Antiangiogenic therapy inhibits human neuroblastoma growth.

Abstract

BACKGROUND:

Angiogenesis plays a crucial role in the progression and metastasis of malignant solid tumors. In many types of cancer, including neuroblastoma, high tumor vascularity correlates with poor outcome. Recently, a number of angiogenic inhibitors have been identified that had antitumor activity in preclinical studies.

PROCEDURE:

To investigate the effect of the antiangiogenic agent TNP-470 on neuroblastoma tumor growth, we treated nude mice with TNP-470 after they were inoculated subcutaneously with 5 x 10(6) cells from the MYCN-amplified, human neuroblastoma cell line NBL-W-N.

RESULTS:

TNP-470 did not significantly affect tumor growth when it was administered to mice with large tumors (>600 mm3). However, when TNP-470 was administered in the setting of microscopic disease 12 hr following tumor cell inoculation, treated mice had a significantly improved tumor-free survival at 12 weeks (P < 0.001), and overall survival at 45 weeks (P < 0.001), compared to control animals.

CONCLUSIONS:

Our studies suggest that TNP-470 treatment may be most effective if it is administered in the setting of microscopic disease. We speculate that TNP-470 may inhibit neuroblastoma growth in children if treatment is initiated following intensive multimodality therapy, when residual disease is minimal.

• Authors: H M Katzenstein, H R Salwen, N N Nguyen, D Meitar, S L Cohn
• Journal: Medical and pediatric oncology (Med Pediatr Oncol) Vol. 36 Issue 1 Pg. 190-3 (Jan 2001) ISSN: 0098-1532 [Print] United States
• PMID: 11464880 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Angiogenesis Inhibitors
• Cyclohexanes
• Sesquiterpenes
• O-(Chloroacetylcarbamoyl)fumagillol

Topics

• Angiogenesis Inhibitors (therapeutic use)
• Animals
• Cell Division
• Cyclohexanes
• Humans
• Male
• Mice
• Mice, Nude
• Neovascularization, Pathologic (drug therapy)
• Neuroblastoma (blood supply, drug therapy, pathology)
• O-(Chloroacetylcarbamoyl)fumagillol
• Sesquiterpenes (therapeutic use)
• Tumor Cells, Cultured (transplantation)
• Xenograft Model Antitumor Assays