A5027838693- Chemotherapy-induced cardiotoxicity and mitigation
- Acute Lymphoblastic Leukemia research
- Cancer therapeutics and mechanisms
- Childhood Cancer Survivors' Quality of Life
- Pharmaceutical studies and practices
- Lung Cancer Research Studies
- DNA Repair Mechanisms
- Hearing, Cochlea, Tinnitus, Genetics
- Cholesterol and Lipid Metabolism
- Pharmacogenetics and Drug Metabolism
- Drug Transport and Resistance Mechanisms
- Genetic Neurodegenerative Diseases
- Plant Molecular Biology Research
- Cytomegalovirus and herpesvirus research
- Neuroblastoma Research and Treatments
- PARP inhibition in cancer therapy
- Lipid metabolism and biosynthesis
- Mitochondrial Function and Pathology
- Genetics and Neurodevelopmental Disorders
- CAR-T cell therapy research
- Hematopoietic Stem Cell Transplantation
- Peroxisome Proliferator-Activated Receptors
- Viral Infectious Diseases and Gene Expression in Insects
- Pharmacology and Obesity Treatment
- Genetic Associations and Epidemiology
Princess Máxima Center
2018-2022
Hospital for Sick Children
2020
Radboud University Nijmegen
2014-2018
Radboud University Medical Center
2014-2018
Antwerp University Hospital
2018
University of British Columbia
2003-2017
Child and Family Research Institute
2006-2017
Rogers (United States)
2011
Montreal Heart Institute
2011
University of British Columbia Hospital
2010
Anthracycline-induced cardiotoxicity (ACT) is a serious adverse drug reaction limiting anthracycline use and causing substantial morbidity mortality. Our aim was to identify genetic variants associated with ACT in patients treated for childhood cancer.We carried out study of 2,977 single-nucleotide polymorphisms (SNPs) 220 key biotransformation genes discovery cohort 156 anthracycline-treated children from British Columbia, replication second 188 across Canada further the top SNP third 96...
Statins reduce cardiovascular morbidity and mortality in appropriately selected patients. However, statin-associated myopathy is a significant risk associated with these agents. Recently, variation the SLCO1B1 gene was reported to predict simvastatin-associated myopathy. The aim of this study replicate association rs4149056 variant severe cohort patients using variety statin medications investigate specific types. We identified 25 cases 84 controls matched for age, gender, type dose. not...
Abstract Background . The use of anthracyclines as effective antineoplastic drugs is limited by the occurrence cardiotoxicity. Multiple genetic variants predictive anthracycline‐induced cardiotoxicity (ACT) in children were recently identified. current study was aimed to assess replication these findings an independent cohort children. Procedure Twenty‐three tested for association with ACT 218 patients. Predictive models including and clinical risk factors constructed original assessed...
Cisplatin is a widely used chemotherapeutic agent for the treatment of solid tumors. A serious complication cisplatin permanent hearing loss. The aim this study was to replicate previous genetic findings in an independent cohort 155 pediatric patients. Associations were replicated variants TPMT (rs12201199, P = 0.0013, odds ratio (OR) 6.1) and ABCC3 (rs1051640, 0.036, OR 1.8). predictive model combining TPMT, ABCC3, COMT with clinical variables (patient age, vincristine treatment, germ-cell...
Aim: To identify novel variants associated with anthracycline-induced cardiotoxicity and to assess these in a genotype-guided risk prediction model. Patients & methods: Two cohorts treated for childhood cancer (n = 344 218, respectively) were genotyped 4578 SNPs drug ADME toxicity genes. Results: Significant associations identified SLC22A17 (rs4982753; p 0.0078) SLC22A7 (rs4149178; 0.0034), replication the second cohort (p 0.0071 0.047, respectively). Additional evidence was found SULT2B1...
The addition of fludarabine to cyclophosphamide as a lymphodepleting regimen prior CD19 chimeric antigen receptor (CAR) T-cell therapy significantly improved outcomes in patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). Fludarabine exposure, previously shown be highly variable when dosing is based on body surface area (BSA), predictor for survival allogeneic hematopoietic cell transplantation (allo-HCT). Hence, we hypothesized that an optimal exposure might...
Human herpes virus 6 (HHV6) is known to reactivate after hematopoietic stem cell transplantation (HSCT), and has been suggested be associated with severe clinical manifestations in adults. The significance children remains unclear. We investigated the incidence of HHV6 reactivation relation HSCT-associated morbidity mortality children. Between January 2004 May 2006, 58 pediatric patients, median age 7.6 years (range: 0.1-18.1 years), received their first allogeneic HSCT. After HSCT, HHV6,...
ATP binding cassette transporter A1 (ABCA1) is a widely expressed lipid essential for the generation of HDL. ABCA1 particularly abundant in liver, suggesting that liver may play major role HDL homeostasis. To determine how hepatic affects plasma cholesterol levels, we treated mice with an adenovirus (Ad)-expressing human under control cytomegalovirus promoter. Treated showed dose-dependent increase protein, ranging from 1.2-fold to 8.3-fold using doses 5 x 108 1.5 109 pfu, maximal expression...
Mutations in ATP-binding cassette transporter A1 ( ABCA1 ) cause Tangier disease and familial hypoalphalipoproteinemia, resulting low to absent plasma high-density lipoprotein cholesterol levels. However, wide variations clinical lipid phenotypes are observed patients with mutations . We hypothesized that the various would be direct result of discrete differing effects on function. To determine whether there is a correlation between phenotypes, we generated vitro 15 missense have been...
Abstract Background Anthracyclines are a class of highly effective chemotherapeutic drugs commonly used to treat cancer patients. Anthracyclines, however, associated with the development serious adverse reactions, including anthracycline‐induced cardiotoxicity (ACT). It is not possible, within current practice, accurately individualize treatment minimize risk. Procedure Recently, genetic variants have been risk ACT in children. Building on these findings and related test, predictive model...