RT Journal Article SR Electronic T1 Isolated Limb Perfusion Based Anti-p21ras Gene Therapy in a Rat Rhabdomyosarcoma JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 2295 OP 2302 VO 24 IS 4 A1 VAN ETTEN, BOUDEWIJN A1 VAN TIEL, SANDRA T. A1 AMBAGTSHEER, GISELA A1 EGGERMONT, ALEXANDER M.M. A1 HAGEN, TIMO L.M. TEN YR 2004 UL http://ar.iiarjournals.org/content/24/4/2295.abstract AB Background: Inhibition of ras oncogene is a promising new strategy. Gene therapy against ras proved successful in human and murine tumour cell lines. Previously we demonstrated effective targeted transfection of tumour in a rat model by using an isolated limb perfusion (ILP) for the delivery of adenoviral vectors. Materials and Methods: This study explores the anti-tumour activity of an adenoviral construct encoding an intracellular single-chain antibody (scFv) against p21ras (Y28). In order to determine the influence of the ras status on the efficacy of the scFv, we used a wild-type rat rhabdomyosarcoma and its ras-oncogene transfectant, for in vitro studies. In vivo we used the ILP delivery method to study anti-tumour activity on established limb tumours. Results: In vitro studies demonstrated an inhibition of growth caused by the Y28 construct. No significant difference between transfected and wild-type cell lines could be demonstrated. Upon ILP, homogeneous transduction was observed in 5% of tumour cells. Perfusion with the Y28 construct, however, did not result in any additional anti-tumour activity compared to controls. Conclusion: Despite in vitro activity and in vivo transfection, no significant tumour response could be detected using anti-p21ras gene therapy in this ILP-tumour model. Copyright© 2004 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved