Effect of the angiogenesis inhibitor Cilengitide (EMD 121974) on glioblastoma growth in nude mice.
OBJECTIVE
To determine the effect of the angiogenesis inhibitor Cilengitide (EMD 121974) on glioblastoma growth and associated angiogenesis in the brains of nude mice.


METHODS
Human glioblastoma cells (10 U87MG cells) in 1 mul of medium were stereotactically injected during a 20-minute period into the caudate/putamen of nude mice. The mice were intraperitoneally treated daily with Cilengitide or solvent (control) beginning 5 days after tumor injection. The mice were sacrificed from 1 hour to 63 days after tumor implantation and examined for tumor size, vascularity, apoptosis, and cell replication.


RESULTS
This injection technique resulted in a highly reproducible, localized, spherical tumor cell placement in the parenchyma without reflux into the subarachnoid space or penetration into the ventricle. Serial brain sections showed the tumor size remained unchanged at 1 to 2 mm for approximately 30 to 40 days. Thereafter, the control tumors showed exponential growth to a volume of 120 mm, with death of the mice at approximately 8 to 9 weeks. Serial staining for Ki-67, a marker for cell replication, and CD31, an indicator for angiogenesis, demonstrated an increase in proportion to the growth of the tumor. In contrast, the tumor volume in Cilengitide-treated mice stayed unchanged at 1 to 2 mm during the entire length of the experiment, with staining for Ki-67 and CD31 remaining low.


CONCLUSIONS
This standardized brain tumor model is highly reproducible and useful for testing new treatment regimens. Cilengitide is highly effective in suppressing blood vessel growth, thereby controlling orthotopic growth of this glioblastoma cell line.
Yamada
Shinya
S
Department of Neurosurgery, Tokai University, School of Medicine, Tokai Oiso Hospital, Kanagawa, Japan.
Bu
Xing-Yao
XY
Khankaldyyan
Vazgen
V
Gonzales-Gomez
Ignacio
I
McComb
J Gordon
JG
Laug
Walter E
WE
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005260:Female; D005909:Glioblastoma / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000473:pathology* / Q000517:prevention & control*; D012910:Snake Venoms / Q000008:administration & dosage*; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D012910:Snake Venoms; C422910:Cilengitide