TY - JOUR
T1 - Complete inhibition of angiogenesis and growth of microtumors by anti- vascular endothelial growth factor neutralizing antibody
T2 - Novel concepts of angiostatic therapy from intravital videomicroscopy
AU - Borgström, Per
AU - Hillan, Kenneth J.
AU - Sriramarao, Pragada
AU - Ferrara, Napoleone
PY - 1996/9/1
Y1 - 1996/9/1
N2 - In the present study, we evaluated the effects of a neutralizing anti- vascular 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 that 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.
AB - In the present study, we evaluated the effects of a neutralizing anti- vascular 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 that 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.
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M3 - Article
C2 - 8752175
AN - SCOPUS:0029816983
SN - 0008-5472
VL - 56
SP - 4032
EP - 4039
JO - Cancer Research
JF - Cancer Research
IS - 17
ER -