Author
Ron H.N. van Schaik
Other affiliations: Erasmus University Medical Center
Bio: Ron H.N. van Schaik is an academic researcher from Erasmus University Rotterdam. The author has contributed to research in topics: Population & Medicine. The author has an hindex of 60, co-authored 302 publications receiving 13286 citations. Previous affiliations of Ron H.N. van Schaik include Erasmus University Medical Center.
Topics: Population, Medicine, Pharmacogenetics, Pharmacogenomics, Tacrolimus
Papers published on a yearly basis
Papers
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Erasmus University Medical Center1, University of Gothenburg2, University of Tampere3, Complutense University of Madrid4, King Juan Carlos University5, Memorial Sloan Kettering Cancer Center6, university of lille7, RMIT University8, Helsinki University Central Hospital9, Queen Mary University of London10
TL;DR: In this update the ERSPC confirms a substantial reduction in prostate cancer mortality attributable to testing of PSA, with a substantially increased absolute effect at 13 years compared with findings after 9 and 11 years.
1,288 citations
TL;DR: The calcineurin inhibitors cyclosporine (INN, ciclosporin) and tacrolimus have a narrow therapeutic index and show considerable interindividual variability in their pharmacokinetics.
Abstract: Background
The calcineurin inhibitors cyclosporine (INN, ciclosporin) and tacrolimus have a narrow therapeutic index and show considerable interindividual variability in their pharmacokinetics. The low oral bioavailability of calcineurin inhibitors is thought to result from the actions of the metabolizing enzymes cytochrome P450 (CYP) 3A4 and CYP3A5 and the multidrug efflux pump P-glycoprotein, encoded by MDR-1.
Objective
Our objective was to determine the role of genetic polymorphisms in CYP3A4, CYP3A5, and MDR-1 with respect to interindividual variability in cyclosporine and tacrolimus pharmacokinetics.
Methods
Kidney transplant recipients receiving cyclosporine (n = 110) or tacrolimus (n = 64) were genotyped for CYP3A4*1B and *3, CYP3A5*3 and *6, and MDR-1 C3435T. Dose-adjusted trough levels were determined and correlated with the corresponding genotype.
Results
Tacrolimus dose-adjusted trough levels were higher in CYP3A5*3/*3 patients (n = 45) than in *1/*3 plus *1/*1 patients (n = 17), as follows: median and range, 94 (34-398) ng/mL per mg/kg versus 61 (37-163) ng/mL per mg/kg (P < .0001, Mann-Whitney test). CYP3A4*1B allele carriers (n = 10) had lower tacrolimus dose-adjusted trough levels compared with those in patients with the wild-type (*1/*1) genotype (n = 54): median and range, 57 (40-163) ng/mL per mg/kg versus 89 (34-398) ng/mL per mg/kg) (P = .003, Mann-Whitney test). No evidence was found supporting a role for the MDR-1 C3435T polymorphism in tacrolimus dose requirement. None of the polymorphisms studied correlated with cyclosporine dose-adjusted predose concentrations.
Conclusion
As a group, patients with the CYP3A5*3/*3 genotype require less tacrolimus to reach target predose concentrations compared with CYP3A5*1 allele carriers, whereas CYP3A4*1B carriers require more tacrolimus to reach target trough concentrations compared with CYP3A4*1 homozygotes.
Clinical Pharmacology & Therapeutics (2003) 74, 245–254; doi: 10.1016/S0009-9236(03)00168-1
636 citations
Fredrick R. Schumacher1, Ali Amin Al Olama2, Sonja I. Berndt3, Sara Benlloch2 +204 more•Institutions (79)
TL;DR: A large meta-analysis combining genome-wide and custom high-density genotyping array data identifies 63 new susceptibility loci for prostate cancer, enhancing fine-mapping efforts and providing insights into the underlying biology of PrCa1.
Abstract: Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10−9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55–2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04–6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa1. A large meta-analysis combining genome-wide and custom high-density genotyping array data identifies 63 new susceptibility loci for prostate cancer, enhancing fine-mapping efforts and providing insights into the underlying biology.
585 citations
TL;DR: Tacrolimus is the mainstay immunosuppressant drug used after solid organ and hematopoietic stem cell transplantation as discussed by the authors, however, individuals who express CYP3A5 (extensive and intermediate metabolizers) generally have decreased dose-adjusted trough concentrations of tacromin as compared with those who are CYP 3A5 nonexpressers (poor metabolizers), possibly delaying achievement of target blood concentrations.
Abstract: Tacrolimus is the mainstay immunosuppressant drug used after solid organ and hematopoietic stem cell transplantation. Individuals who express CYP3A5 (extensive and intermediate metabolizers) generally have decreased dose-adjusted trough concentrations of tacrolimus as compared with those who are CYP3A5 nonexpressers (poor metabolizers), possibly delaying achievement of target blood concentrations. We summarize evidence from the published literature supporting this association and provide dosing recommendations for tacrolimus based on CYP3A5 genotype when known (updates at www.pharmgkb.org).
418 citations
TL;DR: The prostate health index may be useful in prostate cancer screening to decrease unnecessary biopsy in men 50 years old or older with prostate specific antigen 2 to 10 ng/ml and negative digital rectal examination with minimal loss in sensitivity.
383 citations
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TL;DR: This dissertation aims to provide a history of web exceptionalism from 1989 to 2002, a period chosen in order to explore its roots as well as specific cases up to and including the year in which descriptions of “Web 2.0” began to circulate.
Abstract: Kristian Thygesen∗ (Denmark)
Joseph S. Alpert∗ (USA)
Allan S. Jaffe (USA)
Bernard R. Chaitman (USA)
Jeroen J. Bax (The Netherlands)
David A. Morrow (USA)
Harvey D. White∗ (New Zealand)
Hans Mickley (Denmark)
Filippo Crea (Italy)
Frans Van de Werf (Belgium)
Chiara Bucciarelli-Ducci (
3,355 citations
TL;DR: These factors have been shown to substantially affect the biodistribution and blood circulation half-life of circulating nanoparticles by reducing the level of nonspecific uptake, delaying opsonization, and increasing the extent of tissue specific accumulation.
Abstract: Nanoparticle (NP) drug delivery systems (5−250 nm) have the potential to improve current disease therapies because of their ability to overcome multiple biological barriers and releasing a therapeutic load in the optimal dosage range. Rapid clearance of circulating nanoparticles during systemic delivery is a critical issue for these systems and has made it necessary to understand the factors affecting particle biodistribution and blood circulation half-life. In this review, we discuss the factors which can influence nanoparticle blood residence time and organ specific accumulation. These factors include interactions with biological barriers and tunable nanoparticle parameters, such as composition, size, core properties, surface modifications (pegylation and surface charge), and finally, targeting ligand functionalization. All these factors have been shown to substantially affect the biodistribution and blood circulation half-life of circulating nanoparticles by reducing the level of nonspecific uptake, de...
3,009 citations
TL;DR: The derivation of pluripotent embryonic stem (ES) cells from human blastocysts is described, providing a model to study early human embryology, an investigational tool for discovery of novel growth factors and medicines, and a potential source of cells for use in transplantation therapy.
Abstract: We describe the derivation of pluripotent embryonic stem (ES) cells from human blastocysts. Two diploid ES cell lines have been cultivated in vitro for extended periods while maintaining expression of markers characteristic of pluripotent primate cells. Human ES cells express the transcription factor Oct-4, essential for development of pluripotential cells in the mouse. When grafted into SCID mice, both lines give rise to teratomas containing derivatives of all three embryonic germ layers. Both cell lines differentiate in vitro into extraembryonic and somatic cell lineages. Neural progenitor cells may be isolated from differentiating ES cell cultures and induced to form mature neurons. Embryonic stem cells provide a model to study early human embryology, an investigational tool for discovery of novel growth factors and medicines, and a potential source of cells for use in transplantation therapy.
2,945 citations
TL;DR: Recent progress on drug metabolism activity profiles, interindividual variability and regulation of expression, and the functional and clinical impact of genetic variation in drug metabolizing P450s are reviewed.
2,832 citations
Harvard University1, University of Sheffield2, University of Warwick3, Vita-Salute San Raffaele University4, University of Bern5, St James's University Hospital6, Katholieke Universiteit Leuven7, University of Aberdeen8, Aberdeen Royal Infirmary9, Cardiff University10, Netherlands Cancer Institute11, Erasmus University Rotterdam12
TL;DR: The 2016 EAU-STRO-IOG Prostate Cancer (PCa) Guidelines present updated information on the diagnosis, and treatment of clinically localised prostate cancer and reflect the multidisciplinary nature of PCa management.
2,767 citations