title: Antiglycolytic therapy combined with an image-guided minimally invasive delivery strategy for the treatment of breast cancer.
abstract: OBJECTIVE
  The antiglycolytic agent 3-bromopyruvate (3-BrPA) promotes anticancer effects in multiple tumor models. This study evaluated the therapeutic efficacy of ultrasound (US)-guided intratumoral delivery of 3-BrPA in an orthotopic tumor model of breast cancer.
  
  
  METHODS
  Human breast cancer cell line MDA MB 231 was used for in vitro and in vivo studies. The anticancer effect of 3-BrPA was evaluated by viability assay, quantification of adenosine triphosphate (ATP) and lactate levels, and activity of matrix metalloproteinase (MMP)-9. In animal experiments, 15 nude mice with MDA MB 231 breast tumors were divided into three groups for US-guided intratumoral treatment with 1.75 mM 3-BrPA (group 1), 5 mM 3-BrPA (group 2), and saline solution (group 3). Tumor size was measured and subjected to histopathologic examination.
  
  
  RESULTS
  In vitro, treatment with 3-BrPA resulted in a dose-dependent decrease in cell viability. A decrease in ATP and lactate levels, invasion, and MMP9 activity and expression was observed after treatment with concentrations of 3-BrPA that did not affect cell viability. In vivo, a significant difference in tumor volume was observed between 3-BrPA-treated and control animals. At the end of the study, tumor volumes in the 3-BrPA groups were 1,876 mm(3)±346 and 426 mm(3)±180 in the 1.75-mM and 5-mM 3-BrPA groups, respectively, versus 4,447 mm(3)±571 in the control group (P< .05).
  
  
  CONCLUSIONS
  US-guided intratumoral injection of 3-BrPA effectively blocks breast cancer progression in an orthotopic mouse tumor model.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Manon
authors.initials: M
authors.lastname: Buijs
authors.forename: Joost W
authors.initials: JW
authors.lastname: Wijlemans
authors.forename: Byung Kook
authors.initials: BK
authors.lastname: Kwak
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ota
authors.forename: Jean-Francois H
authors.initials: JF
authors.lastname: Geschwind
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D045744:Cell Line, Tumor; D005260:Female; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D015552:Injections, Intralesional; D008327:Mammography / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D011773:Pyruvates / Q000008:administration & dosage*; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional / Q000379:methods*
chemical_list: D011773:Pyruvates; C017092:bromopyruvate