Journal
ULTRASOUND IN MEDICINE AND BIOLOGY
Volume 39, Issue 8, Pages 1376-1387Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ultrasmedbio.2013.01.012
Keywords
Radiosensitization; Therapeutic ultrasound; Microbubbles; Prostate cancer; Endothelial cells; Ceramide pathway; Apoptosis
Funding
- CDMRP
- NSERC
- University of Toronto
- Terry Fox Foundation
- Cancer Care Ontario Research Chair in Experimental Therapeutics and Imaging
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We show here that ultrasound-stimulated microbubbles can enhance cell death within tumors when combined with radiation. The aim of this study was to investigate how different ultrasound parameters, different microbubble concentrations and different radiation doses interact to enhance cell death. Prostate xenograft tumors (PC-3) in severe combined immunodeficiency mice were subjected to ultrasound treatment at various peak negative pressures (250, 570 and 750 kPa) at a center frequency of 500 kHz, different microbubble concentrations (8, 80 and 1000 mu L/kg) and different radiation doses (0, 2 and 8 Gy). Twenty-four hours after treatment, tumors were excised and assessed for cell death. Histologic analyses revealed that increases in radiation dose, microbubble concentration and ultrasound pressure promoted apoptotic cell death and disruption within tumors by as much as 21%, 30% and 43%, respectively. Comparable increases in ceramide, a cell death mediator, were identified using immunohistochemistry. We also show here that even clinically used microbubble concentrations combined with ultrasound can induce significant enhancement of cell death. (E-mail: gregory.czarnota@sunnybrook.ca) (C) 2013 Published by Elsevier Inc. on behalf of World Federation for Ultrasound in Medicine & Biology.
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