title: Effects of biophysical parameters in enhancing radiation responses of prostate tumors with ultrasound-stimulated microbubbles.
abstract: 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 μL/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.
authors: Department of Medical Biophysics, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
authors: Hyunjung Christina
authors: HC
authors: Kim
authors: Azza
authors: A
authors: Al-Mahrouki
authors: Alborz
authors: A
authors: Gorjizadeh
authors: Raffi
authors: R
authors: Karshafian
authors: Gregory J
authors: GJ
authors: Czarnota
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005466:Fluorocarbons / Q000008:administration & dosage* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D045423:Microbubbles / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000532:radiotherapy*; D011829:Radiation Dosage; D016896:Treatment Outcome; D014464:Ultrasonic Therapy / Q000379:methods*
chemical_list: D005466:Fluorocarbons; C042852:perflutren
keywords: Apoptosis; Ceramide pathway; Endothelial cells; Microbubbles; Prostate cancer; Radiosensitization; Therapeutic ultrasound