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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:911.)
© 2003 American Heart Association, Inc.

Letters to the Editor

Rapid Analysis of Angiogenesis Drugs in a Live Fluorescent Zebrafish Assay

Laura M. Cross; Marisa A. Cook; Shuo Lin; Jau-Nian Chen; Amy L. Rubinstein

Zygogen, LLC (L.M.C., M.A.C., S.L., A.L.R.), Atlanta, GA; and Department of Molecular, Cellular, and Developmental Biology (S.L., J.-N.C.), University of California, Los Angeles

An extract of the first 250 words of the full text is provided, because this article has no abstract.

To the Editor:

Solid tumors require an adequate supply of blood vessels to survive, grow, and metastasize.^1–3 New blood vessels that nourish growing tumors form by angiogenesis. Drugs shown to have anti-angiogenic activity are currently in clinical cancer trials.⁴ To date, anti-angiogenic drugs have had mixed success in clinical application. Many new compounds may need to be tested to identify drugs capable of treating a wide range of tumors. The ideal assay for screening new compounds should involve blood vessels growing in their natural environment, such as a whole living organism, yet be amenable to rapid analysis. No current assays provide such a unique combination. We describe here an assay using the zebrafish (Danio rerio) that provides the relevance of an in vivo environment as well as the potential for high throughput drug screening.

The zebrafish has become a well accepted model for studies of vertebrate developmental biology. The vascular system has been well described and shown to be highly conserved in the zebrafish.^5,6 Many zebrafish blood vessels form by angiogenic sprouting and appear to require the same proteins that are necessary for blood vessel growth in mammals. In addition, anti-angiogenic compounds, such as PTK787/ZK222584 and SU5416, have been shown to affect the formation of zebrafish blood vessels.^7,8

Current methods of visualizing blood vessels in the zebrafish include whole mount in situ hybridization,^9,10 detection of endogenous alkaline phosphatase activity,⁸ and microangiography.¹¹ The first two methods are time consuming and involve fixation of embryos and larvae prior to analysis. . . . [Full Text of this Article]

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