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Application of oligonucleotide microarrays to assess the biological effects of neoadjuvant imatinib mesylate treatment for localized prostate cancer.

Publication ,  Journal Article
Febbo, PG; Thorner, A; Rubin, MA; Loda, M; Kantoff, PW; Oh, WK; Golub, T; George, D
Published in: Clin Cancer Res
January 1, 2006

PURPOSE: Neoadjuvant administration of antineoplastic therapies is used to rapidly assess the clinical and biological activity of novel systemic treatments. To assess the feasibility of using microarrays to assess molecular end points following targeted treatment in a heterogeneous tumor, we measured global gene expression in localized prostate cancer before and following neoadjuvant treatment with imatinib mesylate. PATIENTS AND METHODS: Patients with intermediate-risk to high-risk prostate cancer were treated for 6 weeks with 200 to 300 mg of oral imatinib mesylate. Frozen tissue was obtained from pretreatment ultrasound-guided biopsies and posttreatment radical prostatectomy specimens. Oligonucleotide microarray analysis following laser capture microdissection (LCM) and RNA amplification was used to assess gene expression changes associated with imatinib mesylate therapy. Immunohistochemistry was used to measure protein expression of MKP1 and CD31 and to assess cellular apoptosis. RESULTS: Of the 11 patients enrolled, high-quality microarray data was obtained from both biopsies (n = 7) and radical prostatectomy specimens (n = 9). Technically introduced intrasample gene expression variability was found to be significantly less than intertumor biological variability. Large gene expression differences were observed, and the gene with the most consistent differential expression (MKP1) was validated by immunohistochemistry. Gene set enrichment analysis suggests that imatinib mesylate therapy results in apoptosis of microvascular endothelial cells, an observation anecdotally supported by immunohistochemistry. CONCLUSIONS: This study shows that high-quality microarray data can be generated using LCM and RNA amplification to discover potential mechanisms of targeted therapy in cancer.

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Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

January 1, 2006

Volume

12

Issue

1

Start / End Page

152 / 158

Location

United States

Related Subject Headings

  • Pyrimidines
  • Proto-Oncogene Proteins c-akt
  • Prostatic Neoplasms
  • Prostatectomy
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Piperazines
  • Oncology & Carcinogenesis
  • Oligonucleotide Array Sequence Analysis
  • Neoadjuvant Therapy
  • Microdissection
 

Citation

APA
Chicago
ICMJE
MLA
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Febbo, P. G., Thorner, A., Rubin, M. A., Loda, M., Kantoff, P. W., Oh, W. K., … George, D. (2006). Application of oligonucleotide microarrays to assess the biological effects of neoadjuvant imatinib mesylate treatment for localized prostate cancer. Clin Cancer Res, 12(1), 152–158. https://doi.org/10.1158/1078-0432.CCR-05-1652
Febbo, Phillip G., Aaron Thorner, Mark A. Rubin, Massimo Loda, Philip W. Kantoff, William K. Oh, Todd Golub, and Daniel George. “Application of oligonucleotide microarrays to assess the biological effects of neoadjuvant imatinib mesylate treatment for localized prostate cancer.Clin Cancer Res 12, no. 1 (January 1, 2006): 152–58. https://doi.org/10.1158/1078-0432.CCR-05-1652.
Febbo PG, Thorner A, Rubin MA, Loda M, Kantoff PW, Oh WK, et al. Application of oligonucleotide microarrays to assess the biological effects of neoadjuvant imatinib mesylate treatment for localized prostate cancer. Clin Cancer Res. 2006 Jan 1;12(1):152–8.
Febbo, Phillip G., et al. “Application of oligonucleotide microarrays to assess the biological effects of neoadjuvant imatinib mesylate treatment for localized prostate cancer.Clin Cancer Res, vol. 12, no. 1, Jan. 2006, pp. 152–58. Pubmed, doi:10.1158/1078-0432.CCR-05-1652.
Febbo PG, Thorner A, Rubin MA, Loda M, Kantoff PW, Oh WK, Golub T, George D. Application of oligonucleotide microarrays to assess the biological effects of neoadjuvant imatinib mesylate treatment for localized prostate cancer. Clin Cancer Res. 2006 Jan 1;12(1):152–158.

Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

January 1, 2006

Volume

12

Issue

1

Start / End Page

152 / 158

Location

United States

Related Subject Headings

  • Pyrimidines
  • Proto-Oncogene Proteins c-akt
  • Prostatic Neoplasms
  • Prostatectomy
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Piperazines
  • Oncology & Carcinogenesis
  • Oligonucleotide Array Sequence Analysis
  • Neoadjuvant Therapy
  • Microdissection