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Pharmacogenet Genomics. 2014 Sep;24(9):451-8. doi: 10.1097/FPC.0000000000000077.

Gene expression of peripheral blood cells reveals pathways downstream of glucocorticoid receptor antagonism and nab-paclitaxel treatment.

Author information

1
aCommittee on Clinical Pharmacology and Pharmacogenetics Departments of bMedicine cHuman Genetics, The University of Chicago, Chicago, Illinois, USA.

Abstract

OBJECTIVES:

Whereas 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.

METHODS:

As 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).

RESULTS:

We 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.

CONCLUSION:

These results provide insights into the mechanisms of paclitaxel and glucocorticoid receptor inhibition in peripheral blood cells.

PMID:
25000515
PMCID:
PMC4122588
DOI:
10.1097/FPC.0000000000000077
[Indexed for MEDLINE]
Free PMC Article

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