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.

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. Research Abstract Details 

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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. Abstract Text:

Jonathan C Trent,Latha Ramdas,Jheri Dupart,Kelly Hunt,Homer Macapinlac,Ellen Taylor,Limei Hu,August Salvado,James L Abbruzzese,Raphael Pollock,Robert S Benjamin,Wei Zhang,

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.

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. Publishing Authors By Initials

JC Trent,L Ramdas,J Dupart,K Hunt,H Macapinlac,E Taylor,L Hu,A Salvado,JL Abbruzzese,R Pollock,RS Benjamin,W Zhang,

For similar genetic processes: gene expression regulation: up-regulation research abstracts see: genetic processes: gene expression regulation: up-regulation research

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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. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Cancer

VOLUME: 107

Page Numbers: 1898-908

Journal Abbreviation: Cancer

ISSN: 0008-543X

DAY: 15

MONTH: Oct

YEAR: 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. Information

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LANGUAGE: eng

NlmUniqueID: 374236

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. Keywords Mesh Terms:

KEYWORDS: Up-Regulation

MESH TERMS: genetics

Chemical & Substance for Abstract: 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. Information

Substance Name: imatinib

Registry Number: 152459-95-5

Grant and Affiliation Information for 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.

AFFILIATION: Department of Sarcoma Medical Oncology, the University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. jtrent@mdanderson.org

Country: United States

AGENCY: United States NCI

GRANT: R01 CA098570

ACRONYM: CA

MEDLINETA: Cancer

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