Angiogenesis and Therapeutic Approaches to NF1 Tumors
Annual rept. 1 Apr 2005-31 Mar 2006
FLORIDA UNIV GAINESVILLE
Pagination or Media Count:
The main goal of this project is to specify how anti-angiogenic approaches can be effectively applied to NF1 tumors. To this end, we will first determine whether NF1 heterozygosity alters the responsiveness of endothelial cells to angiogenic regulators. We will test if Nf1- endothelial cells are particularly responsive to pro-angiogenic factors produced by NF1 tumor cells and, perhaps even more importantly, which anti-angiogenic factors are most effective in abrogating the angiogenic response evoked by NF1 tumors. In particular, endostatin will be thoroughly examined as a potential anti-angiogenic therapy for NF1 tumors. Gene therapy for NF1 tumors has not been tested due to the lack of an appropriate NF1 tumor model. We have established a working xenograft model of neurofibroma in the mouse in which the efficacy of endostatin gene therapy will be accessed. This model involves the initiation of neurofibromas by implantation of human NF1 tumor-derived, neurofibromin-null Schwann cells into the nerves of mice with an Nf1- background. Tumor progression and vascularity will be assessed in vivo by MRI non-invasive imaging. MRI data will be corroborated by end-point histology using precise labeling of tumor and host cell components.
- Anatomy and Physiology
- Medicine and Medical Research