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Potential future clinical applications for the GPIIb/IIIa antagonist, abciximab in thrombosis, vascular and oncological indications

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Pathology & Oncology Research

Abstract

Abciximab (ReoPro®) is a mouse-human chimeric monoclonal antibody Fab fragment of the parent murine monoclonal antibody 7E3, and was the first of these agents approved for use as adjunct therapy for the prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention (PCI). Abciximab binds with high avidity to both the non-activated and activated form of the GPIIb/IIIa receptor of platelets, the major adhesion receptor involved in aggregation. Additional cardio-vascular indications for abciximab are unstable angina, carotid stenting, ischemic stroke and peripheral vascular diseases. Abciximab also interacts with two other integrin receptors; the αvβ3 receptor, which is present in low numbers on platelets but in high density on activated endothelial and smooth muscle cells, and αMβ2 integrin which is present on activated leukocytes. Cell types that express integrins GPIIb/IIIa and αvβ3 such as platelets, endothelial and tumor cells have been implicated in angiogenesis, tumor growth and metastasis. Since abciximab interacts with high avidity to integrins GPIIb/IIIa and αvβ3, it is reasonable to assume that it may possess anti-angiogenic properties in angiogenesis-related diseases, as well as anti-metastastatic properties in case of disseminating tumors expressing the target integrin receptors.

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References

  1. Davies MJ, Thomas AC, Knapman PA, et al: Intra myocardial platelet aggregation in patients with unstable angina suffering sudden ischemic cardiac death. Circulation 73:418–427, 1986.

    PubMed  CAS  Google Scholar 

  2. Coller BS: The role of platelets in arterial thrombosis and the rationale for blockade of platelet IIb/IIIa receptors as antithrombotic therapy. Eur Heart J 16:11–15, 1995.

    PubMed  CAS  Google Scholar 

  3. International Stroke Trial Collaborative Group: The International Stroke Trial (IST): a randomized trial of aspirin, subcutaneous heparin, both or neither among 19,435 patients with acute ischémic stroke. Lancet 349:1569–1581, 1997.

    Google Scholar 

  4. Chinese Acute Stroke Trial (CAST): Randomized placebo-controlled trial of early aspirin use in 20,000 patients with subacute ischémic stroke. Lancet 349:1641–1649, 1997.

    Google Scholar 

  5. De Scheerder I, Wang K, Wilczek K, et al: Experimental study of thrombogenicity and foreign body reaction induced by heparin-coated stents. Circulation 95(6):1549–1553, 1997.

    PubMed  Google Scholar 

  6. Michelson AD, Furman MI: Laboratory markers of platelet activation and their clinical significance. Curr Opin Hematol 6:342–348, 1999.

    PubMed  CAS  Google Scholar 

  7. Ferguson JJ, Waly HM, Wilson JM: Fundamental of coagulation and glycoprotein IIb/IIIa receptor inhibition. Am Heart J 134:S35-S42, 1998.

    Google Scholar 

  8. Lefkovitz J, Plow EF, Topol EJ: Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine. New Eng J Med 332:1553–1559, 1995.

    Google Scholar 

  9. EPIC Investigators: Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. N Eng J Med 330:956–961, 1994.

    Google Scholar 

  10. The EPILOG Investigators: Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. New Eng J Med 336:1689–1696, 1997.

    Google Scholar 

  11. CAPTURE Investigators: Randomised placebo controlled trial of abciximab before, during and after coronary intervention in refractory unstable angina: the CAPTURE study. Lancet 349:1429–1435, 1997.

    Google Scholar 

  12. The EPISTENT Investigators: Randomised placebo-controlled and balloon angioplasty-controlled trial to assess safety of coronary stenting with use of platelet glycoprotein IIb-IIIa blockade. Lancet 352:87–92, 1998.

    Google Scholar 

  13. Coller BS, Scudder IE, Beer J et al: Monoclonal antibodies to platelet glycoprotein IIb/IIIa as antithrombotic agents. Ann NY Acad Sci 614:193–213, 1991.

    PubMed  CAS  Google Scholar 

  14. Jordan RE, Wagner CL, Mascelli MA, et al: Preclinical development of c7E3 Fab; a mouse/human chimeric monoclonal antibody fragment that inhibits platelet function by blockade of GP IIb/IIIa receptors with observations on the immunogenicity of c7E3 Fab in humans. In: Horton MA, editor. Adhesion receptors as therapeutic targets. New York: CRC Press; 1996, pp. 281–305.

    Google Scholar 

  15. Tcheng JE, Ellis SG, George BS, et al: Pharmacodynamics of chimeric glycoprotein IIb/IIIa integrin antiplatelet antibody Fab 7E3 in high-risk coronary angioplasty. Circulation 90:1757–1764, 1994.

    PubMed  CAS  Google Scholar 

  16. Mascelli, MA, Lance ET, Damaraju L, et al: The pharmacodynamic profile of short-term abciximab treatment demonstrates prolonged platelet inhibition with gradual recovery from GPIIb/IIIa receptor blockade. Circulation 97:1680–88, 1998.

    PubMed  CAS  Google Scholar 

  17. Lincoff AM, Tcheng JE, Califf RM, et al: Sustained suppression of ischemic complications of coronary intervention by platelet GPIIb/IIIa blockade with abciximab. One year outcome of the EPILOG trial. Circulation 99:1951–1958, 1999.

    PubMed  CAS  Google Scholar 

  18. Topol EJ, Ferguson JJ, Weisman HF, et al: Long-term prevention from myocardial ischemic events in a randomized trial of brief integrin3 blockade with percutaneous coronary intervention J Am Med Assoc 278:479–484, 1997.

    CAS  Google Scholar 

  19. Tam SH, Sassoli PM, Jordan RE, et al: Abciximab (ReoPro, chimeric 7E3 Fab) demonstrates equivalent affinity and functional blockade of glycoprotein IIb/IIIa and αvβ3 integrins. Circulation 98:1085–1091, 1998.

    PubMed  CAS  Google Scholar 

  20. Coller BS, Cheresh DA, Asch E, et al: Platelet vitronectin receptor expression differentiates Iraqi-Jewish from Arab patients with Glanzmann thrombasthemia in Israel. Blood 77:75–83, 1991.

    PubMed  CAS  Google Scholar 

  21. Altieri DC, Edgington TS: A monoclonal antibody reacting with distinct adhesion molecules defines a transition in the functional state of the receptor CD11b/CD18 (Mac-1). J Immunol. 1414:2656–2660, 1988.

    Google Scholar 

  22. Simon DI, Xu H Ortlepp S, et al: 7E3 monoclonal antibody directed against the platelet glycoprotein IIb/IIIa cross-reacts with the leukocyte integrin Mac-1 and blocks adhesion to fibrinogen and ICAM-1. Arterioscler Thromb Vasc Biol 17:528–535, 1977.

    Google Scholar 

  23. Wagner CL, Mascelli MA, Neblock DS, et al: Analysis of GPIIb/IIIa receptor number by quantification of 7E3 binding to human platelets. Blood 3:907–914, 1996.

    Google Scholar 

  24. Fidler IJ, Kumar R, Bielenberg DR, et al: Molecular determinants of angiogenesis in cancer metastasis. Canc J Sci Am 4:S58-S66, 1998.

    Google Scholar 

  25. Jones A, Harris AL: New developments in angiogenesis: A major mechanism for tumor growth and target for therapy. Canc J Sci Am 4:209–210, 1998.

    CAS  Google Scholar 

  26. Brooks PC, Montgomery AMP, Rosenfeld M, et al: Integrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell 79:1157–1164, 1994.

    PubMed  CAS  Google Scholar 

  27. Kerr JS, Wexler RS, Mousa SA, et al: Novel small molecule v integrin antagonists: Comparative anti-cancer efficacy with known angiogenesis inhibitors. Anticancer Research 19:959–968, 1999.

    PubMed  CAS  Google Scholar 

  28. Wu H, Beuerlein G, Nie Y, et al: Stepwise in vitro affinity maturation of Vitaxin, an αvβ3-specific humanized mAb. Proc Natl Acad Sci USA 95:6037–6042, 1998.

    PubMed  CAS  Google Scholar 

  29. Stromblad S, Becker JC, Yebra M, et al: Suppression of p53 activity and p21WAFl/CIPI expression by vascular cell integrin alphaVbeta3 during angiogenesis. J Clin Invest 98:426–433, 1996.

    PubMed  CAS  Google Scholar 

  30. Brooks PC, Strömblad S, Sanders LC, et al: Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin αvβ3. Cell 85:683–693, 1996.

    PubMed  CAS  Google Scholar 

  31. Gasparini G, Brooks PC, Biganzoli E, et al: Vascular integrin αvβ3: A new prognostic indicator in breast cancer. Clin Cancer Res 4:2625–2634, 1998.

    PubMed  CAS  Google Scholar 

  32. Carron CP, Meyer DM, Pegg JA, et al: A peptidomimetic antagonist of the integrin αvβ3 inhibits Leydig cell tumor growth and the development of hypercalcemia of malignancy. Cancer Research 58:1930–1935, 1998.

    PubMed  CAS  Google Scholar 

  33. Gutheil JC, Campbell TN, Pierce, PR, et al: Phase I study of Vitaxin, an anti-angiogenic humanized monoclonal antibody to vascular integrin αvβ3. Proc ASCO, 1998 Abstract #832.

  34. Varner JA, Nakada MT Jordan RE, et al: Inhibition of angiogenesis and tumor growth by murine 7E3, the parent antibody of c7E3 Fab (abciximab; ReoPro™). Angiogenesis 3:53–60, 1999.

    PubMed  CAS  Google Scholar 

  35. Hejna M, Raderer M, Zielinski CC: Inhibition of metastases by anticoagulants. J Natl Cancer Inst 91:22–36, 1999.

    PubMed  CAS  Google Scholar 

  36. Tang DG, Honn KV: Adhesion molecules and tumor metastasis: An update. Invasion Metastasis 95:109–131, 1995.

    Google Scholar 

  37. Nierodzik ML, Klepfish A, Karpatkin S: Role of platelets, thrombin, integrin IIb-IIIa, fibronectin and Von Willebrand factor on tumor adhesion in vitro and metastasis in vivo. Thrombosis and Haemostasis 74:282–290, 1995.

    PubMed  CAS  Google Scholar 

  38. Steinert BW Tang DG, Grossi IM, et al: Studies on the role of platelet eicosanoid metabolism and integrin αIIbβ3 in tumorcell-induced platelet aggregation. Int J Cancer 54:92–101, 1993.

    PubMed  CAS  Google Scholar 

  39. Timar J, Chopra H, Rong X, et al: Calcium channel blocker treatment of tumor cells induces alterations in the cytoskeleton, mobility of the integrin αIIbβ3 and tumor-cell-induced platelet aggregation. J Cancer Res Clin Oncol 118:425–434, 1992.

    PubMed  CAS  Google Scholar 

  40. Tang DG, Grossi IM, Tang KQ et al: Inhibition of TPA and 12(S)-HETE-stimulated tumor cell adhesion by prostacyclin and its stable analogs: Rationale for their antimetastatic effects. Int J Cancer 60:418–425, 1995.

    PubMed  CAS  Google Scholar 

  41. Amirkhosravi A, Amaya M, Siddiqui F, et al: Blockade of GPIIb/IIIa inhibits the release of vascular endothelial growth factor (VEGF) from tumor cell-activated platelets and experimental metastasis. Platelets 10:285–292, 1999.

    PubMed  CAS  Google Scholar 

  42. Pinedo HM, Verheul HMW, D’Amato RJ, et al: Involvement of platelets in tumour angiogenesis? Lancet 352:1775–1777, 1998.

    PubMed  CAS  Google Scholar 

  43. Heyn Adu P, Lötter MG, Badenhorst PN, et al: Kinetics distribution and site of destruction of111indium-labeled human platelets. Br J Haematol 44:269–280, 1980.

    Google Scholar 

  44. Chronos N, Marciniak SJ, Nakada MT: Binding specificity and associated effects of platelet GPIIb/IIIa inhibitors. Eur Heart J 1S: E11-E17, 1999.

    Google Scholar 

  45. Möhle R, Green D, Moore MAS, et al: Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets. Proc Natl Acad Sci USA 94:663–668, 1997.

    PubMed  Google Scholar 

  46. Maloney JP, Silliman CC, Ambruso DR, et al: In vitro release of vascular endothelial growth factor during platelet aggregation. Am J Physiol 275:H1054-H1061, 1998.

    PubMed  CAS  Google Scholar 

  47. Hieken TJ, Farolan M, Ronan SG, et al: Integrin expression in melanoma predicts subsequent metastasis. J Surgical Research 63:169–173, 1996.

    CAS  Google Scholar 

  48. Hieken TJ, Ronan SG, Farolan M, et al: Molecular prognostic markers in intermediate-thickness cutaneous malignant melanoma. Cancer 85:375–382, 1999.

    PubMed  CAS  Google Scholar 

  49. Hsu M-Y, Shih D-T, Meier FE, et al: Adenoviral gene transfer of 3 integrin subunit induces conversion from radial to vertical growth phase in primary human melanoma. Am J Pathol 153:1435–1442, 1998.

    PubMed  CAS  Google Scholar 

  50. Montgomery AMP, Reisfeld RA, Cheresh DA: Integrin αvβ3 rescues melanoma cells from apoptosis in three-dimensional dermal collagen. Proc Natl Acad Sci USA 91:8856–8860, 1994.

    PubMed  CAS  Google Scholar 

  51. Felding-Habermann B, Mueller BM, Romerdahl CA, et al: Involvement of integrin v gene expression in human melanoma tumorigenicity. J Clin Invest 89:2018–2022, 1992.

    PubMed  CAS  Google Scholar 

  52. Petitclerc E, Strömblad S, von Schalscha TL, et al: Integrin αvβ3 promotes M21 melanoma growth in human skin by regulating tumor cell survival. Cancer Research 59:2724–2730, 1999.

    PubMed  CAS  Google Scholar 

  53. Puerschel W Ch, Gawaz M, Worret W-I, et al: Immunoreactivity of glycoprotein IIb is present in metastasized but not in non-metastasized primary malignant melanoma. British J Dermatology 135:883–887, 1996.

    CAS  Google Scholar 

  54. Oleksowicz L, Mrowiec Z, Schwartz E, et al: Characterization of tumor-induced platelet aggregation: The role of immunorelated GPIb and GPIIb/IIIa expression by MCF-7 breast cancer cells. Thrombosis Research 79:261–274, 1995.

    PubMed  CAS  Google Scholar 

  55. Timar J, Trikha M, Szekeres K, et al: Autocrine motility factor signals integrin-mediated metastatic melanoma cell adhesion and invasion. Cancer Research 56:1902–1908, 1996.

    PubMed  CAS  Google Scholar 

  56. Chen YQ, Trikha M, Gao X, et al: Ectopic expression of platelet integrin IIb3 in tumor cells from various species and histological origin. Int J Cancer 72:642–648, 1997.

    PubMed  CAS  Google Scholar 

  57. Trikha M, Timar J, Lundy, SK, et al: The high affinity IIb3 integrin is involved in invasion of human melanoma cells. Cancer Research 57:2522–2528, 1997.

    PubMed  CAS  Google Scholar 

  58. Trikha M, Timar J, Lundy SK, et al: Human prostate carcinoma cells express functional IIb3 integrin. Cancer Research 56:5071–5078, 1996.

    PubMed  CAS  Google Scholar 

  59. Noguchi CT, Schechter AN: The intracellular polymerization of sickle hemoglobin and its relevance to sickle cell disease. Blood 58:1057–1068, 1981.

    PubMed  CAS  Google Scholar 

  60. Deisseroth A, Nienhuis A, Lawrence J, et al: Chromosomal localization of the human globin gene to chromosome 11 in somatic cell hybrids. Proc Natl Acad Sci USA 75:1456–1460, 1978.

    PubMed  CAS  Google Scholar 

  61. Kaul DK, Fabry ME, Nagel RL; The pathophysiology of vascular obstruction in the sickle syndromes. Blood 10:29–48, 1996.

    CAS  Google Scholar 

  62. Luzzatto L: Genetics of red cells and susceptibility to malaria. Blood 54:961–967, 1979.

    PubMed  CAS  Google Scholar 

  63. Vichinsky E, Hurst D, Earles A, et al: Newborn screening for sickle cell disease: effect on mortality. Pediatrics 81:749–755, 1988.

    PubMed  CAS  Google Scholar 

  64. Hoppe C, Styles L, Vichinsky E: The natural history of sickle cell disease. Curr Opin Pediatr 10:49–52, 1998.

    PubMed  CAS  Google Scholar 

  65. Solovey A, Lin Y, Browne P, et al: Circulating activated endothelial cells in sickle cell anemia. N Eng J Med 337:1585–1590, 1997.

    Google Scholar 

  66. Joneckis CC, Ackley Rl, Orringer EP, et al: Integrin alpha 4 beta 1 and glycoprotein IV (CD36) are expressed on circulating reticuloxytes in sickle cell anemia. Blood 82:3548–3555, 1993

    PubMed  CAS  Google Scholar 

  67. Sugihara K, Sugihara T, Mohandas N, et al: Thrombospondin mediates adherence of CD36+ sickle reticulocytes to endothelial cells. Blood 80:2634–2642, 1992.

    PubMed  CAS  Google Scholar 

  68. Gee BE, Platt OS: Sickle reticulocytes adhere to VCAM-1. Blood 83:268–274, 1995.

    Google Scholar 

  69. Setty BN, Stuart MJ: Vascular cell adhesion molecule-1 is involved in mediating hypoxia-induced sickle red cell adherence to endothelium: potential role in sickle cell disease. Blood 88:2311–2320, 1996.

    PubMed  CAS  Google Scholar 

  70. Brittain HA, Eckman JR, Swerlick RA, et al: Thrombospondin from activated platelets promotes sickle erythrocyte adherence to human microvascular endothelium under physiologic flow: a potential role for platelet activation in sickle cell vascular occlusion. Blood 81:2137–2143, 1993.

    PubMed  CAS  Google Scholar 

  71. Kaul DK, Chen D, Zhan J: Adhesion of sickle cells to vascular endothelium is critically dependent on changes in density and shape of cells. Blood 83:3006–3017, 1994.

    PubMed  CAS  Google Scholar 

  72. Wick TM, Moake JL, Udden MM, et al: Unusually large von Willebrand factor multimers increase adhesion of sickle erythrocytes to human endothelial cells under controlled flow. J Clin Invest 80:905–910, 1987.

    PubMed  CAS  Google Scholar 

  73. Kaul DK, Tsai HM, Liu XD, et al: Monoclonal antibodies to αvβ3 (7E3 and LM609) inhibit sickle red blood cell-endothelium interactions induced by platelet activating factor. Blood 95:368–374, 2000.

    PubMed  CAS  Google Scholar 

  74. Oh, SO, Ibe BO, Johnson C, et al: Platelet-activating factor in plasma of patients with sickle cell disease in steady state. J Lab Clin Med 130:191–196, 1997.

    PubMed  CAS  Google Scholar 

  75. Hashemi S, Palmer DS, Aye MT, et al: Platelet-activating factor secreted by DDAVP-treated monocytes mediates von Willebrand factor release from endothelial cells. J Cell Physiol 154:496–505, 1993.

    PubMed  CAS  Google Scholar 

  76. Wun T, Paglieroni T, Field CL, et al: Platelet-erythrocyte adhesion in sickle cell disease. J Invest Med 47:121–127, 1999.

    CAS  Google Scholar 

  77. Buerling-Harbury C, Schade SG: Platelet activation during crisis in sickle cell anemia patients. Am J Haematol 31:237–241, 1989.

    Google Scholar 

  78. Sacco RL, Wolf PA, Kannel WB, et al: Survival and recurrence following stroke. The Framingham study. Stroke 13:290–295, 1982.

    PubMed  CAS  Google Scholar 

  79. Goldstein LB, Matchar DB: Clinical assessment of stroke. J Am Med Ass 271:1114–1120, 1994.

    CAS  Google Scholar 

  80. Warlott: Epidemiology of stroke. Lancet 352(Supp III): 1–4, 1998.

    Google Scholar 

  81. Broderick J, Brott T, Kothari R, et al: The Greater Cincinnati/Northern Kentucky Stroke Study: preliminary first-ever and total incidence rates of stroke among blacks. Stroke 29:415–421, 1998.

    PubMed  CAS  Google Scholar 

  82. Gresham GE, Phillips TF, Wolf PA, et al: Epidemiologic profile of long-term stroke disability: the Framingham study. Arch Phys Med Rehabil. 60:487–491, 1979.

    PubMed  CAS  Google Scholar 

  83. Sandercock PAG, van den Belt AGM, Lindley RI, et al: Antithrombotic therapy in acute ischemic stroke: an overview of the completed randomized trials. J Neurol Neurosurg Psychiatr 56:17–25, 1993.

    PubMed  CAS  Google Scholar 

  84. Taylor TN, Davis PH, Torner JQ, et al: Lifetime cost of stroke in the United States. Stroke 27:1459–1466, 1996.

    PubMed  CAS  Google Scholar 

  85. Broderick JP, Phillips SJ, Whisnant JP, et al: Incidence rates of stroke in the eighties: the end of the decline in stroke? Stroke 20:577–582, 1989.

    PubMed  CAS  Google Scholar 

  86. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group: Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 333:1581–1587, 1995.

    Google Scholar 

  87. The NINDS t-PA Stroke Study Group: Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. Stroke 28:2109–2118, 1997.

    Google Scholar 

  88. Hacke W, Kaste M, Fieschi C, et al: Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study. J Am Med Assoc 274:1017–1025, 1995.

    CAS  Google Scholar 

  89. Hacke W, Kaste M, Fieschi C, et al: Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet 352:1245–1251, 1998.

    PubMed  CAS  Google Scholar 

  90. The Multicenter Acute Stroke Trial —Europe Study Group: Thrombolytic therapy with streptokinase in acute ischemic stroke. N Engl J Med 335:145–150, 1996.

    Google Scholar 

  91. Multicentre Acute Stroke Trial —Italy (MAST-I) Group: Randomised controlled trial of streptokinase, aspirin and combination of both in treatment of acute ischemic stroke. Lancet 346:1509–1514, 1995.

    Google Scholar 

  92. CAPRIE Steering Committee: A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 348:1329–39, 1996.

    Google Scholar 

  93. Ohman EM, Lincoff AM, Bode C, et al: Enhanced Early Reperfusion at 60 minutes with Low-does Retaplase Combined with Full-dose Abciximab in Acute Myocardial Infarction: Preliminary Results from the GUSTO-4 Pilot (SPEED) Dose-ranging trial, Circulation 98S1:504–511, 1998.

    Google Scholar 

  94. Antman EM, Giugliano RP, Gibson CM, et al: Abciximab facilitates the rate and extent of thrombolysis: results of the Thrombolysis in Myocardial Infarction (TIMI) 14 trial. Circulation 99:2720–2732, 1999.

    PubMed  CAS  Google Scholar 

  95. Cohen I, Berk DL, White JG: The effect of peptides and monoclonal antibodies that bind to glycoprotein IIb/IIIa complex on the development of clot tension. Blood 73:1880–1887, 1989.

    PubMed  CAS  Google Scholar 

  96. Cox AD, Devine DV: Factor XIIIa binding to activated platelets is mediated through the activation of glycoprotein IIb-IIIa. Blood 83:1006–1016, 1994.

    PubMed  CAS  Google Scholar 

  97. Adams HP, Bogouslavsky Barnathan E, Polzer J, et al: Preliminary safety report of a randomized, double-blind dose escalation trial of abciximab (ReoPro) in acute ischemic stroke. Cerebrovasc Dis 9S1:27, 1999.

    Google Scholar 

  98. Chastain HD, Wong PM, Mathur A, et al: Does abciximab reduce complications of cerebral vascular stenting in high risk sesions? Circulation 96:1–283, 1997.

    Google Scholar 

  99. The Global Use of Strategies to Open Occluded Arteries (GUSTO III) Investigators. report

  100. Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-2) Investigators. A comparison of retaplase with alteplase for acute myocardial infarction. N Engl J Med 337:1118–1123, 1997.

    Google Scholar 

  101. The ASSENT-2 double blind randomized trial: Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction. Lancet 354:716–722, 1999.

    Google Scholar 

  102. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group: Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 2:349–360, 1988.

    Google Scholar 

  103. Kleiman N, Ohman EM, Califf RM, et al: Profound inhibition of platelet aggregation with monoclonal antibody 7E3 fab after thrombolytic therapy: results of the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) 8 pilot study. J Am Coll Cardiol 22:381–389, 1993.

    Article  PubMed  CAS  Google Scholar 

  104. Ohman EM, Kleiman NS, Gacioch G, et al: Combined accelerated tissue-plasminogen activator and platelet glycoprotein IIb/IIIa integrin receptor blockade with Integrilin in acute myocardial infarction: results of a randomized, placebo-controlled, dose-ranging trial. Circulation 95:846–854, 1997.

    PubMed  CAS  Google Scholar 

  105. Moliterno DJ, Harrington RA, Califf RM, et al: Randomized, placebo-controlled study of lamifiban with thrombolytic therapy for the treatment of acute myocardial infarction: rationale and design for the Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction (PARADIGM) study. J Thromb Thrombol 2:165–169, 1995.

    CAS  Google Scholar 

  106. Miller JM, Smalling R, Ohman EM, et al: Effectiveness of early coronary angioplasty and abciximab for failed thrombolysis (reteplase and alteplase) during acite myoccardial infarction (results from the GUSTO-III trial). Am J Card 84:779–784, 1999.

    PubMed  CAS  Google Scholar 

  107. Marso SP, Lincoff AM, Ellis SG, et al: Optimizing the percutaneous interventional oucomes for patients with diabetes mellitis: results of the EPISTENT diabetic substudy. Circulation 100:2477–2484, 1999.

    PubMed  CAS  Google Scholar 

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    Sidney A. Cohen, Mohit Trikha & Mary A. Mascelli

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Cohen, S.A., Trikha, M. & Mascelli, M.A. Potential future clinical applications for the GPIIb/IIIa antagonist, abciximab in thrombosis, vascular and oncological indications. Pathol. Oncol. Res. 6, 163–174 (2000). https://doi.org/10.1007/BF03032368

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