Focused Ultrasound Stimulation of Microbubbles in Combination With Radiotherapy for Acute Damage of Breast Cancer Xenograft Model
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 immunohistochemistry to investigate the effects of combining ra...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2022-11-01
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| Series: | Technology in Cancer Research & Treatment |
| Online Access: | https://doi.org/10.1177/15330338221132925 |
| _version_ | 1811179959763337216 |
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| author | Deepa Sharma PhD Farah Hussein MSc Niki Law BSc MRT(t) Golnaz Farhat PhD Christine Tarapacki MSc Lakshmanan Sannachi PhD Anoja Giles BSc Gregory J. Czarnota MD, PhD |
| author_facet | Deepa Sharma PhD Farah Hussein MSc Niki Law BSc MRT(t) Golnaz Farhat PhD Christine Tarapacki MSc Lakshmanan Sannachi PhD Anoja Giles BSc Gregory J. Czarnota MD, PhD |
| author_sort | Deepa Sharma PhD |
| collection | DOAJ |
| description | 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 immunohistochemistry 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 histologically. 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 treatment 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. |
| first_indexed | 2024-04-11T06:43:21Z |
| format | Article |
| id | doaj.art-2bcc81cb7830426ca8f34ad969ff9844 |
| institution | Directory Open Access Journal |
| issn | 1533-0338 |
| language | English |
| last_indexed | 2024-04-11T06:43:21Z |
| publishDate | 2022-11-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Technology in Cancer Research & Treatment |
| spelling | doaj.art-2bcc81cb7830426ca8f34ad969ff98442022-12-22T04:39:25ZengSAGE PublishingTechnology in Cancer Research & Treatment1533-03382022-11-012110.1177/15330338221132925Focused Ultrasound Stimulation of Microbubbles in Combination With Radiotherapy for Acute Damage of Breast Cancer Xenograft ModelDeepa Sharma PhD0Farah Hussein MSc1Niki Law BSc MRT(t) 2Golnaz Farhat PhD3Christine Tarapacki MSc4Lakshmanan Sannachi PhD5Anoja Giles BSc6Gregory J. Czarnota MD, PhD7 University of Toronto, Toronto, ON, Canada Sunnybrook Health Sciences Centre, Toronto, ON, Canada Sunnybrook Health Sciences Centre, Toronto, ON, Canada Sunnybrook Health Sciences Centre, Toronto, ON, Canada Sunnybrook Health Sciences Centre, Toronto, ON, Canada University of Toronto, Toronto, ON, Canada Sunnybrook Health Sciences Centre, Toronto, ON, Canada University of Toronto, Toronto, ON, CanadaObjective: 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 immunohistochemistry 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 histologically. 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 treatment 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.https://doi.org/10.1177/15330338221132925 |
| spellingShingle | Deepa Sharma PhD Farah Hussein MSc Niki Law BSc MRT(t) Golnaz Farhat PhD Christine Tarapacki MSc Lakshmanan Sannachi PhD Anoja Giles BSc Gregory J. Czarnota MD, PhD Focused Ultrasound Stimulation of Microbubbles in Combination With Radiotherapy for Acute Damage of Breast Cancer Xenograft Model Technology in Cancer Research & Treatment |
| title | Focused Ultrasound Stimulation of Microbubbles in Combination With Radiotherapy for Acute Damage of
Breast Cancer Xenograft Model |
| title_full | Focused Ultrasound Stimulation of Microbubbles in Combination With Radiotherapy for Acute Damage of
Breast Cancer Xenograft Model |
| title_fullStr | Focused Ultrasound Stimulation of Microbubbles in Combination With Radiotherapy for Acute Damage of
Breast Cancer Xenograft Model |
| title_full_unstemmed | Focused Ultrasound Stimulation of Microbubbles in Combination With Radiotherapy for Acute Damage of
Breast Cancer Xenograft Model |
| title_short | Focused Ultrasound Stimulation of Microbubbles in Combination With Radiotherapy for Acute Damage of
Breast Cancer Xenograft Model |
| title_sort | focused ultrasound stimulation of microbubbles in combination with radiotherapy for acute damage of breast cancer xenograft model |
| url | https://doi.org/10.1177/15330338221132925 |
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