Systemic administration of vascular endothelial growth factor monoclonal antibody reduces the growth of papillary thyroid carcinoma in a nude mouse model.
Papillary thyroid carcinomas (PTC) are the most common thyroid cancers in children. Most are successfully treated with surgery and radioactive iodine, but some persist. PTC express high levels of vascular endothelial growth factor (VEGF) and VEGF receptor (Flt-1). PTC with the most intense expression of VEGF have the greatest recurrence risk. We hypothesized that blockade of VEGF would inhibit PTC growth. To test this, we used systemic VEGF monoclonal antibody (VEGF-MAb) to treat PTC xenografts in nude mice. Treated animals (n = 9) received 200 microg VEGF-MAb by daily i.p. injection for 10 wk, while control animals (n = 9) received vehicle alone. Tumor size was significantly reduced in the treatment group (0.28 +/- 0.06 vs 1.05 +/- 0.25 g, p = 0.008). VEGF immunostaining was more intense (2.57 +/- 0.30 vs 1.75 +/- 0.25, p = 0.06) and the number of p53 positive cells was increased (1.66 +/- 0.24 vs 0.83 +/- 0.31, p = 0.048) in treated tumors. Animal weight was similar in both groups (29.1 +/- 1.1 vs 27.4 +/- 1.1 g, p = 0.30). In conclusion, systemic VEGF-MAb significantly reduced the growth of PTC, suggesting that VEGF-MAb might be useful for treatment of resistant PTC.
Bauer
Andrew J
AJ
Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799, USA. abauer@usuhs.mil
Patel
Aneeta
A
Terrell
Richard
R
Doniparthi
Krishna
K
Saji
Motoyasu
M
Ringel
Matthew
M
Tuttle
R Michael
RM
Francis
Gary L
GL
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D002291:Carcinoma, Papillary / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D007124:Immunoenzyme Techniques; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D016159:Tumor Suppressor Protein p53; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A