title: Potentiation of radiotherapy by a localized antiangiogenic gene therapy.
abstract: OBJECTIVE
  We hypothesized that electrotransfer of a plasmid encoding an antiangiogenic factor, the recombinant disintegrin domain of ADAM-15, (pRDD) could modify the tumor microenvironment and radiosensitize tumor.
  
  
  METHODS
  pRDD was injected in the TLT tumor or FSaII fibrosarcomas before electroporation. pO2 in tumors and oxygen consumption in vitro were measured by electronic paramagnetic resonance (EPR) oximetry. Tumor perfusion was assessed by laser doppler imaging and patent blue assay.
  
  
  RESULTS
  pRDD electrotransfer caused a significant delay in TLT growth and an anti-angiogenic effect. It significantly increased tumor pO2 in TLT and FSaII for at least 4 days. pRDD electrotransfer and radiotherapy were more effective than either treatment alone. Modifications of tumor microenvironment were evaluated: tumor perfusion and interstitial fluid pressure were not modified. Oxygen consumption by the cells was decreased resulting both from a decrease in oxygen consumption rate and from a decrease in cell viability.
  
  
  CONCLUSIONS
  The combination of localized antiangiogenic gene therapy and radiotherapy applied in the time of maximal oxygenation could be a promising alternative for cancer treatment.
authors.affiliation: Université Catholique de Louvain, Louvain Drug Research Institute, Pharmaceutics and Drug Delivery, Brussels, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Crokart
authors.forename: Fabienne
authors.initials: F
authors.lastname: Danhier
authors.forename: Liévin
authors.initials: L
authors.lastname: Daugimont
authors.forename: Nelio
authors.initials: N
authors.lastname: Gonçalves
authors.forename: Bénédicte F
authors.initials: BF
authors.lastname: Jordan
authors.forename: Vincent
authors.initials: V
authors.lastname: Grégoire
authors.forename: Olivier
authors.initials: O
authors.lastname: Feron
authors.forename: Céline
authors.initials: C
authors.lastname: Bouquet
authors.forename: Bernard
authors.initials: B
authors.lastname: Gallez
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D020533:Angiogenesis Inhibitors / Q000235:genetics*; D000818:Animals; D015316:Genetic Therapy; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D011836:Radiation Tolerance; D059016:Tumor Microenvironment
chemical_list: D020533:Angiogenesis Inhibitors; D008565:Membrane Proteins; D051722:ADAM Proteins; C098660:ADAM15 protein, human