A5072840045- Biochemical and Molecular Research
- Metabolism and Genetic Disorders
- Colorectal Cancer Treatments and Studies
- Neonatal Health and Biochemistry
- Cancer therapeutics and mechanisms
- Neuroblastoma Research and Treatments
- Pancreatic and Hepatic Oncology Research
- Mitochondrial Function and Pathology
- Cytomegalovirus and herpesvirus research
- Lysosomal Storage Disorders Research
- HIV/AIDS drug development and treatment
- Cancer, Hypoxia, and Metabolism
- Congenital Heart Disease Studies
- Amino Acid Enzymes and Metabolism
- Cardiac Arrhythmias and Treatments
- Genetic Neurodegenerative Diseases
- RNA modifications and cancer
- Erythrocyte Function and Pathophysiology
- Acute Lymphoblastic Leukemia research
- Connective tissue disorders research
- Genetic factors in colorectal cancer
- Pancreatic function and diabetes
- Blood disorders and treatments
- Adrenal Hormones and Disorders
- Cardiac Valve Diseases and Treatments
University of Amsterdam
2016-2025
Amsterdam University Medical Centers
2018-2025
Dutch Cancer Society
2023-2025
Cancer Center Amsterdam
2023-2025
Emma Kinderziekenhuis
2010-2022
Amsterdam UMC Location University of Amsterdam
2010-2019
Leiden University Medical Center
2010-2017
Sint Franciscus Gasthuis
2017
The Netherlands Cancer Institute
2017
Pediatrics and Genetics
2017
6-Fluoro-3-hydroxy-2-pyrazinecarboxamide (T-705) is a novel antiviral compound with broad activity against influenza virus and diverse RNA viruses. Its active metabolite, T-705-ribose-5′-triphosphate (T-705-RTP), recognized by polymerase as substrate competing GTP, giving inhibition of viral synthesis lethal mutagenesis. Which enzymes perform the activation T-705 unknown. We here demonstrate that human hypoxanthine guanine phosphoribosyltransferase (HGPRT) converts into its...
Background Two recombinant enzymes (agalsidase alfa 0.2 mg/kg/every other week and agalsidase beta 1.0 week) have been registered for the treatment of Fabry disease (FD), at equal high costs. An independent international initiative compared clinical biochemical outcomes two enzymes. Methods In this multicentre retrospective cohort study, event rate, left ventricular mass index (LVMI), estimated glomerular filtration rate (eGFR), antibody formation globotriaosylsphingosine (lysoGb3) levels...
Deficiency in dihydropyrimidine dehydrogenase (DPD) enzyme is the main cause of severe and lethal fluoropyrimidine-related toxicity. Various approaches have been developed for DPD-deficiency screening, including DPYD genotyping phenotyping. The goal this prospective observational study was to perform exhaustive exome sequencing examine relationships between variants toxicity advanced breast cancer patients receiving capecitabine.Two-hundred forty-three were analysed (88.5% capecitabine...
Despite enzyme replacement therapy, disease progression is observed in patients with Fabry disease. Identification of factors that predict needed to refine guidelines on initiation and cessation therapy. To study the association potential biochemical clinical prognostic course (clinical events, cardiac renal disease) we retrospectively evaluated 293 treated from three international centers excellence. As expected, age, sex phenotype were important predictors event rate. Clinical events...
We report an inborn error of metabolism caused by expansion a GCA-repeat tract in the 5' untranslated region gene encoding glutaminase (GLS) that was identified through detailed clinical and biochemical phenotyping, combined with whole-genome sequencing. The observed three unrelated patients who presented early-onset delay overall development, progressive ataxia, elevated levels glutamine. In addition to one patient also showed cerebellar atrophy. associated relative deficiency GLS messenger...
In clinical practice, 25–30% of the patients treated with fluoropyrimidines experience severe fluoropyrimidine‐related toxicity. Extensively clinically validated DPYD genotyping tests are available to identify at risk toxicity due decreased activity dihydropyrimidine dehydrogenase (DPD), rate limiting enzyme in fluoropyrimidine metabolism. April 2020, European Medicines Agency recommended that, as an alternative for genotype‐based testing DPD deficiency, also phenotype based on pretreatment...
Abstract Dihydropyrimidine dehydrogenase (DPD) is the initial and rate‐limiting enzyme in catabolism of 5‐fluorouracil (5‐FU), it suggested that patients with a partial deficiency this are at risk developing severe 5‐FU‐associated toxicity. We evaluated importance DPD deficiency, gender presence IVS14+1G>A mutation etiology 5‐FU In 61% cases, decreased activity could be detected peripheral blood mononuclear cells. Furthermore, number females (65%) total group appeared to higher than males...
Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in catabolism of 5-fluorouracil (5FU) a DPD deficiency increasingly being recognized as an important pharmacogenetic factor aetiology severe 5FU-associated toxicity. In this study, we evaluated activity prevalence common splice site mutation IVS14 + 1G>A tumour patients suffering from grade 3-4 toxicity after administration 5FU. was measured with radiochemical assay screening for presence performed by restriction...
A condition called thymine uracilurea has been described that is due to a lack of dihydropyrimidine dehydrogenase (DPD) activity. Cancer patients experiencing acute 5-fluorouracil toxicity also have lower-than-normal DPD activities. However, date, the molecular basis this disorder not addressed. In study, phenotype and genotype family presents patient showing no activity was determined. Fibroblast mRNAs from four members were subjected reverse transcriptase polymerase chain reaction (RT-PCR)...
Dihydropyrimidine dehydrogenase (DPD) is the initial enzyme acting in catabolism of widely used antineoplastic agent 5-fluorouracil (5FU). DPD deficiency known to cause a potentially lethal toxicity following administration 5FU. Here, we report novel genetic mechanisms underlying patients presenting with grade III/IV 5FU-associated toxicity. In one patient genomic DPYD deletion exons 21-23 was observed. five deep intronic mutation c.1129-5923C>G identified creating cryptic splice donor site....
The present article summarizes the discussions of 3rd European Science Foundation–University Barcelona (ESF–UB) Conference in Biomedicine on Pharmacogenetics and Pharmacogenomics, which was held June 2010 Spain. It focused practical applications routine medical practice. We provide recommendations for ten different clinical situations, that have either been approved or not by regulatory agencies. propose some comments might accompany results these tests, indicating best drug doses to be...