0000000000656523

AUTHOR

Joost H.m. Van Delft

showing 2 related works from this author

Human Embryonic Stem Cell Derived Hepatocyte-Like Cells as a Tool for In Vitro Hazard Assessment of Chemical Carcinogenicity

2011

Hepatocyte-like cells derived from the differentiation of human embryonic stem cells (hES-Hep) have potential to provide a human relevant in vitro test system in which to evaluate the carcinogenic hazard of chemicals. In this study, we have investigated this potential using a panel of 15 chemicals classified as noncarcinogens, genotoxic carcinogens, and nongenotoxic carcinogens and measured whole-genome transcriptome responses with gene expression microarrays. We applied an ANOVA model that identified 592 genes highly discriminative for the panel of chemicals. Supervised classification with these genes achieved a cross-validation accuracy of > 95%. Moreover, the expression of the response g…

Carcinogenicity TestsCellular differentiationCell Culture TechniquesGene Expressionsystems toxicologyComputational biologyBiologyToxicologymedicine.disease_causeHazardous SubstancesTranscriptomecomputational biologyCytochrome P-450 Enzyme SystemNaturvetenskapmedicinecarcinogenicityHumansMicroscopy Phase-ContrastEmbryonic Stem CellsCarcinogenAnalysis of VarianceDose-Response Relationship DrugReverse Transcriptase Polymerase Chain ReactionMicroarray analysis techniquesGene Expression ProfilingReproducibility of Resultsrisk assessmentCell DifferentiationMicroarray AnalysisImmunohistochemistryEmbryonic stem cellMolecular biologyGene expression profilingCell culturetoxicogenomicsCarcinogensHepatocytesNatural SciencesCarcinogenesisToxicological Sciences
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Transcriptomic responses generated by hepatocarcinogens in a battery of liver-based in vitro models

2013

As the conventional approach to assess the potential of a chemical to cause cancer in humans still includes the 2-year rodent carcinogenicity bioassay, development of alternative methodologies is needed. In the present study, the transcriptomics responses following exposure to genotoxic (GTX) and non-genotoxic (NGTX) hepatocarcinogens and non-carcinogens (NC) in five liver-based in vitro models, namely conventional and epigenetically stabilized cultures of primary rat hepatocytes, the human hepatoma-derived cell lines HepaRG and HepG2 and human embryonic stem cell-derived hepatocyte-like cells, are examined. For full characterization of the systems, several bioinformatics approaches are emp…

Cancer ResearchGene Expressiongene expression profilingComputational biologyBiologyPharmacologyTranscriptomeRats Sprague-Dawley03 medical and health sciences0302 clinical medicineCell Line TumorBioassayAnimalsHumansGeneCarcinogenEmbryonic Stem Cells030304 developmental biology0303 health sciencesGene Expression ProfilingLiver Neoplasmspathwaysbased analysis liver-based in vitro modelGeneral MedicineHep G2 CellsEmbryonic stem cellIn vitro3. Good healthRatsgenotoxic carcinogens non-genotoxic carcinogensGene expression profilingLiverCell culture030220 oncology & carcinogenesisCarcinogensHepatocytesTumor Suppressor Protein p53TranscriptomeMutagens
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