title: Differential growth inhibition of cerebral metastases by anti-angiogenic compounds.
abstract: BACKGROUND
  The formation of brain metastases is intrinsically linked to concomitant angiogenesis. The purpose of the present study was to investigate the combined effects of interleukin-12 (IL-12) and EMD121974 on the growth and distribution of melanoma brain metastases since both substances may interact with important steps in the cascade of brain metastases formation.
  
  
  METHODS
  Brain metastases were induced by either stereotactic implantation of cells to the brain parenchyma or by injection of the melanoma cells into the internal carotid artery to mimic hematogenous metastatic spread in mice. Naive or IL-12-overexpressing murine K1735 melanoma cells were used either alone or in combination with intraperitoneal anti-integrin treatment using EMD121974.
  
  
  RESULTS
  Solid melanoma metastases were more susceptible to daily low-dose treatment of EMD121974 than multiple hematogenous metastases. Interleukin-12 had a profound effect on both types of brain metastases. After 21 days, a marked reduction of vascularity was observed in both tumor types.
  
  
  CONCLUSIONS
  The combination of endogenous IL-12 production with integrin blockade resulted in additive effects for murine hematogenous brain metastases but not for focal brain metastases.
authors: Department of Neurosurgery, Carl Gustav Carus University Hospital, Dresden University of Technology, Dresden, Germany.
authors: Daniel K
authors: DK
authors: Martin
authors: Department of Neurosurgery, Carl Gustav Carus University Hospital, Dresden University of Technology, Dresden, Germany.
authors: Ortrud
authors: O
authors: Uckermann
authors: Department of Neurosurgery, Carl Gustav Carus University Hospital, Dresden University of Technology, Dresden, Germany.
authors: Aiko
authors: A
authors: Bertram
authors: Department of Neurosurgery, Carl Gustav Carus University Hospital, Dresden University of Technology, Dresden, Germany.
authors: Corina
authors: C
authors: Liebner
authors: Department of Neurosurgery, Carl Gustav Carus University Hospital, Dresden University of Technology, Dresden, Germany.
authors: Sandy
authors: S
authors: Hendruschk
authors: Department of Neurosurgery, Carl Gustav Carus University Hospital, Dresden University of Technology, Dresden, Germany.
authors: Kerim Hakan
authors: KH
authors: Sitoci-Ficici
authors: Department of Neurosurgery, Carl Gustav Carus University Hospital, Dresden University of Technology, Dresden, Germany.
authors: Gabriele
authors: G
authors: Schackert
authors: Department of Microbiology and Immunology, James P. Wilmot Cancer Center, University of Rochester, Rochester, NY, U.S.A.
authors: Edith M
authors: EM
authors: Lord
authors: Department of Neurosurgery, Carl Gustav Carus University Hospital, Dresden University of Technology, Dresden, Germany CRTD/DFG-Center for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, Germany.
authors: Achim
authors: A
authors: Temme
authors: Department of Neurosurgery, Carl Gustav Carus University Hospital, Dresden University of Technology, Dresden, Germany CRTD/DFG-Center for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, Germany matthias.kirsch@uniklinikum-dresden.de.
authors: Matthias
authors: M
authors: Kirsch
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000556:secondary* / Q000628:therapy*; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D005260:Female; D015316:Genetic Therapy; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics*; D008545:Melanoma / Q000098:blood supply / Q000188:drug therapy / Q000556:secondary* / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D010456:Peptides, Cyclic / Q000494:pharmacology*; D012910:Snake Venoms; D014162:Transfection
chemical_list: D020533:Angiogenesis Inhibitors; D010456:Peptides, Cyclic; D012910:Snake Venoms; D018664:Interleukin-12; C422910:Cilengitide
keywords: Brain metastases; EMD121974; brain tumor; cilengitide; interleukin-12; melanoma