Bevacizumab-induced tumor vessel remodeling in rhabdomyosarcoma xenografts increases the effectiveness of adjuvant ionizing radiation

Adrianne L. Myers, Regan Williams, Cathy Y. Ng, Joseph E. Hartwich, Andrew M. Davidoff

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Purpose: Inhibition of vascular endothelial growth factor (VEGF) may effect transient "normalization" of tumor vasculature by pruning immature vessels, resulting in improved tumor perfusion and oxygenation. This may improve the efficacy of adjuvant ionizing radiation (IR). We tested this hypothesis using bevacizumab, an anti-VEGF antibody, in rhabdomyosarcoma (RMS) xenografts. Methods: Mice bearing orthotopic alveolar RMS xenografts were treated with a single dose of bevacizumab, IR, or a combination of the two on different schedules. Tumors were then evaluated for changes in microvessel density, vessel maturity, vessel permeability, intratumoral oxygenation, as well as altered growth. Results: After bevacizumab treatment, a significant decrease in tumor microvessel density and a significant increase in tumor vessel maturity, defined as the ratio of pericytes to endothelial cells, were observed, suggesting pruning of immature vessels lacking pericytes. Tumor vessel permeability was also significantly decreased and intratumoral oxygen tension increased 2 and 5 days after bevacizumab owing to a transient improvement in tumor perfusion. Treatment with IR 2 or 5 days after bevacizumab resulted in the greatest antitumor activity. Conclusion: Our findings support the hypothesis that VEGF inhibition with bevacizumab transiently normalizes the dysfunctional vasculature of RMS xenografts, improving tumor oxygenation and increasing tumor sensitivity to adjuvant IR.

Original languageEnglish (US)
Pages (from-to)1080-1085
Number of pages6
JournalJournal of pediatric surgery
Volume45
Issue number6
DOIs
StatePublished - Jan 1 2010

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Rhabdomyosarcoma
Ionizing Radiation
Heterografts
Neoplasms
Vascular Endothelial Growth Factor A
Pericytes
Microvessels
Permeability
Perfusion
Alveolar Rhabdomyosarcoma
Bevacizumab
Appointments and Schedules
Endothelial Cells
Oxygen
Antibodies

All Science Journal Classification (ASJC) codes

  • Surgery
  • Pediatrics, Perinatology, and Child Health
  • Medicine(all)

Cite this

Bevacizumab-induced tumor vessel remodeling in rhabdomyosarcoma xenografts increases the effectiveness of adjuvant ionizing radiation. / Myers, Adrianne L.; Williams, Regan; Ng, Cathy Y.; Hartwich, Joseph E.; Davidoff, Andrew M.

In: Journal of pediatric surgery, Vol. 45, No. 6, 01.01.2010, p. 1080-1085.

Research output: Contribution to journalArticle

Myers, Adrianne L. ; Williams, Regan ; Ng, Cathy Y. ; Hartwich, Joseph E. ; Davidoff, Andrew M. / Bevacizumab-induced tumor vessel remodeling in rhabdomyosarcoma xenografts increases the effectiveness of adjuvant ionizing radiation. In: Journal of pediatric surgery. 2010 ; Vol. 45, No. 6. pp. 1080-1085.
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