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

Academic Article

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. (18)F-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.
  • Published In

    Keywords

  • Animals, Antibodies, Neoplasm, Basigin, Cell Line, Tumor, Deoxycytidine, Deoxyglucose, Drug Delivery Systems, Female, Mice, Pancreatic Neoplasms, Positron-Emission Tomography, Tumor Burden
  • Digital Object Identifier (doi)

    Author List

  • Kim H; Rigell CJ; Zhai G; Lee SK; Samuel SL; Martin A; Umphrey HR; Stockard CR; Beasley TM; Buchsbaum DJ
  • Start Page

  • 85
  • End Page

  • 94
  • Volume

  • 16
  • Issue

  • 1