Abstract
We have recently demonstrated that mechanical perturbation of endothelial cells from ultrasound-stimulated microbubbles (USMB) results in enhanced tumor radiosensitivity at low 2 Gy doses of radiation. Our hypothesis is that USMB-based endothelial membrane perturbations produce ceramide via a sphingomyelinase (ASMase) pathway, and act synergistically with radiation to enhance overall tumor response. Here, we investigate the role of the SMase-ceramide pathway on USMB-based endothelial radiosensitization. Experiments were carried out in wild type (C57BL/6) and ASMase knockout mice, implanted with a fibrosarcoma line (MCA-129). Animals were treated with radiation doses varying from 0 to 8 Gy alone, or in combination with ultrasound-stimulated microbubbles. Treatment response was assessed with Doppler ultrasound vascularity index acquired at 3, 24, and 72 hrs using a VEVO770 preclinical ultrasound system. Staining using ISEL, ceramide, and CD31 immunohistochemistry of tumor sections was used to complement res...
Published Version
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