ArticlePharmacogenetics and genomics2014
Gene expression of peripheral blood cells reveals pathways downstream of glucocorticoid receptor antagonism and nab-paclitaxel treatment.
Article in Pharmacogenetics and genomics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors at 1 institution in 2 countries.
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Abstract
objectivesWhereas paclitaxel treatment is associated with leukopenia, the mechanisms that underlie this effect are not well-characterized. In addition, despite the importance of glucocorticoid signaling in cancer treatment, the genomic effects of glucocorticoid receptor antagonism by mifepristone treatment in primary human cells have never been described.
methodsAs part of a randomized phase 1 clinical trial, we used microarrays to profile gene expression in peripheral blood cells sampled from each of four patients at baseline, after placebo/nanoparticle albumin-bound paclitaxel (nab-paclitaxel) treatment (cycle 1), and after mifepristone/nab-paclitaxel treatment (cycle 2).
resultsWe found that 63 genes were differentially expressed following treatment with nab-paclitaxel, including multiple genes in the tubulin pathway. We also found 606 genes that were differentially expressed in response to mifepristone; genes downregulated by mifepristone overlapped significantly with those previously identified as being upregulated by dexamethasone.
conclusionThese results provide insights into the mechanisms of paclitaxel and glucocorticoid receptor inhibition in peripheral blood cells.
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