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

Authors
Soh, EY; Eigelberger, MS; Kim, KJ; Wong, MG; Young, DM; Clark, OH; Duh, QY
Citation
Surgery, 128(6):1059-1065, 2000
Journal Title
Surgery
ISSN
0039-60601532-7361
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.
MeSH terms
AnimalsAntibodies, Monoclonal/*therapeutic useEndothelial Growth Factors/*antagonists & inhibitors/physiologyFemaleHumansLymphokines/*antagonists & inhibitors/physiologyMiceMice, Inbred BALB CMice, NudeNeoplasm TransplantationNeovascularization, Pathologic/prevention & controlThyroid Neoplasms/pathology/*therapyTransplantation, HeterologousTumor Cells, CulturedVascular Endothelial Growth Factor AVascular Endothelial Growth Factors
DOI
10.1067/msy.2000.110430
PMID
11114643
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Surgery
AJOU Authors
소, 의영
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