Angiogenesis inhibitor DC101 delays growth of intracerebral glioblastoma but induces morbidity when combined with irradiation.
The combination of irradiation with angiogenic inhibition is increasingly being investigated for treatment of glioblastoma multiforme (GBM). We investigated whether vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitor DC101 affects morbidity and tumor growth in irradiated and non-irradiated intracerebral GBM-bearing mice, controlled with sham treatments. End-points were toxicity, morbidity and histology. Irradiation either or not combined, reduced tumor size strongly, whereas DC101 mono-treatment reduced tumor size by 64%. Irradiation delayed morbidity from 5.8 weeks in sham-treated mice to 10.3 weeks. Morbidity after combined treatment occurred after 5.9 weeks. Treatment with angiogenesis inhibitor DC101 delays tumor growth but it induces morbidity, by itself or combined with irradiation.
Verhoeff
Joost J C
JJ
Center for Experimental and Molecular Medicine, University of Amsterdam, The Netherlands.
Stalpers
Lukas J A
LJ
Van Noorden
Cornelis J F
CJ
Troost
Dirk
D
Ramkema
Marja D
MD
van Bree
Chris
C
Song
Ji-Ying
JY
Donker
Mila
M
Chekenya
Martha
M
Vandertop
W Peter
WP
Richel
Dick J
DJ
van Furth
Wouter R
WR
D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000633:toxicity; D001918:Brachytherapy / Q000009:adverse effects; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D017024:Chemotherapy, Adjuvant; D016371:Cranial Irradiation / Q000009:adverse effects; D005260:Female; D005909:Glioblastoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009336:Necrosis; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control*; D018714:Radiotherapy, Adjuvant; D013997:Time Factors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; C511761:DC101 monoclonal antibody; D040301:Vascular Endothelial Growth Factor Receptor-2