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

Jeffrey C. Crosbie; Robin L. Anderson; Kai Rothkamm; Christina M. Restall; Leonie Cann; Saleela Ruwanpura; Sarah Meachem; Naoto Yagi; Imants Svalbe; Robert A. Lewis; Bryan R.G. Williams; Peter A.W. Rogers

doi:10.1016/j.ijrobp.2010.01.035

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

Jeffrey C. Crosbie, Robin L. Anderson, Kai Rothkamm, Christina M. Restall, Leonie Cann, Saleela Ruwanpura, Sarah Meachem, Naoto Yagi, Imants Svalbe, Robert A. Lewis, Bryan R.G. Williams, Peter A.W. Rogers^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

133 Citations (Scopus)

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 μm-wide, planar, polychromatic, kilovoltage X-ray microbeams, with 200-μm peak separation. Inoculated EMT-6.5 tumor and normal mouse skin tissues were harvested at defined intervals post-MRT. Immunohistochemical detection of γ-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.

Original language	English
Pages (from-to)	886-894
Number of pages	9
Journal	International Journal of Radiation Oncology Biology Physics
Volume	77
Issue number	3
DOIs	https://doi.org/10.1016/j.ijrobp.2010.01.035
Publication status	Published - 2010

Bibliographical note

Funding Information:
Supported by a Cancer Council Victoria Venture Grant (to P.A.W.R., R.A.L., I.S., and B.W.); an Australian Nuclear Science and Technology Organisation (ANSTO) grant (to J.C.C. and P.A.W.R.); a Monash University postgraduate scholarship (to J.C.C.); a National Breast Cancer Foundation Fellowship (to R.L.A.); a Cancer Research UK grant ( C14504/A6116 ; to K.R.); and a National Health and Medical Research Council of Australia Fellowship (Grant No. 143805 ; to P.A.W.R.).

Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.

Keywords

Cellular response
EMT-6
Gamma-H2AX
Microbeam radiation therapy
Synchrotron

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ijrobp.2010.01.035

Cite this

Crosbie, J. C., Anderson, R. L., Rothkamm, K., Restall, C. M., Cann, L., Ruwanpura, S., Meachem, S., Yagi, N., Svalbe, I., Lewis, R. A., Williams, B. R. G., & Rogers, P. A. W. (2010). Tumor Cell Response to Synchrotron Microbeam Radiation Therapy Differs Markedly From Cells in Normal Tissues. International Journal of Radiation Oncology Biology Physics, 77(3), 886-894. https://doi.org/10.1016/j.ijrobp.2010.01.035

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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 μm-wide, planar, polychromatic, kilovoltage X-ray microbeams, with 200-μm peak separation. Inoculated EMT-6.5 tumor and normal mouse skin tissues were harvested at defined intervals post-MRT. Immunohistochemical detection of γ-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.",

keywords = "Cellular response, EMT-6, Gamma-H2AX, Microbeam radiation therapy, Synchrotron",

author = "Crosbie, {Jeffrey C.} and Anderson, {Robin L.} and Kai Rothkamm and Restall, {Christina M.} and Leonie Cann and Saleela Ruwanpura and Sarah Meachem and Naoto Yagi and Imants Svalbe and Lewis, {Robert A.} and Williams, {Bryan R.G.} and Rogers, {Peter A.W.}",

note = "Funding Information: Supported by a Cancer Council Victoria Venture Grant (to P.A.W.R., R.A.L., I.S., and B.W.); an Australian Nuclear Science and Technology Organisation (ANSTO) grant (to J.C.C. and P.A.W.R.); a Monash University postgraduate scholarship (to J.C.C.); a National Breast Cancer Foundation Fellowship (to R.L.A.); a Cancer Research UK grant ( C14504/A6116 ; to K.R.); and a National Health and Medical Research Council of Australia Fellowship (Grant No. 143805 ; to P.A.W.R.). Copyright: Copyright 2010 Elsevier B.V., All rights reserved.",

year = "2010",

doi = "10.1016/j.ijrobp.2010.01.035",

language = "English",

volume = "77",

pages = "886--894",

journal = "International Journal of Radiation Oncology Biology Physics",

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Crosbie, JC, Anderson, RL, Rothkamm, K, Restall, CM, Cann, L, Ruwanpura, S, Meachem, S, Yagi, N, Svalbe, I, Lewis, RA, Williams, BRG & Rogers, PAW 2010, 'Tumor Cell Response to Synchrotron Microbeam Radiation Therapy Differs Markedly From Cells in Normal Tissues', International Journal of Radiation Oncology Biology Physics, vol. 77, no. 3, pp. 886-894. https://doi.org/10.1016/j.ijrobp.2010.01.035

TY - JOUR

T1 - Tumor Cell Response to Synchrotron Microbeam Radiation Therapy Differs Markedly From Cells in Normal Tissues

AU - Crosbie, Jeffrey C.

AU - Anderson, Robin L.

AU - Rothkamm, Kai

AU - Restall, Christina M.

AU - Cann, Leonie

AU - Ruwanpura, Saleela

AU - Meachem, Sarah

AU - Yagi, Naoto

AU - Svalbe, Imants

AU - Lewis, Robert A.

AU - Williams, Bryan R.G.

AU - Rogers, Peter A.W.

N1 - Funding Information: Supported by a Cancer Council Victoria Venture Grant (to P.A.W.R., R.A.L., I.S., and B.W.); an Australian Nuclear Science and Technology Organisation (ANSTO) grant (to J.C.C. and P.A.W.R.); a Monash University postgraduate scholarship (to J.C.C.); a National Breast Cancer Foundation Fellowship (to R.L.A.); a Cancer Research UK grant ( C14504/A6116 ; to K.R.); and a National Health and Medical Research Council of Australia Fellowship (Grant No. 143805 ; to P.A.W.R.). Copyright: Copyright 2010 Elsevier B.V., All rights reserved.

PY - 2010

Y1 - 2010

N2 - 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 μm-wide, planar, polychromatic, kilovoltage X-ray microbeams, with 200-μm peak separation. Inoculated EMT-6.5 tumor and normal mouse skin tissues were harvested at defined intervals post-MRT. Immunohistochemical detection of γ-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.

AB - 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 μm-wide, planar, polychromatic, kilovoltage X-ray microbeams, with 200-μm peak separation. Inoculated EMT-6.5 tumor and normal mouse skin tissues were harvested at defined intervals post-MRT. Immunohistochemical detection of γ-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.

KW - Cellular response

KW - EMT-6

KW - Gamma-H2AX

KW - Microbeam radiation therapy

KW - Synchrotron

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U2 - 10.1016/j.ijrobp.2010.01.035

DO - 10.1016/j.ijrobp.2010.01.035

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C2 - 20510199

AN - SCOPUS:77952572348

SN - 0360-3016

VL - 77

SP - 886

EP - 894

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

IS - 3

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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