Searched for: author:"van de Steeg, E."
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Donkers, J.M. (author), Eslami Amirabadi, H. (author), van de Steeg, E. (author)
Over the past decade, microfluidic intestine-on-a-chip models have been emerging as a novel platform to study intestinal function in health and disease. These microphysiological systems surpass conventional in vitro intestinal model systems, as they add microenvironmental context in the form of mechanical cues or by the incorporation of multiple...
article 2021
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van Berlo, D. (author), van de Steeg, E. (author), Amirabadi, H.E. (author), Masereeuw, R. (author)
The development of new medicines suffers from attrition, especially in the development pipeline. Eight out of nine drug candidates entering the clinical testing phase fail, mostly due to poor safety and efficacy. The low predictive value of animal models, used in earlier phases of drug development, for effects in humans poses a major problem. In...
article 2021
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Stevens, L.J. (author), Donkers, J.M. (author), Dubbel, J. (author), Vaes, W.H.J. (author), van de Steeg, E. (author), Knibbe, C.A.J. (author), Alwayn, I.P.J. (author), van de Steeg, E. (author)
To predict the absorption, distribution, metabolism and excretion (ADME) profile of candidate drugs a variety of preclinical models can be applied. The ADME and toxicological behavior of newly developed drugs are often investigated prior to assessment in humans, which is associated with long time-lines and high costs. Therefore, good predictions...
article 2020
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Stevens, L.J. (author), van Lipzig, M.M.H. (author), Erpelinck, S.L.A. (author), Pronk, A. (author), van Gorp, J. (author), Wortelboer, H.M. (author), van de Steeg, E. (author)
A majority of the preclinical intestinal screening models do not properly reflect the complex physiology of the human intestinal tract, resulting in low translational value to the clinical situation. The often used cell lines such as Caco-2 or HT-29 are not well suited to investigate the different processes that predict oral bioavailability in...
article 2019
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van der Heiden, M.S. (author), Tejeda, H. (author), Rajadurai, S.R.S. (author), Donkers, T. (author), Duivenvoorde, T.L.P. (author), Eslami Amirabadi, H. (author), Ananth, A.N. (author), Lucas, P. (author), van de Steeg, E. (author)
Organ-on-chip technology is based on tissues or (stem)cell derived organ mimicking structures and in microfluidic systems. This technology is used to monitor functional response to stimuli, aiming to enable personalized medicine and to conduct pre-clinical drug development studies. In general, cells in stress exhibit a change in nanomechanical...
other 2019
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Stevens, L. (author), Dubbeld, J. (author), Doppenberg, J. (author), Erpelinck, S. (author), Knibbe, C. (author), Alwayn, I. (author), van de Steeg, E. (author)
Current models to predict biliary excretion often fail due to species differences (rodent/dog) or due to differences in transporter expression in in vitro assays (e.g. sandwich cultured hepatocytes). Especially when drugs are subjective to enterohepatic circulation (EHC), this results difficulties to predict plasma profiles after oral and iv...
public lecture 2019
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Peters, V.B.M. (author), van de Steeg, E. (author), van Bilsen, J. (author), Meijerink, M. (author)
The human body is exposed to many xenobiotic, potentially harmful compounds. The intestinal immune system is crucial in protecting the human body from these substances. Moreover, many microorganisms, residing in the gastrointestinal tract, play an important role in modulating immune responses. Pre- and probiotics may have beneficial effects on...
article 2019
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van de Steeg, E. (author), Schuren, F.H.J. (author), Nooijen, I.H.G. (author), Erpelinck, S. (author), Scott Obach, R. (author), Vaes, W.H.J. (author)
Gut microbiota plays a major role in metabolizing xenobiotics into active, inactive or toxic metabolites, thereby influencing pharmacokinetics, efficacy and toxicity profiles of prescribed drugs, which is currently being underexplored.
public lecture 2019
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Amirabadi, H. Eslami (author), Wierenga, E. (author), Stevens, L.J. (author), Donkers, J. (author), Donkers, T. (author), Ingenhut, B.L.J. (author), Usta, B. (author), Pieters, L. (author), Gröllers, M. (author), Nooijen, I.H.G. (author), Erpelinck, S.L.A. (author), Schuren, F. (author), Masereeuw, R. (author), van de Steeg, E. (author)
The majority of screening and predictive models do not reflect the physiology of the human intestinal tract since they show major limitations to include the processes that determine the oral bioavailability1,2. A major drawback of current intestinal models is the use of single cell lines and the static environment, which is in contrast with the...
public lecture 2019
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Notenboom, S. (author), Weigand, K.M. (author), Proost, J.H. (author), van Lipzig, M.M. (author), van de Steeg, E. (author), van den Broek, P.H.H. (author), Greupink, R. (author), Russel, F.G.M. (author), Groothuis, G.M.M. (author)
The authors regret the molar unit is incorrectly displayed on the x-axis in Fig. 4A and 4C and on the y-axis in Fig. 4B, 4D and Fig. 5. The correct versions of the figures are displayed below together with the unchanged legends. The authors would like to apologise for any inconvenience caused. DOI of original article: 10.1016/j.ejps.2018.01.007 ...
article 2018
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Notenboom, S. (author), Weigand, K.M. (author), Proost, J.H. (author), van Lipzig, M.M.H. (author), van de Steeg, E. (author), van den Broek, P.H.H. (author), Greupink, R. (author), Russel, F.G.M. (author), Groothuis, G.M.M. (author)
Drug-induced liver injury (DILI) is a common reason for drug withdrawal from the market. An important cause of DILI is drug-induced cholestasis. One of the major players involved in drug-induced cholestasis is the bile salt efflux pump (BSEP; ABCB11). Inhibition of BSEP by drugs potentially leads to cholestasis due to increased (toxic)...
article 2018
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van de Steeg, E. (author), Schuren, F.H.J. (author), Obach, R.S. (author), van Woudenbergh, C. (author), Walker, G.S. (author), Heerikhuisen, M. (author), Nooijen, I.H.G. (author), Vaes, W.H.J. (author)
Colon microbiota-based drug metabolism has received little attention thus far in the process of drug development, whereas the role of gut microbiota in clinical safety and efficacy of drugs has become more clear. Many of these studies have been performed using animal studies, but the translational value of these data with respect to drug...
article 2018
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Hanemaaijer, R. (author), van de Steeg, E. (author), Bobeldijk, I. (author), Ostendorf, R. (author)
Over the last 4 years, the ERP Organ function on-a-chip evolved from a seed ERP (2015) into a full ERP (in 2016) and is still further growing towards 2018. The program has three use cases: gut-, liver- and lung-function on a chip. In addition nano-detection of biochemical (proteins) was explored.
other 2018
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van Groen, B.D. (author), van de Steeg, E. (author), Mooij, M.G. (author), van Lipzig, M.M.H. (author), de Koning, B.A.E. (author), Verdijk, R.M. (author), Wortelboer, H.M. (author), Gaedigk, R. (author), Bi, C. (author), Leeder, S. (author), van Schaik, R.H.N. (author), van Rosmalen, J. (author), Tibboel, D. (author), Vaes, W.H. (author), de Wildt, S.N. (author)
Background Hepatic membrane transporters are involved in the transport of many endogenous and exogenous compounds, including drugs. We aimed to study the relation of age with absolute transporter protein expression in a cohort of 62 mainly fetus and newborn samples. Methods Protein expressions of BCRP, BSEP, GLUT1, MCT1, MDR1, MRP1, MRP2, MRP3,...
article 2018
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Vaessen, S.F.C. (author), van Lipzig, M.M.H. (author), Pieters, R.H.H. (author), Krul, C.A.M. (author), Wortelboer, H.M. (author), van de Steeg, E. (author)
Intestinal transporter proteins and metabolizing enzymes play a crucial role in the oral absorption of a wide variety of drugs. The aim of the current study was to characterize better available intestinal in vitro models by comparing expression levels of these proteins and enzymes between porcine intestine, human intestine, and Caco-2 cells. We...
article 2017
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van de Steeg, E. (author), Läppchen, T. (author), Aguilera, B. (author), Jansen, H.T. (author), Muilwijk, D. (author), Vermue, R. (author), van der Hoorn, J.W. (author), Donato, K. (author), Rossin, R. (author), de Visser, P.C. (author), Vlaming, M.L.H. (author)
Antisense oligonucleotides (AONs) are promising candidates for treatment of Duchenne muscular dystrophy (DMD), a severe and progressive disease resulting in premature death. However, more knowledge on the pharmacokinetics of new AON drug candidates is desired for effective application in the clinic. We assessed the feasibility of using...
article 2017
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Wegler, C. (author), Gaugaz, F.Z. (author), Andersson, T.B. (author), Wiśniewski, J.R. (author), Busch, D. (author), Gröer, C. (author), Oswald, S. (author), Norén, A. (author), Weiss, F. (author), Hammer, H.S. (author), Joos, T.O. (author), Poetz, O. (author), Achour, B. (author), Rostami-Hodjegan, A. (author), van de Steeg, E. (author), Wortelboer, H.M. (author), Artursson, P. (author)
Many different methods are used for mass-spectrometry-based protein quantification in pharmacokinetics and systems pharmacology. It has not been established to what extent the results from these various methods are comparable. Here, we compared six different mass spectrometry-based proteomics methods by measuring the expression of clinically...
article 2017
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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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Raaphorst, R.M. (author), Savolainen, H. (author), Cantore, M. (author), van de Steeg, E. (author), van Waarde, A. (author), Colabufo, N.A. (author), Elsinga, P.H. (author), Lammertsma, A.A. (author), Windhorst, A.D. (author), Luurtsema, G. (author)
Positron emission tomography (PET) imaging of P-glycoprotein (P-gp) in the blood-brain barrier can be important in neurological diseases where P-gp is affected, such as Alzheimer’s disease. Radiotracers used in the imaging studies are present at very small, nanomolar, concentration, whereas in vitro assays where these tracers are characterized,...
article 2017
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Mooij, M.G. (author), van de Steeg, E. (author), van Rosmalen, J. (author), Windster, J.D. (author), de Koning, B.A.E. (author), Vaes, W.H.J. (author), van Groen, B.D. (author), Tibboel, D. (author), Wortelboer, H.M. (author), de Wildt, S.N. (author)
Human hepatic membrane-embedded transporter proteins are involved in trafficking endogenous and exogenous substrates. Even though impact of transporters on pharmacokinetics is recognized, little is known on maturation of transporter protein expression levels, especially during early life. We aimed to study the protein expression of 10...
article 2016
Searched for: author:"van de Steeg, E."
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