title: Antitumor effects of combining tumor radiation with the antivascular action of ultrasound stimulated microbubbles.
abstract: OBJECTIVE
  More and more evidence indicates tumor vasculature plays an important role in tumor radiation response. In this study, we investigated ultrasound stimulated microbubbles to enhance the effects of radiation.
  
  
  METHODS
  Human bladder cancer HT-1376 xenografts in severe combined immuno-deficient mice were used. High-frequency (25 MHz) ultrasound was used to image tumor responses caused by ultrasound-stimulated microbubbles in combination with radiation. Human bladder xenografts grown in severe combined immunodeficiency (SCID) mice were treated using microbubbles stimulated with ultrasound at 250, 570, or 750 kPa, and exposed to 0, 2, or 8 Gy of radiation. Tumors were imaged prior to treatment and 24 hours after treatment. Spectral analysis of images acquired from treated tumors revealed overall increases in ultrasound backscatter intensity and the spectral intercept parameter.
  
  
  RESULTS
  There existed 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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Special Diagnosis, Shandong Cancer Hospital and Institute China.
authors.forename: Yanlei
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Internal Medicine, Jinan Second People's Hospital China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Special Diagnosis, Shandong Cancer Hospital and Institute China.
authors.forename: Limei
authors.initials: L
authors.lastname: Shao
authors.affiliation: Department of Special Diagnosis, Shandong Cancer Hospital and Institute China.
authors.forename: Yuehuan
authors.initials: Y
authors.lastname: Zhao
keywords: Ultrasound stimulated microbubbles; antivascular action; radiation; tumor therapy