Role of Angiogenesis in the Etiology and Prevention of Ovarian Cancer
Abstract
Ovarian cancer growth and its dissemination into the peritoneal cavity are dependent on angiogenesis. Therefore, angiogenesis inhibitors can be used in the prevention and treatment of ovarian cancers. One of the objectives of Project 1 is the development of a genetically reengineered angiostatic protein, endostatin. A mutant endostatin containing a single amino acid substitution at position 125 (P125A-endostatin) was found to be more active than the native protein. P125A endostatin was further modified to incorporate vascular targeting sequence, RGD, so that the bioavailability can be increased at the tumor vasculature. Modified endostatins were evaluated for antiangiogenic and antitumor activities in model systems. Genetic modifications significantly improved the biological activity of endostatin. Synthetic peptides corresponding to the mutation site were made to characterize the mechanism of enhanced antiangiogenic activity. Since a slow release formulation was more effective than the bolus injections, a gene therapy approach was developed to deliver the mutant endostatin to inhibit ovarian cancer growth.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2004
- Accession Number
- ADA435700
Entities
People
- Sundaram Ramakrishnan
Organizations
- University of Minnesota