Accession Number : ADA435700


Title :   Role of Angiogenesis in the Etiology and Prevention of Ovarian Cancer


Descriptive Note : Final rept. 1 Oct 1999-30 Sep 2004


Corporate Author : MINNESOTA UNIV MINNEAPOLIS


Personal Author(s) : Ramakrishnan, Sundaram


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a435700.pdf


Report Date : Oct 2004


Pagination or Media Count : 383


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.


Descriptors :   *ETIOLOGY , *PREVENTIVE MEDICINE , *OVARIAN CANCER , *ANGIOGENESIS , PEPTIDES , PROTEINS , FORMULATIONS , NEOPLASMS , MUTATIONS , INHIBITORS , PERITONEUM , CARDIOVASCULAR SYSTEM , GENETICS , AMINO ACIDS , BLOOD VESSELS , INJECTIONS(MEDICINE) , OVARIES , GENE THERAPY


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE