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Automated Network Assembly of Mechanistic Literature for Informed Evidence Identification to Support Cancer Risk Assessment

Krishnan, S. (author), Vermeulen, R. (author), Pronk, A. (author), Gyori, B.M. (author), Bachman, J.A. (author), Vlaanderen, J. (author), Stierum, R. (author)

BACKGROUND: Mechanistic data is increasingly used in hazard identification of chemicals. However, the volume of data is large, challenging the efficient identification and clustering of relevant data. OBJECTIVES: We investigated whether evidence identification for hazard assessment can become more efficient and informed through an automated...

article 2022

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Dual targeting of hepatic fibrosis and atherogenesis by icosabutate, an engineered eicosapentaenoic acid derivative

Stokman, G. (author), van den Hoek, A.M. (author), Denker Thorbekk, D. (author), Pieterman, E.J. (author), Skovgård Veidal, S. (author), Basta, B. (author), Iruarrizaga-Lejarreta, M. (author), van der Hoorn, J.W. (author), Verschuren, L. (author), Berbée, J.F.P. (author), Rensen, P.C.N. (author), Skjæret, T. (author), Alonso, C. (author), Feigh, M. (author), Kastelein, J.J.P. (author), Friedman, S.L. (author), Princen, H.M.G. (author), Fraser, D.A. (author)

article 2020

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Time series analysis of benzo[a]pyrene-induced transcriptome changes suggests that a network of transcription factors regulates the effects on functional gene sets

van Delft, J.H.M. (author), Mathijs, K. (author), Staal, Y.C.M. (author), van Herwijnen, M.H.M. (author), Brauers, K.J.J. (author), Boorsma, A. (author), Kleinjans, J.C.S. (author), TNO Kwaliteit van Leven (author)

Chemical carcinogens may cause a multitude of effects inside cells, thereby affecting transcript levels of genes by direct activation of transcription factors (TF) or indirectly through the formation of DNA damage. As the temporal profiles of these responses may be profoundly different, examining time-dependent changes may provide new insights...

article 2010

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Systems biology guided by Chinese medicine reveals new markers for sub-typing rheumatoid arthritis patients

van Wietmarschen, H. (author), Yuan, K. (author), Lu, C. (author), Gao, P. (author), Wang, J. (author), Xiao, C. (author), Yan, X. (author), Wang, M. (author), Schroën, J. (author), Lu, A. (author), Xu, G. (author), van der Greef, J. (author), TNO Kwaliteit van Leven (author)

BACKGROUND: Complex chronic diseases such as rheumatoid arthritis have become a major challenge in medicine and for the pharmaceutical industry. New impulses for drug development are needed. OBJECTIVE: A systems biology approach is explored to find subtypes of rheumatoid arthritis patients enabling a development towards more personalized...

article 2009

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Macrophage p53 controls macrophage death in atherosclerotic lesions of apolipoprotein E deficient mice

Boesten, L.S.M. (author), Zadelaar, A.S.M. (author), van Nieuwkoop, A. (author), Hu, L. (author), Teunisse, A.F.A.S. (author), Jochemsen, A.G. (author), Evers, B. (author), van de Water, B. (author), Gijbels, M.J.J. (author), van Vlijmen, B.J.M. (author), Havekes, L.M. (author), de Winther, M.P.J. (author), TNO Kwaliteit van Leven (author)

The cellular composition of atherosclerotic lesions is determined by many factors including cell infiltration, proliferation and cell death. Tumor suppressor gene p53 has been shown to regulate both cell proliferation and cell death in many cell types. In the present study, we investigated the role of macrophage p53 in the pathogenesis of early...

article 2009

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Decidual vascularization and the expression of angiogenic growth factors and proteases in first trimester spontaneous abortions

Plaisier, M. (author), Dennert, I. (author), Rost, E. (author), Koolwijk, P. (author), van Hinsbergh, V.W.M. (author), Helmerhorst, F.M. (author), TNO Kwaliteit van Leven (author)

BACKGROUND : Decidual vascular development is important for implantation. This study analysed decidual vascular adaptation to implantation in correlation with miscarriage in decidual secretory endometrium (DSE), decidua parietalis (DP) and decidua basalis (DB) of miscarriage patients and matched controls. METHODS : Decidua was obtained during...

article 2009

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Alkylphospholipids inhibit capillary-like endothelial tube formation in vitro: Antiangiogenic properties of a new class of antitumor agents

Zerp, S.F. (author), Vink, S.R. (author), Ruiter, G.A. (author), Koolwijk, P. (author), Peters, E. (author), van der Luit, A.H. (author), de Jong, D. (author), Budde, M. (author), Bartelink, H. (author), van Blitterswijk, W.J. (author), Verheij, M. (author), TNO Kwaliteit van Leven (author)

Synthetic alkylphospholipids (APLs), such as edelfosine, miltefosine and perifosine, constitute a new class of antineoplastic compounds with various clinical applications. Here we have evaluated the antiangiogenic properties of APLs. The sensitivity of three types of vascular endothelial cells (ECs) (bovine aortic ECs, human umbilical vein ECs...

article 2008

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Stress proteins in CNS inflammation

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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Human apolipoprotein C-I expression in mice impairs learning and memory functions

TNO Kwaliteit van Leven (author), Abildayeva, K. (author), Berbée, J.F.P. (author), Blokland, A. (author), Jansen, P.J. (author), Hoek, F.J. (author), Meijer, O. (author), Lütjohann, D. (author), Gautier, T. (author), Pillot, T. (author), Vente, J.de (author), Havekes, L.M. (author), Ramaekers, F.C.S. (author), Kuipers, F. (author), Rensen, P.C.N. (author), Mulder, M. (author)

The H2 allele of APOC1, giving rise to increased gene expression of apolipoprotein C-I (apoC-I), is in genetic disequilibrium with the APOE4 allele and may provide a major risk factor for Alzheimer's disease (AD). We found that apoC-I protein is present in astrocytes and endothelial cells within hippocampal regions in both human control and AD...

article 2008

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Sirolimus and paclitaxel provoke different vascular pathological responses after local delivery in a murine model for restenosis on underlying atherosclerotic arteries

Pires, N.M.M. (author), Eefting, D. (author), de Vries, M.R. (author), Quax, P.H.A. (author), Jukema, J.W. (author), TNO Kwaliteit van Leven (author)

Background: Drug-eluting stents (DES) have been introduced successfully in clinical practice to prevent post angioplasty restenosis. Nevertheless, concerns about the safety of DES still exist. Objective: To investigate the vascular pathology and transcriptional responses to sirolimus and paclitaxel in a murine model for restenosis on underlying...

article 2007

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Transcriptomics analysis of interactive effects of benzene, trichloroethylene and methyl mercury within binary and ternary mixtures on the liver and kidney following subchronic exposure in the rat

Hendriksen, P.J.M. (author), Freidig, A.P. (author), Jonker, D. (author), Thissen, U. (author), Bogaards, J.J.P. (author), Mumtaz, M.M. (author), Groten, J.P. (author), Stierum, R.H. (author), TNO Kwaliteit van Leven (author)

The present research aimed to study the interaction of three chemicals, methyl mercury, benzene and trichloroethylene, on mRNA expression alterations in rat liver and kidney measured by microarray analysis. These compounds were selected based on presumed different modes of action. The chemicals were administered daily for 14 days at the Lowest...

article 2007

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Protective and therapeutic role for αB-crystallin in autoimmune demyelination

Ousman, S.S. (author), Tomooka, B.H. (author), van Noort, J.M. (author), Wawrousek, E.F. (author), O'Conner, K. (author), Hafler, D.A. (author), Sobel, R.A. (author), Robinson, W.H. (author), Steinman, L. (author), TNO Kwaliteit van Leven (author)

αB-crystallin (CRYAB) is the most abundant gene transcript present in early active multiple sclerosis lesions, whereas such transcripts are absent in normal brain tissue. This crystallin has anti-apoptotic and neuroprotective functions. CRYAB is the major target of CD4+ T-cell immunity to the myelin sheath from multiple sclerosis brain. The...

article 2007

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Binary PAH mixtures cause additive or antagonistic effects on gene expression but synergistic effects on DNA adduct formation

Staal, Y.C.M. (author), Hebels, D.G.A.J. (author), van Herwijnen, M.H.M. (author), Gottschalk, R.W.H. (author), van Schooten, F.J. (author), van Delft, J.H.M. (author), TNO Kwaliteit van Leven (author)

Polycyclic aromatic hydrocarbons (PAHs) cover a wide range of structurally related compounds which differ greatly in their carcinogenic potency. PAH exposure usually occurs through mixtures rather than individual compounds. Therefore, we assessed whether the effects of binary PAH mixtures on gene expression, DNA adduct formation, apoptosis and...

article 2007

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Activation of nuclear receptor Nur77 by 6-mercaptopurine protects against neointima formation

TNO Kwaliteit van Leven (author), Pires, N.M.M. (author), Pols, T.W.H. (author), de Vries, M.R. (author), Tiel, C.M.van (author), Bonta, P.I. (author), Vos, M. (author), Arkenbout, E.K. (author), Pannekoek, H. (author), Jukema, J.W. (author), Quax, P.H.A. (author), de Vries, C.J.M. (author)

BACKGROUND - Restenosis is a common complication after percutaneous coronary interventions and is characterized by excessive proliferation of vascular smooth muscle cells (SMCs). We have shown that the nuclear receptor Nur77 protects against SMC-rich lesion formation, and it has been demonstrated that 6-mercaptopurine (6-MP) enhances Nur77...

article 2007

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ACE inhibition with perindopril and endothelial function. Results of a substudy of the EUROPA study: PERTINENT

TNO Kwaliteit van Leven (author), Ceconi, C. (author), Fox, K.M. (author), Remme, W.J. (author), Simoons, M.L. (author), Bertrand, M. (author), Parrinello, G. (author), Kluft, C. (author), Blann, A. (author), Cokkinos, D. (author), Ferrari, R. (author)

Objectives: EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease [EUROPA] demonstrates reduction in cardiovascular mortality and myocardial infarction for a possible vascular and antiatherosclerotic effect of angiotensin-converting enzyme (ACE) inhibition with perindopril. Our objective was to study...

article 2007

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Mediators of apoptosis Fas and FasL predict disability progression in multiple sclerosis over a period of 10 years

Lopatinskaya, L. (author), Zwemmer, J. (author), Uitdehaag, B. (author), Lucas, K. (author), Polman, C. (author), Nagelkerken, L. (author), TNO Kwaliteit van Leven (author)

TNF-α, IL-12p35, IL-12p40, IL-4, IL-10, TGF-β1, CCR3, CXCR3, CCR5, Fas and FasL mRNA levels in PBMC of 25 multiple sclerosis (MS) patients were quantified at baseline by real-time PCR according to a post-hoc study design. The baseline values of the different markers were analysed with respect to their correlation with the increase in disability...

article 2006

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Inhibition of complement component C3 reduces vein graft atherosclerosis in apolipoprotein E3-Leiden transgenic mice

Schepers, A. (author), de Vries, M.R. (author), van Leuven, C.J. (author), Grimbergen, J.M. (author), Holers, V.M. (author), Daha, M.R. (author), van Bockel, J.H. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)

BACKGROUND - Venous bypass grafts may fail because of development of intimal hyperplasia and accelerated atherosclerosis. Inflammation plays a major role in these processes. Complement is an important part of the immune system and participates in the regulation of inflammation. The exact role of complement in the process of accelerated...

article 2006

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Macrophage retinoblastoma deficiency leads to enhanced atherosclerosis development in ApoE-deficient mice

Boesten, L.S.M. (author), Zadelaar, A.S.M. (author), van Nieuwkoop, A. (author), Hu, L. (author), Jonkers, J. (author), van de Water, B. (author), Gijbels, M.J.J. (author), van der Made, I. (author), de Winther, M.P.J. (author), Havekes, L.M. (author), van Vlijmen, B.J.M. (author), TNO Kwaliteit van Leven (author)

The cellular composition of an atherosclerotic lesion is determined by cell infiltration, proliferation, and apoptosis. The tumor suppressor gene retinoblastoma (Rb) has been shown to regulate both cell proliferation and cell death in many cell types. To study the role of macrophage Rb in the development of atherosclerosis, we used apoE...

article 2006

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Mdm2, but not Mdm4, protects terminally differentiated smooth muscle cells from p53-mediated caspase-3-independent cell death

TNO Kwaliteit van Leven (author), Boesten, L.S.M. (author), Zadelaar, A.S.M. (author), de Clercq, S. (author), Francoz, S. (author), van Nieuwkoop, A. (author), Biessen, E.A.L. (author), Hofmann, F. (author), Feil, S. (author), Feil, R. (author), Jochemsen, A.G. (author), Zurcher, C. (author), Havekes, L.M. (author), van Vlijmen, B.J.M. (author), Marine, J.C. (author)

p53 is a potent inhibitor of cell growth and an inducer of apoptosis. During embryonic development, Mdm2 and Mdm4 inhibit the growth suppressive activities of p53. However, whether tight surveillance of p53 activity is required in quiescent cells is unknown. To test this, conditional inactivation of mdm2 and mdm4 was carried out in smooth muscle...

article 2006

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Androgenic switch: An example of plant embryogenesis from the male gametophyte perspective

Maraschin, S.F. (author), de Priester, W. (author), Spaink, H.P. (author), Wang, M. (author)

Embryogenesis in plants is a unique process in the sense that it can be initiated from a wide range of cells other than the zygote. Upon stress, microspores or young pollen grains can be switched from their normal pollen development towards an embryogenic pathway, a process called androgenesis. Androgenesis represents an important tool for...

article 2005