title: Antagonistic effects of anti-EMMPRIN antibody when combined with chemotherapy against hypovascular pancreatic cancers.
abstract: OBJECTIVE
  To examine the antagonistic effects of anti-extracellular matrix metalloprotease inducer (anti-EMMPRIN) antibody when combined with chemotherapy using a hypovascular pancreatic tumor model.
  
  
  METHODS
  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.
authors.affiliation: Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, 35294-0019, USA, Hyunki@uab.edu.
authors.forename: Hyunki
authors.initials: H
authors.lastname: Kim
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Rigell
authors.forename: Guihua
authors.initials: G
authors.lastname: Zhai
authors.forename: S Kyle
authors.initials: SK
authors.lastname: Lee
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Samuel
authors.forename: Amber
authors.initials: A
authors.lastname: Martin
authors.forename: Heidi R
authors.initials: HR
authors.lastname: Umphrey
authors.forename: Cecil R
authors.initials: CR
authors.lastname: Stockard
authors.forename: T Mark
authors.initials: TM
authors.lastname: Beasley
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Buchsbaum
authors.forename: Long Shan
authors.initials: LS
authors.lastname: Li
authors.forename: David A
authors.initials: DA
authors.lastname: Boothman
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Zinn
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology*; D051926:Basigin / Q000276:immunology*; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D003847:Deoxyglucose; D016503:Drug Delivery Systems; D005260:Female; D051379:Mice; D010190:Pancreatic Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology; D049268:Positron-Emission Tomography; D047368:Tumor Burden / Q000187:drug effects; D000093542:Gemcitabine
chemical_list: D000912:Antibodies, Neoplasm; D003841:Deoxycytidine; D051926:Basigin; D003847:Deoxyglucose; D000093542:Gemcitabine