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Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases.

Abstract：

:The recent landmark Phase III clinical trial with a VEGF-specific antibody suggests that antiangiogenic therapy must be combined with cytotoxic therapy for the treatment of solid tumors. However, there are no guidelines for optimal scheduling of these therapies. Here we show that VEGFR2 blockade creates a "normalization window"--a period during which combined radiation therapy gives the best outcome. This window is characterized by an increase in tumor oxygenation, which is known to enhance radiation response. During the normalization window, but not before or after it, VEGFR2 blockade increases pericyte coverage of brain tumor vessels via upregulation of Ang1 and degrades their pathologically thick basement membrane via MMP activation.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Winkler F,Kozin SV,Tong RT,Chae SS,Booth MF,Garkavtsev I,Xu L,Hicklin DJ,Fukumura D,di Tomaso E,Munn LL,Jain RK

doi

10.1016/j.ccr.2004.10.011

keywords:

subject

Has Abstract

pub_date

2004-12-01 00:00:00

pages

553-63

issue

6

eissn

1535-6108

issn

1878-3686

pii

S1535610804003058

journal_volume

6

pub_type

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