Abstract | BACKGROUND: 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.
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Authors | Kimberly W McCrudden, Benjamin Hopkins, Jason Frischer, Anna Novikov, Jianzhong Huang, Angela Kadenhe, Tamara New, Akiko Yokoi, Darrell J Yamashiro, Jessica J Kandel, William Middlesworth |
Journal | Journal of pediatric surgery
(J Pediatr Surg)
Vol. 38
Issue 3
Pg. 308-14; discussion 308-14
(Mar 2003)
ISSN: 1531-5037 [Electronic] United States |
PMID | 12632340
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 2003, Elsevier Science (USA). All rights reserved. |
Chemical References |
- Angiogenesis Inhibitors
- Antibodies, Monoclonal
- Endothelial Growth Factors
- Intercellular Signaling Peptides and Proteins
- Lymphokines
- Neoplasm Proteins
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factors
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Topics |
- Angiogenesis Inhibitors
(therapeutic use)
- Animals
- Antibodies, Monoclonal
(immunology, therapeutic use)
- Antibody Specificity
- Endothelial Growth Factors
(antagonists & inhibitors, immunology)
- Female
- Hepatoblastoma
(blood supply, drug therapy, secondary)
- Humans
- Intercellular Signaling Peptides and Proteins
(immunology)
- Liver Neoplasms
(blood supply, drug therapy)
- Lymphokines
(antagonists & inhibitors, immunology)
- Mice
- Mice, Nude
- Neoplasm Proteins
(antagonists & inhibitors, 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
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