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Title: Tumor Cell Response to Synchrotron Microbeam Radiation Therapy Differs Markedly From Cells in Normal Tissues

Abstract

Purpose: High-dose synchrotron microbeam radiation therapy (MRT) can be effective at destroying tumors in animal models while causing very little damage to normal tissues. The aim of this study was to investigate the cellular processes behind this observation of potential clinical importance. Methods and Materials: MRT was performed using a lattice of 25 {mu}m-wide, planar, polychromatic, kilovoltage X-ray microbeams, with 200-{mu}m peak separation. Inoculated EMT-6.5 tumor and normal mouse skin tissues were harvested at defined intervals post-MRT. Immunohistochemical detection of {gamma}-H2AX allowed precise localization of irradiated cells, which were also assessed for proliferation and apoptosis. Results: MRT significantly reduced tumor cell proliferation by 24 h post-irradiation (p = 0.002). An unexpected finding was that within 24 h of MRT, peak and valley irradiated zones were indistinguishable in tumors because of extensive cell migration between the zones. This was not seen in MRT-treated normal skin, which appeared to undergo a coordinated repair response. MRT elicited an increase in median survival times of EMT-6.5 and 67NR tumor-inoculated mice similar to that achieved with conventional radiotherapy, while causing markedly less normal tissue damage. Conclusions: This study provides evidence of a differential response at a cellular level between normal and tumor tissues after synchrotronmore » MRT.« less

Authors:
 [1];  [2];  [2];  [2];  [3];  [2];  [4];  [3];  [5];  [6];  [7];  [8];  [1];  [1];  [2];  [6];  [5]
  1. School of Physics, Monash University, Clayton, Victoria (Australia)
  2. (Australia)
  3. PeterMacCallum Cancer Centre, Melbourne (Australia)
  4. Health Protection Agency, Radiation Protection Division, Oxfordshire (United Kingdom)
  5. Centre for Women's Health Research, Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria (Australia)
  6. Monash Institute of Medical Research, Monash University, Clayton, Victoria (Australia)
  7. Prince Henry's Institute of Medical Research, Clayton, Victoria (Australia)
  8. Research and Utilisation Division, JASRI, SPring-8, Mikazuki-cho, Sayo-gun, Hyogo (Japan)
Publication Date:
OSTI Identifier:
21436050
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 77; Journal Issue: 3; Other Information: DOI: 10.1016/j.ijrobp.2010.01.035; PII: S0360-3016 (10)00135-5; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; APOPTOSIS; CELL PROLIFERATION; MICE; NEOPLASMS; RADIOTHERAPY; SKIN; SYNCHROTRONS; TUMOR CELLS; X RADIATION; ACCELERATORS; ANIMAL CELLS; ANIMALS; BODY; CYCLIC ACCELERATORS; DISEASES; ELECTROMAGNETIC RADIATION; IONIZING RADIATIONS; MAMMALS; MEDICINE; NUCLEAR MEDICINE; ORGANS; RADIATIONS; RADIOLOGY; RODENTS; THERAPY; VERTEBRATES

Citation Formats

Crosbie, Jeffrey C., Monash Centre for Synchrotron Science, Monash University, Clayton, Victoria, Centre for Women's Health Research, Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, William Buckland Radiotherapy Centre, Alfred Hospital, Melbourne, Anderson, Robin L., Department of Pathology, University of Melbourne, Rothkamm, Kai, Restall, Christina M., Cann, Leonie, Ruwanpura, Saleela, Meachem, Sarah, Yagi, Naoto, Svalbe, Imants, Lewis, Robert A., Monash Centre for Synchrotron Science, Monash University, Clayton, Victoria, Williams, Bryan R.G., and Rogers, Peter A.W., E-mail: Peter.Rogers@med.monash.edu.a. Tumor Cell Response to Synchrotron Microbeam Radiation Therapy Differs Markedly From Cells in Normal Tissues. United States: N. p., 2010. Web. doi:10.1016/j.ijrobp.2010.01.035.
Crosbie, Jeffrey C., Monash Centre for Synchrotron Science, Monash University, Clayton, Victoria, Centre for Women's Health Research, Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, William Buckland Radiotherapy Centre, Alfred Hospital, Melbourne, Anderson, Robin L., Department of Pathology, University of Melbourne, Rothkamm, Kai, Restall, Christina M., Cann, Leonie, Ruwanpura, Saleela, Meachem, Sarah, Yagi, Naoto, Svalbe, Imants, Lewis, Robert A., Monash Centre for Synchrotron Science, Monash University, Clayton, Victoria, Williams, Bryan R.G., & Rogers, Peter A.W., E-mail: Peter.Rogers@med.monash.edu.a. Tumor Cell Response to Synchrotron Microbeam Radiation Therapy Differs Markedly From Cells in Normal Tissues. United States. doi:10.1016/j.ijrobp.2010.01.035.
Crosbie, Jeffrey C., Monash Centre for Synchrotron Science, Monash University, Clayton, Victoria, Centre for Women's Health Research, Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, William Buckland Radiotherapy Centre, Alfred Hospital, Melbourne, Anderson, Robin L., Department of Pathology, University of Melbourne, Rothkamm, Kai, Restall, Christina M., Cann, Leonie, Ruwanpura, Saleela, Meachem, Sarah, Yagi, Naoto, Svalbe, Imants, Lewis, Robert A., Monash Centre for Synchrotron Science, Monash University, Clayton, Victoria, Williams, Bryan R.G., and Rogers, Peter A.W., E-mail: Peter.Rogers@med.monash.edu.a. Thu . "Tumor Cell Response to Synchrotron Microbeam Radiation Therapy Differs Markedly From Cells in Normal Tissues". United States. doi:10.1016/j.ijrobp.2010.01.035.
@article{osti_21436050,
title = {Tumor Cell Response to Synchrotron Microbeam Radiation Therapy Differs Markedly From Cells in Normal Tissues},
author = {Crosbie, Jeffrey C. and Monash Centre for Synchrotron Science, Monash University, Clayton, Victoria and Centre for Women's Health Research, Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria and William Buckland Radiotherapy Centre, Alfred Hospital, Melbourne and Anderson, Robin L. and Department of Pathology, University of Melbourne and Rothkamm, Kai and Restall, Christina M. and Cann, Leonie and Ruwanpura, Saleela and Meachem, Sarah and Yagi, Naoto and Svalbe, Imants and Lewis, Robert A. and Monash Centre for Synchrotron Science, Monash University, Clayton, Victoria and Williams, Bryan R.G. and Rogers, Peter A.W., E-mail: Peter.Rogers@med.monash.edu.a},
abstractNote = {Purpose: High-dose synchrotron microbeam radiation therapy (MRT) can be effective at destroying tumors in animal models while causing very little damage to normal tissues. The aim of this study was to investigate the cellular processes behind this observation of potential clinical importance. Methods and Materials: MRT was performed using a lattice of 25 {mu}m-wide, planar, polychromatic, kilovoltage X-ray microbeams, with 200-{mu}m peak separation. Inoculated EMT-6.5 tumor and normal mouse skin tissues were harvested at defined intervals post-MRT. Immunohistochemical detection of {gamma}-H2AX allowed precise localization of irradiated cells, which were also assessed for proliferation and apoptosis. Results: MRT significantly reduced tumor cell proliferation by 24 h post-irradiation (p = 0.002). An unexpected finding was that within 24 h of MRT, peak and valley irradiated zones were indistinguishable in tumors because of extensive cell migration between the zones. This was not seen in MRT-treated normal skin, which appeared to undergo a coordinated repair response. MRT elicited an increase in median survival times of EMT-6.5 and 67NR tumor-inoculated mice similar to that achieved with conventional radiotherapy, while causing markedly less normal tissue damage. Conclusions: This study provides evidence of a differential response at a cellular level between normal and tumor tissues after synchrotron MRT.},
doi = {10.1016/j.ijrobp.2010.01.035},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 3,
volume = 77,
place = {United States},
year = {Thu Jul 01 00:00:00 EDT 2010},
month = {Thu Jul 01 00:00:00 EDT 2010}
}
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