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Desprez, B. (author), Birk, B. (author), Blaauboer, B. (author), Boobis, A. (author), Carmichael, P. (author), Cronin, M.T.D. (author), Curie, R. (author), Daston, G. (author), Hubesch, B. (author), Jennings, P. (author), Klaric, M. (author), Kroese, D. (author), Mahony, C. (author), Ouédraogo, G. (author), Piersma, A. (author), Richarz, A.N. (author), Schwarz, M. (author), van Benthem, J. (author), van de Water, B. (author), Vinken, M. (author)Repeated dose toxicity evaluation aims at assessing the occurrence of adverse effects following chronic or repeated exposure to chemicals. Non-animal approaches have gained importance in the last decades because of ethical considerations as well as due to scientific reasons calling for more human-based strategies. A critical aspect of this...article 2019
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Reisinger, K. (author), Blatz, V. (author), Brinkmann, J. (author), Downs, T.R. (author), Fischer, A. (author), Henkler, F. (author), Hoffmann, S. (author), Krul, C. (author), Liebsch, M. (author), Luch, A. (author), Pirow, R. (author), Reus, A.A. (author), Schulz, M. (author), Pfuhler, S. (author)Recently revised OECD Testing Guidelines highlight the importance of considering the first site-of-contact when investigating the genotoxic hazard. Thus far, only in vivo approaches are available to address the dermal route of exposure. The 3D Skin Comet and Reconstructed Skin Micronucleus (RSMN) assays intend to close this gap in the in vitro...article 2018
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Kooter, I.M. (author), Grollers-Mulderij, M. (author), Duistermaat, E. (author), Kuper, C.F. (author)Mucilair 3D bronchial airway models, cultured at an air-liquid interface, were exposed to aerosols of copper oxide (CuO) nanoparticles in Vitrocell air exposure modules. Four cell donors, four exposure modules and four exposure concentrations were varied within four different exposure sessions using a statistical experimental design called a...article 2017
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Detection of the mechanism of immunotoxicity of cyclosporine A in murine in vitro and in vivo modelsSchmeits, P.C.J. (author), Schaap, M.M. (author), Luijten, M. (author), van Someren, E. (author), Boorsma, A. (author), van Loveren, H. (author), Peijnenburg, A.A.C.M. (author), Hendriksen, P.J.M. (author)Transcriptomics in combination with in vitro cell systems is a powerful approach to unravel modes of action of toxicants. An important question is to which extent the modes of action as revealed by transcriptomics depend on cell type, species and study type (in vitro or in vivo). To acquire more insight into this, we assessed the transcriptomic...article 2015
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Teunis, M.A.T. (author), Spiekstra, S.W. (author), Smits, M. (author), Adriaens, E. (author), Eltze, T. (author), Galbiati, V. (author), Krul, C.A.M. (author), Landsiedel, R. (author), Pieters, R. (author), Reinders, J. (author), Roggen, E. (author), Corsini, E. (author), Gibbs, S. (author)This study describes the international ring trial of the epidermal-equivalent (EE) sensitizer potency assay. This assay does not distinguish a sensitizer from a non-sensitizer, but may classify known skin sensitizers according to their potency. It assesses the chemical concentration resulting in 50% cytotoxicity (EE-EC50) or the 2-fold increase...article 2014
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Zimmer, B. (author), Pallocca, G. (author), Dreser, N. (author), Foerster, S. (author), Waldmann, T. (author), Westerhout, J. (author), Julien, S. (author), Krause, K.H. (author), van Thriel, C. (author), Hengstler, J.G. (author), Sachinidis, A. (author), Bosgra, S. (author), Leist, M. (author)Developmental toxicity in vitro assays have hitherto been established as stand-alone systems, based on a limited number of toxicants. Within the embryonic stem cell-based novel alternative tests project, we developed a test battery framework that allows inclusion of any developmental toxicity assay and that explores the responses of such test...article 2014
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Bastiaansen-Jenniskens, Y.M. (author), Siawash, M. (author), van de Lest, C.H.A. (author), Verhaar, J.A.N. (author), Kloppenburg, M. (author), Zuurmond, A.M. (author), Stojanovic-Susulic, V. (author), van Osch, G.J.V.M. (author), Clockaerts, S. (author)Purpose: Osteoarthritis (OA) is associated with obesity in which altered fatty acid levels have been observed. We investigated whether the most common fatty acids in synovial fluid influence cartilage deterioration in OA. Design: Cartilage was obtained from OA patients undergoing total knee arthroplasty. Chondrocytes or cartilage explants were...article 2013
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Molhoek, E.M. (author), van Dijk, A. (author), Veldhuizen, E.J.A. (author), Haagsman, H.P. (author), Bikker, F.J. (author)A truncated version of host defense peptide chicken cathelicidin-2, C1-15, possesses potent, broad spectrum antibacterial activity. A variant of this peptide, F2,5,12W, which contains 3 phenylalanine to tryptophan substitutions, possesses improved antibacterial activity and lipopolysaccharide (LPS) neutralizing activity compared to C1-15. In...article 2011
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Molhoek, E.M. (author), van Dijk, A. (author), Veldhuizen, E.J.A. (author), Dijk-Knijnenburg, H. (author), Mars-Groenendijk, R.H. (author), Boele, L.C.L. (author), Kaman-van Zanten, W.E. (author), Haagsman, H.P. (author), Bikker, F.J. (author), TNO Defensie en Veiligheid (author)Host defence peptides (HDPs) are considered to be excellent candidates for the development of novel therapeutic agents. Recently, it was demonstrated that the peptide C1-15, an N-terminal segment of chicken HDP cathelicidin-2, exhibits potent antibacterial activity while lacking cytotoxicity towards eukaryotic cells. In the present study, we...article 2010
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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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de Jong, E. (author), Louisse, J. (author), Verwei, M. (author), Blaauboer, B.J. (author), van de Sandt, J.J.M. (author), Woutersen, R.A. (author), Rietjens, I.M.C.M. (author), Piersma, A.H. (author), TNO Kwaliteit van Leven (author)The embryonic stem cell test (EST) has been proposed as an in vitro assay that might reduce animal experimentation in regulatory developmental toxicology. So far, evaluation of the EST was not performed using compounds within distinct chemical classes. Evaluation within a distinct class of chemically related compounds can define the usefulness...article 2009
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Kuhlmann, K.F.D. (author), van Geer, M.A. (author), Bakker, C.T. (author), Dekker, J.E.M. (author), Havenga, M.J.E. (author), Oude Elferink, R.P.J. (author), Gouma, D.J. (author), Bosma, P.J. (author), Wesseling, J.G. (author), TNO Kwaliteit van Leven (author)Survival of patients with pancreatic cancer is poor. Adenoviral (Ad) gene therapy employing the commonly used serotype 5 reveals limited transduction efficiency due to the low amount of coxsackie-adenovirus receptor on pancreatic cancer cells. To identify fiber-chimeric adenoviruses with improved gene transfer, a library of Ad vectors based on...article 2009
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TNO Kwaliteit van Leven (author), Lindeman, J.H.N. (author), Abdul-Hussien, H. (author), van Bockel, J.H. (author), Wolterbeek, R. (author), Kleemann, R. (author)Background-Doxycycline has been shown to effectively inhibit aneurysm formation in animal models of abdominal aortic aneurysm. Although this effect is ascribed to matrix metalloproteinase-9 inhibition, such an effect is unclear in human studies. We reevaluated the effect of doxycycline on aortic wall protease content in a inical trial and found...article 2009
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van Noort, J.M. (author), TNO Kwaliteit van Leven (author)Stress proteins or heat shock proteins (HSPs) are ubiquitous cellular components that have long been known to act as molecular chaperones. By assisting proper folding and transport of proteins, and by assisting in the degradation of aberrant proteins, they play key roles in cellular metabolism. The frequent accumulation of insoluble protein...article 2008
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Lindeman, J.H.N. (author), Abdul-Hussien, H. (author), Schaapherder, A.F.M. (author), van Bockel, J.H. (author), von der Thüsen, J.H. (author), Roelen, D.L. (author), Kleemann, R. (author)Inflammation plays a key role in the pathogenesis of an AAA (abdominal aortic aneurysm); however, the nature of the inflammatory factors and cellular response(s) involved in AAA growth is controversial. In the present study, we set out to determine the aortic levels of inflammatory cytokines in relation to downstream inflammatory transcription...article 2008
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Zvinavashe, E. (author), van den Berg, H. (author), Soffers, A.E.M.F. (author), Vervoort, J. (author), Freidig, A. (author), Murk, A.J. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)Quantitative structure-activity relationship (QSAR) models are expected to play a crucial role in reducing the number of animals to be used for toxicity testing resulting from the adoption of the new European Union chemical control system called Registration, Evaluation, and Authorization of Chemicals (REACH). The objective of the present study...article 2008
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van Wijk, F. (author), Nierkens, S. (author), de Jong, W. (author), Wehrens, E.J.M. (author), Boon, L. (author), van Kooten, P. (author), Knippels, L.M.J. (author), Pieters, R. (author), TNO Kwaliteit van Leven (author)Dendritic cells are believed to play an essential role in regulating the balance between immunogenic and tolerogenic responses to mucosal Ags by controlling T cell differentiation and activation via costimulatory and coinhibitory signals. The CD28/CTLA-4-CD80/CD86 signaling pathway appears to be one of the most important regulators of T cell...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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Kienhuis, A.S. (author), Wortelboer, H.M. (author), Hoflack, J.C. (author), Moonen, E.J. (author), Kleinjans, J.C.S. (author), van Ommen, B. (author), van Delft, J.H.M. (author), Stierum, R.H. (author), TNO Kwaliteit van Leven (author)Sandwich-cultured primary rat hepatocytes are often used as an in vitro model in toxicology and pharmacology. However, loss of liver-specific functions, in particular, the decline of cytochrome P450 (P450) enzyme activity, limits the value of this model for prediction of in vivo toxicity. In this study, we investigated whether a hepatic in vitro...article 2006
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- Eskes, C. (author), Bessou, S. (author), Bruner, L. (author), Curren, R. (author), Harbell, J. (author), Jones, P. (author), Kreiling, R. (author), Liebsch, M. (author), McNamee, P. (author), Pape, W. (author), Prinsen, M.K. (author), Seidle, T. (author), Vanparys, P. (author), Worth, A. (author), Zuang, V. (author), TNO Kwaliteit van Leven (author) article 2005