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American Association of Endocrine Surgeons| Volume 128, ISSUE 6, P1059-1066, December 2000

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Neutralizing vascular endothelial growth factor activity inhibits thyroid cancer growth in vivo

  • Euy Y. Soh
    Affiliations
    Departments of Surgery, Ajou University School of Medicine, University of California San Francisco/Mount Zion Medical Center, University of California San Francisco/San Francisco General Hospital, and the Veterans Affairs Medical Center, San Francisco, and Genentech, South San Francisco San Francisco, Calif
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  • Monica S. Eigelberger
    Affiliations
    Departments of Surgery, Ajou University School of Medicine, University of California San Francisco/Mount Zion Medical Center, University of California San Francisco/San Francisco General Hospital, and the Veterans Affairs Medical Center, San Francisco, and Genentech, South San Francisco San Francisco, Calif
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  • K.Jin Kim
    Affiliations
    Departments of Surgery, Ajou University School of Medicine, University of California San Francisco/Mount Zion Medical Center, University of California San Francisco/San Francisco General Hospital, and the Veterans Affairs Medical Center, San Francisco, and Genentech, South San Francisco San Francisco, Calif
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  • Mariwil G. Wong
    Affiliations
    Departments of Surgery, Ajou University School of Medicine, University of California San Francisco/Mount Zion Medical Center, University of California San Francisco/San Francisco General Hospital, and the Veterans Affairs Medical Center, San Francisco, and Genentech, South San Francisco San Francisco, Calif
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  • David M. Young
    Affiliations
    Departments of Surgery, Ajou University School of Medicine, University of California San Francisco/Mount Zion Medical Center, University of California San Francisco/San Francisco General Hospital, and the Veterans Affairs Medical Center, San Francisco, and Genentech, South San Francisco San Francisco, Calif
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  • Orlo H. Clark
    Affiliations
    Departments of Surgery, Ajou University School of Medicine, University of California San Francisco/Mount Zion Medical Center, University of California San Francisco/San Francisco General Hospital, and the Veterans Affairs Medical Center, San Francisco, and Genentech, South San Francisco San Francisco, Calif
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  • Quan-Yang Duh
    Affiliations
    Departments of Surgery, Ajou University School of Medicine, University of California San Francisco/Mount Zion Medical Center, University of California San Francisco/San Francisco General Hospital, and the Veterans Affairs Medical Center, San Francisco, and Genentech, South San Francisco San Francisco, Calif
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      Abstract

      Background. Without angiogenesis, tumor growth is limited to a few millimeters, the limit of diffusion. Vascular endothelial growth factor (VEGF) is an endothelial-specific mitogen and a major regulator of angiogenesis. Methods. To investigate the relationship between VEGF and thyroid tumor angiogenesis, we xenografted human dermal matrix inoculated with FTC-133 cells into nude mice or directly injected FTC-133 cells subcutaneously. To block the function of VEGF, the neutralizing anti-VEGF monoclonal antibody A.4.6.1 (mAb A.4.6.1) was injected intraperitoneally twice weekly. As control, an antibody of the same isotype (Ab 5B6) or phosphate buffer saline solution (PBS) was used. To evaluate the dermal matrix as a model for angiogenesis studies, recombinant human VEGF was inoculated into the dermal matrix pocket and xenografted into mice. Results. In the dermal matrix angiogenesis model, the number of blood vessels paralleled the concentration of recombinant human VEGF and was highest at 100 ng/mL. Mice that were treated with the mAb A4.6.1 developed fewer blood vessels (mean, 6.6 per HPF) than control mice (18 per HPF in Ab 5B6 and 22 per HPF in PBS; P <.01). Tumors from mice that were treated with mAb A.4.6.1 were much smaller (mean ± SD, 0.09 ± 0.02 gm) at 5 weeks, compared with the tumors treated with Ab 5B6 (5.38 ± 1.15 gm) or PBS (4.0 ± 0.72 gm; P ≤.001). Conclusions. VEGF is produced by the follicular thyroid cancer cell line and stimulates angiogenesis and growth of thyroid cancer. This stimulation can be blocked by mAb A.4.6.1. (Surgery 2000;128:1059-66.)
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