Tumor radiation response enhancement by acoustical stimulation of the vasculature

We have discovered that ultrasound-mediated microbubble vascular disruption can enhance tumor responses to radiation in vivo. We demonstrate this effect using a human PC3 prostate cancer xenograft model. Results indicate a synergistic effect in vivo with combined single treatments of ultrasound-stim...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2012-07, Vol.109 (30), p.E2033-E2041
Main Authors: Czarnota, Gregory J, Karshafian, Raffi, Burns, Peter N, Wong, Shun, Al Mahrouki, Azza, Lee, Justin W, Caissie, Amanda, Tran, William, Kim, Christina, Furukawa, Melissa, Wong, Emily, Giles, Anoja
Format: Article
Language:English
Subjects:
Acoustic Stimulation - methods
Acoustics
Analysis of Variance
Animals
Apoptosis
Apoptosis - radiation effects
Biological Sciences
Cell Line, Tumor
Ceramides - metabolism
Combined Modality Therapy - methods
Dose-Response Relationship, Radiation
endothelial cells
Endothelium, Vascular - cytology
Endothelium, Vascular - radiation effects
Histological Techniques
Humans
in vivo studies
Lysophospholipids - metabolism
Male
Mice
Mice, SCID
microbubbles
Microbubbles - therapeutic use
Microscopy, Fluorescence
Physical Sciences
PNAS Plus
Prostate cancer
prostatic neoplasms
Prostatic Neoplasms - diagnostic imaging
Prostatic Neoplasms - radiotherapy
Radiation therapy
Radiation Tolerance - physiology
Sphingosine - analogs & derivatives
Sphingosine - metabolism
synergism
Transplantation, Heterologous
Tumors
Ultrasonic imaging
ultrasonics
Ultrasonography
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Summary:We have discovered that ultrasound-mediated microbubble vascular disruption can enhance tumor responses to radiation in vivo. We demonstrate this effect using a human PC3 prostate cancer xenograft model. Results indicate a synergistic effect in vivo with combined single treatments of ultrasound-stimulated microbubble vascular perturbation and radiation inducing an over 10-fold greater cell kill with combined treatments. We further demonstrate with experiments in vivo that induction of ceramide-related endothelial cell apoptosis, leading to vascular disruption, is a causative mechanism. In vivo experiments with ultrasound and bubbles permit radiation doses to be decreased significantly for comparable effect. We envisage this unique combined ultrasound-based vascular perturbation and radiation treatment method being used to enhance the effects of radiation in a tumor, leading to greater tumor eradication.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1200053109