%0 Journal Article %1 Shaked.2005 %A Shaked, Y. %A Bertolini, F. %A Man, S. %A Rogers, M. S. %A Cervi, D. %A Foutz, T. %A Rawn, K. %A Voskas, D. %A Dumont, D. J. %A Ben-David, Y. %A Lawler, J. %A Henkin, J. %A Huber, J. %A Hicklin, D. J. %A D'Amato, R. J. %A Kerbel, R. S. %D 2005 %J Cancer Cell %K A Angiogenesis Animals Antibodies Assay Biological Cell Cells Cytometry Dose-Response Drug Endothelial Factor Factors Fibroblast Flow Growth Humans Inbred Inhibitors Male Markers Mice Neovascularization Pathologic Phenotype Receptor Receptor-2 Relationship Research Stem Strains Survival TIE-2 Transgenic Vascular analysis blood cells drug effects genetics metabolism methods pharmacology physiology therapy %N 1 %P 101-111 %T Genetic heterogeneity of the vasculogenic phenotype parallels angiogenesis; Implications for cellular surrogate marker analysis of antiangiogenesis %U PM:15652753 %V 7 %X 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

@article{Shaked.2005, abstract = {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}, added-at = {2010-02-05T11:28:39.000+0100}, author = {Shaked, Y. and Bertolini, F. and Man, S. and Rogers, M. S. and Cervi, D. and Foutz, T. and Rawn, K. and Voskas, D. and Dumont, D. J. and Ben-David, Y. and Lawler, J. and Henkin, J. and Huber, J. and Hicklin, D. J. and D'Amato, R. J. and Kerbel, R. S.}, biburl = {https://www.bibsonomy.org/bibtex/2143003368877346ca533901f7be0d1b1/kanefendt}, interhash = {4462dc6cadef2e215dd2c86cca86b6cc}, intrahash = {143003368877346ca533901f7be0d1b1}, journal = {Cancer Cell}, keywords = {A Angiogenesis Animals Antibodies Assay Biological Cell Cells Cytometry Dose-Response Drug Endothelial Factor Factors Fibroblast Flow Growth Humans Inbred Inhibitors Male Markers Mice Neovascularization Pathologic Phenotype Receptor Receptor-2 Relationship Research Stem Strains Survival TIE-2 Transgenic Vascular analysis blood cells drug effects genetics metabolism methods pharmacology physiology therapy}, number = 1, pages = {101-111}, timestamp = {2010-02-05T11:28:43.000+0100}, title = {Genetic heterogeneity of the vasculogenic phenotype parallels angiogenesis; Implications for cellular surrogate marker analysis of antiangiogenesis}, url = {PM:15652753}, volume = 7, year = 2005 }