title: Intra-arterial bevacizumab with blood brain barrier disruption in a glioblastoma xenograft model.
abstract: OBJECTIVE
  In this study we investigated the treatment response and survival of intra-arterial (IA) compared to intra-peritoneal (IP) delivery of bevacizumab (BV) in a glioblastoma (GBM) xenograft mouse model.
  
  
  METHODS
  3x10(5) U87-Luc cells were stereotactically implanted into the cortex of 35 nude mice and grouped for treatment (n = 7 in each group): IP saline (group 1), single IP BV (group 2), biweekly IP BV for 3 weeks (group 3), single intra-arterial (IA) BV alone (group 4) and single IA BV with blood brain barrier disruption (BBBD) (group 5). Tumor growth was monitored every 3 to 4 days using bioluminescence imaging (BLI) and survival was analyzed by the Kaplan Meier method. Tumor tissue was analyzed using H&E staining and immunohistochemistry.
  
  
  RESULTS
  Based on BLI, BV treated mice showed a delayed tumor growth over time compared to control. Kaplan Meier analysis demonstrated a median survival time of 28 days for group 1,31 days for group 2, 34 days for group 3, 36 days for group 4 and 36 days for group 5 (p < 0.0001). Mice treated with repeated IP BV (p = 0.003) or single IA BV with (p = 0.015) or without (p = 0.005) BBBD showed a significant survival benefit compared to single IP BV treated mice. Post mortem analysis revealed a histological pattern with a more discontinuous border between tumor and mouse brain in the repeated IP BV and single IA BV with or without BBBD treated mice compared to the sharply defined edges of single IP BV treated and control mice.
  
  
  CONCLUSIONS
  In this study we showed a significant survival benefit of repeated IP BV and single IA BV with or without BBBD treated mice compared to single IP BV treated and control mice in a U87 xenograft model.
authors.affiliation: Department of Neurological Surgery, New York-Presbyterian Hospital, Weill Cornell Medical College, NY 10021, USA.
authors.forename: Jan-Karl
authors.initials: JK
authors.lastname: Burkhardt
authors.forename: Alejandro
authors.initials: A
authors.lastname: Santillan
authors.forename: Christoph P
authors.initials: CP
authors.lastname: Hofstetter
authors.forename: Paul
authors.initials: P
authors.lastname: Christos
authors.forename: Nick
authors.initials: N
authors.lastname: Berry
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Shin
authors.forename: Conor P
authors.initials: CP
authors.lastname: Foley
authors.forename: Demirkan B
authors.initials: DB
authors.lastname: Gürsel
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Ballon
authors.forename: Y Pierre
authors.initials: YP
authors.lastname: Gobin
authors.forename: John A
authors.initials: JA
authors.lastname: Boockvar
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000068258:Bevacizumab; D001812:Blood-Brain Barrier / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D007269:Injections, Intra-Arterial; D007274:Injections, Intraperitoneal; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068258:Bevacizumab