Page 184 - 2014 Printable Abstract Book
P. 184
and accelerated recovery of monocytes and white blood cells. Examination of spleens from irradiated,
CDX-301 treated mice suggest a reduction in apoptosis.The views expressed are those of the authors and
do not reflect the official policy or position of the Armed Forces Radiobiology Research Institute, the
Uniformed Services University, the Department of Defense, or the United States Government.
(PS2-82) Optimal dose and duration of BIO 300 for mitigating radiation induced lung injury in C57L/J
mice. Juliana A. Medina; Carolyn Buck; Radmila Pavlovic; Shabnam Salimi, PhD; Chiwei Hung, PhD; Isabel
L. Jackson, PhD; and Zeljko Vujaskovic, MD,PhD, University of Maryland - Baltimore, Baltimore, MD
BIO 300 (Humanetics Corp.) is being developed as a medical countermeasure (MCM) for
pneumonitis/fibrosis following acute radiation exposure. BIO 300 is an oral nanosuspension containing
synthetic genistein that has improved oral bioavailability. The aim of this study was to determine the
optimal BIO 300 dose and dosing duration to improve survival and reduce lung dysfunction following
whole thorax lung irradiation (WTLI). Age-matched female (F) and male (M) C57L/J mice were randomized
to treatment groups at 10-14w of age. Sham, 11 Gy, or 12.5 Gy irradiation (1.25cGy min-1, HVL ~ 1mm
Cu) was delivered in a single dose to the whole thorax. BIO 300 (200 or 400mg/kg; oral gavage) was started
24h post-IR and continued daily (2, 4, 6 or 10w duration). Morbidity/mortality was monitored daily for
180 days for females and 220 days for males. Body weights, breathing frequency and enhanced pause
measurements were acquired biweekly. Lung tissues were harvested for histopathology at necropsy. In
the 11Gy WTLI group, 400mg/kg BIO 300 for 4w was the most effective treatment regimen resulting in
62% survival (M + F, 18/29) compared to 35% survival (M + F, 11/31) in the non-treated control group
(p=0.0395). Similar improvement was observed in the 12.5Gy WTLI group where survival was 30-33% in
the 4-6w treatment groups (M + F, 8/27 in 4w (p=0.0796) and 10/30 in 6w group (p=0.039)) vs. 11% in the
control group (M + F, 3/28). Survivors had improved respiratory function (less pulmonary edema,
respiratory dysfunction and distress). BIO 300 was effective at improving survival and reducing damage
post WTLI when given at 400mg/kg starting 24h post-IR by oral gavage for 4-6w. Our results provide
support for the further development of BIO 300 as a MCM in case of radiological or nuclear incident.
Future studies should clarify the mechanisms by which BIO 300 mitigates lung damage and improves
survival. This project has been funded in whole or in part with Federal funds from the Biomedical
Advanced Research and Development Authority, Office of the Assistant Secretary for Preparedness and
Response, Department of Health and Human Services under Contract #HHSO100201100026C. BARDA
acknowledges the presentation, data analysis, and the interpretation are the choice of the Contractor and
do not necessarily represent the only possible analysis and interpretation.
(PS2-83) Valproic acid enhances the efficacy of radiation therapy by protecting normal hippocampal
neurons and sensitizing malignant glioblastoma cells. Dinesh Thotala, PhD; Rowan M. Karvas, BS; John
A. Engelbach, BS; Joel R. Garbow, PhD; Sandeep R. Bhave, MD; Andrew N. Hallahan, BS; Todd A.
DeWees, PhD; and Dennis E. Hallahan, MD, Washington University, Saint Louis, MO
Valproic acid is an antiepileptic drug given to patients with brain tumors to manage seizures.
Retrospective clinical studies suggest that VPA could improve outcome in both adults and children with
brain neoplasms. We evaluated valproic acid (VPA), both as a radio-protector that could prevent normal
tissue injury following cranial irradiation, as well as a radiosensitizer of malignant gliomas. To determine
182 | P a g e
CDX-301 treated mice suggest a reduction in apoptosis.The views expressed are those of the authors and
do not reflect the official policy or position of the Armed Forces Radiobiology Research Institute, the
Uniformed Services University, the Department of Defense, or the United States Government.
(PS2-82) Optimal dose and duration of BIO 300 for mitigating radiation induced lung injury in C57L/J
mice. Juliana A. Medina; Carolyn Buck; Radmila Pavlovic; Shabnam Salimi, PhD; Chiwei Hung, PhD; Isabel
L. Jackson, PhD; and Zeljko Vujaskovic, MD,PhD, University of Maryland - Baltimore, Baltimore, MD
BIO 300 (Humanetics Corp.) is being developed as a medical countermeasure (MCM) for
pneumonitis/fibrosis following acute radiation exposure. BIO 300 is an oral nanosuspension containing
synthetic genistein that has improved oral bioavailability. The aim of this study was to determine the
optimal BIO 300 dose and dosing duration to improve survival and reduce lung dysfunction following
whole thorax lung irradiation (WTLI). Age-matched female (F) and male (M) C57L/J mice were randomized
to treatment groups at 10-14w of age. Sham, 11 Gy, or 12.5 Gy irradiation (1.25cGy min-1, HVL ~ 1mm
Cu) was delivered in a single dose to the whole thorax. BIO 300 (200 or 400mg/kg; oral gavage) was started
24h post-IR and continued daily (2, 4, 6 or 10w duration). Morbidity/mortality was monitored daily for
180 days for females and 220 days for males. Body weights, breathing frequency and enhanced pause
measurements were acquired biweekly. Lung tissues were harvested for histopathology at necropsy. In
the 11Gy WTLI group, 400mg/kg BIO 300 for 4w was the most effective treatment regimen resulting in
62% survival (M + F, 18/29) compared to 35% survival (M + F, 11/31) in the non-treated control group
(p=0.0395). Similar improvement was observed in the 12.5Gy WTLI group where survival was 30-33% in
the 4-6w treatment groups (M + F, 8/27 in 4w (p=0.0796) and 10/30 in 6w group (p=0.039)) vs. 11% in the
control group (M + F, 3/28). Survivors had improved respiratory function (less pulmonary edema,
respiratory dysfunction and distress). BIO 300 was effective at improving survival and reducing damage
post WTLI when given at 400mg/kg starting 24h post-IR by oral gavage for 4-6w. Our results provide
support for the further development of BIO 300 as a MCM in case of radiological or nuclear incident.
Future studies should clarify the mechanisms by which BIO 300 mitigates lung damage and improves
survival. This project has been funded in whole or in part with Federal funds from the Biomedical
Advanced Research and Development Authority, Office of the Assistant Secretary for Preparedness and
Response, Department of Health and Human Services under Contract #HHSO100201100026C. BARDA
acknowledges the presentation, data analysis, and the interpretation are the choice of the Contractor and
do not necessarily represent the only possible analysis and interpretation.
(PS2-83) Valproic acid enhances the efficacy of radiation therapy by protecting normal hippocampal
neurons and sensitizing malignant glioblastoma cells. Dinesh Thotala, PhD; Rowan M. Karvas, BS; John
A. Engelbach, BS; Joel R. Garbow, PhD; Sandeep R. Bhave, MD; Andrew N. Hallahan, BS; Todd A.
DeWees, PhD; and Dennis E. Hallahan, MD, Washington University, Saint Louis, MO
Valproic acid is an antiepileptic drug given to patients with brain tumors to manage seizures.
Retrospective clinical studies suggest that VPA could improve outcome in both adults and children with
brain neoplasms. We evaluated valproic acid (VPA), both as a radio-protector that could prevent normal
tissue injury following cranial irradiation, as well as a radiosensitizer of malignant gliomas. To determine
182 | P a g e
