Format

Send to

Choose Destination
J Pediatr Surg. 2001 Aug;36(8):1177-81.

Combination antiangiogenic therapy: increased efficacy in a murine model of Wilms tumor.

Author information

1
Division of Pediatric Surgery, and the Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.

Abstract

BACKGROUND/PURPOSE:

Antibody to vascular endothelial growth factor (anti-VEGF) suppresses tumor growth and metastasis in experimental Wilms tumor. However, tumor growth accelerates if antibody is withdrawn. As recently shown, low-dose, frequently administered topotecan, a topoisomerase-1 inhibitor, has anti-angiogenic activity. The authors hypothesized that combined topotecan/anti-VEGF therapy would suppress tumor growth and metastasis more durably than either agent alone.

METHODS:

Xenografts were induced by intrarenal injection of human Wilms tumor cells in athymic mice (n = 59). Mice were divided into control (n = 10), anti-VEGF (n = 16), topotecan (n = 17), and topotecan plus anti-VEGF (n = 16) groups. All control and half the treated mice were killed at week 6. Remaining ("rebound") mice were maintained without treatment until week 8. Tumor vasculature was mapped by fluorescein angiography/PECAM immunostaining. Endothelial apoptosis was assessed by TUNEL assay.

RESULTS:

6 weeks: Tumor weights were reduced significantly in treated mice (P <.003 v control). Seven of ten control and 1 of 25 treated mice displayed lung metastases (P <.003). Rebound tumors were largest in topotecan-only, intermediate in antibody-treated, and smallest in combination-treated mice. Immunostaining and angiography results showed sparse vascularity in treated xenografts. Endothelial apoptosis was observed only in treated tumors.

CONCLUSION:

Combination low-dose topotecan and anti-VEGF antibody therapy is antiangiogenic and suppresses tumor growth and metastasis in experimental Wilms tumor more durably than either agent alone.

PMID:
11479851
DOI:
10.1053/jpsu.2001.25747
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center