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van Zanden, J.J. (author), Geraets, L. (author), Wortelboer, H.M. (author), van Bladeren, P.J. (author), Rietjens, I.M.C.M. (author), Cnubben, N.H.P. (author), TNO Voeding (author)
The objective of this study was to investigate the structural requirements necessary for inhibition of glutathione S-transferase P1-1 (GSTP1-1) and GS-X pump (MRP1 and MRP2) activity by structurally related flavonoids, in GSTP1-1 transfected MCF7 cells (pMTG5). The results reveal that GSTP1-1 activity in MCF7 pMTG5 cells can be inhibited by some...
article 2004
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Jeurissen, S.M.F. (author), Claassen, F.W. (author), Havlik, J. (author), Bouwmans, E.E. (author), Cnubben, N.H.P. (author), Sudhölter, E.J.R. (author), Rietjens, I.M.C.M. (author), van Beek, T.A. (author), TNO Kwaliteit van Leven (author)
An on-line HPLC screening method for detection of inhibitors of human cytochrome P450 1A2 in extracts was developed. HPLC separation of extracts is connected to a continuous methoxyresorufin-O-demethylation (MROD) assay in which recombinant human P450 1A2 converts methoxyresorufin to its fluorescent metabolite resorufin. The system was tested...
article 2007
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Jeurissen, S.M.F. (author), Punt, A. (author), Boersma, M.G. (author), Bogaards, J.J.P. (author), Fiamegos, Y.C. (author), Schilter, B. (author), van Bladeren, P.J. (author), Cnubben, N.H.P. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)
Human cytochrome P450 enzymes involved in the bioactivation of estragole to its proximate carcinogen 1′-hydroxyestragole were identified and compared to the enzymes of importance for 1′-hydroxylation of the related alkenylbenzenes methyleugenol and safrole. Incubations with Supersomes revealed that all enzymes tested, except P450 2C8, are...
article 2007
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Cnubben, N.H. (author), Wortelboer, H.M. (author), van Zanden, J.J. (author), Rietjens, I.M. (author), van Bladeren, P.J. (author), TNO Kwaliteit van Leven (author)
Membrane transport proteins belonging to the ATP-binding cassette (ABC) family of transport proteins play a central role in the defence of organisms against toxic compounds, including anticancer drugs. However, for compounds that are designed to display a toxic effect, this defence system diminishes their effectiveness. This is typically the...
article 2005
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van Mierlo, G.J.D. (author), Cnubben, N.H.P. (author), Wouters, D. (author), Wolbink, G.J. (author), Hart, M.H.L. (author), Rispens, T. (author), Ganderup, N.C. (author), Kuper, C.F. (author), Aarden, L. (author), Penninks, A.H. (author)
Immunogenicity is a major issue of concern for monoclonal antibodies used in human diseases and is by default mainly determined in non-human primates (NHP), as target molecules are considered most similar in NHP compared to human. In this manuscript the predictive value of immunogenicity testing in minipigs for human safety is evaluated, as the...
article 2014
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Boersma, M.G. (author), van der Woude, H. (author), Bogaards, J. (author), Boeren, S. (author), Vervoort, J. (author), Cnubben, N.H.P. (author), van Iersel, M.L.P.S. (author), van Bladeren, P.J. (author), Rietjens, I.M.C.M. (author), TNO Voeding (author)
article 2002
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Cnubben, N.H.P. (author), Rommens, A.J.M. (author), Oudshoorn, M.J. (author), van Bladeren, P.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)
article 1998
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van den Berg, R. (author), van Vliet, T. (author), Broekmans, W.M.R. (author), Cnubben, N.H.P. (author), Vaes, W.H.J. (author), Roza, L. (author), Haenen, G.R.M.M. (author), Bast, A. (author), van den Berg, H. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)
The potential benefits of a high fruit and vegetable intake on the antioxidant status and on relevant biomarkers of oxidative damage to lipids, proteins and DNA and on (functional) markers of oxidative stress were evaluated. A randomized, free living, open placebo-controlled cross-over trial of 3 wk, with a 2-wk washout period between treatments...
article 2001
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Usta, M. (author), Wortelboer, H.M. (author), Vervoort, J. (author), Boersma, M.G. (author), Rietjens, I.M.C.M. (author), van Bladeren, P.J. (author), Cnubben, N.H.P. (author), TNO Kwaliteit van Leven (author)
Curcumin, an α,β-unsaturated carbonyl compound, reacts with glutathione, leading to the formation of two monoglutathionyl curcumin conjugates. In the present study, the structures of both glutathione conjugates of curcumin were identified by LC-MS and one- and two-dimensional 1H NMR analysis, and their formation in incubations with human...
article 2007
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van Iersel, M.L.P.S. (author), Cnubben, N.H.P. (author), Smink, N. (author), Koeman, J.H. (author), van Bladeren, P.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)
The cyclopentenone prostaglandin A2 (PGA2) is known to inhibit cell proliferation, and metabolism of this compound thus might be important in controlling its ultimate function. The glutathione-related metabolism of PGA2 was therefore investigated both with purified glutathione S-transferase P1-1 (GSTP1-1) and with IGR-39 human melanoma cells....
article 1999
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van Zanden, J.J. (author), van der Woude, H. (author), Vaessen, J. (author), Usta, M. (author), Wortelboer, H.M. (author), Cnubben, N.H.P. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)
The present study characterises the effect of phase II metabolism, especially methylation and glucuronidation, of the model flavonoid quercetin on its capacity to inhibit human MRP1 and MRP2 activity in Sf9 inside-out vesicles. The results obtained reveal that 3′-O-methylation does not affect the MRP inhibitory potential of quercetin. However, 4...
article 2007
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Wopereis, S. (author), Radonjic, M. (author), Rubingh, C. (author), van Erk, M. (author), Smilde, A. (author), van Duyvenvoorde, W. (author), Cnubben, N. (author), Kooistra, T. (author), van Ommen, B. (author), Kleemann, R. (author)
The prevalence of diabetes mellitus Type 2 could be significantly reduced by early identification of subjects at risk, allowing for better prevention and earlier treatment. Glucose intolerance (GI) is a hallmark of the prediabetic stage. This study aims at identifying 1) prognostic biomarkers predicting the risk of developing GI later in life...
article 2012
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van Erk, M.J. (author), Wopereis, S. (author), Rubingh, C. (author), van Vliet, T. (author), Verheij, E. (author), Cnubben, N.H. (author), Pedersen, T.L. (author), Newman, J.W. (author), Smilde, A.K. (author), Greef, J.V.D. (author), Hendriks, H.F. (author), van Ommen, B. (author), TNO Kwaliteit van Leven (author)
Background. Chronic systemic low-grade inflammation in obese subjects is associated with health complications including cardiovascular diseases, insulin resistance and diabetes. Reducing inflammatory responses may reduce these risks. However, available markers of inflammatory status inadequately describe the complexity of metabolic responses to...
article 2010
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van Iersel, M.L.P.S. (author), Cnubben, N.H.P. (author), Smink, N. (author), Koeman, J.H. (author), van Bladeren, P.J. (author)
article 1999
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Buscher, B.A.P. (author), Gerritsen, H. (author), van Schöll, I. (author), Cnubben, N.H.P. (author), Brüll, L.P. (author), TNO Kwaliteit van Leven (author)
An LC-MS/MS method has been developed for the quantitative determination of a protein drug (Tenecteplase; MW 58,777 Da) in rat plasma. The protein was digested with trypsin without prior clean-up of the plasma sample, without the use of a label nor internal standard. A limited validation was performed to assess the linearity, the sensitivity and...
article 2007
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van de Sandt, J.J.M. (author), Meuling, W.J.A. (author), Elliott, G.R. (author), Cnubben, N.H.P. (author), Hakkert, B.C. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)
In vitro and in vivo skin absorption of the pesticide propoxur (2-isopropoxyphenyl N-methyl carbamate, commercially Baygon(TM) and Unden(TM); log Po/w 1.56, MW 209.2) was investigated. In vivo studies were performed in rats and human volunteers, applying the test compound to the dorsal skin and the volar aspect of the forearm, respectively. In...
article 2000
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van Mierlo, G.J.D. (author), Cnubben, N.H.P. (author), Kuper, C.F. (author), Wolthoorn, J. (author), van Meeteren-Kreikamp, A.P. (author), Nagtegaal, M.M. (author), Doornbos, R. (author), Ganderup, N.-C. (author), Penninks, A.H. (author)
The use of recombinant human proteins for the treatment of several diseases has increased considerably during the last decades. A major safety and efficacy issue of biopharmaceuticals is their potential immunogenicity. To prevent immunogenicity, biotechnology-derived proteins are engineered to be as human-like as possible. Immunogenicity is...
article 2013
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van Zanden, J.J. (author), Hamman, O.B. (author), van Iersel, M.L.P.S. (author), Boeren, S. (author), Cnubben, N.H.P. (author), Lo Bello, M. (author), Vervoort, J. (author), van Bladeren, P.J. (author), Rietjens, I.M.C.M. (author)
In the present study, the inhibition of human glutathione S-transferase P1-1 (GSTP1-1) by the flavonoid quercetin has been investigated. The results show a time- and concentration-dependent inhibition of GSTP1-1 by quercetin. GSTP1-1 activity is completely inhibited upon 1 h incubation with 100 μM quercetin or 2 h incubation with 25 μM quercetin...
article 2003
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Jeurissen, S.M.F. (author), Bogaards, J.J.P. (author), Boersma, M.G. (author), ter Horst, J.P.F. (author), Awad, H.M. (author), Fiamegos, Y.C. (author), van Beek, T.A. (author), Alink, G.M. (author), Sudhölter, E.J.R. (author), Cnubben, N.H.P. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)
In vitro studies were performed to elucidate the human cytochrome P450 enzymes involved in the bioactivation of methyleugenol to its proximate carcinogen 1′-hydroxymethyleugenol. Incubations with Supersomes, expressing individual P450 enzymes to a high level, revealed that P450 1A2, 2A6, 2C9, 2C19, and 2D6 are intrinsically able to 1′...
article 2006
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Bakker, G.C.M. (author), van Erk, M.J. (author), Pellis, L. (author), Wopereis, S. (author), Rubingh, C.M. (author), Cnubben, N.H.P. (author), Kooistra, T. (author), van Ommen, B. (author), Hendriks, H.F.J. (author), TNO Kwaliteit van Leven (author)
Background: Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Objective: It was hypothesized that specific dietary components are able to reduce low-grade inflammation as well as metabolic and oxidative stress. Design: Dietary products [resveratrol, green tea extract, α-tocopherol,...
article 2010
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