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and sensitive measure of inversion frequency. Importantly, dGH is simultaneously capable of detecting
translocations and dicentrics as well. The goal of the current work is to test the utility of dGH as a
biodosimetric approach on a population of surviving US military veterans accidentally exposed during
nuclear bomb testing in the 1950s. We plan to establish in vitro dose-response relationships (calibration
curves) for the induction of chromosome aberrations (translocations and inversions) in a cohort of 80-
year old control individuals, as well as a cohort of 25-year olds, to address age at exposure as a variable.
Resulting individual dose estimates for the exposed individuals will be used to help reduce the large
uncertainties associated with measurements of physical dose.
(PS3-71) NIAID Radiation and Nuclear Countermeasures Program: challenges, successes, and strategies
for the future. Carmen I. Rios; David R. Cassatt; Andrea L. DiCarlo; Francesca Macchiarini; and Bert W.
Maidment, DAIT, NIAID, NIH, Bethesda, MD
The possibility of a radiological or nuclear incident in the United States remains a national security
level threat. The gravity of such a scenario would be exacerbated if necessary medical treatments were
not available. Unfortunately, there are currently no FDA-approved drugs available in the Strategic National
Stockpile that are licensed for the treatment of acute and/or delayed radiation health complications. Since
2004, the National Institute of Allergy and Infectious Diseases (NIAID), Radiation and Nuclear
Countermeasures Program (RNCP) has addressed these concerns by building and managing a program for
the research and development of safe and efficacious medical countermeasures (MCMs) to mitigate and
treat the consequences of radiation exposure. The RNCP’s research priorities are focused on the
development of MCMs (with over 150 currently under evaluation), decorporation agents targeting
internal radionuclide contamination and biodosimetric tools that measure radiation exposure of victims.
Among the MCMs evaluated by RNCP to date, Neupogen (filgrastim) was demonstrated to increase
survival by 38% in GLP studies in a non-human primate (NHP) model of hematopoietic acute radiation
syndrome (He-ARS). Neulasta (pegfilgrastim), a more stable, pegylated form of Neupogen, shows an even
higher efficacy by improving survival by 44%. The survival increases observed in both studies are
significant and have warranted the unprecedented submission of these two compounds to the FDA. These
submissions triggered FDA to convene an Advisory Committee meeting on May 3, 2013 to discuss the
safety and efficacy of all currently approved leukocyte growth factors as potential treatments He-ARS. Key
strategies of the RNCP are to help researchers navigate the challenging path of drug development, while
continuing to introduce new initiatives and processes that will enhance the MCM program in years to
come. These include an improvement in drug screening programs, as well as exploring areas of unmet
needs, such as drug formulations for special populations and qualification of animal models that will
advance drug development for human use.
(PS3-72) Inhibition of Lysophosphatidic acid receptor 1 radiosensitizes lung cancer cell lines. Rowan M.
Karvas, BS; David Y. Dadey, BS; Dennis Hallahan, MD; and Dinesh Thotala, PhD; Washington University
School of Medicine in St. Louis, St. Louis, MO
Inhibition of Lysophosphatidic Acid Receptor 1 radiosensitizes lung cancer cells Abstract: Recent advances
in lung cancer treatment with radiation such as IMRT and SBRT have improved outcomes. Lung cancer still
remains the most lethal cancer in the US. Molecularly targeted radiosensitizers enhance the effects of
226 | P a g e
translocations and dicentrics as well. The goal of the current work is to test the utility of dGH as a
biodosimetric approach on a population of surviving US military veterans accidentally exposed during
nuclear bomb testing in the 1950s. We plan to establish in vitro dose-response relationships (calibration
curves) for the induction of chromosome aberrations (translocations and inversions) in a cohort of 80-
year old control individuals, as well as a cohort of 25-year olds, to address age at exposure as a variable.
Resulting individual dose estimates for the exposed individuals will be used to help reduce the large
uncertainties associated with measurements of physical dose.
(PS3-71) NIAID Radiation and Nuclear Countermeasures Program: challenges, successes, and strategies
for the future. Carmen I. Rios; David R. Cassatt; Andrea L. DiCarlo; Francesca Macchiarini; and Bert W.
Maidment, DAIT, NIAID, NIH, Bethesda, MD
The possibility of a radiological or nuclear incident in the United States remains a national security
level threat. The gravity of such a scenario would be exacerbated if necessary medical treatments were
not available. Unfortunately, there are currently no FDA-approved drugs available in the Strategic National
Stockpile that are licensed for the treatment of acute and/or delayed radiation health complications. Since
2004, the National Institute of Allergy and Infectious Diseases (NIAID), Radiation and Nuclear
Countermeasures Program (RNCP) has addressed these concerns by building and managing a program for
the research and development of safe and efficacious medical countermeasures (MCMs) to mitigate and
treat the consequences of radiation exposure. The RNCP’s research priorities are focused on the
development of MCMs (with over 150 currently under evaluation), decorporation agents targeting
internal radionuclide contamination and biodosimetric tools that measure radiation exposure of victims.
Among the MCMs evaluated by RNCP to date, Neupogen (filgrastim) was demonstrated to increase
survival by 38% in GLP studies in a non-human primate (NHP) model of hematopoietic acute radiation
syndrome (He-ARS). Neulasta (pegfilgrastim), a more stable, pegylated form of Neupogen, shows an even
higher efficacy by improving survival by 44%. The survival increases observed in both studies are
significant and have warranted the unprecedented submission of these two compounds to the FDA. These
submissions triggered FDA to convene an Advisory Committee meeting on May 3, 2013 to discuss the
safety and efficacy of all currently approved leukocyte growth factors as potential treatments He-ARS. Key
strategies of the RNCP are to help researchers navigate the challenging path of drug development, while
continuing to introduce new initiatives and processes that will enhance the MCM program in years to
come. These include an improvement in drug screening programs, as well as exploring areas of unmet
needs, such as drug formulations for special populations and qualification of animal models that will
advance drug development for human use.
(PS3-72) Inhibition of Lysophosphatidic acid receptor 1 radiosensitizes lung cancer cell lines. Rowan M.
Karvas, BS; David Y. Dadey, BS; Dennis Hallahan, MD; and Dinesh Thotala, PhD; Washington University
School of Medicine in St. Louis, St. Louis, MO
Inhibition of Lysophosphatidic Acid Receptor 1 radiosensitizes lung cancer cells Abstract: Recent advances
in lung cancer treatment with radiation such as IMRT and SBRT have improved outcomes. Lung cancer still
remains the most lethal cancer in the US. Molecularly targeted radiosensitizers enhance the effects of
226 | P a g e
