Emerging Links between Thrombosis, Inflammation and Cancer: Role of Heparin

References

• Weitz J. I. Low-molecular-weight heparin. N Engl J Med, 1997, 337: 688–98.
   Google Scholar
• Mousa S. A., Fareed J. W. Advances in anticoagulant, antithrombotic and thrombolytic drugs. Exp Opin Invest Drugs, 2001, 10: 157–62.
   Google Scholar
• Mousa S. A. Comparative efficacy among different low molecular weight heparin (LMWHs) & drug interaction: implications in the management of vascular disorders. Thromb Haemost, 2000, 26 (Suppl 1): 39–46.
   Google Scholar
• Aguilar D., Goldhaber S. Z. Clinical uses of low molecular weight heparin. Chest, 1999, 115: 1418–23.
   Google Scholar
• Taheri S. A., Lazar L., Haddad G., Castaldo R., Wilson M., Mousa S. Diagnosis of deep venous thrombosis by use of soluble necrosis factor receptor. Angiology, 1998, 49: 537–41.
   Google Scholar
• Nelson R. M., Cecconi O., Roberts W. G., Aruffo A., Linhardt R. J., Bevilacqua M. P. Heparin oligosaccharides bind L-and P-selectin and inhibit acute inflammation. Blood, 1993, 82: 3253–8.
   Google Scholar
• Lantz M., Thysell H., Nilsson E., Olsson I. On the binding of tumor necrosis factor (TNF) to heparin and the release in vivo of the TNF-binding protein i by heparin. J Clin Invest, 1991, 88: 2026–31.
   Google Scholar
• Tyrell D. J., Kilfeather S., Page C. P. Therapeutic uses of heparin beyond its traditional role as an anticoagulant. Trends Pharmacol Sci, 1995, 16: 198–204.
   Google Scholar
• Hocking D., Ferro T. J., Johnson A. Dextran sulfate and heparin sulfate inhibit platelet-activating factor-induced pulmonary edema. JApplPhysiol, 1992, 72: 179–85.
   Google Scholar
• Darien B. J., Fareed J., Centgraf K. S., et al. Low molecular weight heparin prevents the pulmonary hemodynamic and patho-morphologic effects of endotoxin in a porcine acute lung injury model. Shock, 1998, 9: 274–81.
   Google Scholar
• Meyer J., Cox C. S., Herndon D. N., et al. Heparin in experimental hyperdynamic sepsis. Crit Care Med, 1993, 21: 84–9.
   Google Scholar
• Hiebert L. M., Liu J. M. Heparin protects cultured arterial endothelial cells from damage by toxic oxygen metabolites. Atherosclerosis, 1990, 83: 47–51.
   Google Scholar
• Matzner Y., Marx G., Drexler R., Eldor A. The inhibitory effect of heparin and related glycosaminoglycans on neutrophil chemotaxis. Thromb Haemost 1984, 52: 134–7.
   Google Scholar
• Bazzoni G., Beltran Nunez A., Mascellani G., Bianchini P., Dejana E., Del Maschio A. Effect of heparin, dermatan sulfate, and related oligo-derivatives on human polymorphonuclear leukocyte functions. J Lab Clin Med, 1993, 121: 268–75.
   Google Scholar
• Vancheri C., Mastruzzo C., Armato F., et al. Intranasal heparin reduces eosinophil recruitment after nasal allergen challenge in patients with allergic rhinitis. J Allergy Clin Immunol, 2001, 108: 703–8.
   Google Scholar
• Diamant Z., Timmers M. C., van der Veen H., Page C. P., van der Meer F. J., Sterk P. J. Effect of inhaled heparin on allergen-induced early and late asthmatic responses in patients with atopic asthma. Am JRespir Crit Care Med, 1996, 153: 1790–5.
   Google Scholar
• Garrigo J., Danta I., Ahmed T. Time course of the protective effect of inhaled heparin on exercise-induced asthma. Am J Respir Crit Care Med, 1996, 153: 1702–7.
   Google Scholar
• Gaffney A., Gaffney P. Rheumatoid arthritis and heparin. Br J Rheumatol, 1996, 35: 808.
   Google Scholar
• Bowler S. D., Smith S. M., Lavercombe P. S. Heparin inhibits the immediate response to antigen in the skin and lungs of allergic subjects. Am Rev Respir Dis, 1993, 147: 160–3.
   Google Scholar
• Dwarakanath A. D., Yu L. G., Brookes C., Pryce D., Rhodes J. M. Sticky neutrophils, pathergic arthritis, and response to heparin in pyoderma gangrenosum complicating ulcerative colitis. Gut, 1995, 37: 585–8.
   Google Scholar
• Petitou M., Hérault J.-P., Bernat A., et al. Synthesis of throm-bin-inhibiting heparin mimetics without side effects. Nature, 1999, 398: 417–22.
   Google Scholar
• Tyrrel D. J., Horne A. P., Holme K. R., Preuss J. M. H., Page C. P. Heparin in inflammation: potential therapeutic applications beyond anticoagulation. Adv Pharmacol, 1999, 46: 151208.
   Google Scholar
• Salas A., Sans M., Soriano A., et al. Heparin attenuates TNF-a induced inflammatory response through a CD 11b dependent mechanism. Gut, 2000, 47: 88–96.
   Google Scholar
• Panés J., Perry M., Granger D. N. Leukocyte-endothelial cell adhesion: avenues for therapeutic intervention. Br J Pharmacol, 1999, 126: 537–50.
   Google Scholar
• Lever R., Hoult J. R. S., Page C. P. The effects of heparin and related molecules upon the adhesion of human polymorphonu-clear leukocytes to vascular endothelium in vitro. Br JPharma-col, 2000, 129: 533–40.
   Google Scholar
• Gaffney P. R., Doyle C. T., Gaffney A., Hogan J., Hayes D. P., Annis P. Paradoxical response to heparin in 10 patients with ulcerative colitis. Am J Gastroenterology, 1995, 90: 220–3.
   Google Scholar
• Gaffney P., Gaffney A. Heparin therapy in refractory ulcerative colitis-an update. Gastroenterology, 1996, 110: A913.
   Google Scholar
• Evans R. C., Rhodes J. M. Treatment of corticosteroid-resistant ulcerative colitis with heparin: a report of nine cases. Gut, 1995, 37: A49.
   Google Scholar
• Brazier F., Yzet T., Duchmann J. C., et al. Effect of heparin treatment on extra intestinal manifestations associated with inflammatory bowel diseases. Gastroenterology, 1996, 110: A872.
   Google Scholar
• Brazier F., Yzet T., Boruchowicz A., et al. Treatment of ulcerative colitis with heparin. Gastroenterology, 1996, 110: A872.
   Google Scholar
• Dupas J. L., Brazier F., Yzet T., et al. Treatment of active Crohn’s disease with heparin. Gastroenterology, 1996, 110: A900.
   Google Scholar
• Folwaczny C., Spannagl M., Wiebecke W., et al. Heparin in the treatment of highly active inflammatory bowel disease (IBD). Gastroenterology, 1996, 110: A908 [abstract].
   Google Scholar
• Dwarakanath A. D., Yu L. G., Brookes C., Pryce D., Rhodes J. M. “Sticky” neutrophils, pathergic arthritis, and response to heparin in pyoderma gangrenosum complicating ulcerative colitis. Gut, 1995, 37: 585–8.
   Google Scholar
• Teixeira M. M., Hellewell P. G. Suppression by intradermal administration of heparin of eosinophil accumulation but not edema formation in inflammatory reactions in guinea-pig skin. Br J Pharmacol, 1993, 110: 1496–500.
   Google Scholar
• Carr J. The anti-inflammatory action of heparin: heparin as an antagonist to histamine, bradykinin and prostaglandin E1. Thromb Res 1979, 16: 507–16.
   Google Scholar
• KOENIG A., Norgard-Sumnicht K., Linhardt R., Varki A. Differential interactions of heparin and heparan sulfate gly-cosaminoglycans with the selectins: implications for the use of unfractionated and low molecular weight heparins as therapeutic agents. J Clin Invest, 1998, 101: 877–89.
   Google Scholar
• Diamond M. S., Alon R., Parkos C. A., Quinn M. T., Springer T. A. Heparin is an adhesive ligand for the leukocyte integrin Mac-1 (CD11b/CD18). J Cell Biol, 1995, 130: 1473–82.
   Google Scholar
• Benimetskaya L., Loike J. D., Khaled Z., et al. Mac-1 (CD11b/CD18) is an oligodeoxy-nucleotide-binding protein. Nat Med, 1997, 3: 414–20.
   Google Scholar
• Hirsh J., Levine M. N. Low molecular weight heparin. Blood, 1992, 79: 1–17.
   Google Scholar
• Nielsen J. I., Ostergaard P. Chemistry of heparin and low molecular weight heparin. Acta Chir Scand Suppl 1988, 543: 52–6.
   Google Scholar
• Linhardt R. J., Gunay N. S. Production and chemical processing of low molecular weight heparins. Semin Thromb Haemost, 1999, 25: 5–16.
   Google Scholar
• Emmanuele R. M., Fareed J. The effect of molecular weight on the bioavailability of heparin. Thromb Res 1987, 48: 591–6.
   Google Scholar
• Brieger D., Dawes J. Production method affects the pharmaco-kinetic and ex vivo biological properties of low molecular weight heparins. Thromb Haemost, 1997, 77: 317–22.
   Google Scholar
• Mousa S. A., Mohamed S. Inhibition of endothelial cell tube formation by the low molecular weight heparin, tinzaparin, is mediated by tissue factor pathway inhibitor. Thromb Haemost, 2004, 92: 627–33.
   Google Scholar
• Mousa S. A., Kaiser B. Tissue factor pathway inhibitor in thrombosis and beyond: role of heparin. Drugs of the Future, 2004, 29: 751–66.
   Google Scholar
• Boneu B., Caranobe C., Cadroy Y., et al. Pharmacokinetic studies of standard unfractionated heparin, and low molecular weight heparins in the rabbit. Semin Thromb Hemost 1988, 14: 18–27.
   Google Scholar
• Sutor A. H., Massicotte P., Leaker M., Andrew M. Heparin therapy in pediatric patients. Semin Thromb Hemost, 1997, 23: 303–19.
   Google Scholar
• Majerus P., Broze J. G., Miletich J. Anticoagulant, thrombolytic and antiplatelet drugs. In: Hardman J., Limbird L., Molinoff P., Ruddon R., Goodman A. (eds.). Goodman & Gilman’s, the pharmacological basis of therapeutics. 9th edition. New York: McGraw-Hill, 1996: 1341–59.
   Google Scholar
• Silverstein R. Drugs affecting hemostosis. In: Munson P, Mueller R, Breeze G, eds. Munson’s principles of pharmacology. New York: Chapman & Hall, 1995: 1123–43.
   Google Scholar
• Theroux P., Waters D., Qiu S., McCans J., de Guise P., Juneau M. Aspirin versus heparin to prevent myocardial infarction during the acute phase of unstable angina. Circulation, 1993, 88: 2045–8.
   Google Scholar
• Itoh K., Nakao A., Kishimoto W., Takagi H. Heparin effects on superoxide production by neutrophils. Eur Surg Res, 1995; 27: 184–8.
   Google Scholar
• Attanasio M., Gori A. M., Giusti B., et al. Cytokine gene expression in human LPS-and IFNgamma-stimulated mononu-clear cells is inhibited by heparin. Thromb Haemost, 1998, 79: 959–62.
   Google Scholar
• Dandona P., Qutob T., Hamouda W., Bakri F., Aljada A., Kumbkarni Y. Heparin inhibits reactive oxygen species generation by polymorphonuclear and mononuclear leucocytes. Thromb Res, 1999, 96: 437–43.
   Google Scholar
• Friedrichs G. S., Kilgore K. S., Manley P. J., Gralinski M. R., Lucchesi B. R. Effects of heparin and N-acetyl heparin on ischemia/reperfusion-induced alterations in myocardial function in the rabbit isolated heart. Circ Res, 1994, 75: 701–10.
   Google Scholar
• Black S. C., Gralinski M. R., Friedrichs G. S., Kilgore K. S., Driscoll E. M., Lucchesi B. R. Cardioprotective effects of heparin or N-acetylheparin in an in vivo model of myocardial ischaemic and reperfusion injury. Cardiovasc Res, 1995, 29: 629–36.
   Google Scholar
• Lucchesi B. R., Kilgore K. S. Complement inhibitors in myo-cardial ischemia/reperfusion injury. Immunopharmacology, 1997, 38: 27–42.
   Google Scholar
• Hawari F. I., Shykoff B. E., Izzo J. L. Jr. Heparin attenuates nor-epinephrine-induced venoconstriction. Vasc Med, 1998, 3: 951–00.
   Google Scholar
• De Caterina R., Libby P., Peng H. B., et al. Nitric oxide decreases cytokine-induced endothelial activation: nitric oxide selectively reduces endothelial expression of adhesion molecules and pro-inflammatory cytokines. J Clin Invest, 1995, 96: 60–8.
   Google Scholar
• Trousseau A. Phlegmasia alba dolens. In: Baillier JB, ed. Clinique de l’Hotel-Dieu de Paris, 2nd ed. London: New Sydenham Society, 1865; Chapter 3:94. [Key historical observation linking thrombosis and cancer.]
   Google Scholar
• Schiller H., Bartscht T., Arlt A., et al. Thrombin as a survival factor for cancer cells: thrombin activation in malignant effusions in vivo and inhibition of idarubicin-induced cell death in vitro. Int J Clin Pharmacol Ther, 2002, 40: 329–35.
   Google Scholar
• Sorensen H., Mellemkjaer L., Olsen J., et al. Prognosis of cancers associated with venous thromboembolism. N Engl J Med, 2000, 343: 1846–50.
   Google Scholar
• Caine G. J., Lip G. Y. Anticoagulants as anticancer agents ? Lancet Oncol, 2002, 3: 591–2.
   Google Scholar
• Lebeau B., Chastang C., Brechot J.-M., et al. Subcutaneous heparin treatment increases survival in small cell lung cancer. Cancer, 1994, 74: 38–45. [Key clinical observation defining benefits of anticoagulation in the enhancement of chemo response rate and improved clinical outcome.]
   Google Scholar
• Chahinian A., Propert K., Ware J., et al. A randomized trial of anticoagulation with warfarin and of alternating chemotherapy in extensive small-cell lung cancer by the Cancer and Leukemia Group B. J Clin Oncol 1989, 7: 993–1002.
   Google Scholar
• Thornes R. Coumarins, melanoma and cellular immunity. In: McBrien D, Slator T, eds. Protective agents in cancer. London: Academic Press, 1983: 43–56.
   Google Scholar
• Saba H. I., Khalil F. K., Morelli G. A., et al. Thrombo-embolism preceding cancer: a correlation study. Am J Hematol, 2003, 72: 109–14.
   Google Scholar
• Goldberg R. J., Seneff M., Gore J. M. Occult malignant neoplasm in patients with deep venous thrombosis. Ann Intern Med 1987, 147: 251–3.
   Google Scholar
• Baron J. A., Gridley G., Weiderpass E., et al. Venous thromboembolism and cancer. Lancet, 1998, 351: 1077–80.
   Google Scholar
• Rickles F. R., Edwards R. L. Activation of blood coagulation in cancer: Trousseau’s syndrome revisited. Blood 1982, 62: 14–31.
   Google Scholar
• Levine M. N. Prevention of thrombotic disorders in cancer patients undergoing chemotherapy. Thromb Haemost, 1997, 78: 133–6.
   Google Scholar
• Falanga A. Mechanisms of hypercoagulation in malignancy and during chemotherapy. Haemostasis, 1998, 28: 50–60.
   Google Scholar
• Kakkar A. J., De Ruvo N., Tebbutt S., et al. Extrinsic pathway activation with elevated tissue factor and factor viia in patients with cancer. Lancet, 1995, 346: 1004–5.
   Google Scholar
• Simonneau G., Sors H., Charbonnier B., et al. A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism. N Engl J Med, 1997, 337: 6639.
   Google Scholar
• Koopman M. M. W., Prandoni P., Piovella F., et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. N Engl J Med, 1996, 334: 682–7.
   Google Scholar
• Pintucci G., Froum S., Pinnell J., et al. Trophic effects of platelets on cultured endothelial cells are mediated by platelet-associated fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF). Thromb Haemost, 2002, 88: 834–42.
   Google Scholar
• Manegold P. C., Hutter J., Pahernik S. A., et al. Platelet-endothelial interaction in tumor angiogenesis and microcirculation. Blood, 2003, 101: 1970–6.
   Google Scholar
• Werther K., Christensen I. J., Nielsen H. J. Determination of vascular endothelial growth factor (vEGF) in circulating blood: significance of VEGF in various leucocytes and platelets. Scand J Clin Lab Invest, 2002, 62: 343–50.
   Google Scholar
• Verheul H. M., Pinedo H. M. Tumor growth: a putative role for platelets ? Oncologist, 1998, 3(2): II.
   Google Scholar
• Verheul H. M., Hoekman व., Luykx-de Bakker S., et al. Platelet: transporter of vascular endothelial growth factor. Clin Cancer Res, 1997, 3 (12 Pt 1): 2187–90.
   Google Scholar
• Amirkhosravi A., Amaya M., Desai H., et al. Latelet-CD40 lig-and interaction with melanoma cell and monocyte CD40 enhances cellular pro-coagulant activity. Blood Coagul Fibrinolysis, 2002, 13: 505–12.
   Google Scholar
• Gasic G. J., Gasic T. B., Stewart C. C. Anti-metastatic effect associated with platelet reduction. Pathology, 1998, 61: 46–52.
   Google Scholar
• Karpatkin S., Pearlstein E., Ambrogio C., et al. Role of adhesive proteins in platelet tumor interaction in vitro and metastasis formation in vivo. J Clin Invest 1988, 81: 1012–9.
   Google Scholar
• Trikha M., Zhou Z., Timar J., et al. Multiple roles for platelet GPIIb/IIIa and alphavbeta3 integrins in tumor growth, angiogen-esis, and metastasis. Cancer Res, 2002, 62: 2824–33.
   Google Scholar
• Varki N. M., Varki A. Heparin inhibition of selectin-mediated interactions during the hematogenous phase of carcinoma metastasis: rationale for clinical studies in humans. 5emin Thromb Hemost, 2002, 28: 53–66.
   Google Scholar
• Kakkar A. J., Williamson R. C. Prevention of venous throm-boembolism in cancer using low molecular weight heparin. Haemostasis, 1997, 27(Suppl 1): 32–7.
   Google Scholar
• Zacharski L. R., Ornstein D. L. Heparin and cancer. Thromb Haemost, 1998, 80: 10–23.
   Google Scholar
• von Tempelhoff G. F., Harenberg J., Neimann F., et al. Effect of low molecular weight heparin (Certoparin) versus unfractionated heparin on cancer survival following breast and pelvic cancer surgery: a prospective randomized double-blind trial. Int Oncol, 2000, 16: 815–24. [Key double blind trial illustrating the survival benefits of LMWH over UFH post-surgery in ovarian and uterine but not breast cancer (well defined tumor type).]
   Google Scholar
• Zacharski L. R. Anticoagulant in cancer treatment: malignancy as a solid phase coagulopathy. Cancer Lett, 2002, 186: 1–9.
   Google Scholar
• Meyers G., Marjanovic Z., Valcke J., et al. Comparison of LMWH and wafarin for the secondary prevention of venous thromboembolism in patients with cancer. Arch Intern Med, 2002, 162: 1729–35.
   Google Scholar
• Mousa S. A. Anticoagulants in thrombosis and cancer: the missing link. Semin Thromb Haemost, 2002, 28: 45–52.
   Google Scholar
• Trousseau A. Plegmasia alba dolens. In: Baillier J. B. (ed.). Clinique de l’Hotel-Dieu de Paris, 2nd ed. London: New Syndenham Society, 1865; Chapter 3: 654–712.
   Google Scholar
• Haward W. Phlebitis and thrombosis. Lancet 1906, 1: 650–5.
   Google Scholar
• Dvorak H. F. Thrombosis and cancer. Hum Pathol 1987, 18: 275–84.
   Google Scholar
• Kakkar A. K., Levine M. N., Prandoni P., et al. What is the role for antithrombotics in cancer care ? Interactive session with panel discussion. Cancer Treat Rev, 2002, 28: 157–9.
   Google Scholar
• Dvorak H. F., Senger D. R., Dvorak A. M. Fibrin as a component of the tumor stroma: origins and biological significance. Cancer Metastasis Rev 1983, 2: 41–73.
   Google Scholar
• Hull R. D., Raskob G. E., Pineo G. F., et al. Subcutaneous low-molecular weight heparin compared with continuous intravenous heparin in the treatment of proximal-vein thrombosis. N Engl J Med, 1992, 326: 975–82. [This is a key double blind clinical trial comparing the efficacy and safety of LMWH to UFH in-patients with VTE].
   Google Scholar
• Levine M., Hirsh J., Gent M., et al. Double-blind randomised trial of a very-low-dose warfarin for prevention of thrombo-embolism in stage IV breast cancer. Lancet, 1994, 343: 886–9.
   Google Scholar
• Mousa S. A., Mousa A. S. Angiogenesis inhibitors: current and future directions. Curr Pharmaceutical Design, 2004, 10: 1–9.
   Google Scholar
• Mousa S. A., Mohamed S. Anti-angiogenic mechanisms and efficacy of the low molecular weight heparin, tinzaparin: anticancer efficacy. Oncol Rep, 2004, 12: 683–8.
   Google Scholar
• Folkman J., Shing Y. Control of angiogenesis by heparin and other sulfated polysaccharides. Adv Exp Med Biol, 1992, 313: 355–64.
   Google Scholar
• Amirkhosravi A., Mousa S. A., Amaya M., et al. Antimetastatic effect of tinzaparin, a low molecular weight heparin. J Thromb Haemost, 2003, 1: 1972–6.
   Google Scholar
• Ludwig R. J., Boehme B., Podda M., et al. Endothelial P-selectin as a target of heparin action in experimental melanoma lung metastasis. Cancer Res, 2004, 64: 2743–50.
   Google Scholar
• Falanga A., Rickles F. R. Pathophysiology of the thrombophilic state in the cancer patient. Semin Thromb Hemost, 1999, 25: 173–82.
   Google Scholar
• Markus G. The role of haemostasis and fibrinolysis in the metastatic spread of cancer. Thromb Haemost 1984, 10: 6172.
   Google Scholar
• Ruf W., Mueller B. M. Tissue factor in cancer angiogenesis and metastasis. Curr Opin Hematol, 1996, 3: 379–84.
   Google Scholar
• Paredes N., Xu L., Berry L. R., et al. The effects of chemother-apeutic agents on the regulation of thrombin on cell surfaces. Br JHaematol, 2003, 120: 315–24.
   Google Scholar
• Pinedo H., Verheul H., D’Amato R., et al. Involvement of platelets in tumor angiogenesis ? Lancet, 1998, 352: 1775–7.
   Google Scholar
• Chambers A. F., MacDonald I. C., Schmidt E. E., et al. Steps in tumor metastasis: new concepts from intra-vital video microscopy. Cancer Metastasis Rev, 1995, 14: 279–301.
   Google Scholar
• Wojtukiewicz M., Zacharski L., Memoli V., et al. Fibrinogen-fibrin transformation in situ in renal cell carcinoma. Anticancer Res, 1990, 10: 579–82.
   Google Scholar
• Zacharski L., Wojtukiewicz M., Costantini V., et al. Pathways of coagulation/fibrinolysis activation in malignancy. Semin Thromb Hemostasis, 1992, 18: 104–16.
   Google Scholar
• Zhang Y., Deng Y., Luther T., et al. Tissue factor controls the balance of angiogenic and anti-angiogenic properties of tumor cells in mice. J Clin Invest, 1994, 94: 1320–7.
   Google Scholar
• Engelberg H. Actions of heparin in the atherosclerotic process. Pharmacol Rev, 1996, 48: 327–52.
   Google Scholar
• Borsig L., Wong R., Feramisco J., et al. Heparin and cancer revisited: mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis. Proc Natl Acad Sci USA, 2001, 98: 3352–7. [Key study linking heparin to platelet-tumor interactions and metstasis.]
   Google Scholar
• Chambers A. F. The metastatic process: basic research and clinical implications. Oncol Res, 1999, 11: 161–8.
   Google Scholar
• Mousa S. A. Anticoagulants in thrombosis and cancer: the missing link. Expert Rev Anticancer Ther, 2002, 2: 227–33.
   Google Scholar
• Varki A., Varki N. M. P-selectin, carcinoma metastasis and heparin: novel mechanistic connections with therapeutic implications. Braz J Med Biol Res, 2001, 34: 711–7.
   Google Scholar
• Engelberg H. Actions of heparin that may affect the malignant process. Cancer, 1999, 85: 257–72.
   Google Scholar
• Rickles F. R., Levine M. N. Epidemiology of thrombosis in cancer. Acta Haematol, 2001, 106: 6–12.
   Google Scholar
• Mousa S. A. Prevention and treatment of tumor growth, metastsis, and thrombembolic complications in cancer patients. US Patent, 2002, 10/125, 882.
   Google Scholar