Page 55 - 2014 Printable Abstract Book
P. 55
(S1005) Development and performance of a rapid, high throughput, gene expression based
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biodosimetric assay. Robert Terbrueggen, PhD ; Majid Abedi ; Nelson Chao, MD, MBA ; John Chute, MD ;
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Holly Dressman, PhD ; Ed Iversen, PhD ; Aviva Jacobs, PhD ; Joel Lucas, PhD ; Gary Phillips ; Joel Ross,
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PhD ; and Frederic Zenhausern, PhD, MBA, DxTerity Diagnostics, Rancho Dominguez, CA ; Duke
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University Medical Center, Durham, NC ; UCLA School of Medicine, Westwood, CA ; Duke University,
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Institute of Genome Sciences and Policy, Durham, NC ; Duke University, Durham, NC ; Predictive
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Analytics, Quintiles, Durham, NC ; and University of Arizona, Center of Applied Nanobioscience and
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Medicine, Phoenix, AZ
Following a mass scale nuclear event caused by detonation of a nuclear weapon or a nuclear
accident, the rapid and accurate biodosimetry of thousands of potentially affected individuals will be
essential for effective medical management of the crisis. Currently, health care providers lack an accurate,
high throughput biodosimetric assay that is suitable for the testing of large numbers of potential radiation
victims. Here, we describe the development and performance of a genomic assay suitable for the high-
throughput determination of individualized levels of radiation exposure for up to 7 days post-exposure.
The multi-gene assay was developed by cross-correlating the time dependent (6 hours to 7 days post
exposure) RNA gene expression of peripheral blood collected from in-vivo irradiated mice, in-vivo
irradiated non-human primates (NHPs), ex vivo irradiated human peripheral blood, and human cancer
patients undergoing total body irradiation (TBI) in preparation for bone marrow transplantation. Gene
orthologues between mice, humans, and NHPs were mapped. Genes that showed similar response
profiles to radiation exposure in all species were determined and used to develop a multi-gene predictor
capable of highly accurate prediction of human radiation status (irradiated vs non-irradiated) and
discrimination of medically relevant radiation dose levels in human and NHP samples. We have further
developed the gene predictor into a Chemical Ligation-dependent Probe Amplification Radiation Exposure
Test (CLPA-RET) capable of rapid analysis of stabilized blood samples without requiring isolation of the
RNA. The performance of CLPA-RET is being evaluated in pre-clinical and blinded studies involving
irradiated NHPs (up to 7 days post-exposure), human TBI patients, and more than 1000 non-irradiated
human subjects with potentially confounding diseases and mixed ethnicities. The results of these studies
will be presented.
S11 NOVEL THERAPEUTICS IN RADIATION ONCOLOGY
An evolving body of recent literature alludes to the potential to use novel techniques to sensitize
tumors to radiation therapy. Since the literature relating to the diverse disciplines involved in these efforts
spans across multiple specialties (clinical radiation oncology, radiation physics, radiation biology,
nanotechnology, material science, biomedical engineering, pharmacology, chemistry, and tumor biology)
and numerous specialty journals, there is no single compilation of extant research in this arena or forum
for merging analogous concepts and paradigms. This symposium will provide such a venue. The first talk
is on use of gold nanoparticles for radiosensitization either via radiation dose enhancement or via
hyperthermia. The second talk is on the use of focused ultrasound for radiosensitization. The third talk is
on the use of triggered intravascualr release to improve drug penetration into tumors. And the last talk is
on the use of systemically delivered miRNA to overcome radiation resistance.
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3
biodosimetric assay. Robert Terbrueggen, PhD ; Majid Abedi ; Nelson Chao, MD, MBA ; John Chute, MD ;
5
1
4
6
2
Holly Dressman, PhD ; Ed Iversen, PhD ; Aviva Jacobs, PhD ; Joel Lucas, PhD ; Gary Phillips ; Joel Ross,
2
1
7
PhD ; and Frederic Zenhausern, PhD, MBA, DxTerity Diagnostics, Rancho Dominguez, CA ; Duke
2
3
University Medical Center, Durham, NC ; UCLA School of Medicine, Westwood, CA ; Duke University,
4
5
Institute of Genome Sciences and Policy, Durham, NC ; Duke University, Durham, NC ; Predictive
6
Analytics, Quintiles, Durham, NC ; and University of Arizona, Center of Applied Nanobioscience and
7
Medicine, Phoenix, AZ
Following a mass scale nuclear event caused by detonation of a nuclear weapon or a nuclear
accident, the rapid and accurate biodosimetry of thousands of potentially affected individuals will be
essential for effective medical management of the crisis. Currently, health care providers lack an accurate,
high throughput biodosimetric assay that is suitable for the testing of large numbers of potential radiation
victims. Here, we describe the development and performance of a genomic assay suitable for the high-
throughput determination of individualized levels of radiation exposure for up to 7 days post-exposure.
The multi-gene assay was developed by cross-correlating the time dependent (6 hours to 7 days post
exposure) RNA gene expression of peripheral blood collected from in-vivo irradiated mice, in-vivo
irradiated non-human primates (NHPs), ex vivo irradiated human peripheral blood, and human cancer
patients undergoing total body irradiation (TBI) in preparation for bone marrow transplantation. Gene
orthologues between mice, humans, and NHPs were mapped. Genes that showed similar response
profiles to radiation exposure in all species were determined and used to develop a multi-gene predictor
capable of highly accurate prediction of human radiation status (irradiated vs non-irradiated) and
discrimination of medically relevant radiation dose levels in human and NHP samples. We have further
developed the gene predictor into a Chemical Ligation-dependent Probe Amplification Radiation Exposure
Test (CLPA-RET) capable of rapid analysis of stabilized blood samples without requiring isolation of the
RNA. The performance of CLPA-RET is being evaluated in pre-clinical and blinded studies involving
irradiated NHPs (up to 7 days post-exposure), human TBI patients, and more than 1000 non-irradiated
human subjects with potentially confounding diseases and mixed ethnicities. The results of these studies
will be presented.
S11 NOVEL THERAPEUTICS IN RADIATION ONCOLOGY
An evolving body of recent literature alludes to the potential to use novel techniques to sensitize
tumors to radiation therapy. Since the literature relating to the diverse disciplines involved in these efforts
spans across multiple specialties (clinical radiation oncology, radiation physics, radiation biology,
nanotechnology, material science, biomedical engineering, pharmacology, chemistry, and tumor biology)
and numerous specialty journals, there is no single compilation of extant research in this arena or forum
for merging analogous concepts and paradigms. This symposium will provide such a venue. The first talk
is on use of gold nanoparticles for radiosensitization either via radiation dose enhancement or via
hyperthermia. The second talk is on the use of focused ultrasound for radiosensitization. The third talk is
on the use of triggered intravascualr release to improve drug penetration into tumors. And the last talk is
on the use of systemically delivered miRNA to overcome radiation resistance.
53 | P a g e
