title: Controlling tumor invasion: bevacizumab and BMP4 for glioblastoma.
abstract: OBJECTIVE
  Bevacizumab has been reported to result in increased tumor invasion when used to treat malignant glioma. We hypothesized that BMP4 would prevent diffuse tumor infiltration induced by bevacizumab for malignant glioma in a xenograft model.
  
  
  METHODS
  Human glioblastoma (GBM) tumor cells were implanted in the striatum of immunocompromised mice. The animals were treated with bevacizumab and BMP4. Tumor growth and invasion were measured.
  
  
  RESULTS
  The bevacizumab-treated mice had increased survival compared with control animals (p = 0.02). BMP4 alone did not result in improved survival (p = 1.0). The bevacizumab (p = 0.006) and bevacizumab plus BMP4 (p = 0.006) groups demonstrated significantly decreased total tumor size compared with control. Tumor invasion was significantly decreased in the bevacizumab (p = 0.005), BMP4 (p = 0.04) alone and bevacizumab plus BMP4 (p = 0.002) groups compared with control. No synergistic effect between bevacizumab and BMP4 was observed.
  
  
  CONCLUSIONS
  Bevacizumab treatment did not result in diffuse infiltration of human GBM in a mouse xenograft model. BMP4 did have an independent favorable effect on GBM that was not synergistic with bevacizumab treatment.
authors: Department of Neurosurgery, University of Florida, Gainesville, FL, USA. n maryam.rahman@neurosurgery.ufl.edu
authors: Maryam
authors: M
authors: Rahman
authors: Hassan
authors: H
authors: Azari
authors: Loic
authors: L
authors: Deleyrolle
authors: Sebastien
authors: S
authors: Millette
authors: Huadong
authors: H
authors: Zeng
authors: Brent A
authors: BA
authors: Reynolds
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D005260:Female; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D006801:Humans; D007124:Immunoenzyme Techniques; D008279:Magnetic Resonance Imaging; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D015996:Survival Rate; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D000068258:Bevacizumab