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Tumor Biology

Complete Inhibition of Angiogenesis and Growth of Microtumors by Anti-Vascular Endothelial Growth Factor Neutralizing Antibody: Novel Concepts of Angiostatic Therapy from Intravital Videomicroscopy

Per Borgström, Kenneth J. Hillan, Pragada Sriramarao and Napolenone Ferrara
Per Borgström
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Kenneth J. Hillan
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Pragada Sriramarao
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Napolenone Ferrara
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DOI:  Published September 1996
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Abstract

In the present study, we evaluated the effects of a neutralizing antivascular endothelial growth factor (anti-VEGF) antibody on angiogenesis and growth of tumor spheroids using an intravital microscopic technique permitting noninvasive, in vivo and in situ study of tumor angiogenesis and tumor growth in conscious mice. Tumor spheroids of the human rhabdomyosarcoma cell line A673, with a diameter between 600 and 1000 µm, were implanted in dorsal skinfold chambers inserted on Beige nude/xid mice. Tumor cells were prelabeled with a fluorescent vital dye [(5-(and-6)-((4-chloromethyl)benzoyl)amino)tetramethylrhodamine], which allowed estimation of the growth of the implanted tumor spheroids. Treatment (i.p.) with the monoclonal antibody A4.6.1, specific for VEGF, completely inhibited neovascularization of the microtumors and suppressed their growth to the extent that tumors implanted in treated animals leveled off at a volume less than 1 mm3, i.e., the anti-VEGF antibody dramatically changed the growth characteristics of the tumor line from being a rapidly growing malignancy to a dormant microcolony.

Footnotes

  • ↵1 To whom requests for reprints should be addressed, at La Jolla Institute for Experimental Medicine, 11077 North Torrey Pines Road, La Jolla, CA 92037. Phone: (619) 587-8788; Fax: (619) 458-9072.

  • Received April 12, 1996.
  • Accepted July 2, 1996.
  • ©1996 American Association for Cancer Research.
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September 1996
Volume 56, Issue 17
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Complete Inhibition of Angiogenesis and Growth of Microtumors by Anti-Vascular Endothelial Growth Factor Neutralizing Antibody: Novel Concepts of Angiostatic Therapy from Intravital Videomicroscopy
Per Borgström, Kenneth J. Hillan, Pragada Sriramarao and Napolenone Ferrara
Cancer Res September 1 1996 (56) (17) 4032-4039;

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Complete Inhibition of Angiogenesis and Growth of Microtumors by Anti-Vascular Endothelial Growth Factor Neutralizing Antibody: Novel Concepts of Angiostatic Therapy from Intravital Videomicroscopy
Per Borgström, Kenneth J. Hillan, Pragada Sriramarao and Napolenone Ferrara
Cancer Res September 1 1996 (56) (17) 4032-4039;
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