Genomes and Genes
Edward L LeCluyse
Affiliation: The Hamner Institutes for Health Sciences
- Organotypic liver culture models: meeting current challenges in toxicity testingEdward L LeCluyse
The Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC, USA
Crit Rev Toxicol 42:501-48. 2012..In the future, a balanced approach between sample throughput and biological relevance should provide better in vitro tools that are complementary with animal testing and assist in conducting more predictive human risk assessment...
- Xenobiotic-metabolizing enzyme and transporter gene expression in primary cultures of human hepatocytes modulated by ToxCast chemicalsDaniel M Rotroff
US Environmental Protection Agency, Office of Research and Development, National Center for Computational Toxicology, Research Triangle Park, North Carolina, USA
J Toxicol Environ Health B Crit Rev 13:329-46. 2010..Significant relative risk associations with rodent in vivo chronic toxicity effects are reported for the five major receptor pathways. These gene expression data are being incorporated into the larger ToxCast predictive modeling effort...
- Liver biomarker and in vitro assessment confirm the hepatic origin of aminotransferase elevations lacking histopathological correlate in beagle dogs treated with GABAA receptor antagonist NP260Alison H Harrill
College of Public Health, The University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA The Hamner University of North Carolina Institute for Drug Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA Electronic address
Toxicol Appl Pharmacol 277:131-7. 2014..Taken together, the data indicate that a diagnostic biomarker approach, coupled with sensitive in vitro screening strategies, may facilitate interpretation of toxicity potential when an adaptive event masks the underlying toxicity. ..
- Incorporating human dosimetry and exposure into high-throughput in vitro toxicity screeningDaniel M Rotroff
National Center for Computational Toxicology, Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA
Toxicol Sci 117:348-58. 2010..Importantly, these tools are necessary to move beyond hazard rankings to estimates of possible in vivo responses based on in vitro screens...
- Cross-species comparisons of transcriptomic alterations in human and rat primary hepatocytes exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxinMichael B Black
The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709, USA
Toxicol Sci 127:199-215. 2012..The results provide evidence for divergent cross-species gene expression changes in response to TCDD and are consistent with epidemiological and clinical evidence showing humans to be less sensitive to TCDD-induced hepatotoxicity...
- Human CYP2C8 is transcriptionally regulated by the nuclear receptors constitutive androstane receptor, pregnane X receptor, glucocorticoid receptor, and hepatic nuclear factor 4alphaStephen S Ferguson
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
Mol Pharmacol 68:747-57. 2005..In summary, the present studies show that CAR, PXR, GR, and HNF4alpha can regulate CYP2C8 expression and identify specific cis-elements within the promoter that control these regulatory pathways...
- Isolation and culture of primary hepatocytes from resected human liver tissueEdward L LeCluyse
CellzDirect Invitrogen Corp, Durham, NC, USA
Methods Mol Biol 640:57-82. 2010....
- Co-culture of Hepatocytes and Kupffer Cells as an In Vitro Model of Inflammation and Drug-Induced HepatotoxicityKelly A Rose
The Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709
J Pharm Sci 105:950-64. 2016..These results indicate the utility of the HKCC model system to discern compound-specific effects that may lead to enhanced or mitigate hepatocellular injury due to innate or adaptive immune responses. ..
- A map of the PPARα transcription regulatory network for primary human hepatocytesPatrick D McMullen
The Hamner Institutes for Health Sciences, Institute for Chemical Safety Sciences, 6 Davis Drive, PO Box 12137, Research Triangle Park, NC 27709, USA
Chem Biol Interact 209:14-24. 2014....
- CYP3A induction by N-hydroxyformamide tumor necrosis factor-alpha converting enzyme/matrix metalloproteinase inhibitors use of a pregname X receptor activation assay and primary hepatocyte culture for assessing induction potential in humansTimothy K Tippin
Drug Metabolism and Pharmacokinetics Department, Metabolic and Viral Diseases Center of Excellence in Drug Discovery, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA
Drug Metab Dispos 31:870-7. 2003..In conclusion, GW3333 is a potential inducer of CYP3A expression in vivo in humans, but other N-hydroxyformamides are less likely to induce CYP3A...