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Prepublished online as a Blood First Edition Paper on September 25, 2003; DOI 10.1182/blood-2003-07-2192. This Article Full Text (PDF) All Versions of this Article: 2003-07-2192v1 103/2/601    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Staton, C. A Articles by Lewis, C. E Search for Related Content PubMed PubMed Citation Articles by Staton, C. A Articles by Lewis, C. E Social Bookmarking                   What's this? Submitted July 2, 2003 Accepted September 8, 2003 Alphastatin, a 24 amino acid fragment of human fibrinogen, is a potent new inhibitor of activated endothelial cells in vitro and in vivo Carolyn A Staton, Nicola J Brown, Gary R Rodgers, Kevin P Corke, Simon Tazzyman, James C Underwood, and Claire E Lewis* Tumour Targeting Group, University of Sheffield Medical School, Sheffield, United Kingdom Microcirculation Research Unit, University of Sheffield Medical School, Sheffield, United Kingdom Institute of Cancer Research, University of Sheffield Medical School, Sheffield, United Kingdom * Corresponding author; email: claire.lewis{at}sheffield.ac.uk. Angiogenesis, the development of new blood vessels from existing vasculature, is crucial for the development and metastasis of solid tumors. Here, we show for the first time that a 24-amino acid peptide derived from the amino terminus of the alpha chain of human fibrinogen (termed 'alphastatin') has potent anti-angiogenic properties, inhibiting both the migration and tubule formation of human dermal microvascular endothelial cells in response to VEGF or bFGF in vitro. Moreover, alphastatin markedly inhibits the growth of tumors in a syngeneic murine model. Tumors from mice receiving daily injections of alphastatin for 12 days exhibited large areas of intravascular disruption and thrombosis, with substantial cellular necrosis. Importantly, alphastatin administration had no detectable effect on vessels in such healthy tissues as liver, lungs and kidney. Taken together, these data indicate that alphastatin is a potent new anti-angiogenic agent in vitro and anti-vascular agent in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Z. Li, M. A. Nardi, Y.-S. Li, W. Zhang, R. Pan, S. Dang, H. Yee, D. Quartermain, S. Jonas, and S. Karpatkin C-terminal ADAMTS-18 fragment induces oxidative platelet fragmentation, dissolves platelet aggregates, and protects against carotid artery occlusion and cerebral stroke Blood, June 11, 2009; 113(24): 6051 - 6060. [Abstract] [Full Text] [PDF] Y. Huang, H. Shi, H. Zhou, X. Song, S. Yuan, and Y. Luo The angiogenic function of nucleolin is mediated by vascular endothelial growth factor and nonmuscle myosin Blood, May 1, 2006; 107(9): 3564 - 3571. [Abstract] [Full Text] [PDF] V. W.M. van Hinsbergh, M. A. Engelse, and P. H.A. Quax Pericellular Proteases in Angiogenesis and Vasculogenesis Arterioscler Thromb Vasc Biol, April 1, 2006; 26(4): 716 - 728. [Abstract] [Full Text] [PDF] C. Lewis and C. Murdoch Macrophage Responses to Hypoxia: Implications for Tumor Progression and Anti-Cancer Therapies Am. J. Pathol., September 1, 2005; 167(3): 627 - 635. [Abstract] [Full Text] [PDF]

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