title: Therapeutic effect of neural stem cells expressing TRAIL and bortezomib in mice with glioma xenografts.
abstract: Treatment of glioblastoma remains a challenge in neuro-oncology. We investigated if treatment with neural stem cells engineered to express membrane-bound TRAIL (NSCs-mTRAIL) alone or in combination with proteasome inhibitors is a feasible therapeutic approach for experimental glioma. Glioma cells showed resistance to soluble TRAIL and proteasome inhibitors alone, but responded well to their combined treatment. In co-culture with NSCs-mTRAIL, glioma cells appeared to be more prone to apoptosis than to treatment with soluble TRAIL, which was enhanced by proteasome inhibitor bortezomib. In vivo, the survival of animals bearing intracranial glial xenografts was significantly improved by NSCs-mTRAIL. The addition of bortezomib further enhanced the efficacy of NSCs-TRAIL treated group in one of examined tumor models. These data demonstrate that therapy with NSCs-mTRAIL is a potent cell based approach for treatment of glioma. Such an approach warrants further search for therapeutics capable of increasing sensitivity of glioma cells to mTRAIL in vivo.
authors.affiliation: The Brain Tumor Center, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Balyasnikova
authors.forename: Sherise D
authors.initials: SD
authors.lastname: Ferguson
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.forename: Feifei
authors.initials: F
authors.lastname: Liu
authors.forename: Maciej S
authors.initials: MS
authors.lastname: Lesniak
mesh_terms: D000818:Animals; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D005910:Glioma / Q000188:drug therapy / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D019169:Jurkat Cells; D008297:Male; D051379:Mice; D008819:Mice, Nude; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D011719:Pyrazines / Q000494:pharmacology*; D033581:Stem Cell Transplantation / Q000379:methods*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D000069286:Bortezomib