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Induction of Glioblastoma Apoptosis Using Neural Stem Cell-mediated Delivery
of Tumor Necrosis Factor-related Apoptosis-inducing Ligand
Moneeb Ehtesham, Peter Kabos, Mervin A.
R. Gutierrez, Nancy H. C. Chung, Thomas S. Griffith,
Keith L. Black and John S. Yu
Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical
Center, Los Angeles, California 90048 [M. E., P. K., M. A. R. G., N. H. C. C.,
K. L. B., J. S. Y.] and Department of Surgery, University of Iowa School of
Medicine, Iowa City, Iowa 52242 [T. S. G.].
Correspondence should be addressed to J.S.Y. , at Maxine Dunitz
Neurosurgical Institute, Suite 800E, 8631 West 3rd Street, Los
Angeles, CA 90048. Phone: (310) 423-0845; Fax: (310) 423-0810; E-mail:
yuj@cshs.org.
Current therapies for gliomas fail to address their highly infiltrative nature.
Standard treatments often leave behind microscopic neoplastic reservoirs,
resulting in eventual tumor recurrence.
Neural stem cells (NSCs) are
capable of tracking disseminating glioma cells.
To exploit this
tropism to develop a therapeutic strategy that targeted tumor
satellites, we inoculated human glioblastoma xenografts with tumor
necrosis factor-related apoptosis-inducing ligand-secreting NSCs.
This resulted in the dramatic induction of apoptosis in treated
tumors and tumor satellites and was associated with significant
inhibition of tumor growth.
These results add credence to the
potential of NSCs as therapeutically effective delivery vehicles for
the treatment of intracranial glioma.
© 2002 American Association for Cancer Research
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