Within this investiga tion, we determined the efficacy of targeted liposomes carrying doxorubicin in cell culture versions and a glioma tumor bearing mouse model. Almost all of the brain tumors conferred drug resistance to glioma cells as a consequence of the expression of P glycoprotein. The uptake and accumulation of IL 13 conjugated liposomes in glioma cells was analyzed making use of fluorescence microscopy and FACS examination. The effects within the liposomes encapsulating pharmaceutical agents had been compared with unencapsulated cytotoxins or non targeted liposomal cytotoxins in U251 glioma cells. For our animal experiments, U251 glioma cells have been implanted subcutaneously in female nude mice. Two weeks after implantation, once the tumors reached 21 mm2, we injected the IL 13 conjugated liposomes encapsulated with DXR intraperitoneally when per week. The dimension within the tumors was measured weekly.
The results with the in vitro cell culture model indicated that the cytotoxicity of IL 13 conjugated liposomal DXR was larger than that of unconjugated liposomal DXR. The level of DXR detected during the cells right after delivery through IL 13 conjugated liposomes was even higher than that observed with selleck chemicals absolutely free DXR and cyclosporine A, a Pgp Idarubicin inhibitor. From the in vivo model, the tumor dimension decreased by 66% following weekly injections of 15 mg/kg physique excess weight of DXR but not 7. 5 mg/kg entire body weight of DXR over a two week time period. To date, only one of 5 animals in group 1 has died. The tumors in animals injected with PBS alone have continued to develop. The in vivo stud ies are ongoing. ET 28. Targeting THE CANCER Unique MUTANT EGF RECEPTOR WITH DELTA 24 RIVER ONCOLYTIC ADENOVIRUS Y. J. Piao, H. Jiang, J. Xu, Y. J. Ji, M. M. Alonso, O K. Lee, C. Conrad, C. Gomez Manzano, and J. Fueyo, Brain Tumor Center, The University of Texas M. D.
Anderson Cancer Center, Houston, TX, USA Malignant gliomas are

characterized by infiltrative growth that causes progressive neurologic dysfunction and, almost invariably, death. Currently there is no effective treatment for glioblastoma, however, recent advances in our understanding of brain tumor biology suggest that treatment strategies that target the fundamental molecular defects of brain tumors may provide effective and selective therapies. Oncolytic adenoviruses are a promising therapy for the treatment of gliomas. Previously, we studied the antiglioma activity within the tumor selective Delta 24 adenovirus, which encompasses an early 1A adenoviral deletion while in the retinoblastoma protein binding region. However, the paucity of Coxsackie adenovirus receptor on tumor cells is a major stumbling block for adenovirus based treatment. In this study, we enhanced the tropism of Delta 24 through genetic incorporation of cancer receptor binding peptides to improve antiglioma efficiency and maintain replication selectivity for cancer cells.