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European Journal of Cancer & Clinical... May 1984Plasminogen activator is a protease which catalyses the conversion of the inactive plasminogen to the active plasmin. Most transformed cell lines and solid tumors... (Review)
Review
Plasminogen activator is a protease which catalyses the conversion of the inactive plasminogen to the active plasmin. Most transformed cell lines and solid tumors produce elevated levels of plasminogen activator compared with nontransformed counterparts. This increased synthesis of plasminogen activator may play a role in tumorigenesis, cancer invasion and metastasis. Measurement of plasminogen activator in tumor extracts and body fluids may provide diagnostic and prognostic information. Finally, since plasminogen activator is an estradiol-inducible enzyme, its measurement in breast carcinomas might be a marker for a functional estrogen receptor.
Topics: Animals; Breast Neoplasms; Cell Line; Cell Transformation, Neoplastic; Chick Embryo; Female; Humans; Male; Mice; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Plasminogen Activators; Rats; Urokinase-Type Plasminogen Activator
PubMed: 6376129
DOI: 10.1016/0277-5379(84)90001-4 -
Clinical Cardiology Jun 1990Thrombotic disorders such as myocardial infarction and stroke are the leading causes of death and disability in industrialized nations. Timely institution of... (Review)
Review
Thrombotic disorders such as myocardial infarction and stroke are the leading causes of death and disability in industrialized nations. Timely institution of thrombolytic therapy can achieve a reduction of infarct size, a preservation of left ventricular function, and a reduction in mortality. The administration of streptokinase, urokinase, and acylated plasminogen-streptokinase activator complex (APSAC) can be associated with a complete breakdown of the hemostatic system. Tissue-type plasminogen activator (t-PA) and single-chain urokinase-type plasminogen activator (scu-PA, prourokinase) are more fibrin specific; however, at the large dosages of activator needed for therapeutic efficacy, bleeding complications are still a problem. New approaches to optimizing the risk/benefit ratio for the patient by improving efficacy without sacrificing specificity include the use of synergistic combinations of plasminogen activators, mutants of t-PA and scu-PA, chimeric molecules, and antibody-targeted thrombolytic agents. The last approach opens the possibility of targeting several different components of the clot with either fibrinolytic or antiplatelet effector functions in one optimized molecule.
Topics: Animals; Antibodies, Monoclonal; Drug Synergism; Humans; Myocardial Infarction; Plasminogen Activators; Thrombolytic Therapy
PubMed: 2188764
DOI: 10.1002/clc.4960130602 -
Seminars in Ophthalmology Mar 2000Tissue plasminogen activator (tPA) is a thrombolytic agent that activates plasminogen into plasmin almost exclusively in the presence of fibrin. Intraocular injection of... (Review)
Review
Tissue plasminogen activator (tPA) is a thrombolytic agent that activates plasminogen into plasmin almost exclusively in the presence of fibrin. Intraocular injection of tPA has been proposed for the treatment of vitreoretinal diseases, such as vitreous hemorrhage, postvitrectomy fibrin formation, submacular hemorrhage, retinal vascular occlusive disorders, suprachoroidal hemorrhage and endophthalmitis. Currently, intraocular tPA is only used in the treatment of postvitrectomy fibrin formation and submacular hemorrhage. For other indications, tPA has not been shown to be safe or effective. This article reviews the use of tPA in the treatment of vitreoretinal disorders.
Topics: Animals; Anterior Chamber; Eye Diseases; Humans; Injections; Intraoperative Period; Molecular Structure; Plasminogen Activators; Postoperative Period; Retina; Retinal Diseases; Tissue Plasminogen Activator; Treatment Outcome; Vitrectomy; Vitreous Body
PubMed: 10749314
DOI: 10.3109/08820530009037850 -
Seminars in Thrombosis and Hemostasis Jun 2013Plasminogen activator inhibitor 1 (PAI-1) is the main inhibitor of tissue-type (t-PA) and urokinase-type (u-PA) plasminogen activator and therefore plays an important... (Review)
Review
Plasminogen activator inhibitor 1 (PAI-1) is the main inhibitor of tissue-type (t-PA) and urokinase-type (u-PA) plasminogen activator and therefore plays an important role in the plasminogen-plasmin system. PAI-1 is involved in a variety of cardiovascular diseases (mainly through inhibition of t-PA) as well as in cell migration and tumor development (mainly through inhibition of u-PA and interaction with vitronectin). PAI-1 is a unique member of the serpin superfamily, exhibiting particular unique conformational and functional properties. Because of its involvement in various biologic and pathophysiologic processes, PAI-1 has been the subject of many studies, including extensive structural investigations, in vitro cell biologic studies, in vivo animal studies, and epidemiologic studies. The review provides an overview on the current knowledge on PAI-1.
Topics: Animals; Fibrinolysis; Humans; Plasminogen Activator Inhibitor 1; Plasminogen Activators
PubMed: 23504606
DOI: 10.1055/s-0033-1334487 -
The Journal of Clinical Investigation Jun 2002
Review
Topics: Animals; Cell Death; Hippocampus; Humans; Neurons; Plasminogen; Plasminogen Activators; Seizures; Tissue Plasminogen Activator
PubMed: 12070298
DOI: 10.1172/JCI15961 -
The Journal of Cell Biology Apr 1987
Review
Topics: Animals; Enzyme Precursors; Genes; Humans; Plasminogen Activators; Receptors, Cell Surface; Receptors, Urokinase Plasminogen Activator; Urokinase-Type Plasminogen Activator
PubMed: 3031083
DOI: 10.1083/jcb.104.4.801 -
Haemostasis 1986Plasminogen activator was purified from the soluble fraction of bronchoalveolar lavage fluid, and biological and immunological characteristics of the activator were...
Plasminogen activator was purified from the soluble fraction of bronchoalveolar lavage fluid, and biological and immunological characteristics of the activator were examined by electrophoretic enzymography. The purified fraction showed a single band with a molecular weight of 53,000. The enzyme activity was eliminated in the presence of DFP and did not display fibrin affinity. Immunological tests revealed that the plasminogen activator reacted with IgG of antiurokinase but not with that of tissue-type plasminogen activator. However, the plasminogen activator cleaved S-2288 to a greater extent than S-2444 in contrast to urokinase.
Topics: Adult; Aged; Body Fluids; Bronchi; Female; Humans; Immunochemistry; Male; Middle Aged; Molecular Weight; Oligopeptides; Plasminogen Activators; Pulmonary Alveoli; Urokinase-Type Plasminogen Activator
PubMed: 3699585
DOI: 10.1159/000215268 -
Haemostasis 2001Plasminogen activators are enzymes found in all vertebrate species investigated so far. Their physiological function is the generation of localized proteolysis in the... (Comparative Study)
Comparative Study Review
Plasminogen activators are enzymes found in all vertebrate species investigated so far. Their physiological function is the generation of localized proteolysis in the context of tissue remodeling, wound healing and neuronal plasticity. The common vampire bat (Desmodus rotundus) is a New World species that feeds exclusively on blood. Its saliva contains highly potent plasminogen activators, specialized in rapid lysis of fresh blood clots. Biochemical and pharmacological evidence indicates that these plasminogen activators represent a new class of thrombolytics with pharmacological and toxicological properties superior to human tissue-type plasminogen activator, the clot dissolving agent now most frequently used in medicine. A form of the enzyme produced by recombinant DNA technology is currently employed to test this hypothesis in clinical studies.
Topics: Animals; Chiroptera; Clinical Trials as Topic; Fibrinolytic Agents; Humans; Plasminogen Activators; Selection, Genetic; Tissue Plasminogen Activator
PubMed: 11910176
DOI: 10.1159/000048054 -
Molecular Biology & Medicine Apr 1991Hybrid molecules containing the catalytic domain of either tissue plasminogen activator (tPA) or single chain urokinase-type plasminogen activator (scuPA), and the... (Review)
Review
Hybrid molecules containing the catalytic domain of either tissue plasminogen activator (tPA) or single chain urokinase-type plasminogen activator (scuPA), and the fibrin binding domain of a murine antifibrin monoclonal antibody were constructed using either cDNA or genomic DNA encoding the plasminogen activator and genomic DNA encoding antifibrin monoclonal antibody 59D8. In order to optimize expression of these fusion proteins in hybridoma cells, we compared plasminogen activator 3' UT domains (which decrease mRNA stability) with immunoglobulin and beta globin 3' UT domains (which increase mRNA stability). The presence of the plasminogen activator 3' UT domain resulted in approximately tenfold lower steady-state mRNA levels, and 300 to 500-fold lower levels of expressed functional protein. The initial goal of these studies was to increase the fibrinolytic potency and selectivity of tPA or scuPA. Fusion proteins comprising an antifibrin antibody domain and the catalytic domain of either tPA or scuPA were expressed and shown to have very different properties. The fusion protein that comprised the Fab portion of an antifibrin antibody and the catalytic domain of tPA, while displaying antigen binding properties indistinguishable from those of the parent antibody and amidolytic activity similar to that of tPA, was not more efficient than tPA in an in vitro clot lysis assay. In contrast, it had been shown that tPA chemically coupled to the same antibody was four- to sixfold more efficient in fibrinolysis both in vitro and in vivo. A recombinant scuPA-antifibrin antibody hybrid, however, was sixfold more potent than scuPA in vitro and 20-fold more potent in a rabbit thrombolysis model. An explanation for this apparent discrepancy may relate to the requirement for stimulation by fibrin in order for tPA to achieve its maximal catalytic activity, a property that was demonstrated to have been lost in the antifibrin-tPA fusion protein. In contrast, the activity of urokinase is independent of the presence of fibrin. This may explain the greater success achieved in enhancing catalytic activity in the urokinase-antifibrin fusion protein. It is of additional interest that fibrin or soluble fibrin fragments stimulate the catalytic activity of both tPA and the isolated tPA B chain, demonstrating that at least part of the enhanced catalytic activity of tPA observed in the presence of fibrin is independent of fibrin binding either by the tPA kringles or finger domain (or any heavy chain domain). These data indicate that it is possible to construct recombinant hybrid molecules in which both plasminogen activator catalytic function and antibody binding are preserved.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Amino Acid Sequence; Animals; Antibodies, Monoclonal; Fibrin; Molecular Sequence Data; Plasminogen Activators; Recombinant Fusion Proteins
PubMed: 1806766
DOI: No ID Found -
Eye (London, England) 1992Measurements were made of the nature and levels of plasminogen activator in human tears using, as a model of inflammation, patients undergoing cataract surgery. Tissue...
Measurements were made of the nature and levels of plasminogen activator in human tears using, as a model of inflammation, patients undergoing cataract surgery. Tissue plasminogen activator (t-PA) but not urokinase plasminogen activator (u-PA) was found in tears. A wide variation in the range of t-PA in pre-operative tears was found. In those patients not receiving per-operative subconjunctival betamethasone a significant rise in t-PA was found in tears on the first post-operative day over pre-operative levels. A significant fall was noted in those receiving per-operative subconjunctival betamethasone.
Topics: Betamethasone; Cataract Extraction; Humans; Plasminogen Activators; Postoperative Period; Tears; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator
PubMed: 1289146
DOI: 10.1038/eye.1992.140