Author/Authors :
Batchelor، نويسنده , , Tracy T. and Sorensen، نويسنده , , A. Gregory and di Tomaso، نويسنده , , Emmanuelle and Zhang، نويسنده , , Wei-Ting and Duda، نويسنده , , Dan G. and Cohen، نويسنده , , Kenneth S. and Kozak، نويسنده , , Kevin R. and Cahill، نويسنده , , Daniel P. and Chen، نويسنده , , Poe-Jou and Zhu، نويسنده , , Mingwang and Ancukiewicz، نويسنده , , Marek J. Mrugala، نويسنده , , Maciej M. and Plotkin، نويسنده , , Scott and Drappatz، نويسنده , , Jan and Louis، نويسنده , , David N. and Ivy، نويسنده , , Percy and Scadden، نويسنده , , David T. and Benner، نويسنده , , Thomas and Loeffler، نويسنده , , Jay S. and Wen، نويسنده , , Patrick Y. and Jain، نويسنده , , Rakesh K.، نويسنده ,
Abstract :
Summary
MRI techniques, we show here that normalization of tumor vessels in recurrent glioblastoma patients by daily administration of AZD2171—an oral tyrosine kinase inhibitor of VEGF receptors—has rapid onset, is prolonged but reversible, and has the significant clinical benefit of alleviating edema. Reversal of normalization began by 28 days, though some features persisted for as long as four months. Basic FGF, SDF1α, and viable circulating endothelial cells (CECs) increased when tumors escaped treatment, and circulating progenitor cells (CPCs) increased when tumors progressed after drug interruption. Our study provides insight into different mechanisms of action of this class of drugs in recurrent glioblastoma patients and suggests that the timing of combination therapy may be critical for optimizing activity against this tumor.
