RT Journal Article
SR Electronic
T1 Tyrosine Kinase Inhibition of Multiple Angiogenic Growth Factor Receptors Improves Survival in Mice Bearing Colon Cancer Liver Metastases by Inhibition of Endothelial Cell Survival Mechanisms
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 1464
OP 1468
VO 61
IS 4
A1 Shaheen, Raymond M.
A1 Tseng, William W.
A1 Davis, Darren W.
A1 Liu, Wenbiao
A1 Reinmuth, Niels
A1 Vellagas, Roberto
A1 Wieczorek, Andrew A.
A1 Ogura, Yasuhiro
A1 McConkey, David J.
A1 Drazan, Kenneth E.
A1 Bucana, Corazon D.
A1 McMahon, Gerald
A1 Ellis, Lee M.
YR 2001
UL http://cancerres.aacrjournals.org/content/61/4/1464.abstract
AB Redundant mechanisms mediate colon cancer angiogenesis. Targeting multiple angiogenic factors simultaneously may improve survival of mice with colon cancer metastases. BALB/c mice underwent splenic injection with CT-26 colon cancer cells to generate liver metastases and received administration of either vehicle alone or a tyrosine kinase inhibitor for vascular endothelial growth factor, basic fibroblast growth factor, and platelet-derived growth factor receptors (SU6668). Mice were sacrificed when they became moribund as determined by a blinded observer. In a parallel experiment, groups of mice were sacrificed at earlier time points to better define the kinetics of the effect of SU6668 on angiogenic parameters over time. SU6668 increased median survival by 58% (P < 0.001) and led to a progressive increase in tumor cell and endothelial cell apoptosis that increased over time. In addition, pericyte vessel coverage and tumor vascularity were significantly decreased in mice treated with SU6668. Based on current knowledge of endothelial cell survival, these data suggest that SU6668 may prevent tumor endothelial cell survival directly (vascular endothelial growth factor) and indirectly (pericyte coverage) by affecting endothelial cell survival mechanisms. ©2001 American Association for Cancer Research.