Inducible Anti-Angiogenic Gene Therapy
Abstract
Clinical studies have indicated that high breast tumor levels of plasminogen activator inhibitor-1 (PAI-1) are associated with an increased risk for metastasis, decreased patient survival, a well developed angiogenic response, and overall poor prognosis. Since PAI-1 is required for tumor-dependent angiogenesis and inhibits capillary regression, a targeted molecular genetic approach was devised to ablate PAI-1 synthesis in endothelial cells using antisense PAI-1 expression constructs. Work in year 2001 established that constructs prepared in the Rc/CMV and retroviral pLNCX2 vectors, in fact, significantly attenuated PAI-1 synthesis in mouse (MS1) and rat (T2) endothelial cells confirming proof of principal for the original hypothesis. of a total of 11 different clones isolated following transfection of the PAI-1 antisense Rc/CMVIAP plasmid, 4 MS1- and 2 T2-derived lines were essentially PAI-1-null. A host mouse breeding colony was also established in order to maintain, at relatively low cost, a sufficient number of mice to meet the goals of this program.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2003
- Accession Number
- ADA417784
Entities
People
- Paul J. Higgins
Organizations
- Albany Medical College