignant transformation of human fibroblasts correlates with increased activity of receptor-bound plasminogen activator. 184 59

A truncated version of the human urokinase plasminogen activator receptor has been obtained by in vitro mutagenesis by insertion of a premature nonsense codon in the urokinase plasminogen activator receptor cDNA. This results in a protein truncated immediately upstream of the region which appears to be required for membrane attachment of the receptor via a glycolipid anchor. The modified receptor cDNA inserted into an expression vector has been transfected into mouse LB6 cells. Transfectants produce a urokinase plasminogen activator (u-PA)-binding protein that is secreted into the medium. It can be cross-linked to iodinated ATF (amino-terminal fragment of u-PA) and can also inhibit binding of iodinated ATF to mouse LB6 cells that express the wild type human receptor. The soluble u-PA receptor will be used in a variety of experiments aimed at identifying the role and mechanism of u-PA in physiological and pathological invasive processes, as well as in therapeutical attempts to block or decrease cancer cell invasion and in general u-PA-mediated tissue destruction.
 ...
PMID:A soluble, ligand binding mutant of the human urokinase plasminogen activator receptor. 185 Nov 52

Fourteen human colon adenocarcinomas were examined by in situ hybridization for the presence of mRNA for plasminogen activator inhibitor type 1 (PAI-1). All specimens contained PAI-1 mRNA in endothelial cells of some vessels in the stroma immediately surrounding the invasive tumor glands, in granulation tissue, and in some capillaries located under the free luminal surface of carcinomatous epithelium. In addition, a limited number of stromal cells in the cancerous areas located at the periphery of newly formed capillary networks, and presumably representing sprouting endothelial cells, contained PAI-1 mRNA. Cancer cells were devoid of detectable PAI-1 mRNA in all cases. PAI-1 mRNA was not seen in three biopsies of normal colon. Together with previous findings of urokinase-type plasminogen activator and its mRNA being located in fibroblast-like cells in the tumor stroma and mRNA for the urokinase receptor in the cancer cells at invasive foci, these results indicate a complex cooperativity among several cell types in regulation of plasminogen activation in colon cancer. A possible role of PAI-1 in protecting the extracellular matrix in the tumor tissue against degradation and a role in tumor-induced angiogenesis are discussed.
Cancer Res 1991 Aug 01
PMID:The plasminogen activation system in human colon cancer: messenger RNA for the inhibitor PAI-1 is located in endothelial cells in the tumor stroma. 185 21


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