title: Gene expression of peripheral blood cells reveals pathways downstream of glucocorticoid receptor antagonism and nab-paclitaxel treatment.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  These results provide insights into the mechanisms of paclitaxel and glucocorticoid receptor inhibition in peripheral blood cells.
authors.affiliation: aCommittee on Clinical Pharmacology and Pharmacogenetics Departments of bMedicine cHuman Genetics, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Maranville
authors.forename: Rita
authors.initials: R
authors.lastname: Nanda
authors.forename: Gini F
authors.initials: GF
authors.lastname: Fleming
authors.forename: Maxwell N
authors.initials: MN
authors.lastname: Skor
authors.forename: Anna
authors.initials: A
authors.lastname: Di Rienzo
authors.forename: Suzanne D
authors.initials: SD
authors.lastname: Conzen
mesh_terms: D000418:Albumins / Q000008:administration & dosage* / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015735:Mifepristone / Q000008:administration & dosage* / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors*
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003907:Dexamethasone; D017239:Paclitaxel