RRC ID 73070
Author McCrudden KW, Hopkins B, Frischer J, Novikov A, Huang J, Kadenhe A, New T, Yokoi A, Yamashiro DJ, Kandel JJ, Middlesworth W.
Title Anti-VEGF antibody in experimental hepatoblastoma: suppression of tumor growth and altered angiogenesis.
Journal J Pediatr Surg
Abstract BACKGROUND:Hepatoblastoma is the most common primary hepatic malignancy of childhood, frequently presenting as advanced disease. Vascular endothelial growth factor (VEGF) is an endothelial mitogen and survival factor critical to growth and angiogenesis in many human cancers. Inhibition of VEGF effectively suppresses tumorigenesis in multiple experimental models. The authors hypothesized that anti-VEGF antibody would alter vascular architecture and impede tumor growth in experimental hepatoblastoma.
METHODS:The Institutional Animal Care and Use Committee of Columbia University approved all protocols. Xenografts were established in athymic mice by intrarenal injection of cultured human hepatoblastoma cells. Anti-VEGF antibody (100 microg/dose) or vehicle was administered intraperitoneally 2 times per week for 5 weeks. At week 6, 10 control/treated mice were killed and remaining animals maintained without treatment until week 8. Tumor weights were compared by Kruskal-Wallis analysis, and vascular alterations ascertained by fluorescein angiography and specific immunostaining.
RESULTS:Anti-VEGF antibody significantly inhibited tumor growth at 6 weeks (1.85 g +/- 0.60 control, 0.05 +/- 0.03 antibody, P <.0003). In comparison with controls, treated xenografts showed decreased vascularity and dilated surviving vessels with prominent vascular smooth muscle elements.
CONCLUSIONS:Specific anti-VEGF therapy inhibits neoangiogenesis and significantly suppresses tumor growth in experimental hepatoblastoma. Surviving vasculature displays dilation and increased vascular smooth muscle. Anti-VEGF agents may represent new therapeutic alternatives for children with advanced disease.
Volume 38(3)
Pages 308-14; discussion 308-14
Published 2003-3-1
DOI 10.1053/jpsu.2003.50099
PII S0022346802631070
PMID 12632340
MeSH Angiogenesis Inhibitors / therapeutic use* Animals Antibodies, Monoclonal / immunology Antibodies, Monoclonal / therapeutic use* Antibody Specificity Endothelial Growth Factors / antagonists & inhibitors* Endothelial Growth Factors / immunology Female Hepatoblastoma / blood supply Hepatoblastoma / drug therapy* Hepatoblastoma / secondary Humans Intercellular Signaling Peptides and Proteins / immunology Liver Neoplasms / blood supply Liver Neoplasms / drug therapy* Lymphokines / antagonists & inhibitors* Lymphokines / immunology Mice Mice, Nude Neoplasm Proteins / antagonists & inhibitors* Neoplasm Proteins / immunology Neoplasm Transplantation Neovascularization, Pathologic / drug therapy* Peritoneal Neoplasms / secondary Tumor Cells, Cultured Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Xenograft Model Antitumor Assays
Human and Animal Cells HuH-6(RCB1367)