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Eslami Amirabadi, H. (author), Tuerlings, M. (author), Hollestelle, A. (author), SahebAli, S. (author), Luttge, R. (author), van Donkelaar, C.C. (author), Martens, J.W.M. (author), den Toonder, J.M.J. (author)E-cadherin is a cell-cell adhesion protein that plays a prominent role in cancer invasion. Inactivation of E-cadherin in breast cancer can arise from gene promoter hypermethylation or genetic mutation. Depending on their E-cadherin status, breast cancer cells adopt different morphologies with distinct invasion modes. The tumor microenvironment ...article 2019
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Li, M. (author), de Graaf, I.A.M. (author), van de Steeg, E. (author), de Jager, M.H. (author), Groothuis, G.M.M. (author)Intestinal P-gp and CYP3A4 work coordinately to reduce the intracellular concentration of drugs, and drug-drug interactions (DDIs) based on this interplay are of clinical importance and require pre-clinical investigation. Using precision-cut intestinal slices (PCIS) of human jejunum, ileum and colon, we investigated the P-gp/CYP3A4 interplay and...article 2017
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Joosen, M.J.A. (author), Vester, S.M. (author), Hamelink, J. (author), Klaassen, S.D. (author), van den Berg, R.M. (author)One of the shortcomings of current treatment of nerve agent poisoning is that not all drugs effectively penetrate the blood-brain barrier (BBB), whereas most nerve agents easily do. P-glycoprotein (Pgp) efflux transporters at the BBB may contribute to this aspect. It was previously shown that Pgp inhibition by tariquidar enhanced the efficacy of...article 2016
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Vlaming, M.L.H. (author), Läppchen, T. (author), Jansen, H.T. (author), Kivits, S. (author), van Driel, A. (author), van der Steeg, E. (author), van der Hoorn, J.W. (author), Sio, C.F. (author), Steinbach, O.C. (author), de Groot, J. (author)Introduction: The efflux transporters P-glycoprotein (P-gp, ABCB1) and breast cancer resistance protein (BCRP, ABCG2) are expressed at the blood-brain barrier (BBB), and can limit the access of a wide range of drugs to the brain. In this study we developed a PET-CT imaging method for non-invasive, quantitative analysis of the effect of ABCB1 and...article 2015
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de Paula Faria, D. (author), Vlaming, M.L.H. (author), Copray, S.C.V.M. (author), Tielen, F. (author), Anthonijsz, H.J.A. (author), Sijbesma, J.W.A. (author), Buchpiguel, C.A. (author), Dierckx, R.A.J.O. (author), van der Hoorn, J.W.A. (author), de Vries, E.F.J. (author)The experimental autoimmune encephalomyelitis model is a model of multiple sclerosis that closely mimics the disease characteristics in humans. The main hallmarks of multiple sclerosis are neuroinflammation (microglia activation, monocyte invasion, and T-cell infiltration) and demyelination. PET imaging may be a useful noninvasive technique for...article 2014
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Joosen, M.J.A. (author), van der Schans, M.J. (author), van Dijk, C.G.M. (author), Kuijpers, W.C. (author), Wortelboer, H.M. (author), van Helden, H.P.M. (author)One of the shortcomings of current treatment of nerve agent poisoning is that oximes hardly penetrate the blood-brain barrier (BBB), whereas nerve agents easily do. Increasing the concentration of oximes in the brain, would therefore provide an attractive approach to improve medical countermeasures. An explanation for limited penetration might...article 2011
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Treijtel, N. (author), Eijkeren, J.C.H.v. (author), Nijmeijer, S. (author), van der Greef de - Sandt, I.C.J. (author), Freidig, A.P. (author), TNO Kwaliteit van Leven (author)The metabolism and active transport of ritonavir and saquinavir were studied using sandwich-cultured rat hepatoyctes and rat liver microsomes. For ritonavir four comparable metabolites were observed in the sandwich-culture and in microsomes. For saquinavir eight metabolites were observed in sandwich-culture and 14 different metabolites in...article 2009
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End, C. (author), Bikker, F.J. (author), Renner, M. (author), Bergmann, G. (author), Lyer, S. (author), Blaich, S. (author), Hudler, M. (author), Helmke, B. (author), Gassler, N. (author), Autschbach, F. (author), Ligtenberg, A.J.M. (author), Benner, A. (author), Holmskov, U. (author), Schirmacher, P. (author), Nieuw Amerongen, A.V. (author), Rosenstiel, P. (author), Sina, C. (author), Franke, A. (author), Hafner, M. (author), Kioschis, P. (author), Schreiber, S. (author), Poustka, A. (author), Mollenhauer, J. (author)Deleted in malignant brain tumors 1 (DMBT1) is a secreted glycoprotein displaying a broad bacterial-binding spectrum. Recent functional and genetic studies linked DMBT1 to the suppression of LPS-induced TLR4-mediated NF-kappaB activation and to the pathogenesis of Crohn's disease. Here, we aimed at unraveling the molecular basis of its function...article 2009
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Hamer, H.M. (author), Jonkers, D.M.A.E. (author), Loof, A. (author), van Houtvin, S.A.L.W. (author), Troost, F.J. (author), Venema, K. (author), Kodde, A. (author), Koek, G.H. (author), Schipper, R.G. (author), van Heerde, W.L. (author), Brummer, R.J. (author), TNO Kwaliteit van Leven (author)Background: The mucus layer is an important dynamic component of the epithelial barrier. It contains mucin glycoproteins and other compounds secreted by the intestinal epithelium, such as secretory IgA. However, a standardized in vivo sampling technique of mucus in humans is not yet available. Aim: To assess the validity and feasibility of mucin...article 2009
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Glycolipid-dependent sorting of melanosomal from lysosomal membrane proteins by lumenal determinantsGroux-Degroote, S. (author), van Dijk, S.M. (author), Wolthoorn, J. (author), Neumann, S. (author), Theos, A.C. (author), de Mazière, A.M. (author), Klumperman, J. (author), van Meer, G. (author), Sprong, H. (author), TNO Kwaliteit van Leven (author)Melanosomes are lysosome-related organelles that coexist with lysosomes in mammalian pigment cells. Melanosomal and lysosomal membrane proteins share similar sorting signals in their cytoplasmic tail, raising the question how they are segregated. We show that in control melanocytes, the melanosomal enzymes tyrosinase-related protein 1 (Tyrp1)...article 2008
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van Boxtel, E.L. (author), Koppelman, S.J. (author), van den Broek, L.A.M. (author), Gruppen, H. (author), TNO Kwaliteit van Leven (author), KvL (author)This study was aimed at the determination of the pepsin-susceptible and pepsin-resistant epitopes in native and heat-treated Ara h 1, a major allergen from peanuts. Both the oligomeric structure and the trimeric structure of the allergen were investigated. Under the in vitro conditions applied, oligomeric Ara h 1, either unheated or preheated,...article 2008
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TNO Kwaliteit van Leven (author), Gerritsen, G. (author), van der Hoogt, C.C. (author), Schaap, F.G. (author), Voshol, P.J. (author), Kypreos, K.E. (author), Maeda, N. (author), Groen, A.K. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), van Dijk, K.W. (author)Apolipoprotein E2 (apoE2)-associated hyperlipidemia is characterized by a disturbed clearance of apoE2-enriched VLDL remnants. Because excess apoE2 inhibits LPL-mediated triglyceride (TG) hydrolysis in vitro, we in vestigated whether direct or indirect stimulation of LPL activity in vivo reduces the apoE2-associated hypertriglyc-eridemia. Here,...article 2008
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van Boxtel, E.L. (author), van den Broek, L.A.M. (author), Koppelman, S.J. (author), Vincken, J.-P. (author), Gruppen, H. (author), TNO Kwaliteit van Leven (author)Mildly extracted peanut allergen Ara h 1 was previously reported to occur as an oligomeric complex. In this paper we describe how the protein in this oligomeric complex interacts noncovalently with phenolic compounds of the proanthocyanidin type. These interactions are being disrupted during anion exchange chromatography, resulting in the...article 2007
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Huls, M. (author), Kramers, C. (author), Levtchenko, E.N. (author), Wilmer, M.J.G. (author), Dijkman, H.B.P.M. (author), Kluijtmans, L.A.J. (author), van der Hoorn, J.W.A. (author), Russel, F.G.M. (author), Masereeuw, R. (author), TNO Kwaliteit van Leven (author)The multidrug resistance gene 1 product, P-glycoprotein (P-gp), is expressed in several excretory organs, including the apical membrane of proximal tubules. After inducing acute renal failure, P-gp expression is upregulated and this might be a protective function by pumping out toxicants and harmful products of oxidative stress. We characterized...article 2007
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Flinterman, A.E. (author), van Hoffen, E. (author), den Hartog Jager, C.F. (author), Koppelman, S. (author), Pasmans, S.G. (author), Hoekstra, M.O. (author), Bruijnzeel-Koomen, C.A. (author), Knulst, A.C. (author), Knol, E.F. (author), TNO Kwaliteit van Leven (author)Background: In peanut-allergic adults, IgE is mainly directed to Ara h1 and Ara h2. More recently, a role for Ara h6 has been suggested. In contrast to adults, IgE in children can fluctuate over time. Therefore, children may have a more dynamic reactivity to peanut. Objective: To examine the IgE reactivity to major peanut allergens in peanut...article 2007
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Zafranskaya, M. (author), Oschmann, P. (author), Engel, R. (author), Weishaupt, A. (author), van Noort, J.M. (author), Jomaa, H. (author), Eberl, M. (author), TNO Kwaliteit van Leven (author)Therapy with interferon-β (IFN-β) has well-established clinical effects in multiple sclerosis (MS), albeit the immunomodulatory mechanisms are not fully understood. We assessed the prevalence and functional capacity of CD4+ and CD8+ T cells in healthy donors, and in untreated and IFN-β-treated MS patients, in response to myelin oligodendrocyte...article 2007
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Peeters, K.A.B.M. (author), Koppelman, S.J. (author), van Hoffen, E. (author), van der Tas, C.W.H. (author), den Hartog Jager, C.F. (author), Penninks, A.H. (author), Hefle, S.L. (author), Bruijnzeel-Koomen, C.A.F.M. (author), Knol, E.F. (author), Knulst, A.C. (author), TNO Kwaliteit van Leven (author)Background: Recognition of specific peanut allergens or the diversity of IgE binding to peanut allergens may play a role in the elicitation of severe allergic reactions. Objective: To investigate whether sensitization to individual allergens Ara h 1, Ara h 2, Ara h 3 and Ara h 6 is correlated with clinical severity. Methods: The reactivity of...article 2007
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van Wijk, F. (author), Knippels, L. (author), TNO Kwaliteit van Leven (author)Immediately after birth the mucosa of the gastrointestinal tract, which represents the greatest body surface area exposed to the outside environment, is confronted with a large variety of foreign antigens. The immune system of the intestine now has to meet the task of discriminating between pathogens and harmless antigens, such as food proteins...article 2007
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van Bezooijen, R.L. (author), Svensson, J.P. (author), Eefting, D. (author), Visser, A. (author), van der Horst, G. (author), Karperien, M. (author), Quax, P.H.A. (author), Vrieling, H. (author), Papapoulos, S.E. (author), ten Dijke, P. (author), Löwik, W.G.M.C. (author), TNO Kwaliteit van Leven (author)Sclerostin is an osteocyte-derived negative regulator of bone formation. It inhibits BMP-stimulated bone formation both in vitro and in vivo but has no direct effect on BMP signaling. Instead, sclerostin inhibits Wnt signaling that is required for BMP-stimulated osteoblastic differentiation. Introduction: Sclerostin is a member of the Dan family...article 2007
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Westerterp, M. (author), van der Hoogt, C.C. (author), de Haan, W. (author), Offerman, E.H. (author), Dallinga-Thie, G.M. (author), Jukema, J.W. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)OBJECTIVE - The role of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is still undergoing debate. Therefore, we evaluated the effect of human CETP expression on atherosclerosis in APOE*3-Leiden (E3L) mice with a humanized lipoprotein profile. METHODS AND RESULTS - E3L mice were crossbred with human CETP...article 2006