André B. P. van Kuilenburg

Learn More
Dihydropyrimidine dehydrogenase (DPD) deficiency is an infrequently described autosomal recessive disorder of the pyrimidine degradation pathway and can lead to mental and motor retardation and convulsions. DPD deficiency is also known to cause a potentially lethal toxicity following administration of the antineoplastic agent 5-fluorouracil. In an ongoing(More)
The effect of the CTP synthetase inhibitor cyclopentenyl cytosine (CPEC) on the metabolism and cytotoxicity of 2′,2′-difluorodeoxycytidine (dFdC, gemcitabine) and the expression and activity of deoxycytidine kinase (dCK) was studied in human neuroblastoma cell lines. The cytotoxicity of dFdC and CPEC was studied in a panel of MYCN-amplified and(More)
Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-fluorouracil (5FU), and it is suggested that patients with a partial deficiency of this enzyme are at risk from developing a severe 5FU-associated toxicity. In this study, we demonstrated that a lethal toxicity after a treatment with 5FU was attributable to(More)
Colorectal cancer (CRC) is the leading cause of cancer death among human around the world. The vitamin D receptor gene (VDR) is a member of the nuclear receptor super family, which is expressed in the tissue of gastrointestinal tract, known to modulate the rate of cell proliferation. We aimed to investigate the genotype and allele frequencies and(More)
We identified a novel missense mutation, c.424G>C (p.Val142Leu) in PRPS1 in a patient with uric acid overproduction without gout but with developmental delay, hypotonia, hearing loss, and recurrent respiratory infections. The uric acid overproduction accompanying this combination of symptoms suggests that the patient presented with(More)
The experimental anticancer drug cyclopentenyl cytosine (CPEC) was associated with cardiotoxicity in a phase I study. The aim of the present study was twofold; first we investigated whether the observed effects could be reproduced in in-vitro and in-vivo rat models. Second, we intended to investigate the underlying mechanism of the possible cardiotoxicity(More)
Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of the pyrimidine bases uracil, thymine and the antineoplastic agent 5-fluorouracil. Genetic variations in the gene encoding DPD (DPYD) have emerged as predictive risk alleles for 5FU-associated toxicity. Here we report an in-depth analysis of genetic variants in(More)
Dihydropyrimidine dehydrogenase (DPD) is a critical determinant of 5-fluorouracil pharmacology, and reduced activity of DPD as a result of deleterious polymorphisms in the gene encoding DPD (DPYD) can result in severe treatment-related toxicity. Dosing recommendations to individualize treatment have been provided for three DPYD variants (DPYD*2A, c.2846A>T,(More)
t Thiss paper describes the effects of cyclopentenyl cytosine (CPEC) on the proliferation and cell-cyclee distribution of the SK-N-BE(2)c and SK-N-SH neuroblastoma cell lines, as well as theirr ability to recover from treatment with CPEC. The IC5o value of SK-N-BE(2)c for CPEC, determinedd after 48 h, was 80 nM. SK-N-BE(2)c cells showed a time and(More)
t Inn this paper, it is demonstrated that al\-trans, 9-cis and 13-cis retinoic acid (RA) decreasedd the sensitivity of SK-N-BE(2)c neuroblastoma cells towards the chemotherapeutic agentt cyclopentenyl cytosine (CPEC), a potent inhibitor of CTP synthetase. RA attenuated CPEC-inducedd apoptosis as reflected by a decreased caspase-3 induction. RA decreased the(More)