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[Cancer Research 61, 7048-7051, October 1, 2001]
© 2001 American Association for Cancer Research


Advances in Brief

In Vivo Intracellular Signaling as a Marker of Antiangiogenic Activity1

Carmen C. Solorzano, Young D. Jung, Corazon D. Bucana, David J. McConkey, Gary E. Gallick, Gerald McMahon and Lee M. Ellis2

Departments of Surgical Oncology [C. C. S., L. M. E.] and Cancer Biology [Y. D. J., C. D. B., D. J. M., G. E. G., L. M. E.], University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, and SUGEN, Inc., South San Francisco, California 94080 [G. M.]

Alterations in endothelial cell (EC) signaling could serve as a marker of effective antiangiogenic therapy. We determined the effect of an antiangiogenic tyrosine kinase inhibitor, SU6668, on tumor EC signaling in liver metastases in mice. In vitro immunofluorescence verified that pretreatment of ECs with SU6668 before exposure to VEGF decreased in vitro phosphorylation of Erk and Akt. Using double-fluorescence immunohistochemistry, phosphorylated Erk and Akt were constitutively expressed in ECs in liver metastases in untreated mice, but SU6668 blocked activation of these signaling intermediates. Determining the activation status of the Erk and Akt signaling pathways in tumor ECs may serve as a surrogate marker for the effectiveness of antiangiogenic regimens.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
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Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2001 by the American Association for Cancer Research.