Print Email Facebook Twitter Analysis of coagulation cascade and endothelial cell activation during inhibition of vascular endothelial growth factor/vascular endothelial growth factor receptor pathway in cancer patients Title Analysis of coagulation cascade and endothelial cell activation during inhibition of vascular endothelial growth factor/vascular endothelial growth factor receptor pathway in cancer patients Author Kuenen, B.C. Levi, M. Meijers, J.C.M. Kakkar, A.K. van Hinsbergh, V.W.M. Kostense, P.J. Pinedo, H.M. Hoekman, K. Gaubius Instituut TNO Publication year 2002 Abstract Objective - The angiogenesis inhibitor SU5416 is a potent inhibitor of vascular endothelial growth factor (VEGF) receptor-1 and -2. VEGF may be involved in hemostasis by altering the hemostatic properties of endothelial cells. We analyzed the effects of SU5416 on the coagulation cascade and the vessel wall in patients with advanced cancer. Methods and Results - Markers for thrombin generation, activation of the protein C pathway, fibrinolysis, and endothelial cell activation were measured in patients with renal cell carcinoma, soft tissue sarcoma, or melanoma on days 0, 14, and 28 of treatment with SU5416. Three of 17 sampled patients developed a thromboembolic event in the fifth week of treatment. Markers for thrombin generation and fibrinolysis did not show significant changes. We observed a significant increase in endogenous thrombin potential and of parameters reflecting endothelial cell activation (von Willebrand antigen, soluble tissue factor, and soluble E-selectin) in all patients (P≤0.001). In patients experiencing a thromboembolic event, endogenous thrombin potential, soluble tissue factor, and soluble E-selectin increased to a significantly greater extent (P=0.029, P=0.021, and P=0.007, respectively). Conclusions - VEGF is not only a permeability, proliferation, and migration factor, but it is also a maintenance and protection factor for endothelial cells. Chemicals/CAS: Angiogenesis Inhibitors; Indoles; Protein C; Proto-Oncogene Proteins; Pyrroles; Receptor Protein-Tyrosine Kinases, EC 184.108.40.206; Receptors, Growth Factor; Receptors, Vascular Endothelial Growth Factor, EC 220.127.116.11; SU 5416; Thrombin, EC 18.104.22.168; Vascular Endothelial Growth Factor Receptor-1, EC 22.214.171.124 Subject Angiogenesis InhibitorsBlood CoagulationBlood PlateletsCarcinoma, Renal CellCell DivisionCell Membrane PermeabilityCell MovementDrug Administration ScheduleEndothelium, VascularFibrinolysisHemostasisIndolesKidney NeoplasmsMelanomaNeovascularization, PathologicProtein CProto-Oncogene ProteinsPyrrolesReceptor Protein-Tyrosine KinasesReceptors, Growth FactorReceptors, Vascular Endothelial Growth FactorSarcomaThrombinVascular Endothelial Growth Factor Receptor-1 To reference this document use: http://resolver.tudelft.nl/uuid:0e5e8793-425c-44dd-9ca1-89f07c28fa7d DOI https://doi.org/10.1161/01.atv.0000030186.66672.36 TNO identifier 236675 ISSN 1079-5642 Source Arteriosclerosis, Thrombosis, and Vascular Biology, 22 (9), 1500-1505 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.