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Eefting, D. (author), Seghers, L. (author), Grimbergen, J.M. (author), de Vries, M.R. (author), de Boer, H.C. (author), Lardenoye, J.W.H.P. (author), Jukema, J.W. (author), van Bockel, J.H. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)Aims Matrix metalloproteinases (MMP) and plasminogen activator (PA)/plasmin-mediated proteolysis, especially at the cell surface, play important roles in matrix degeneration and smooth muscle cell migration, which largely contributes to vein graft failure. In this study, a novel hybrid protein was designed to inhibit both protease systems...article 2010
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Hawinkels, L.J.A.C. (author), Verspaget, H.W. (author), van der Reijden, J.J. (author), van der Zon, J.M. (author), Verheijen, J.H. (author), Hommes, D.W. (author), Lamers, C.B.H.W. (author), Sier, C.F.M. (author), TNO Kwaliteit van Leven (author)Transforming growth factor-β1 (TGF-β1), a cytokine involved in various stages of cancer, is produced as a latent complex and requires processing to become active. We have determined total and active TGF-β1 levels in homogenates of colorectal neoplasia. In contrast to total TGF-β levels, showing a stepwise increase in the mucosa-adenoma-carcinoma...article 2009
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Rijken, D.C. (author), Hoegee-de Nobel, E. (author), Jie, A.F.H. (author), Atsma, D.E. (author), Schalij, M.J. (author), Nieuwenhuizen, W. (author), TNO Kwaliteit van Leven (author)Background: The development of global tests for the fibrinolytic capacity in blood is hampered by the low base-line fibrinolytic activity in blood, by the involvement of both plasmatic components and blood cells in the fibrinolytic system and by the loss of fibrinolytic activity as a result of the action of plasminogen activator inhibitor-1 (PAI...article 2008
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Plaisier, M. (author), Koolwijk, P. (author), Willems, F. (author), Helmerhorst, F.M. (author), van Hinsbergh, V.W.M. (author), TNO Kwaliteit van Leven (author)Proteolysis is essential for decidual development during embryonic implantation, but little is known regarding the expression and functions of membrane-type matrix metalloproteinases (MT-MMPs) and urokinase-type plasminogen activator (uPA) and its receptor uPAR in decidua. Therefore, their protein and mRNA levels were analysed in three first...article 2008
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TNO Kwaliteit van Leven (author), Hawinkels, L.J.A.C. (author), Verspaget, H.W. (author), van Duijn, W. (author), van der Zon, J.M. (author), Zuidwijk, K. (author), Kubben, F.J.G.M. (author), Verheijen, J.H. (author), Hommes, D.W. (author), Lamers, C.B.H.W. (author), Sier, C.F.M. (author)Transforming growth factor-beta1 (TGF-beta1), a tumour suppressing as well as tumour-promoting cytokine, is stored as an extracellular matrix-bound latent complex. We examined TGF-beta1 activation and localisation of TGF-beta1 activity in gastric cancer. Gastric tumours showed increased stromal and epithelial total TGF-beta1 staining by...article 2007
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van Hinsbergh, V.W.M. (author), Engelse, M.A. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)Pericellular proteases play an important role in angiogenesis and vasculogenesis. They comprise (membrane-type) matrix metalloproteinases [(MT-)MMPs], serine proteases, cysteine cathepsins, and membrane-bound aminopeptidases. Specific inhibitors regulate them. Major roles in initiating angiogenesis have been attributed to MT1-matrix...article 2006
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Rijken, D.C. (author), Barrett-Bergshoeff, M.M. (author), Jie, A.F.H. (author), Criscuoli, M. (author), Sakharov, D.V. (author), Gaubius Instituut TNO (author)Amediplase (K2tu-PA) is a hybrid plasminogen activator, consisting of the kringle 2 domain of alteplase and the protease domain of urokinase. The objective of this study was to determine the in vitro clot penetration of amediplase in relation to its fibrin binding and to compare the properties with those of alteplase. The clot lysis activity of...article 2004
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Plaisier, M. (author), Kapiteijn, K. (author), Koolwijk, P. (author), Fijten, C. (author), Hanemaaijer, R. (author), Grimbergen, J.M. (author), Mulder-Stapel, A. (author), Quax, P.H.A. (author), Helmerhorst, F.M. (author), van Hinsbergh, V.W.M. (author), Gaubius Instituut TNO (author)In the endometrium, angiogenesis is a physiological process, whereas in most adult tissues neovascularization is initiated only during tissue repair or pathological conditions. Pericellular proteolysis plays an important role in angiogenesis being required for endothelial cell migration, invasion, and tube formation. We studied the expression of...article 2004
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van Hensbergen, Y. (author), Broxterman, H.J. (author), Peters, E. (author), Rana, S. (author), Elderkamp, Y.W. (author), van Hinsbergh, V.W.M. (author), Koolwijk, P. (author), Gaubius Instituut TNO (author)The aminopeptidase inhibitor bestatin has been shown to have anti-angiogenic effects in a number of model systems. These effects are thought to result from inhibition of CD13 activity. Because tumor angiogenesis can evolve in a fibrin-rich stroma matrix we have studied for the first time the effects of bestatin on microvascular endothelial...article 2003
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Lamfers, M.L.M. (author), Grimbergen, J.M. (author), Aalders, M.C. (author), Havenga, M.J. (author), de Vries, M.R. (author), Huisman, L.G.M. (author), van Hinsbergh, V.W.M. (author), Quax, P.H.A. (author), Gaubius instituut TNO (author)Proteases of the plasminogen activator (PA) and matrix metalloproteinase (MMP) system play an important role in smooth muscle cell (SMC) migration and neointima formation after vascular injury. Inhibition of either PAs or MMPs has previously been shown to result in decreased neointima formation in vivo. To inhibit both protease systems...article 2002
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Schulter, V. (author), Koolwijk, P. (author), Peters, E. (author), Frank, S. (author), Hrzenjak, A. (author), Graier, W.F. (author), van Hinsbergh, V.W.M. (author), Kostner, G.M. (author), Gaubius Instituut TNO (author)Angiostatin, which consists of the kringle I-IV domains of plasminogen and which is secreted into urine, is an efficient inhibitor of angiogenesis and tumor growth. Because N-terminal apolipoprotein(a) [apo(a)] fragments, which also contain several types of kringle IV domains, are found in urine as well, we evaluated the potential angiostatic...article 2001
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Páramo, U.A. (author), Panizo, C. (author), Montes, R. (author), Orbe, J. (author), Alegría, E. (author), Martínez-Caro, D. (author), Dooijewaard, G. (author), Gaubius instituut TNO (author)To characterize the extent of activation of the hemostatic system and to detect local alterations which may favour thrombus formation we obtained samples from the right atrium (RA) and left ventricle (LV) of 60 stable angina patients (mean age 59 years, M/F: 49/11) during the cardiac catheterization procedure. None of the patients had a recent...article 1999
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Larsson, P.T. (author), Wallén, N.H. (author), Wiman, B. (author), Dooijewaard, G. (author), Gaubius instituut TNO (author)Objective: To study the influence of α- and β-adrenoceptor stimulation in vivo on fibrinolysis in healthy male volunteers. Design: Infusions were given in a single blind fashion and in a randomized order if placebo infusions were included. Setting: University Department (Karolinska Hospital). Subjects: Thirty-four healthy, non-smoking male...article 1999
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Braat, E.A.M. (author), Los, P. (author), Rijken, D.C. (author), Gaubius Instituut TNO (author)Thrombin cleaves single-chain urokinase-type plasminogen activator (scu- PA) into a virtually inactive two-chain form (tcu-PA/T), a process which may contribute to the maintenance of a fresh blood clot. We have examined the inactivation of scu-PA by thrombin in a plasma milieu to get more insight in the physiological relevance of this phenomenon...article 1998
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- van der Kaaden, M.E. (author), Rijken, D.C. (author), van Berkel, T.J.C. (author), Kuiper, J. (author), Gaubius Instituut TNO (author) article 1998
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Hanemaaijer, R. (author), Visser, H. (author), Konttinen, Y.T. (author), Koolwijk, P. (author), Verheijen, J.H. (author), Gaubius Instituut TNO (author)Here we describe a new principle for accessing the activity of the different members of the human matrix-metalloproteinases (MMPs) by a colorimetric assay. Using protein engineering, a modified pro-urokinase was made in which the activation sequence, normally recognized by plasmin (ProArgPheLys ↓ IlelleGlyGly), was replaced by a sequence that is...article 1998
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Quax, P.H.A. (author), Grimbergen, J.M. (author), Lansink, M. (author), Bakker, A.H.F. (author), Blatter, M.C. (author), Belin, D. (author), van Hinsbergh, V.W.M. (author), Verheijen, J.H. (author), Gaubius Instituut TNO (author)Urokinase-type plasminogen activator (UPA), particularly when bound to its receptor (UPAR), is thought to play a major role in local proteolytic processes, thus facilitating cell migration as may occur during angiogenesis, neointima and atherosclerotic plaque formation, and tumor cell invasion. To facilitate understanding of the need and...article 1998
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Emeis, J.J. (author), van den Hoogen, C.M. (author), Diglio, C.A. (author), Gaubius Instituut TNO (author)The synthesis, storage and regulated secretion (acute release) of tissue-type plasminogen activator (tPA) were studied in cultured rat heart endothelial (RHE) cells. In this study, special attention was paid to the correspondence between tPA metabolism in RHE cells in vitro and tPA metabolism in rats in vivo. RHE cells synthetized tPA, as shown...article 1998
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Wijnberg, M.J. (author), Nieuwenbroek, N.M.E. (author), Slomp, J. (author), Quax, P.H.A. (author), Verheijen, J.H. (author), Gaubius Laboratory TNO Preventie en Gezondheid (author)The objective of this study was to investigate the role of the plasminogen activation system in the migration of human vascular smooth muscle cells in vitro. After wounding of confluent human smooth muscle cell cultures by stripping cells from their extracellular matrix, cells start to migrate from the wounded edge into the denuded area....article 1996
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Braat, E.A.M. (author), Nauland, U. (author), Dooijewaard, G. (author), Rijken, D.C. (author), Gaubius Instituut TNO (author)Thrombin cleaves single-chain urokinase-type plasminogen activator (scu-PA) into a two-chain form (tcu-PA/T), which is virtually inactive in plasminogen activator assays. Little is known about the physiological importance of tcu-PA/T. To examine the occurrence of tcu-PA/T in vivo, we developed a sensitive and specific bioimmunoassay (BIA) for...article 1996
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