Page 136 - 2014 Printable Abstract Book
P. 136
spectrometry showed that TEX derived from 20Gy treated TSA displayed a markedly different proteomic
profile compared to TEX from mock treated TSA, with >500 unique proteins. Among them, DAVID analysis
identified many proteins (~50) related to DNA damage repair (DDR). Interestingly, TEX from 8Gyx3 treated
TSA showed fewer protein species compared to 20Gy-TSA TEX, with the notable absence of DDR proteins.
Importantly, 44 proteins were uniquely present only in 8Gyx3-TEX. This data suggests that irradiation
profoundly alters the protein composition of TEX and that radiation regimen influences TEX proteomic
profiles. We have previously shown that 8Gyx3 radiotherapy synergized with anti-CTLA-4 immunotherapy
and induced an abscopal effect in mice, while 20Gy did not (Dewan, et. al., Clin Cancer Res, 2009). It is
intriguing to consider if TEX contain biomarkers that define the ability of radiotherapy to synergize with
immunotherapy, and that if delivered to non-irradiated tumors enhance their susceptibility to anti-tumor
T cells. We are currently investigating this possibility in an in vivo treatment model. Exosome-mediated
communication networks may provide a new therapeutic target for treatment of metastatic cancer.
(PS1-64) Evaluation of scattered synchrotron radiation and its implications for bystander effects. Pavel
2;3
1
4
2
2
Lobachevsky ; Alesia Ivashkevich ; Carl N. Sprung ; Helen Forrester ; Andrew Stevenson ; Christopher J.
4
Hall ; and Olga Martin, 1;5 Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre,
2
1
Melbourne, Australia ; Monash Institute of Medical Research, Monash University, Melbourne, Australia ;
3
Cancer Research Laboratory, Radiation Oncology, Canberra Hospital, Canberra, Australia ; Australian
4
Synchrotron, Melbourne, Australia ; and Division of Radiation Oncology and Cancer Imaging, Peter
MacCallum Cancer Centre, Melbourne, Australia 5
Synchrotron radiation presents a convenient tool for investigation of bystander effects in cell and animal
models given the well-defined and controllable configuration of the synchrotron beam. Such an
investigation is also important in the context of potential advantage of the synchrotron microbeam
radiotherapy (MRT) as compared to the conventional radiotherapy. The contribution of dose exposure
from the scattered radiation, however, still remains a concern in the studies of bystander effect.
Therefore, we evaluated the potential role of the scattered radiation in detection of bystander effects
induced by synchrotron radiation in biological in vitro and in vivo models. We employed radiochromic
XRQA2 film based dosimetry to measure absorbed dose of the scattered radiation in several locations at
various distances from a target exposed to microbeam radiotherapy (MRT) and broad beam (BB) X-ray
radiation produced by the Imaging and Medical Beamline at the Australian Synchrotron. In parallel, we
investigated the yield of γH2AX foci in cultured cells positioned at the same locations, and evaluated the
absorbed dose from these yield values based on the dose response of γH2AX foci count that was
stablished in a separate experiment. Our results demonstrated the dependence of the level of scattered
radiation on the distance, dose in the target zone and beam mode, and the correlation of absorbed dose
values measured by physical (radiochromic film) and biological (γH2AX assay) methods. The results
indicated that the γH2AX assay can be exploited as a biodosimeter for low doses in the range starting from
a few mGy, and potentially allows detection of the scattered radiation contribution to bystander effects
induced by synchrotron radiation.
134 | P a g e
profile compared to TEX from mock treated TSA, with >500 unique proteins. Among them, DAVID analysis
identified many proteins (~50) related to DNA damage repair (DDR). Interestingly, TEX from 8Gyx3 treated
TSA showed fewer protein species compared to 20Gy-TSA TEX, with the notable absence of DDR proteins.
Importantly, 44 proteins were uniquely present only in 8Gyx3-TEX. This data suggests that irradiation
profoundly alters the protein composition of TEX and that radiation regimen influences TEX proteomic
profiles. We have previously shown that 8Gyx3 radiotherapy synergized with anti-CTLA-4 immunotherapy
and induced an abscopal effect in mice, while 20Gy did not (Dewan, et. al., Clin Cancer Res, 2009). It is
intriguing to consider if TEX contain biomarkers that define the ability of radiotherapy to synergize with
immunotherapy, and that if delivered to non-irradiated tumors enhance their susceptibility to anti-tumor
T cells. We are currently investigating this possibility in an in vivo treatment model. Exosome-mediated
communication networks may provide a new therapeutic target for treatment of metastatic cancer.
(PS1-64) Evaluation of scattered synchrotron radiation and its implications for bystander effects. Pavel
2;3
1
4
2
2
Lobachevsky ; Alesia Ivashkevich ; Carl N. Sprung ; Helen Forrester ; Andrew Stevenson ; Christopher J.
4
Hall ; and Olga Martin, 1;5 Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre,
2
1
Melbourne, Australia ; Monash Institute of Medical Research, Monash University, Melbourne, Australia ;
3
Cancer Research Laboratory, Radiation Oncology, Canberra Hospital, Canberra, Australia ; Australian
4
Synchrotron, Melbourne, Australia ; and Division of Radiation Oncology and Cancer Imaging, Peter
MacCallum Cancer Centre, Melbourne, Australia 5
Synchrotron radiation presents a convenient tool for investigation of bystander effects in cell and animal
models given the well-defined and controllable configuration of the synchrotron beam. Such an
investigation is also important in the context of potential advantage of the synchrotron microbeam
radiotherapy (MRT) as compared to the conventional radiotherapy. The contribution of dose exposure
from the scattered radiation, however, still remains a concern in the studies of bystander effect.
Therefore, we evaluated the potential role of the scattered radiation in detection of bystander effects
induced by synchrotron radiation in biological in vitro and in vivo models. We employed radiochromic
XRQA2 film based dosimetry to measure absorbed dose of the scattered radiation in several locations at
various distances from a target exposed to microbeam radiotherapy (MRT) and broad beam (BB) X-ray
radiation produced by the Imaging and Medical Beamline at the Australian Synchrotron. In parallel, we
investigated the yield of γH2AX foci in cultured cells positioned at the same locations, and evaluated the
absorbed dose from these yield values based on the dose response of γH2AX foci count that was
stablished in a separate experiment. Our results demonstrated the dependence of the level of scattered
radiation on the distance, dose in the target zone and beam mode, and the correlation of absorbed dose
values measured by physical (radiochromic film) and biological (γH2AX assay) methods. The results
indicated that the γH2AX assay can be exploited as a biodosimeter for low doses in the range starting from
a few mGy, and potentially allows detection of the scattered radiation contribution to bystander effects
induced by synchrotron radiation.
134 | P a g e
