Angiogenesis and Therapeutic Approaches to NF1 Tumors
Abstract
The goal of this project is to specify how anti-angiogenic approaches can be effectively applied to NF1 tumors. Invivo and in vitro models were used to firmly conclude that Nf1 haploinsufficiency in endothelial cells results inexaggerated proliferation and angiogenesis in response to key pro-angiogenic factors. Results implicate these growthfactor pathways as potential targets for therapeutic agents. In addition, endostatin was found to be a potent inhibitorof Nf1+/- endothelial cell migration in vitro, suggesting endostatin may be an effective antiangiogenic agent forreducing NF1 tumor growth. Two intraneural xenograft models of NF1 peripheral nerve sheath tumors weredeveloped and characterized. Tumor growth and vascularity of NF1 tumor xenografts was quantified by advancedMRI, gadolinium permeability and dynamic contrast enhancement that match results obtained by conventionalhistological measurements. Several methods to deliver endostatin in vivo were tested and several difficulties wereencountered. Finally, cell factories made by alginate-encapsulation of 293 cells transfected with AAV-endostatinwere developed and are being refined to deliver consistent, high-dose systemic levels of endostatin. The effects ofsystemic endostatin on NF1 xenograft tumor growth will be completed in a no-cost extension of this project.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2007
- Accession Number
- ADA475785
Entities
People
- David F. Muir
Organizations
- University of Florida