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Blood, 14 May 2009, Vol. 113, No. 20, pp. 5019-5027. Prepublished online as a Blood First Edition Paper on January 28, 2009; DOI 10.1182/blood-2008-04-150318. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-04-150318v1 113/20/5019    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Bieker, R. Articles by Berdel, W. E. Search for Related Content PubMed PubMed Citation Articles by Bieker, R. Articles by Berdel, W. E. Related Collections Thrombosis and Hemostasis Vascular Biology Clinical Trials and Observations Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  VASCULAR BIOLOGY Infarction of tumor vessels by NGR-peptide–directed targeting of tissue factor: experimental results and first-in-man experience Ralf Bieker1, Torsten Kessler1, Christian Schwöppe1, Teresa Padró1, Thorsten Persigehl2, Christoph Bremer2, Johannes Dreischalück1, Astrid Kolkmeyer1, Walter Heindel2, Rolf M. Mesters1,*, and Wolfgang E. Berdel1,* Departments of 1 Medicine/Hematology and Oncology and 2 Clinical Radiology, University of Muenster, Muenster, Germany We induced thrombosis of blood vessels in solid tumors in mice by a fusion protein consisting of the extracellular domain of tissue factor (truncated tissue factor, tTF) and the peptide GNGRAHA, targeting aminopeptidase N (CD13) and the integrin vβ3 (CD51/CD61) on tumor vascular endothelium. The designed fusion protein tTF-NGR retained its thrombogenic activity as demonstrated by coagulation assays. In vivo studies in mice bearing established human adenocarcinoma (A549), melanoma (M21), and fibrosarcoma (HT1080) revealed that systemic administration of tTF-NGR induced partial or complete thrombotic occlusion of tumor vessels as shown by histologic analysis. tTF-NGR, but not untargeted tTF, induced significant tumor growth retardation or regression in all 3 types of solid tumors. Thrombosis induction in tumor vessels by tTF-NGR was also shown by contrast enhanced magnetic resonance imaging (MRI). In the human fibrosarcoma xenograft model, MRI revealed a significant reduction of tumor perfusion by administration of tTF-NGR. Clinical first-in-man application of low dosages of this targeted coagulation factor revealed good tolerability and decreased tumor perfusion as measured by MRI. Targeted thrombosis in the tumor vasculature induced by tTF-NGR may be a promising strategy for the treatment of cancer. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: NGR and isoDGR are separate moieties binding to different receptors Gian-Paolo Rizzardi and Claudio Bordignon Blood 2009 113: 5366. [Full Text] [PDF] Response: NGR and isoDGR are separate moieties binding to different receptors Christian Schwöppe, Ralf Bieker, Rolf M. Mesters, and Wolfgang E. Berdel Blood 2009 113: 5367. [Full Text] [PDF] Flipping the wound that doesn't heal: the upside of coagulation in cancer Beverly A. Teicher Blood 2009 113: 4827-4828. [Full Text] [PDF] This article has been cited by other articles: R. S. Kasthuri, M. B. Taubman, and N. Mackman Role of Tissue Factor in Cancer J. Clin. Oncol., October 10, 2009; 27(29): 4834 - 4838. [Abstract] [Full Text] [PDF] G.-P. Rizzardi and C. Bordignon NGR and isoDGR are separate moieties binding to different receptors Blood, May 21, 2009; 113(21): 5366 - 5366. [Full Text] [PDF] B. A. Teicher Flipping the wound that doesn't heal: the upside of coagulation in cancer Blood, May 14, 2009; 113(20): 4827 - 4828. [Full Text] [PDF]

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