Ashish Jani1, Fauzia Shaikh1, Sunjay Barton1, Callen Willis2, Debarshi Banerjee3, Jason Mitchell2, Sonia L Hernandez4, Tom Hei1, Angela Kadenhe-Chiweshe2, Darrell J Yamashiro5, Eileen P Connolly6. 1. Department of Radiation Oncology, Columbia University Medical Center, New York, New York. 2. Department of Surgery, Columbia University Medical Center, New York, New York. 3. Department of Pediatrics, Columbia University Medical Center, New York, New York. 4. Department of Surgery, University of Chicago, Chicago, Illinois. 5. Department of Surgery, Columbia University Medical Center, New York, New York; Department of Pediatrics, Columbia University Medical Center, New York, New York; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York. 6. Department of Radiation Oncology, Columbia University Medical Center, New York, New York. Electronic address: epc2116@cumc.columbia.edu.
Abstract
PURPOSE: To characterize the effects of high-dose radiation therapy (HDRT) on neuroblastoma tumor vasculature, including the endothelial cell (EC)-pericyte interaction as a potential target for combined treatment with antiangiogenic agents. METHODS AND MATERIALS: The vascular effects of radiation therapy were examined in a xenograft model of high-risk neuroblastoma. In vivo 3-dimensional contrast-enhanced ultrasonography (3D-CEUS) imaging and immunohistochemistry (IHC) were performed. RESULTS: HDRT significantly reduced tumor blood volume 6 hours after irradiation compared with the lower doses used in conventionally fractionated radiation. There was a 63% decrease in tumor blood volume after 12-Gy radiation compared with a 24% decrease after 2 Gy. Analysis of tumor vasculature by lectin angiography showed a significant loss of small vessel ends at 6 hours. IHC revealed a significant loss of ECs at 6 and 72 hours after HDRT, with an accompanying loss of immature and mature pericytes at 72 hours. CONCLUSIONS: HDRT affects tumor vasculature in a manner not observed at lower doses. The main observation was an early reduction in tumor perfusion resulting from a reduction of small vessel ends with a corresponding loss of endothelial cells and pericytes.
PURPOSE: To characterize the effects of high-dose radiation therapy (HDRT) on neuroblastoma tumor vasculature, including the endothelial cell (EC)-pericyte interaction as a potential target for combined treatment with antiangiogenic agents. METHODS AND MATERIALS: The vascular effects of radiation therapy were examined in a xenograft model of high-risk neuroblastoma. In vivo 3-dimensional contrast-enhanced ultrasonography (3D-CEUS) imaging and immunohistochemistry (IHC) were performed. RESULTS: HDRT significantly reduced tumor blood volume 6 hours after irradiation compared with the lower doses used in conventionally fractionated radiation. There was a 63% decrease in tumor blood volume after 12-Gy radiation compared with a 24% decrease after 2 Gy. Analysis of tumor vasculature by lectin angiography showed a significant loss of small vessel ends at 6 hours. IHC revealed a significant loss of ECs at 6 and 72 hours after HDRT, with an accompanying loss of immature and mature pericytes at 72 hours. CONCLUSIONS: HDRT affects tumor vasculature in a manner not observed at lower doses. The main observation was an early reduction in tumor perfusion resulting from a reduction of small vessel ends with a corresponding loss of endothelial cells and pericytes.
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