title: Combinatorial administration of molecules that simultaneously inhibit angiogenesis and invasion leads to increased therapeutic efficacy in mouse models of malignant glioma.
abstract: OBJECTIVE
  We investigated the ability of the combinatorial administration of different inhibitors with activities on glioma angiogenesis, migration, and proliferation to produce a prolonged inhibition of glioma growth.
  
  
  METHODS
  We combined inhibitors affecting solely tumor angiogenesis (PF-4/CTF, cyclo-VEGI) or inhibitors affecting both angiogenesis and invasion together (PEX, PF-4/DLR).
  
  
  RESULTS
  When administered in combination, these drugs produced a prolonged and increased inhibition of glioma growth independently from the type of inhibitor used. The combinatory administration was more effective than the administration of a single inhibitor alone, and a strong therapeutic response was reached with a significantly lower amount of protein. The strongest inhibition was observed when human PEX and PF-4/DLR, which affect both glioma angiogenesis and invasion by separate mechanisms, were combined.
  
  
  CONCLUSIONS
  This supports the concept that prolonged glioma growth inhibition can be achieved by simultaneous delivery of molecules that target both tumor and endothelial cells and acting by separate mechanisms.
authors.affiliation: Neurosurgery, Department of Neurological Sciences, University of Milano, Ospedale Maggiore di Milano, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy. lorenzo.bello@unimi.it
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Bello
authors.forename: Valeria
authors.initials: V
authors.lastname: Lucini
authors.forename: Francesco
authors.initials: F
authors.lastname: Costa
authors.forename: Mauro
authors.initials: M
authors.lastname: Pluderi
authors.forename: Carlo
authors.initials: C
authors.lastname: Giussani
authors.forename: Francesco
authors.initials: F
authors.lastname: Acerbi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Carrabba
authors.forename: Marilou
authors.initials: M
authors.lastname: Pannacci
authors.forename: Dario
authors.initials: D
authors.lastname: Caronzolo
authors.forename: Silvia
authors.initials: S
authors.lastname: Grosso
authors.forename: Svetlana
authors.initials: S
authors.lastname: Shinkaruk
authors.forename: Federica
authors.initials: F
authors.lastname: Colleoni
authors.forename: Xavier
authors.initials: X
authors.lastname: Canron
authors.forename: Giustino
authors.initials: G
authors.lastname: Tomei
authors.forename: Gerard
authors.initials: G
authors.lastname: Deleris
authors.forename: Andreas
authors.initials: A
authors.lastname: Bikfalvi
mesh_terms: D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003094:Collagen; D004195:Disease Models, Animal; D004338:Drug Combinations; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000473:pathology; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007797:Laminin; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000473:pathology; D009389:Neovascularization, Pathologic; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; D010456:Peptides, Cyclic / Q000096:biosynthesis; D010978:Platelet Factor 4 / Q000096:biosynthesis; D011506:Proteins / Q000378:metabolism; D011509:Proteoglycans; D011994:Recombinant Proteins / Q000737:chemistry; D013997:Time Factors
chemical_list: D004338:Drug Combinations; D016228:Endothelial Growth Factors; D007797:Laminin; D010456:Peptides, Cyclic; D011506:Proteins; D011509:Proteoglycans; D011994:Recombinant Proteins; C478485:cyclo-VEGI; C059485:matrigel; D010978:Platelet Factor 4; D003094:Collagen; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human; C506232:Phex protein, mouse