title: Antisense efficacy : site-restricted in vivo and ex vivo models.
abstract: In the laboratory, antisense oligodeoxynucleotides (ODN) have repeatedly demonstrated efficacy in modulating the expression of various genes, thus providing important insights into their roles in tumorigenesis or normal growth and development (1-3). Although attention has been focused recently on the development of antisense ODN as therapeutics for a variety of diseases, including cancer (4), systemic application of ODN to treat tumors other than those of the hematopoietic system presents several problems, not least of which is the ability of systemically administered antisense to reach distant tumor sites. This is particularly true when considering tumors of the central nervous system (CNS), such as glioblastomas and HIV-associated B-cell lymphomas. In this case, the blood-brain barrrer poses an additional obstacle to successful delivery of anionic ODN. On the other hand, the intractability of CNS tumors to standard chemotherapy makes them interesting candidates for antisense intervention. The first model system we will discuss mvolves direct mfusron of ODN into the CNS for the purpose of continuous perfusion of tumor cells.
authors.affiliation: Clinical Pharmacology Branch, National Cancer Institute, Bethesda, MD.
authors.forename: L M
authors.initials: LM
authors.lastname: Neckers
authors.forename: D
authors.initials: D
authors.lastname: Geselowitz
authors.forename: C
authors.initials: C
authors.lastname: Chavany
authors.forename: L
authors.initials: L
authors.lastname: Whitesell
authors.forename: R
authors.initials: R
authors.lastname: Bergan