Anti-VEGF antibody in experimental hepatoblastoma: suppression of tumor growth and altered angiogenesis.
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.
McCrudden
Kimberly W
KW
Division of Pediatric Surgery, Children's Hospital of New York-Presbyterian, Columbia University, New York, New York 10032, USA.
Hopkins
Benjamin
B
Frischer
Jason
J
Novikov
Anna
A
Huang
Jianzhong
J
Kadenhe
Angela
A
New
Tamara
T
Yokoi
Akiko
A
Yamashiro
Darrell J
DJ
Kandel
Jessica J
JJ
Middlesworth
William
W
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000918:Antibody Specificity; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors* / Q000276:immunology; D005260:Female; D018197:Hepatoblastoma / Q000098:blood supply / Q000188:drug therapy* / Q000556:secondary; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D008222:Lymphokines / Q000037:antagonists & inhibitors* / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010534:Peritoneal Neoplasms / Q000556:secondary; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D009363:Neoplasm Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors