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Start Over Author "M E Dolan" Journal clinical pharmacology and therapeutics
2 results on '"M E Dolan"'

1. Integrating Cell-Based and Clinical Genome-Wide Studies to Identify Genetic Variants Contributing to Treatment Failure in Neuroblastoma Patients

Author

Amy L. Stark, Wendy B. London, Navin Pinto, Sharon J. Diskin, Nancy J. Cox, M E Dolan, Susan L. Cohn, Hae Kyung Im, Nirav N. Antao, Eric R. Gamazon, Jamie Myers, Anuar Konkashbaev, John M. Maris, and Susan M. Ludeman

Subjects
Oncology, Quality Control, medicine.medical_specialty, ZPBP2, Single-nucleotide polymorphism, Genome-wide association study, Biology, Malignancy, Bioinformatics, Real-Time Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Risk Assessment, Article, Disease-Free Survival, Cohort Studies, Neuroblastoma, Polymorphism (computer science), Internal medicine, Cell Line, Tumor, Genetic variation, medicine, Humans, Pharmacology (medical), Genetic Predisposition to Disease, Treatment Failure, RNA, Small Interfering, cell-based models, Child, Antineoplastic Agents, Alkylating, Cyclophosphamide, Genetic association, Pharmacology, pharmacogenomics, Cyclohexylamines, expression quantitative trait loci, Brain Neoplasms, Cancer, Genetic Variation, IKZF3, medicine.disease, 3. Good health, Phenotype, Drug Resistance, Neoplasm, Genome-Wide Association Study
Abstract

High-risk neuroblastoma is an aggressive malignancy, with high rates of treatment failure. We evaluated genetic variants associated with in vitro sensitivity to two derivatives of cyclophosphamide for association with clinical response in a separate replication cohort of neuroblastoma patients (n = 2,709). To determine sensitivity, lymphoblastoid cell lines (LCLs) were exposed to increasing concentrations of 4-hydroperoxycyclophosphamide (4HC; n = 422) and phosphoramide mustard (PM; n = 428). Genome-wide association studies were performed to identify single-nucleotide polymorphisms (SNPs) associated with sensitivity to 4HC and PM. SNPs consistently associated with LCL sensitivity were analyzed for associations with event-free survival (EFS) in patients. Two linked SNPs, rs9908694 and rs1453560, were found to be associated with (i) sensitivity to PM in LCLs across populations and (ii) EFS in all patients (P = 0.01) and within the high-risk subset (P = 0.05). Our study highlights the value of cell-based models to identify candidate variants that may predict response to treatment in patients with cancer. Clinical Pharmacology & Therapeutics (2014); 95 6, 644–652. doi:10.1038/clpt.2014.37

Published
2014

2. The pharmacogenetics research network: from SNP discovery to clinical drug response

Author

Dan M. Roden, Scott T. Weiss, Rachel F. Tyndale, David A. Flockhart, Alan R. Shuldiner, Kelan G. Tantisira, Daniel F. Hayes, M E Dolan, Ronald M. Krauss, Liewei Wang, Issam Zineh, Richard M. Weinshilboum, Neal L. Benowitz, M. V. Relling, Teri E. Klein, Claire M. Brett, Catherine Schaefer, Kathleen M. Giacomini, Victor I. Reus, Deanna L. Kroetz, Howard L. McLeod, Anne T. Nguyen, Mark J. Ratain, Julie A. Johnson, Todd C. Skaar, and Russ B. Altman

Subjects
Drug, Lung Diseases, PharmGKB, Informatics, Substance-Related Disorders, media_common.quotation_subject, Disease, Pharmacology, Bioinformatics, Polymorphism, Single Nucleotide, Article, Drug Therapy, Neoplasms, SNP, Medicine, Animals, Humans, Pharmacology (medical), media_common, business.industry, Addiction, Cardiovascular Agents, Pharmaceutical Preparations, Cardiovascular Diseases, Pharmacogenetics, Pharmacogenomics, business, Carrier Proteins, Platelet Aggregation Inhibitors
Abstract

The NIH Pharmacogenetics Research Network (PGRN) is a collaborative group of investigators with a wide range of research interests, but all attempting to correlate drug response with genetic variation. Several research groups concentrate on drugs used to treat specific medical disorders (asthma, depression, cardiovascular disease, addiction of nicotine, and cancer), whereas others are focused on specific groups of proteins that interact with drugs (membrane transporters and phase II drug-metabolizing enzymes). The diverse scientific information is stored and annotated in a publicly accessible knowledge base, the Pharmacogenetics and Pharmacogenomics Knowledge base (PharmGKB). This report highlights selected achievements and scientific approaches as well as hypotheses about future directions of each of the groups within the PGRN. Seven major topics are included: informatics (PharmGKB), cardiovascular, pulmonary, addiction, cancer, transport, and metabolism.

Published
2007

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