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Semin Thromb Hemost 2014; 40(05): 585-591
DOI: 10.1055/s-0034-1383545
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

From Fibrinolysis to the Plasminogen–Plasmin System and Beyond: A Remarkable Growth of Knowledge, with Personal Observations on the History of Fibrinolysis[*]

Hau C. Kwaan
1   Division of Hematology/Oncology, Feinberg School of Medicine, and the Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois
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Publikationsdatum:
07. Juli 2014 (online)

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Abstract

Great advances have been made in our understanding of the fibrinolytic system from the initial discovery of proteolysis of fibrin by plasmin to the multifaceted and complex role of the plasminogen–plasmin (P–P) system. We now know that the P–P system is composed of several serine proteases and their inhibitors (serpins). This system is involved in many physiological functions, including embryogenesis, cell migration, and wound healing. They also play an important role in the pathogenesis of many diseases, including atherosclerosis, obesity, cancer, and even autoimmune disorders, and neuronal degeneration. Knowledge of their role in cancer enables their use as a prognostic factor. Therapeutic use of various forms of proteases derived from this system has been employed as thrombolytic agents. In addition, small molecules designed to inhibit many of the components of the P–P system are now available for clinical trial, aimed at treatment of these various disorders. The history of such remarkable development of our knowledge on fibrinolysis is reviewed in this article.

Keywords

fibrinolysis - plasminogen - plasminogen activator - PAI-1

* This article is dedicated to my mentor Alexander J. S. McFadzean, FRCP, who started it all for me.


 

  • References

  • 1 Morgagni GB. Founders of Modern Medicine: Giovanni Battista Morgagni. (1682–1771). Med Library Hist J 1903; 1: 270-277
    PubMedGoogle Scholar
  • 2 Hunter J. A treatise on the blood, inflammation, and gun-shot wounds, by the late John Hunter. To which is prefixed, A short account of the author's life, by his brother-in-law, Everard Home. London: printed by John Richardson, for George Nicol; 1794
    Google Scholar
  • 3 Virchow R. Die cellularpathologie 1871; 194
    PubMed
  • 4 Morawitz P. Uber einige post-mortale blutveranderunguen. Beitr z chem Physiol u Path 1906; 8: 1-10
    PubMedGoogle Scholar
  • 5 Yudin SS. Transfusion of cadaver blood. J Am Med Assoc 1936; 106: 997-999
    CrossrefPubMedGoogle Scholar
  • 6 Denis P. Essai sur l'application de la chimie a l'etude physiologique du sang de l'homme, et a l'etude physiologico-pathologique, hygienique et therapeutiques de maladies de cette humeur. Paris: Bechet jne; 1838
    Google Scholar
  • 7 Green JR. Note on the Action of Sodium Chloride in dissolving Fibrin. J Physiol 1887; 8 (6) 372-377
    CrossrefPubMedGoogle Scholar
  • 8 Dastre A. Fibrinolyse dans le sang. Arch de physiol norm et path 1893; 5: 661-663
    PubMedGoogle Scholar
  • 9 Hedin SG. On the presence of a proteolytic enzyme in the normal serum of the ox. J Physiol 1903; 30 (2) 195-201
    CrossrefPubMedGoogle Scholar
  • 10 Opie EL, Barker BI. Leucoprotease and anti-leucoprotease of mammals and of birds. J Exp Med 1907; 9 (2) 207-221
    CrossrefPubMedGoogle Scholar
  • 11 Sur RF. les proteinases contenues dans la fraction “acidglobulines” de divers plasma. Schweiz Med Wochenschr 1942; 72: 156-172
    PubMedGoogle Scholar
  • 12 Tillett WS, Garner RL. The Fibrinolytic Activity of Hemolytic Streptococci. J Exp Med 1933; 58 (4) 485-502
    CrossrefPubMedGoogle Scholar
  • 13 Milstone JH. A factor in normal human blood which participates in streptococcal fibrinolysis. J Immunol 1941; 42: 109-116
    PubMedGoogle Scholar
  • 14 Kaplan MH. Nature and role of the lytic factor in hemolytic streptococcal fibrinolysis. Proceedings of the Society of Experimental Biology, New York: 1944. 57. 40-50
    Google Scholar
  • 15 Christensen LR. Streptococcal Fibrinolysis: A Proteolytic Reaction Due to a Serum Enzyme Activated by Streptococcal Fibrinolysin. J Gen Physiol 1945; 28 (4) 363-383
    CrossrefPubMedGoogle Scholar
  • 16 Christensen LR, Macleod CM. A Proteolytic Enzyme of Serum: Characterization, Activation, and Reaction with Inhibitors. J Gen Physiol 1945; 28 (6) 559-583
    CrossrefPubMedGoogle Scholar
  • 17 Tillett WS, Sherry S. The effect in patients of streptococcal fibrinolysin and streptococcal desoxyribonuclease on fibrinous, purulent, and sanguinous pleural exudations. J Clin Invest 1949; 28: 173-190
    CrossrefPubMedGoogle Scholar
  • 18 Fletcher AP, Alkjaersig N, Smyrniotis FE, Sherry S. The treatment of patients suffering from early myocardial infarction with massive and prolonged streptokinase therapy. Trans Assoc Am Physicians 1958; 71: 287-296
    PubMedGoogle Scholar
  • 19 Imperati L. Contributo sperimentale alla interprezione del mechanismo causale fibrinolisi post-opertoria. Rivdi patsper 1939; 23: 313-316
    PubMedGoogle Scholar
  • 20 Rocha e silva M, Andrade SO, Teixeira RM. Fibrinolysis in peptone and anaphylactic shock in the dog. Nature 1946; 157: 801
    PubMedGoogle Scholar
  • 21 Tagnon HJ, Levenson SM et al. The occurrence of fibrinolysis in shock, with observations on the prothrombin time and the plasma fibrinogen during hemorrhagic shock. Am J Med Sci 1946; 211: 88-96
    CrossrefPubMedGoogle Scholar
  • 22 Fantl P, Simon SE. Fibrinolysis following electrically induced convulsions. Aust J Exp Biol Med Sci 1948; 26 (Pt. 6) 521-529
    CrossrefPubMedGoogle Scholar
  • 23 Macfarlane RG. Fibrinolysis following operation. Lancet 1937; i: 10-12
    PubMedGoogle Scholar
  • 24 Truelove SC. Fibrinolysis and eosinopenia after surgical operations. Clin Sci (Lond) 1952; 11 (2) 107-112
    PubMedGoogle Scholar
  • 25 Biggs R, MacFARLANE RG, Pilling J. Observations on fibrinolysis; experimental activity produced by exercise or adrenaline. Lancet 1947; 1 (6448) 402-405
    PubMedGoogle Scholar
  • 26 Stefanini M. Fibrinolysis and “fibrinolytic purpura”. Blood 1952; 7 (10) 1044-1046
    CrossrefPubMedGoogle Scholar
  • 27 Crosby WH, Stefanini M. Pathogenesis of the plasma transfusion reaction with especial reference to the blood coagulation system. J Lab Clin Med 1952; 40 (3) 373-386
    PubMedGoogle Scholar
  • 28 Ungar G, Damgaard E. Protein breakdown in thermal injury. Proc Soc Exp Biol Med 1954; 87 (2) 378-383
    CrossrefPubMedGoogle Scholar
  • 29 Tagnon HJ, Schulman P, Whitmore WF, Leone LA. Prostatic fibrinolysin; study of a case illustrating role in hemorrhagic diathesis of cancer of the prostate. Am J Med 1953; 15 (6) 875-884
    CrossrefPubMedGoogle Scholar
  • 30 Moloney WC, Egan WJ, Gorman AJ. Acquired afibrinogenemia in pregnancy. N Engl J Med 1949; 240 (15) 596-598
    CrossrefPubMedGoogle Scholar
  • 31 Weiner AE, Reid DE, Roby CC. Coagulation defects associated with premature separation of the normally implanted placenta. Am J Obstet Gynecol 1950; 60 (2) 379-386
    PubMedGoogle Scholar
  • 32 Dieckmann WJ. Blood chemistry and renal function in abruptio placentae. Am J Obstet Gynecol 1936; 31: 734-745
    PubMedGoogle Scholar
  • 33 Coon WW, Hodgson PE. Fibrinolysis in surgery patients. I. Possible relationship to a hemorrhagic diathesis. Surg Gynecol Obstet 1952; 95 (6) 717-724
    PubMedGoogle Scholar
  • 34 Cliffton EE, Grossi C, Siegel M. Hemorrhage during and after operation secondary to changes in the clotting mechanism; physiology and methods of control. Surgery 1956; 40: 37-51 ; discussion, 51–53
    PubMedGoogle Scholar
  • 35 Ratnoff OD. Studies on a proteolytic enzyme in human plasma. VII. A fatal hemorrhagic state associated with excessive plasma proteolytic activity in a patient undergoing surgery for carcinoma of the head of the pancreas. J Clin Invest 1952; 31 (5) 521-528
    CrossrefPubMedGoogle Scholar
  • 36 Goodpasturl EW. Fibrinolysis in chronic hepatic insufficiency. Bull Johns Hopkins Hosp 1914; 25: 330-336
    PubMedGoogle Scholar
  • 37 Ratnoff OD. Studies on a proteolytic enzyme in human plasma; the rate of lysis of plasma clots in normal and diseased individuals, with particular reference to hepatic diseases. Bull Johns Hopkins Hosp 1949; 84 (1) 29-42
    PubMedGoogle Scholar
  • 38 Kwaan HC, McFadzean AJ. Plasma fibrinolytic activity in cirrhosis of the liver. Lancet 1956; 270 (6929) 968-969
    PubMedGoogle Scholar
  • 39 Kwaan HC, McFadzean AJ, Cook J. On plasma fibrinolytic activity in cryptogenetic splenomegaly. Scott Med J 1957; 2 (4) 137-150
    PubMedGoogle Scholar
  • 40 Kwaan HC, Lo R, McFadzean AJ. The production of plasma fibrinolytic activity in vivo by serotonin (5-hydroxytryptamine) creatinine sulphate. Clin Sci (Lond) 1957; 16 (2) 255-259
    PubMedGoogle Scholar
  • 41 Kwaan HC, Lo R, McFadzean AJ. On the production of plasma fibrinolytic activity within veins. Clin Sci (Lond) 1957; 16 (2) 241-253
    PubMedGoogle Scholar
  • 42 Kwaan HC, Lo R, Mcfadzean JS. On the lysis of thrombi experimentally produced within veins. Br J Haematol 1958; 4 (1) 51-62
    CrossrefPubMedGoogle Scholar
  • 43 O'Rourke J, Jiang X, Hao Z, Cone RE, Hand AR. Distribution of sympathetic tissue plasminogen activator (tPA) to a distant microvasculature. J Neurosci Res 2005; 79 (6) 727-733
    CrossrefPubMedGoogle Scholar
  • 44 Hao Z, Guo C, Jiang X , et al. New transgenic evidence for a system of sympathetic axons able to express tissue plasminogen activator (t-PA) within arterial/arteriolar walls. Blood 2006; 108 (1) 200-202
    CrossrefPubMedGoogle Scholar
  • 45 Kwaan HC, McFadzean AJ. The inhibition of clot lysis by corticotrophin. Lancet 1956; 270 (6908) 136-137
    PubMedGoogle Scholar
  • 46 Astrup T. The biological significance of fibrinolysis. Lancet 1956; 271 (6942) 565-568
    PubMedGoogle Scholar
  • 47 Astrup T. Fibrinolysis in the organism. Blood 1956; 11 (9) 781-806
    PubMedGoogle Scholar
  • 48 Astrup T, Sterndorff I. Fibrinolysokinase activity in animal and human tissue. Acta Physiol Scand 1956; 37 (1) 40-47
    CrossrefPubMedGoogle Scholar
  • 49 Astrup T. Fibrinolysis. Acta Haematol 1952; 7( (5) ): 271-280
    PubMedGoogle Scholar
  • 50 Astrup T, Sterndorff I. Fibrinolytic activity of tissue extracts and of trypsin. Nature 1952; 170 (4336) 981
    PubMedGoogle Scholar
  • 51 Astrup T, Stage A. Isolation of a soluble fibrinolytic activator from animal tissue. Nature 1952; 170 (4335) 929
    PubMedGoogle Scholar
  • 52 Astrup T, Albrechtsen OK. Estimation of the plasminogen activator and the trypsin inhibitor in animal and human tissues. Scand J Clin Lab Invest 1957; 9 (3) 233-243
    CrossrefPubMedGoogle Scholar
  • 53 Albrechtsen OK. The fibrinolytic activity of human tissues. Br J Haematol 1957; 3 (3) 284-291
    CrossrefPubMedGoogle Scholar
  • 54 Albrechtsen OK. The fibrinolytic activity of animal tissues. Acta Physiol Scand 1957; 39 (2-3) 284-290
    CrossrefPubMedGoogle Scholar
  • 55 Todd AS. The histological localisation of fibrinolysin activator. J Pathol Bacteriol 1959; 78: 281-283
    CrossrefPubMedGoogle Scholar
  • 56 Kwaan HC, Astrup T. Localization of Fibrinolytic Activity in the Eye. Arch Pathol 1963; 76: 595-601
    PubMedGoogle Scholar
  • 57 Kwaan HC, Astrup T. Demonstration of cellular fibrinolytic activity by the histochemical fibrin slide technique. Lab Invest 1967; 17 (2) 140-145
    PubMedGoogle Scholar
  • 58 Kwaan HC, Cocco A, Mendeloff AI, Astrup T. Fibrinolytic activity in the normal and inflamed rectal mucosa. Scand J Gastroenterol 1969; 4 (5) 441-445
    CrossrefPubMedGoogle Scholar
  • 59 Kwaan HC, Astrup T. Fibrinolytic Activity of Reparative Connective Tissue. J Pathol Bacteriol 1964; 87: 409-414
    CrossrefPubMedGoogle Scholar
  • 60 Kwaan HC, Astrup T. Localization of Fibrinolytic Activity in Myocardial Infarcts in Rats. Thromb Diath Haemorrh 1964; 12: 407-417
    PubMedGoogle Scholar
  • 61 Kwaan HC, Astrup T. Fibrinolytic activity in thrombosed veins. Circ Res 1965; 17 (6) 477-483
    CrossrefPubMedGoogle Scholar
  • 62 Kwaan HC, Astrup T. Fibrinolytic activity in human atherosclerotic coronary arteries. Circ Res 1967; 21 (6) 799-804
    CrossrefPubMedGoogle Scholar
  • 63 Kwaan HC, Albrechtsen OK. Histochemical study of fibrinolytic activity in the rat uterus in normal and hormonally induced estrus. Am J Obstet Gynecol 1966; 95 (4) 468-473
    PubMedGoogle Scholar
  • 64 Kwaan H, Markus G. Cell biology of fibrinolysis. Tenth International Congress on Fibrinolysis. August 1990. Semin Thromb Hemost 1991; 17 (3) 159-312
    PubMedGoogle Scholar
  • 65 Kwaan HC. The biologic role of components of the plasminogen-plasmin system. Prog Cardiovasc Dis 1992; 34 (5) 309-316
    CrossrefPubMedGoogle Scholar
  • 66 Castellino FJ, Violand BN. The fibrinolytic system—basic considerations. Prog Cardiovasc Dis 1979; 21 (4) 241-254
    CrossrefPubMedGoogle Scholar
  • 67 Ploug M, Rønne E, Behrendt N, Jensen AL, Blasi F, Danø K. Cellular receptor for urokinase plasminogen activator. Carboxyl-terminal processing and membrane anchoring by glycosyl-phosphatidylinositol. J Biol Chem 1991; 266 (3) 1926-1933
    PubMedGoogle Scholar
  • 68 Cesarman GM, Guevara CA, Hajjar KA. An endothelial cell receptor for plasminogen/tissue plasminogen activator (t-PA). II. Annexin II-mediated enhancement of t-PA-dependent plasminogen activation. J Biol Chem 1994; 269 (33) 21198-21203
    PubMedGoogle Scholar
  • 69 Hajjar KA, Jacovina AT, Chacko J. An endothelial cell receptor for plasminogen/tissue plasminogen activator. I. Identity with annexin II. J Biol Chem 1994; 269 (33) 21191-21197
    PubMedGoogle Scholar
  • 70 Hajjar KA, Menell JS. Annexin II: a novel mediator of cell surface plasmin generation. Ann N Y Acad Sci 1997; 811: 337-349
    CrossrefPubMedGoogle Scholar
  • 71 Miles LA, Parmer RJ. Plasminogen receptors: the first quarter century. Semin Thromb Hemost 2013; 39 (4) 329-337
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 72 O'Connell PA, Madureira PA, Berman JN, Liwski RS, Waisman DM. Regulation of S100A10 by the PML-RAR-α oncoprotein. Blood 2011; 117 (15) 4095-4105
    CrossrefPubMedGoogle Scholar
  • 73 Loskutoff DJ, van Mourik JA, Erickson LA, Lawrence D. Detection of an unusually stable fibrinolytic inhibitor produced by bovine endothelial cells. Proc Natl Acad Sci USA 1983; 80 (10) 2956-2960
    CrossrefPubMedGoogle Scholar
  • 74 Nielsen LS, Lecander I, Andreasen PA, Henschen A, Astedt B, Danø K. Plasminogen activator inhibitors from placenta and fibrosarcoma cells are antigenically different as evaluated with monoclonal and polyclonal antibodies. Thromb Res 1987; 46 (3) 411-423
    CrossrefPubMedGoogle Scholar
  • 75 Lecander I, Astedt B. Specific plasminogen activator inhibitor of placental type PAI 2 occurring in amniotic fluid and cord blood. J Lab Clin Med 1987; 110 (5) 602-605
    PubMedGoogle Scholar
  • 76 Heeb MJ, España F, Geiger M, Collen D, Stump DC, Griffin JH. Immunological identity of heparin-dependent plasma and urinary protein C inhibitor and plasminogen activator inhibitor-3. J Biol Chem 1987; 262 (33) 15813-15816
    PubMedGoogle Scholar
  • 77 Strickland S, Reich E, Sherman MI. Plasminogen activator in early embryogenesis: enzyme production by trophoblast and parietal endoderm. Cell 1976; 9 (2) 231-240
    CrossrefPubMedGoogle Scholar
  • 78 Strickland S, Beers WH. Studies on the role of plasminogen activator in ovulation. In vitro response of granulosa cells to gonadotropins, cyclic nucleotides, and prostaglandins. J Biol Chem 1976; 251 (18) 5694-5702
    PubMedGoogle Scholar
  • 79 Beers WH, Strickland S, Reich E. Ovarian plasminogen activator: relationship to ovulation and hormonal regulation. Cell 1975; 6 (3) 387-394
    CrossrefPubMedGoogle Scholar
  • 80 Friedman GC, Seeds NW. Tissue plasminogen activator expression in the embryonic nervous system. Brain Res Dev Brain Res 1994; 81 (1) 41-49
    CrossrefPubMedGoogle Scholar
  • 81 Reddington M, Haas C, Kreutzberg GW. The plasminogen activator system in neurons and glia during motoneuron regeneration. Neuropathol Appl Neurobiol 1994; 20 (2) 188-190
    PubMedGoogle Scholar
  • 82 Melchor JP, Strickland S. Tissue plasminogen activator in central nervous system physiology and pathology. Thromb Haemost 2005; 93 (4) 655-660
    PubMedGoogle Scholar
  • 83 Strickland S. Tissue plasminogen activator in nervous system function and dysfunction. Thromb Haemost 2001; 86 (1) 138-143
    PubMedGoogle Scholar
  • 84 Schaefer U, Machida T, Vorlova S, Strickland S, Levi R. The plasminogen activator system modulates sympathetic nerve function. J Exp Med 2006; 203 (9) 2191-2200
    CrossrefPubMedGoogle Scholar
  • 85 Jiang Q, Yasothornsrikul S, Taupenot L, Miles LA, Parmer RJ. The local chromaffin cell plasminogen/plasmin system and the regulation of catecholamine secretion. Ann N Y Acad Sci 2002; 971: 445-449
    CrossrefPubMedGoogle Scholar
  • 86 Syrovets T, Lunov O, Simmet T. Plasmin as a proinflammatory cell activator. J Leukoc Biol 2012; 92 (3) 509-519
    CrossrefPubMedGoogle Scholar
  • 87 Rømer J, Bugge TH, Pyke C et al. Plasminogen and wound healing. Nat Med 1996; 2 (7) 725
    PubMedGoogle Scholar
  • 88 Creemers E, Cleutjens J, Smits J et al. Disruption of the plasminogen gene in mice abolishes wound healing after myocardial infarction. Am J Pathol 2000; 156 (6) 1865-1873
    CrossrefPubMedGoogle Scholar
  • 89 Suelves M, Vidal B, Ruiz V et al. The plasminogen activation system in skeletal muscle regeneration: antagonistic roles of urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1). Front Biosci 2005; 10: 2978-2985
    CrossrefPubMedGoogle Scholar
  • 90 Kwaan HC, Keer HN. Fibrinolysis and cancer. Semin Thromb Hemost 1990; 16 (3) 230-235
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 91 Kwaan HC. The plasminogen-plasmin system in malignancy. Cancer Metastasis Rev 1992; 11 (3-4) 291-311
    CrossrefPubMedGoogle Scholar
  • 92 Danø K, Behrendt N, Høyer-Hansen G et al. Plasminogen activation and cancer. Thromb Haemost 2005; 93 (4) 676-681
    PubMedGoogle Scholar
  • 93 Nicholl SM, Roztocil E, Davies MG. Plasminogen activator system and vascular disease. Curr Vasc Pharmacol 2006; 4 (2) 101-116
    CrossrefPubMedGoogle Scholar
  • 94 Collen D, Lijnen HR. Thrombolytic agents. Thromb Haemost 2005; 93 (4) 627-630
    PubMedGoogle Scholar
  • 95 Sherry S. The fibrinolytic activity of streptokinase activated human plasmin. J Clin Invest 1954; 33 (7) 1054-1063
    CrossrefPubMedGoogle Scholar
  • 96 Collen D. The plasminogen (fibrinolytic) system. Thromb Haemost 1999; 82 (2) 259-270
    PubMedGoogle Scholar
  • 97 Kwaan HC, Markus G. Cell biology of fibrinolysis. Semin Thromb Hemost 1991; 17: 161-312
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 98 Kwaan HC, Mazar AP. Biologic role of the plasminogen-plasmin system: thrombolysis, bleeding, and beyond. Semin Thromb Hemost 2013; 39 (4) 327-328
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 99 Carrel A, Burrows MT. Cultivation in Vitro of Malignant Tumors. J Exp Med 1911; 13 (5) 571-575
    CrossrefPubMedGoogle Scholar
  • 100 Ossowski L, Quigley JP, Kellerman GM, Reich E. Fibrinolysis associated with oncogenic transformation. Requirement of plasminogen for correlated changes in cellular morphology, colony formation in agar, and cell migration. J Exp Med 1973; 138 (5) 1056-1064
    CrossrefPubMedGoogle Scholar
  • 101 Astedt B, Holmberg L. Immunological identity of urokinase and ovarian carcinoma plasminogen activator released in tissue culture. Nature 1976; 261 (5561) 595-597
    CrossrefPubMedGoogle Scholar
  • 102 Kwaan HC, McMahon B. The role of plasminogen-plasmin system in cancer. Cancer Treat Res 2009; 148: 43-66
    PubMedGoogle Scholar
  • 103 Kwaan HC, Mazar AP, McMahon BJ. The apparent uPA/PAI-1 paradox in cancer: more than meets the eye. Semin Thromb Hemost 2013; 39 (4) 382-391
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 104 Duffy MJ. The urokinase plasminogen activator system: role in malignancy. Curr Pharm Des 2004; 10 (1) 39-49
    CrossrefPubMedGoogle Scholar
  • 105 Duffy MJ. Urokinase plasminogen activator and its inhibitor, PAI-1, as prognostic markers in breast cancer: from pilot to level 1 evidence studies. Clin Chem 2002; 48 (8) 1194-1197
    PubMedGoogle Scholar
  • 106 Look M, van Putten W, Duffy M et al. Pooled analysis of prognostic impact of uPA and PAI-1 in breast cancer patients. Thromb Haemost 2003; 90 (3) 538-548
    PubMedGoogle Scholar
  • 107 Jänicke F, Prechtl A, Thomssen C et al; German N0 Study Group. Randomized adjuvant chemotherapy trial in high-risk, lymph node-negative breast cancer patients identified by urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 J Natl Cancer Inst 2001; 93 (12) 913-920
    CrossrefPubMed
  • 108 Harbeck N, Schmitt M, Paepke S, Allgayer H, Kates RE. Tumor-associated proteolytic factors uPA and PAI-1: critical appraisal of their clinical relevance in breast cancer and their integration into decision-support algorithms. Crit Rev Clin Lab Sci 2007; 44 (2) 179-201
    CrossrefPubMedGoogle Scholar
  • 109 Harris L, Fritsche H, Mennel R et al; American Society of Clinical Oncology. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol 2007; 25 (33) 5287-5312
    CrossrefPubMedGoogle Scholar
  • 110 Annecke K, Schmitt M, Euler U et al. uPA and PAI-1 in breast cancer: review of their clinical utility and current validation in the prospective NNBC-3 trial. Adv Clin Chem 2008; 45: 31-45
    PubMedGoogle Scholar
  • 111 Duffy MJ, Duggan C. The urokinase plasminogen activator system: a rich source of tumour markers for the individualised management of patients with cancer. Clin Biochem 2004; 37 (7) 541-548
    CrossrefPubMedGoogle Scholar
  • 112 Duffy MJ, Sturgeon C, Lamerz R et al. Tumor markers in pancreatic cancer: a European Group on Tumor Markers (EGTM) status report. Ann Oncol 2010; 21 (3) 441-447
    CrossrefPubMedGoogle Scholar
  • 113 Schmitt M, Harbeck N, Brünner N et al. Cancer therapy trials employing level-of-evidence-1 disease forecast cancer biomarkers uPA and its inhibitor PAI-1. Expert Rev Mol Diagn 2011; 11 (6) 617-634
    CrossrefPubMedGoogle Scholar
  • 114 Cantero D, Friess H, Deflorin J et al. Enhanced expression of urokinase plasminogen activator and its receptor in pancreatic carcinoma. Br J Cancer 1997; 75 (3) 388-395
    CrossrefPubMedGoogle Scholar
  • 115 Gutova M, Najbauer J, Gevorgyan A et al. Identification of uPAR-positive chemoresistant cells in small cell lung cancer. PLoS ONE 2007; 2 (2) e243
    CrossrefPubMedGoogle Scholar
  • 116 Soff GA, Sanderowitz J, Gately S et al. Expression of plasminogen activator inhibitor type 1 by human prostate carcinoma cells inhibits primary tumor growth, tumor-associated angiogenesis, and metastasis to lung and liver in an athymic mouse model. J Clin Invest 1995; 96 (6) 2593-2600
    CrossrefPubMedGoogle Scholar
  • 117 Rabbani SA, Ateeq B, Arakelian A et al. An anti-urokinase plasminogen activator receptor antibody (ATN-658) blocks prostate cancer invasion, migration, growth, and experimental skeletal metastasis in vitro and in vivo. Neoplasia 2010; 12 (10) 778-788
    CrossrefPubMedGoogle Scholar
  • 118 Meyer JE, Brocks C, Graefe H et al. The Oral Serine Protease Inhibitor WX-671 - First Experience in Patients with Advanced Head and Neck Carcinoma. Breast Care (Basel) 2008; 3 (s) 20-24
    PubMedGoogle Scholar
  • 119 Heinemann VEM, Pinter T, Mala C, Nevile N, Bevan P. Randomized Phase II trial with an uPA inhibitor (WX-671) in patients with locally advanced non-metastatic pancreatic cancer. European Society of Medical Oncology (ESMO) 2010; Abstract 712OD
    PubMedGoogle Scholar
  • 120 Goldstein L, J OC, Heinrich B. , et al. A randomized double-blind phase II study of the combination of WX-671 plus capecitabine vs. capecitabine monotherapy in first-line HER-2 negative metastatic breast cancer (MBC). Cancer Res 2012; 72 (Suppl. 24) P5- 20-21
    CrossrefPubMedGoogle Scholar
  • 121 Garner RL, Tillett WS. Biochemical studies on the fibrinolytic activity of hemolytic streptococci: I. isolation and characterization of fibrinolysin. J Exp Med 1934; 60 (2) 239-254
    CrossrefPubMedGoogle Scholar
  • 122 Garner RL, Tillett WS. Biochemical Studies on the Fibrinolytic Activity of Hemolytic Streptococci: Ii. Nature of the Reaction. J Exp Med 1934; 60 (2) 255-267
    CrossrefPubMedGoogle Scholar
  • 123 Johnson AJ, Tillett WS. The lysis in rabbits of intravascular blood clots by the streptococcal fibrinolytic system (streptokinase). J Exp Med 1952; 95 (5) 449-464
    CrossrefPubMedGoogle Scholar
  • 124 Nydick I, Ruegsegger P, Abarquez R, Cliffton EE, Ladue JS. The effect of fibrinolytic agents on myocardial infarction. Prog Cardiovasc Dis 1960; 3: 13-28
    CrossrefPubMedGoogle Scholar
  • 125 Clarke RL, Cliffton EE. The treatment of cerebrovascular thromboses and embolism with fibrinolytic agents. Am J Cardiol 1960; 6: 546-551
    CrossrefPubMedGoogle Scholar
  • 126 Sherry S, Alkjaersig N. Biochemical experimental, and clinical studies of proteolytic enzymes with particular reference to the fibrinolytic enzyme of human plasma. Ann N Y Acad Sci 1957; 68 (1) 52-66
    CrossrefPubMedGoogle Scholar
  • 127 Ambrus JL, Ambrus CM, Back N, Sokal JE, Collins GL. Clinical and experimental studies on fibrinolytic enzymes. Ann N Y Acad Sci 1957; 68: 97-136 , discussion 136–137
    CrossrefPubMedGoogle Scholar
  • 128 Fletcher AP, Sherry S, Alkjaersig N, Smyrniotis FE, Jick S. The maintenance of a sustained thrombolytic state in man. II. Clinical observations on patients with myocardial infarction and other thromboembolic disorders. J Clin Invest 1959; 38 (7) 1111-1119
    CrossrefPubMedGoogle Scholar
  • 129 Johnson AJ, McCARTY WR. The lysis of artificially induced intravascular clots in man by intravenous infusions of streptokinase. J Clin Invest 1959; 38: 1627-1643
    CrossrefPubMedGoogle Scholar
  • 130 Kaste M. Stroke: advances in thrombolysis. Lancet Neurol 2013; 12 (1) 2-4
    CrossrefPubMedGoogle Scholar
  • 131 del Zoppo GJ. Plasminogen activators and ischemic stroke: conditions for acute delivery. Semin Thromb Hemost 2013; 39 (4) 406-425
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 132 Boucek RJ, Murphy Jr WP. Segmental perfusion of the coronary arteries with fibrinolysin in man following a myocardial infarction. Am J Cardiol 1960; 6: 525-533
    CrossrefPubMedGoogle Scholar
  • 133 Dotter CT, Rösch J, Seaman AJ. Selective clot lysis with low-dose streptokinase. Radiology 1974; 111 (1) 31-37
    CrossrefPubMedGoogle Scholar
  • 134 Oklu R, Wicky S. Catheter-directed thrombolysis of deep venous thrombosis. Semin Thromb Hemost 2013; 39 (4) 446-451
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 135 Wicky S, Pinto EG, Oklu R. Catheter-directed thrombolysis of arterial thrombosis. Semin Thromb Hemost 2013; 39 (4) 441-445
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 136 Van De Craen B, Declerck PJ, Gils A. The Biochemistry, Physiology and Pathological roles of PAI-1 and the requirements for PAI-1 inhibition in vivo. Thromb Res 2012; 130 (4) 576-585
    CrossrefPubMedGoogle Scholar
  • 137 Vaughan DE. PAI-1 antagonists: the promise and the peril. Trans Am Clin Climatol Assoc 2011; 122: 312-325
    PubMedGoogle Scholar
  • 138 Vaughan DE, De Taeye BM, Eren M. PAI-1 antagonists: predictable indications and unconventional applications. Curr Drug Targets 2007; 8 (9) 962-970
    CrossrefPubMedGoogle Scholar
  • 139 Declerck PJ, Gils A. Three decades of research on plasminogen activator inhibitor-1: a multifaceted serpin. Semin Thromb Hemost 2013; 39 (4) 356-364
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 140 Van De Craen B, Scroyen I, Vranckx C , et al. Maximal PAI-1 inhibition in vivo requires neutralizing antibodies that recognize and inhibit glycosylated PAI-1. Thromb Res 2012; 129 (4) e126-e133
    CrossrefPubMedGoogle Scholar
  • 141 Izuhara Y, Yamaoka N, Kodama H , et al. A novel inhibitor of plasminogen activator inhibitor-1 provides antithrombotic benefits devoid of bleeding effect in nonhuman primates. J Cereb Blood Flow Metab 2010; 30 (5) 904-912
    CrossrefPubMedGoogle Scholar
  • 142 Yamaoka N, Kawano Y, Izuhara Y, Miyata T, Meguro K. Structure-activity relationships of new 2-acylamino-3-thiophenecarboxylic acid dimers as plasminogen activator inhibitor-1 inhibitors. Chem Pharm Bull (Tokyo) 2010; 58 (5) 615-619
    CrossrefPubMedGoogle Scholar