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Profiling of Nutrient Transporter Expression in Human Stem Cell-Derived Cardiomyocytes Exposed to Tyrosine Kinase Inhibitor Anticancer Drugs Using RBD Ligands.
Li, Jianliang; Cousin, Christelle; Tinkler, Hayley; Touhami, Jawida; Petit, Vincent; Thomas, Nick.
Affiliation
  • Li J; GE Healthcare, The Maynard Centre, Forest Farm, Whitchurch, Cardiff, UK.
  • Cousin C; METAFORA Biosystems, Pépinière Genopole Entreprises, Evry, France.
  • Tinkler H; GE Healthcare, The Maynard Centre, Forest Farm, Whitchurch, Cardiff, UK.
  • Touhami J; METAFORA Biosystems, Pépinière Genopole Entreprises, Evry, France.
  • Petit V; METAFORA Biosystems, Pépinière Genopole Entreprises, Evry, France.
  • Thomas N; GE Healthcare, The Maynard Centre, Forest Farm, Whitchurch, Cardiff, UK nick.thomas@ge.com.
J Biomol Screen ; 19(8): 1185-92, 2014 Sep.
Article in En | MEDLINE | ID: mdl-24809354
We applied a novel profiling approach using receptor binding domain (RBD) ligands to cell surface domains of a panel of nutrient transporters to characterize the impact of a number of tyrosine kinase inhibitor anticancer drugs on human stem cell-derived cardiomyocytes. High-content screening and flow cytometry analysis showed diagnostic changes in nutrient transporter expression correlating with glycolysis and oxidative phosphorylation-based cell metabolism in glucose and galactose media. Cluster analysis of RBD binding signatures of drug-treated cells cultured in glucose medium showed good correlation with sensitization of mitochondrial toxicity in cells undergoing oxidative phosphorylation in galactose medium. These data demonstrate the potential for RBD ligands as profiling tools to improve the clinical predictivity of in vitro cell assays for drug toxicity.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Protein-Tyrosine Kinases / Carrier Proteins / Myocytes, Cardiac / Protein Kinase Inhibitors / Antineoplastic Agents Limits: Humans Language: En Journal: J Biomol Screen Journal subject: BIOLOGIA MOLECULAR Year: 2014 Document type: Article Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Protein-Tyrosine Kinases / Carrier Proteins / Myocytes, Cardiac / Protein Kinase Inhibitors / Antineoplastic Agents Limits: Humans Language: En Journal: J Biomol Screen Journal subject: BIOLOGIA MOLECULAR Year: 2014 Document type: Article Country of publication: United States