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Effect of neutralizing sera on factor X-mediated adenovirus serotype 5 gene transfer

Parker, A.L. (author), Waddington, S.N. (author), Buckley, S.M.K. (author), Custers, J. (author), Havenga, M.J.E. (author), van Rooijen, N. (author), Goudsmit, J. (author), McVey, J.H. (author), Nicklin, S.A. (author), Baker, A.H. (author), TNO Kwaliteit van Leven (author)

The deployment of adenovirus serotype 5 (Ad5)-based vectors is hampered by preexisting immunity. When such vectors are delivered intravenously, hepatocyte transduction is mediated by the hexon-coagulation factor X (FX) interaction. Here, we demonstrate that human sera efficiently block FX-mediated cellular binding and transduction of Ad5-based...

article 2009

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Fiber-chimeric adenoviruses expressing fibers from serotype 16 and 50 improve gene transfer to human pancreatic adenocarcinoma

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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Lactobacilli expressing variable domain of llama heavy-chain antibody fragments (lactobodies) confer protection against rotavirus-induced diarrhea

Pant, N. (author), Hultberg, A. (author), Zhao, Y. (author), Svensson, L. (author), Pan-Hammarström, Q. (author), Johansen, K. (author), Pouwels, P.H. (author), Ruggeri, F.M. (author), Hermans, P. (author), Frenken, L. (author), Borén, T. (author), Marcotte, H. (author), Hammarström, L. (author), TNO Preventie en Gezondheid (author)

Background. Rotavirus-induced diarrhea poses a worldwide medical problem in causing substantial morbidity and mortality among children in developing countries. We therefore developed a system for passive immunotherapy in which recombinant lactobacilli constitutively express neutralizing variable domain of llama heavy-chain (VHH) antibody...

article 2006

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Human CD46-transgenic mice in studies involving replication-incompetent adenoviral type 35 vectors

Verhaagh, S. (author), de Jong, E. (author), Goudsmit, J. (author), Lecollinet, S. (author), Gillissen, G. (author), de Vries, M. (author), van Leuven, K. (author), Que, I. (author), Ouwehand, K. (author), Mintardjo, R. (author), Weverling, G.J. (author), Radošević, K. (author), Richardson, J. (author), Eloit, M. (author), Lowik, C. (author), Quax, P. (author), Havenga, M. (author), TNO Kwaliteit van Leven (author)

Wild-type strains of mice do not express CD46, a high-affinity receptor for human group B adenoviruses including type 35. Therefore, studies performed to date in mice using replication-incompetent Ad35 (rAd35) vaccine carriers may underestimate potency or result in altered vector distribution. Here, it is reported that CD46 transgenic mice (MYII...

article 2006

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Generation of a novel replication-incompetent adenoviral vector derived from human adenovirus type 49: Manufacture on PER.C6 cells, tropism and immunogenicity

TNO Kwaliteit van Leven (author), Lemckert, A.A.C. (author), Grimbergen, J. (author), Smits, S. (author), Hartkoorn, E. (author), Holterman, L. (author), Berkhout, B. (author), Barouch, D.H. (author), Vogels, R. (author), Quax, P. (author), Goudsmit, J. (author), Havenga, M.J.E. (author)

Recombinant adenoviral vectors based on type 5 (rAd5) show great promise as a vaccine carrier. However, neutralizing activity against Ad5 is prevalent and high-titred among human populations, and significantly dampens Ad5-based vaccine modalities. The generation of alternative adenoviral vectors with low seroprevalence thus receives much...

article 2006

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The solvent-tolerant Pseudomonas putida S12 as host for the production of cinnamic acid from glucose

Nijkamp, K. (author), van Luijk, N. (author), de Bont, J.A.M. (author), Wery, J. (author), TNO Kwaliteit van Leven TNO Voeding (author)

A Pseudomonas putida S12 strain was constructed that efficiently produced thefine chemical cinnamic acid from glucose or glycerol via the central metabolite phenylalanine. The gene encoding phenylalanine ammonia lyase from the yeast Rhodosporidium toruloides was introduced. Phenylalanine availability was the main bottleneck in cinnamic acid...

article 2005

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Efficient targeting of adenoviral vectors to integrin positive vascular cells utilizing a CAR-cyclic RGD linker protein

Krom, Y.D. (author), Gras, J.C.E. (author), Frants, R.R. (author), Havekes, L.M. (author), van Berkel, T.J. (author), Biessen, E.A.L. (author), van Dijk, K.W. (author), TNO Kwaliteit van Leven (author)

Vascular smooth muscle (VSMC) and endothelial cells (EC) are particularly resistant to infection by type 5 adenovirus (Ad) vectors. To overcome this limitation and target Ad vectors to ubiquitously expressed α Vβ3/5 integrins, we have generated a linker protein consisting of the extracellular domain of the coxsackie adenovirus receptor (CAR)...

article 2005

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Involvement of furin-like proprotein convertases in the arterial response to injury

TNO Kwaliteit van Leven (author), Sluijter, J.P.G. (author), Verloop, R.E. (author), Pulskens, W.P.C. (author), Velema, E. (author), Grimbergen, J.M. (author), Quax, P.H. (author), Goumans, M.J. (author), Pasterkamp, G. (author), Kleijn, D.P.V.de (author)

Background: Furin-like proprotein convertases (PCs) are proteolytic activators of proproteins, like membrane type 1-matrix metalloproteinase (MT1-MMP) and transforming growth factor beta (TGF-beta), that are described in the arterial response to injury. However, the involvement of furin-like PCs in the arterial response to injury has not been...

article 2005

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A hepatocyte nuclear factor-3 site in the fibrinogen beta promoter is important for interleukin 6-induced expression, and its activity is influenced by the adjacent -148C/T polymorphism

TNO Kwaliteit van Leven (author), Verschuur, M. (author), Jong, M.de (author), Felida, L. (author), Maat, M.P.M.de (author), Vos, H.L. (author)

An elevated plasma fibrinogen level is an independent risk factor for cardiovascular disease. Therefore, an understanding of the regulation of fibrinogen expression is important. Inflammation and genetic variation of the fibrinogen beta gene regulate plasma fibrinogen levels, and there are indications that inflammation and genetic variation...

article 2005

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Vascular endothelial growth factor overexpression in ischemic skeletal muscle enhances myoglobin expression in vivo

van Weel, V. (author), Deckers, M.M.L. (author), Grimbergen, J.M. (author), van Leuven, K.J.M. (author), Lardenoye, J.W.H.P. (author), Schlingemann, R.O. (author), van Nieuw Amerongen, G.P. (author), van Bockel, J.H. (author), van Hinsbergh, V.W.M. (author), Quax, P.H.A. (author), Gaubius Instituut TNO (author)

Therapeutic angiogenesis using vascular endothelial growth factor (VEGF) is considered a promising new therapy for patients with arterial obstructive disease. Clinical improvements observed consist of improved muscle function and regression of rest pain or angina. However, direct evidence for improved vascularization, as evaluated by angiography...

article 2004

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Membrane-type matrix metalloproteinase-mediated angiogenesis in a fibrin-collagen matrix

Collen, A. (author), Hanemaaijer, R. (author), Lupu, F. (author), Quax, P.H.A. (author), van Lent, N. (author), Grimbergen, J. (author), Peters, E. (author), Koolwijk, P. (author), van Hinsbergh, V.W.M. (author), Gaubius Instituut TNO (author)

Adult angiogenesis, associated with pathologic conditions, is often accompanied by the formation of a fibrinous exudate. This temporary matrix consists mainly of fibrin but is intermingled with plasma proteins and collagen fibers. The formation of capillary structures in a fibrinous matrix in vivo was mimicked by an in vitro model, in which...

article 2003

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Overproduction of the Aspergillus niger feruloyl esterase for pulp bleaching application

Record, E. (author), Asther, M. (author), Sigoillot, C. (author), Pagès, S. (author), Punt, P.J. (author), Delattre, M. (author), Haon, M. (author), van den Hondel, C.A.M.J.J. (author), Sigoillot, J.C. (author), Lesage-Meessen, L. (author), Asther, M. (author), TNO Voeding (author)

A well-known industrial fungus for enzyme production, Aspergillus niger, was selected to produce the feruloyl esterase FAEA by homologous overexpression for pulp bleaching application. The gpd gene promoter was used to drive FAEA expression. Changing the nature and concentration of the carbon source nature (maltose to glucose; from 2.5 to 60 g l...

article 2003

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Replication-deficient human adenovirus type 35 vectors for gene transfer and vaccination: Efficient human cell infection and bypass of preexisting adenovirus immunity

Vogels, R. (author), Zuijdgeest, D. (author), van Rijnsoever, R. (author), Hartkoorn, E. (author), Damen, I. (author), de Béthune, M.-P. (author), Kostense, S. (author), Penders, G. (author), Helmus, N. (author), Koudstaal, W. (author), Cecchini, M. (author), Wetterwald, A. (author), Sprangers, M. (author), Lemckert, A. (author), Ophorst, O. (author), Koel, B. (author), van Meerendonk, M. (author), Quax, P. (author), Panitti, L. (author), Grimbergen, J. (author), Bout, A. (author), Goudsmit, J. (author), Havenga, M. (author)

Replication-deficient human adenovirus type 5 (Ad5) can be produced to high titers in complementing cell lines, such as PER.C6, and is widely used as a vaccine and gene therapy vector. However, preexisting immunity against Ad5 hampers consistency of gene transfer, immunological responses, and vector-mediated toxicities. We report the...

article 2003

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Cartilage degradation and invasion by rheumatoid synovial fibroblasts is inhibited by gene transfer of TIMP-1 and TIMP-3

van der Laan, W.H. (author), Quax, P.H.A. (author), Seemayer, C.A. (author), Huisman, L.G.M. (author), Pieterman, E.J. (author), Grimbergen, J.M. (author), Verheijen, J.H. (author), Breedveld, F.C. (author), Gay, R.E. (author), Gay, S. (author), Huizinga, T.W.J. (author), Pap, T. (author), Gaubius Instituut TNO (author)

Matrix metalloproteinases (MMPs) are believed to be pivotal enzymes in the invasion of articular cartilage by synovial tissue in rheumatoid arthritis (RA). Here, we investigated the effects of gene transfer of tissue inhibitors of metalloproteinases (TIMPs) on the invasiveness of RA synovial fibroblasts (RASF) in vitro and in vivo. Adenoviral...

article 2003

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Induction of atherosclerotic plaque rupture in apolipoprotein E-/- mice after adenovirus-mediated transfer of p53

von der Thüsen, J.H. (author), van Vlijmen, B.J.M. (author), Hoeben, R.C. (author), Kockx, M.M. (author), Havekes, L.M. (author), van Berkel, T.J.C. (author), Biessen, E.A.L. (author)

Background - The presence of the tumor-suppressor gene p53 in advanced atherosclerotic plaques and the sensitivity to p53-induced cell death of smooth muscle cells isolated from these plaques have fueled speculation about the role of p53 in lesion destabilization and plaque rupture. In this study, we describe a strategy to promote (thrombotic)...

article 2002

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Structural and functional analysis of the S-layer protein crystallisation domain of Lactobacillus acidophilus ATCC 4356 : evidence for protein : protein interaction of two subdomains

Smit, E. (author), Jager, D. (author), Martinez, B. (author), Tielen, F.J. (author), Pouwels, P.H. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

The structure of the crystallisation domain, SAN, of the S A-protein of Lactobacillus acidophilus ATCC 4356 was analysed by insertion and deletion mutagenesis, and by proteolytic treatment. Mutant S A-protein synthesised in Escherichia coli with 7-13 amino acid insertions near the N terminus or within regions of sequence variation in SAN (amino...

article 2002

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Adenovirus-mediated transfer of the 39 kD receptor-associated protein increases fibrinolytic capacity

Goedde, M.F. (author), Grimbergen, J.M. (author), Toet, K.H. (author), Sitter, T. (author), Quax, P.H. (author), Kooistra, T. (author), Gaubius Instituut TNO (author)

Background. The mesothelium has an important role in maintaining an adequate fibrinolytic capacity in the peritoneal cavity and thus in preventing the formation of fibrinous peritoneal adhesions by secreting the fibrinolytic enzyme tissue-type plasminogen activator (t-PA). The fibrinolytic activity of human mesothelial cells (HMCs) is...

article 2001

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Adenoviral expression of a urokinase receptor - Targeted protease inhibitor inhibits neointima formation in murine and human blood vessels

Quax, P.H.A. (author), Lamfers, M.L.M. (author), Lardenoye, J.H.P. (author), Grimbergen, J.M. (author), de Vries, M.R. (author), Slomp, J. (author), de Ruiter, M.C. (author), Kockx, M.M. (author), Verheijen, J.H. (author), van Hinsbergh, V.W.M. (author), Gaubius Instituut TNO (author)

Background - Smooth muscle cell migration, in addition to proliferation, contributes to a large extent to the neointima formed in humans after balloon angioplasty or bypass surgery. Plasminogen activator/plasmin-mediated proteolysis is an important mediator of this smooth muscle cell migration. Here, we report the construction of a novel hybrid...

article 2001

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In vivo suppression of restenosis in balloon-injured rat carotid artery by adenovirus-mediated gene transfer of the cell surface-directed plasmin inhibitor ATF.BPTI

Lamfers, M.L.M. (author), Lardenoye, J.H.P. (author), de Vries, M.R. (author), Aalders, M.C. (author), Engelse, M.A. (author), Grimbergen, J.M. (author), van Hinsbergh, V.W.M. (author), Quax, P.H.A. (author), Gaubius Instituut TNO (author)

Injury-induced neointimal development results from migration and proliferation of vascular smooth muscle cells (SMC). Cell migration requires controlled proteolytic degradation of extracellular matrix surrounding the cell. Plasmin is a major contributor to this process by degrading various matrix proteins directly, or indirectly by activating...

article 2001

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Bifidobacteria: Genetic modification and the study of their role in the colon

van der Werf, M. (author), Venema, K. (author), TNO Voeding (author)

Bifidobacteria are among the most common bacteria in the human intestine and are thought to have a positive effect on human health. Therefore, there is an increasing interest in using these microorganisms as probiotics, either in fermented dairy products or formulated as tablets. However, convincing scientific data supporting their health claims...

article 2001