H U Xu1, Frank Bihari1, Shawn Whitehead2, Eugene Wong3, Susanne Schmid2, Matthew O Hebb4. 1. Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada. 2. Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada. 3. Department of Physics and Astronomy, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada. 4. Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada mhebb@uwo.ca.
Abstract
BACKGROUND/AIM: This proof-of-concept study evaluated the antitumor impact of a direct electrical stimulation technique, termed intratumoral modulation therapy (IMT) on glioblastoma (GBM) cells. MATERIALS AND METHODS: An in vitro IMT model comprised of a calibrated electrode to deliver continuous, low-intensity stimulation within GBM preparations. Viability and apoptosis assays were performed in treated immortalized and patient-derived GBM cells, and post-mitotic neurons. IMT was delivered alone and with temozolomide, or gene silencing of the tumor-promoting chaperone, heat-shock protein 27 (HSP27). RESULTS: GBM cells, but not neurons, exhibited >40% loss of viability, caspase-3 activation and apoptosis with IMT. Cell death was modest with temozolomide alone (30%) but increased significantly with concomitant IMT (70%). HSP27 silencing alone produced 30% viability loss, with significant enhancement of target knockdown and GBM cell death (65%), when combined with IMT. CONCLUSION: These findings warrant further evaluation of IMT as a potential novel therapeutic strategy for GBM. Copyright
BACKGROUND/AIM: This proof-of-concept study evaluated the antitumor impact of a direct electrical stimulation technique, termed intratumoral modulation therapy (IMT) on glioblastoma (GBM) cells. MATERIALS AND METHODS: An in vitro IMT model comprised of a calibrated electrode to deliver continuous, low-intensity stimulation within GBM preparations. Viability and apoptosis assays were performed in treated immortalized and patient-derived GBM cells, and post-mitotic neurons. IMT was delivered alone and with temozolomide, or gene silencing of the tumor-promoting chaperone, heat-shock protein 27 (HSP27). RESULTS: GBM cells, but not neurons, exhibited >40% loss of viability, caspase-3 activation and apoptosis with IMT. Cell death was modest with temozolomide alone (30%) but increased significantly with concomitant IMT (70%). HSP27 silencing alone produced 30% viability loss, with significant enhancement of target knockdown and GBM cell death (65%), when combined with IMT. CONCLUSION: These findings warrant further evaluation of IMT as a potential novel therapeutic strategy for GBM. Copyright
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