breast cancer xenografts, cell death, focused ultrasound, radiation therapy, ultrasound-stimulated microbubbles
Objective: Several studies have focused on the use of ultrasound-stimulated microbubbles (USMB) to induce vascular damage in order to enhance tumor response to radiation. Methods: In this study, power Doppler imaging was used along with immunohisto- chemistry to investigate the effects of combining radiation therapy (XRT) and USMB using an ultrasound-guided focused ultrasound (FUS) therapy system in a breast cancer xenograft model. Specifically, MDA-MB-231 breast cancer xenograft tumors were induced in severe combined immuno-deficient female mice. The mice were treated with FUS alone, ultrasound and microbubbles (FUS + MB) alone, 8 Gy XRT alone, or a combined treatment consisting of ultrasound, microbubbles, and XRT (FUS + MB + XRT). Power Doppler imaging was conducted before and 24 h after treatment, at which time mice were sacrificed and tumors assessed histolog- ically. The immunohistochemical analysis included terminal deoxynucleotidyl transferase dUTP nick end labeling, hematoxylin and eosin, cluster of differentiation-31 (CD31), Ki-67, carbonic anhydrase (CA-9), and ceramide labeling. Results: Tumors receiving treat- ment of FUS + MB combined with XRT demonstrated significant increase in cell death (p = 0.0006) compared to control group. Furthermore, CD31 and Power Doppler analysis revealed reduced tumor vascularization with combined treatment indicating (P < .0001) and (P = .0001), respectively compared to the control group. Additionally, lesser number of proliferating cells with enhanced tumor hypoxia, and ceramide content were also reported in group receiving a treatment of FUS + MB + XRT. Conclusion: The study results demonstrate that the combination of USMB with XRT enhances treatment outcomes.
Faculty of Applied Science and Technology (FAST)
Technology in Cancer Research & Treatment
©Deepa Sharma, Farah Hussein, Niki Law, Golnaz Farhat, Christine Tarapacki, Lakshmanan Sannachi, Anoja Giles, Gregory J. Czarnota
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This work is licensed under a Creative Commons Attribution 4.0 License.
Original Publication Citation
Sharma, D., Hussein, F., Law, N., Farhat, G.,Tarapacki, C., Sannachi, L., Giles, A., & Czarnota, G., J. (2022). Focused ultrasound stimulation of microbubbles in combination with radiotherapy for acute damage of breast cancer xenograft model. Technology in Cancer Research & Treatment, 21, 1-10. 10.1177/15330338221132925
Sharma, Deepa; Hussein, Farah; Law, Niki; Farhat, Golnaz; Tarapacki, Christine; Sannachi, Lakshmanan; Giles, Anoja; and Czarnota, Gregory J., "Focused Ultrasound Stimulation of Microbubbles in Combination With Radiotherapy for Acute Damage of Breast Cancer Xenograft Model" (2022). Publications and Scholarship. 83.