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Publication : Genetic heterogeneity of the vasculogenic phenotype parallels angiogenesis; Implications for cellular surrogate marker analysis of antiangiogenesis.

First Author  Shaked Y Year  2005
Journal  Cancer Cell Volume  7
Issue  1 Pages  101-11
PubMed ID  15652753 Mgi Jnum  J:96033
Mgi Id  MGI:3528784 Doi  10.1016/j.ccr.2004.11.023
Citation  Shaked Y, et al. (2005) Genetic heterogeneity of the vasculogenic phenotype parallels angiogenesis; Implications for cellular surrogate marker analysis of antiangiogenesis. Cancer Cell 7(1):101-11
abstractText  Development of antiangiogenic therapies would be significantly facilitated by quantitative surrogate pharmacodynamic markers. Circulating peripheral blood endothelial cells (CECs) and/or their putative progenitor subset (CEPs) have been proposed but not yet fully validated for this purpose. Herein, we provide such validation by showing a striking correlation between highly genetically heterogeneous bFGF- or VEGF-induced angiogenesis and intrinsic CEC or CEP levels measured by flow cytometry, among eight different inbred mouse strains. Moreover, studies using genetically altered mice showed that levels of these cells are affected by regulators of angiogenesis, including VEGF, Tie-2, and thrombospondin-1. Finally, treatment with a targeted VEGFR-2 antibody caused a dose-dependent reduction in viable CEPs that precisely paralleled its previously and empirically determined antitumor activity.
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