title: High-Dose, Single-Fraction Irradiation Rapidly Reduces Tumor Vasculature and Perfusion in a Xenograft Model of Neuroblastoma.
abstract: OBJECTIVE
  To characterize the effects of high-dose radiation therapy (HDRT) on neuroblastoma tumor vasculature, including the endothelial cell (EC)-pericyte interaction as a potential target for combined treatment with antiangiogenic agents.
  
  
  METHODS
  The vascular effects of radiation therapy were examined in a xenograft model of high-risk neuroblastoma. In vivo 3-dimensional contrast-enhanced ultrasonography (3D-CEUS) imaging and immunohistochemistry (IHC) were performed.
  
  
  RESULTS
  HDRT significantly reduced tumor blood volume 6 hours after irradiation compared with the lower doses used in conventionally fractionated radiation. There was a 63% decrease in tumor blood volume after 12-Gy radiation compared with a 24% decrease after 2 Gy. Analysis of tumor vasculature by lectin angiography showed a significant loss of small vessel ends at 6 hours. IHC revealed a significant loss of ECs at 6 and 72 hours after HDRT, with an accompanying loss of immature and mature pericytes at 72 hours.
  
  
  CONCLUSIONS
  HDRT affects tumor vasculature in a manner not observed at lower doses. The main observation was an early reduction in tumor perfusion resulting from a reduction of small vessel ends with a corresponding loss of endothelial cells and pericytes.
authors.affiliation: Department of Radiation Oncology, Columbia University Medical Center, New York, New York.
authors.forename: Ashish
authors.initials: A
authors.lastname: Jani
authors.affiliation: Department of Radiation Oncology, Columbia University Medical Center, New York, New York.
authors.forename: Fauzia
authors.initials: F
authors.lastname: Shaikh
authors.affiliation: Department of Radiation Oncology, Columbia University Medical Center, New York, New York.
authors.forename: Sunjay
authors.initials: S
authors.lastname: Barton
authors.affiliation: Department of Surgery, Columbia University Medical Center, New York, New York.
authors.forename: Callen
authors.initials: C
authors.lastname: Willis
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, New York, New York.
authors.forename: Debarshi
authors.initials: D
authors.lastname: Banerjee
authors.affiliation: Department of Surgery, Columbia University Medical Center, New York, New York.
authors.forename: Jason
authors.initials: J
authors.lastname: Mitchell
authors.affiliation: Department of Surgery, University of Chicago, Chicago, Illinois.
authors.forename: Sonia L
authors.initials: SL
authors.lastname: Hernandez
authors.affiliation: Department of Radiation Oncology, Columbia University Medical Center, New York, New York.
authors.forename: Tom
authors.initials: T
authors.lastname: Hei
authors.affiliation: Department of Surgery, Columbia University Medical Center, New York, New York.
authors.forename: Angela
authors.initials: A
authors.lastname: Kadenhe-Chiweshe
authors.affiliation: Department of Surgery, Columbia University Medical Center, New York, New York; Department of Pediatrics, Columbia University Medical Center, New York, New York; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York.
authors.forename: Darrell J
authors.initials: DJ
authors.lastname: Yamashiro
authors.affiliation: Department of Radiation Oncology, Columbia University Medical Center, New York, New York. Electronic address: epc2116@cumc.columbia.edu.
authors.forename: Eileen P
authors.initials: EP
authors.lastname: Connolly
mesh_terms: D000792:Angiography / Q000379:methods; D000818:Animals; D017209:Apoptosis; D002450:Cell Communication; D045744:Cell Line, Tumor; D004730:Endothelium, Vascular / Q000166:cytology / Q000528:radiation effects; D064593:Heterografts; D006801:Humans; D037102:Lectins; D008819:Mice, Nude; D009447:Neuroblastoma / Q000098:blood supply / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D020286:Pericytes / Q000166:cytology / Q000528:radiation effects; D011879:Radiotherapy Dosage; D011897:Random Allocation; D012039:Regional Blood Flow / Q000528:radiation effects*; D013997:Time Factors; D014463:Ultrasonography
chemical_list: D037102:Lectins