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Early effects of imatinib mesylate on the expression of insulin-like growth factor binding protein-3 and positron emission tomography in patients with gastrointestinal stromal tumor.

Publication ,  Journal Article
Trent, JC; Ramdas, L; Dupart, J; Hunt, K; Macapinlac, H; Taylor, E; Hu, L; Salvado, A; Abbruzzese, JL; Pollock, R; Benjamin, RS; Zhang, W
Published in: Cancer
October 15, 2006

BACKGROUND: Imatinib has demonstrated marked clinical efficacy against gastrointestinal stromal tumor (GIST). Microarray technology, real-time polymerase chain reaction (PCR) validation, and fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging were used to study the early molecular effects of imatinib antitumor activity in GIST. METHODS: After exposure of sensitive and resistant sarcoma cell lines to imatinib for 24 to 48 hours, the changes in gene expression were evaluated using a 1146 unique pathway array with Western blot validation. Real-time PCR was used to confirm changes in gene expression in human GIST samples (preimatinib biopsy and postimatinib surgical specimen after 3-7 days of therapy). FDG-PET was performed to correlate radiographic findings with the effects of imatinib on gene expression in GIST. RESULTS: In all, 55 genes demonstrated a > or = 2-fold change after imatinib treatment of the GIST882 cells. Among these genes there was up-regulation of insulin-like growth factor binding protein-3 (IGFBP-3), a protein that modulates proliferation and apoptosis. Western blot analysis confirmed the increase of IGFBP-3 only in imatinib-sensitive GIST882 cells. Up to a 7-fold induction (49% mean increase; P = .08) of IGFBP-3 mRNA was found in tumor samples from patients with low residual FDG uptake, whereas there was an up to 12-fold reduction (-102% mean decrease; P = .03) in IGFBP-3 in those patients with high residual FDG uptake after imatinib therapy. CONCLUSIONS: In the current study, imatinib appears to regulate numerous genes and specifically induces IGFBP-3 in GIST cells and tumor samples. IGFBP-3 levels also were found to be inversely correlated with residual FDG uptake in GIST patients early in imatinib therapy. These initial observations suggest that IGFBP-3 is an important early marker of antitumor activity of imatinib in GIST.

Duke Scholars

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Published In

Cancer

DOI

ISSN

0008-543X

Publication Date

October 15, 2006

Volume

107

Issue

8

Start / End Page

1898 / 1908

Location

United States

Related Subject Headings

  • Up-Regulation
  • Sarcoma
  • Radiography
  • Pyrimidines
  • Positron-Emission Tomography
  • Piperazines
  • Oncology & Carcinogenesis
  • Insulin-Like Growth Factor Binding Proteins
  • Insulin-Like Growth Factor Binding Protein 3
  • Imatinib Mesylate
 

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Trent, J. C., Ramdas, L., Dupart, J., Hunt, K., Macapinlac, H., Taylor, E., … Zhang, W. (2006). Early effects of imatinib mesylate on the expression of insulin-like growth factor binding protein-3 and positron emission tomography in patients with gastrointestinal stromal tumor. Cancer, 107(8), 1898–1908. https://doi.org/10.1002/cncr.22214
Trent, Jonathan C., Latha Ramdas, Jheri Dupart, Kelly Hunt, Homer Macapinlac, Ellen Taylor, Limei Hu, et al. “Early effects of imatinib mesylate on the expression of insulin-like growth factor binding protein-3 and positron emission tomography in patients with gastrointestinal stromal tumor.Cancer 107, no. 8 (October 15, 2006): 1898–1908. https://doi.org/10.1002/cncr.22214.
Trent JC, Ramdas L, Dupart J, Hunt K, Macapinlac H, Taylor E, Hu L, Salvado A, Abbruzzese JL, Pollock R, Benjamin RS, Zhang W. Early effects of imatinib mesylate on the expression of insulin-like growth factor binding protein-3 and positron emission tomography in patients with gastrointestinal stromal tumor. Cancer. 2006 Oct 15;107(8):1898–1908.
Journal cover image

Published In

Cancer

DOI

ISSN

0008-543X

Publication Date

October 15, 2006

Volume

107

Issue

8

Start / End Page

1898 / 1908

Location

United States

Related Subject Headings

  • Up-Regulation
  • Sarcoma
  • Radiography
  • Pyrimidines
  • Positron-Emission Tomography
  • Piperazines
  • Oncology & Carcinogenesis
  • Insulin-Like Growth Factor Binding Proteins
  • Insulin-Like Growth Factor Binding Protein 3
  • Imatinib Mesylate