Antagonistic effects of anti-EMMPRIN antibody when combined with chemotherapy against hypovascular pancreatic cancers

Hyunki Kim, Christopher J. Rigell, Guihua Zhai, S. Kyle Lee, Sharon L. Samuel, Amber Martin, Heidi R. Umphrey, Cecil R. Stockard, T. Mark Beasley, Donald J. Buchsbaum, Long Shan Li, David A. Boothman, Kurt R. Zinn

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9 Scopus citations

Abstract

Purpose: To examine the antagonistic effects of anti-extracellular matrix metalloprotease inducer (anti-EMMPRIN) antibody when combined with chemotherapy using a hypovascular pancreatic tumor model. Procedures: Severely compromised immunodeficient mice bearing orthotopic MIA PaCa-2 tumors were used (five to six animals per group). Dynamic contrast-enhanced magnetic resonance imaging was used to examine the relationship between tumor vascularity and size. Therapy was initiated when tumors were hypovascular. Treatments included: (1) gemcitabine alone, (2) anti-EMMPRIN antibody alone, and (3) combination, each for 2 weeks. Additionally, another treatment arm included β-lapachone, an NAD(P)H/quinone 1 (NQO1) bioactivated agent. 18F-fluoro-D-glucose- positron emission tomography/computed tomography imaging was used weekly to monitor therapeutic effects. Results: Gemcitabine or anti-EMMPRIN monotherapy significantly delayed tumor growth, but the combination therapy showed an antagonistic effect. Similarly, tumor growth was significantly suppressed by β-lapachone alone, and additive effects were noted when combined with gemcitabine, but the therapeutic efficacy was reduced when anti-EMMPRIN antibody was added. Conclusions: Anti-EMMPRIN antibody with chemotherapy in hypovascular tumors results in antagonistic effects.

Original languageEnglish
Pages (from-to)85-94
Number of pages10
JournalMolecular Imaging and Biology
Volume16
Issue number1
DOIs
StatePublished - Feb 1 2014
Externally publishedYes

Keywords

  • DCE-MRI
  • EMMPRIN
  • FDG-PET/CT
  • Gemcitabine
  • Pancreatic cancer
  • β-Lapachone

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    Kim, H., Rigell, C. J., Zhai, G., Lee, S. K., Samuel, S. L., Martin, A., Umphrey, H. R., Stockard, C. R., Beasley, T. M., Buchsbaum, D. J., Li, L. S., Boothman, D. A., & Zinn, K. R. (2014). Antagonistic effects of anti-EMMPRIN antibody when combined with chemotherapy against hypovascular pancreatic cancers. Molecular Imaging and Biology, 16(1), 85-94. https://doi.org/10.1007/s11307-013-0665-4