title: Highly specific antiangiogenic therapy is effective in suppressing growth of experimental Wilms tumors.
abstract: OBJECTIVE
  Pathologic angiogenesis in tumors is a potential target for novel therapies. Vascular endothelial growth factor (VEGF) is an angiogenic promoter present in a wide variety of human tumors. VEGF is expressed as 4 isoforms; one of these, VEGF165, predominates in human tumors. The authors hypothesized that antagonism of VEGF165 by a specific aptamer would block tumor growth in an experimental model of Wilms tumor.
  
  
  METHODS
  VEGF isoform expression in clinical (n = 2) and experimental tumors were evaluated by reverse transcription polymerase chain reaction (RT-PCR). Tumors were induced in NCR nude mice (n = 32) by intrarenal injection of 10(6) cultured Wilms tumor cells. At 1 week, aptamer (n = 16) or vehicle (n = 16) treatment was started and continued daily for 5 weeks.
  
  
  RESULTS
  At 6 weeks tumors weighed 84% less in treated versus control animals (0.69 v 4.41 g; P <.028), without observed adverse effects and similar to suppression previously reported using nonisoform-specific anti-VEGF antibody (94% to 96%).
  
  
  CONCLUSIONS
  Anti-VEGF165 aptamer effectively suppressed primary tumor growth in experimental animals with no observed adverse effects. Development of highly specific antiangiogenic therapies may be of particular benefit to pediatric patients.
authors.affiliation: Division of Pediatric Surgery, Department of Pathology, College of Physicians & Surgeons, Columbia University, and Babies & Children's Hospital of New York, the New York Presbyterian Hospital, New York, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.forename: J
authors.initials: J
authors.lastname: Moore
authors.forename: S
authors.initials: S
authors.lastname: Soffer
authors.forename: E
authors.initials: E
authors.lastname: Kim
authors.forename: D
authors.initials: D
authors.lastname: Rowe
authors.forename: C A
authors.initials: CA
authors.lastname: Manley
authors.forename: K
authors.initials: K
authors.lastname: O'Toole
authors.forename: W
authors.initials: W
authors.lastname: Middlesworth
authors.forename: C
authors.initials: C
authors.lastname: Stolar
authors.forename: D
authors.initials: D
authors.lastname: Yamashiro
authors.forename: J
authors.initials: J
authors.lastname: Kandel
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors; D007680:Kidney Neoplasms / Q000628:therapy*; D051379:Mice; D023421:Models, Animal; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D009396:Wilms Tumor / Q000628:therapy*
chemical_list: D020533:Angiogenesis Inhibitors; D016228:Endothelial Growth Factors