Inhibitory effect of bevacizumab on the angiogenesis and growth of retinoblastoma.
OBJECTIVE
To evaluate the potential effect of bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), on the angiogenesis and tumor growth of retinoblastoma in vitro and in vivo.


METHODS
The antiangiogenic effects of bevacizumab were evaluated in a coculture of a Y-79 human retinoblastoma cell line and a human umbilical vein endothelial cell line by means of a cell proliferation assay kit and a VEGF enzyme-linked immunosorbent assay. The Y-79 xenotransplanted nude mice were treated with bevacizumab intraperitoneally twice weekly for 4 weeks, during which each tumor was measured once a week. The mice were then euthanized, and the weight of each tumor and its microvessel density were determined via CD34 immunohistochemical staining.


RESULTS
The mean (standard error of the mean) increased human umbilical vein endothelial cell proliferation, when cocultured with Y-79 (156% [1%]), was suppressed 58% (5%) by the blockage of VEGF induced by bevacizumab. By causing a 2-fold reduction in microvessel density in the Y-79 xenograft model, bevacizumab induced a 75% reduction in the growth of the retinoblastomas without producing significant systemic toxicity. Conclusions and Clinical Relevance Treatment with bevacizumab suppressed the angiogenesis and growth of retinoblastoma in vitro and in vivo. Bevacizumab is likely to be of benefit in the treatment of retinoblastoma.
Lee
Sun Young
SY
Department of Ophthalmology, University of Ulsan, Asan Medical Center, 388-1 Poongnap-dong, Songpa-gu, Seoul 138-736, Korea.
Kim
Dong-Kyu
DK
Cho
Jae Hyung
JH
Koh
Jae-Young
JY
Yoon
Young Hee
YH
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018952:Antigens, CD34 / Q000378:metabolism; D000068258:Bevacizumab; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D008858:Microscopy, Phase-Contrast; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D019572:Retinal Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D012175:Retinoblastoma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018952:Antigens, CD34; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab