A5010266465- Pharmacogenetics and Drug Metabolism
- Colorectal Cancer Treatments and Studies
- Renal Transplantation Outcomes and Treatments
- Pharmacological Effects and Toxicity Studies
- Cancer Treatment and Pharmacology
- DNA Repair Mechanisms
- Cancer Genomics and Diagnostics
- Estrogen and related hormone effects
- Drug Transport and Resistance Mechanisms
- Cancer, Hypoxia, and Metabolism
- Cancer therapeutics and mechanisms
- Glutathione Transferases and Polymorphisms
- Immune cells in cancer
- Monoclonal and Polyclonal Antibodies Research
- Carcinogens and Genotoxicity Assessment
- Pharmaceutical studies and practices
- Inflammatory mediators and NSAID effects
- Salmonella and Campylobacter epidemiology
- Growth Hormone and Insulin-like Growth Factors
- HER2/EGFR in Cancer Research
- Lung Cancer Treatments and Mutations
- PI3K/AKT/mTOR signaling in cancer
- Organ Transplantation Techniques and Outcomes
- Molecular Biology Techniques and Applications
- Acute Lymphoblastic Leukemia research
Leiden University Medical Center
2009-2018
Leiden University
1995-2015
University Medical Center
2015
Loyola University Medical Center
2014
PharmacoGenetics (China)
2009-2013
Erasmus University Rotterdam
2009
University Medical Center Groningen
2009
Erasmus MC
2009
The Netherlands Cancer Institute
2009
China Medical University
2008
To identify genetic markers in the pharmacokinetic and pharmacodynamic pathways of sunitinib that predispose for development toxicities: thrombocytopenia, leukopenia, mucosal inflammation, hand-foot syndrome, any toxicity according to National Cancer Institute Common Toxicity Criteria higher than grade 2.A multicenter pharmacogenetic association study was performed 219 patients treated with single-agent sunitinib. A total 31 single nucleotide polymorphisms 12 candidate genes, together...
To prevent acute rejection episodes, it is important to reach adequate tacrolimus (TRL) exposure early after kidney transplantation. With a better understanding of the high variability in pharmacokinetics TRL, starting dose can be individualized, resulting reduction adjustments obtain target exposure. A population pharmacokinetic analysis was performed estimate effects demographic factors, hematocrit, serum albumin concentration, prednisolone dose, TRL interval, polymorphisms genes coding...
Cyclosporine, everolimus, and tacrolimus are the cornerstone of immunosuppressive therapy in renal transplantation. These drugs characterized by narrow therapeutic windows, highly variable pharmacokinetics (PK), metabolism CYP3A enzymes. Recently, decreased activity allele, CYP3A4*22, was described as a potential predictive marker for CYP3A4 activity. This study investigated effect CYP3A5*3, combined genotypes on cyclosporine, PK transplant patients. CYP3A4*22 carriers showed significant...
To investigate which hairpin structures within the 5′ untranslated region of hepatitis C virus (HCV) are necessary for cap‐independent translation, mutants were constructed that lack one or more structures. Here we demonstrate, by constructing precisely defined deletion mutants, with exception most located structure, on shows an increase each predicted hairpins is found to be essential translation. In addition, demonstrate HCV 5′UTR driven translation stimulated poliovirus 2A pro co‐expression.
Bicistronic RNAs containing the 373-nucleotide-long 5' nontranslated region (NTR) of classical swine fever virus (CSFV) genome as intercistronic spacer were used to show presence an internal ribosome entry site (IRES) in end CSFV genome. By coexpression poliovirus 2A protease it was demonstrated that NTR-driven translation is independent functional eukaryotic initiation factor eIF-4F. Deletion analysis indicated border IRES located between nucleotides 28 and 66. The role a proposed...
In a recent randomized phase III clinical trial in metastatic colorectal cancer patients, the addition of anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) cetuximab to bevacizumab and chemotherapy resulted decreased progression-free survival, particular for patients with high-affinity FcγRIIIA.The presence natural killer (NK) cells type 2 (M2) macrophages was determined by immunohistochemistry, using antibodies lineage-specific markers NKp46 CD68 CD163, respectively....
Cytochrome P450 2D6 (CYP2D6) is among the most important genes involved in drug metabolism. Specific variants are associated with changes enzyme's amount and activity. Multiple technologies exist to determine these variants, like AmpliChip CYP450 test, Taqman qPCR, or Second-Generation Sequencing, however, sequence homology between cytochrome pseudogene CYP2D7 impairs reliable CYP2D6 genotyping, variant phasing cannot accurately be determined using assays. To circumvent this, we sequenced...
The aim of the study was to investigate associations between UGT1A1*28 genotype and (1) response rates, (2) febrile neutropenia (3) dose intensity in patients with metastatic colorectal cancer treated irinotecan. determined 218 receiving irinotecan (either first-line therapy capecitabine or second-line as monotherapy) for cancer. TA7 homozygotes combination had a higher incidence (18.2%) compared other genotypes (TA6/TA6 : 1.5%; TA6/TA7 6.5%, P=0.031). heterozygotes monotherapy also suffered...
Clinical response to methotrexate (MTX) treatment differs among rheumatoid arthritis patients. Genetic variation can partly account for this phenomenon. In study, functional polymorphisms in genes related the mechanism of action MTX or immunopathogenesis were studied association with outcome a Dutch cohort patients early arthritis. Furthermore, tests replication previous research on these genetic variants performed according reported end points.Seven seven analyzed 205 genotyped active All...
The current study investigates whether or not functional polymorphisms in the ATP-binding cassette transporter gene ABCG2 might affect gefitinib activity and/or toxicity non-small-cell lung cancer (NSCLC) patients.Towards this end, and expression were assessed DNA tumors from 94 NSCLC patients treated with gefitinib, whereas their associations toxicity/response time-to-progression/overall survival evaluated using Pearson-χ(2) log-rank-test, respectively.Patients carrying an -15622T/T...
Breast cancer patients with absent or reduced CYP2D6 activity and consequently low endoxifen levels may benefit less from tamoxifen treatment. poor intermediate metabolizers need a personalized increased dose to achieve effective serum concentrations, without increasing toxicity. From prospective study population of early breast using (CYPTAM: NTR1509), 12 were selected included in one-step escalation during 2 months. The escalated was calculated by multiplying the individual's level at...
The once daily formulation of tacrolimus is an important immunosuppressive drug. Interpatient variability in metabolism has been related to genetic variation CYP3A4 and CYP3A5. However, liver transplantation, both donor recipient genotypes may affect pharmacokinetics. primary objective this study was investigate the effect CYP3A4*22 CYP3A5*3 on secondary develop a limited sampling model able accurately predict exposure. Stable transplant patients receiving (N = 66) were included. Population...
The purpose of this study was to evaluate single-nucleotide polymorphisms (SNPs) in genes encoding key metabolising enzymes or involved pharmacodynamics for possible associations with paclitaxel-induced peripheral neuropathy. population consists 188 women from the multicenter, randomised, phase II ATX trial (BOOG2006-06; EudraCT number 2006-006058-83) that received paclitaxel and bevacizumab without capecitabine as first-line palliative therapy HER2-negative metastatic breast cancer....
Coronaviruses synthesize a nested set of six to eight subgenomic (sg) mRNAs in infected cells. These are produced different, but constant, molar ratios. It is unclear which factors control the different levels sg mRNAs. To determine whether intergenic sequence (IS) involved mRNA synthesis could affect transcription efficiencies other ISs and this way regulate levels, we inserted multiple at positions into mouse hepatitis virus defective interfering RNA. Quantitation RNAs by identical...
Objective As no single nucleotide polymorphism has emerged as pivotal to predict the lack of efficacy and dose-limiting toxicities methotrexate (MTX), we evaluated contribution gene–gene interactions effects this prodrug in rheumatoid arthritis. Methods A total 255 patients treated with MTX for at least 3 months were assessed using European League Against Rheumatism response criteria or a physician's assessment patient's visual analog scale. Gastrointestinal neurological idiosyncrasies...
Recombinant human GH (rhGH) replacement in adults is aimed at improving signs and symptoms of the adult deficiency (GHD) syndrome. In children, a common polymorphism receptor (exon-3 deletion, d3GHR) increases response to rhGH replacement. The aim this study was assess effects on adults.Prospective intervention with during 1 yr (n = 99) subset 5 53).The presence d3GHR variant established GHD patients linked short-term long-term IGF-I, lipid metabolism, anthropometric parameters, bone mineral...
The insulin-like growth factor 1 (IGF-1) pathway is involved in cell and proliferation associated with tumorigenesis therapy resistance. This study aims to elucidate whether variation the IGF-1 predictive for pathologic response early HER2 negative breast cancer (BC) patients, taking part phase III NEOZOTAC trial, randomizing between 6 cycles of neoadjuvant TAC chemotherapy or without zoledronic acid.Formalin-fixed paraffin-embedded tissue samples pre-chemotherapy biopsies operation...
The aim of the study was to evaluate impact genomic deletion exon 3 GH receptor (d3GHR) on long-term clinical outcome acromegaly in a well-characterized cohort patients with remission acromegaly.We conducted cross-sectional study.The presence d3GHR polymorphism assessed 86 acromegalic disease control and related anthropometric parameters, cardiovascular risk factors, osteoarthritis, bone mineral density, colonic polyps diverticulae, dolichocolon.Fifty-one had two wild-type alleles (59%),...
Busulfan is used in preparative regimens prior to stem cell transplantation pediatric patients. There significant interpatient variability busulfan pharmacokinetics (PK) and exposure related outcome. To date, only polymorphisms genes encoding for glutathione-S-transferases were studied, but could explain a small portion of the PK.To investigate effect seven genetic markers on clearance ontogenesis these variants population.In an earlier study our group GSTA1, CYP2C19, CYP39A1, ABCB4, SLC22A4...