Abstract
In the development of targeted oncology drugs, it is important to assess drug effectiveness in individual patients. We evaluated the possibility of reproducing in an ex-vivo system the biological effects observed in vitro and in vivo by the combined administration of two chemotherapeutic drugs, gemcitabine and a small inhibitor of Wee1. We found that modulation of both CDC2 phosphorylation and of a previously-identified gene signature was detectable in human skin equivalents obtained with primary keratinocytes from three individuals. Therefore, we suggest that human skin equivalents could represent a promising tool for the identification and validation of novel pharmacodynamic biomarkers.
MeSH terms
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3T3 Cells
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Animals
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Biomarkers / metabolism*
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CDC2 Protein Kinase
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Cell Cycle Proteins / antagonists & inhibitors
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Cell Cycle Proteins / metabolism
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Cells, Cultured
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Cyclin B / metabolism
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Cyclin-Dependent Kinases
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Deoxycytidine / analogs & derivatives
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Deoxycytidine / pharmacology
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Drug Screening Assays, Antitumor / methods*
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Fibroblasts / drug effects
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Fibroblasts / metabolism
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Gemcitabine
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Humans
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Keratinocytes / drug effects
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Keratinocytes / metabolism
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Mice
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Nuclear Proteins / antagonists & inhibitors
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Nuclear Proteins / metabolism
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Phosphorylation / drug effects
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / metabolism
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Skin / drug effects*
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Skin / metabolism*
Substances
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Biomarkers
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Cell Cycle Proteins
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Cyclin B
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Nuclear Proteins
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Deoxycytidine
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Protein-Tyrosine Kinases
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WEE1 protein, human
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CDC2 Protein Kinase
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CDK1 protein, human
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Cyclin-Dependent Kinases
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Gemcitabine