Page 180 - 2014 Printable Abstract Book
P. 180
radiation exposure. Knockdown of NFkBp65 by small interfering RNA (siRNA) significantly suppressed IL-
1β-induced miR-30 expression in CD34+ cells. Thus, our data suggest that DT3 protects human and mouse
cells from radiation damage through suppression of IL-1β-induced NFκB/miR-30 signaling.
(PS2-76) A novel device for preventing Acute Radiation Syndrome and reducing cumulative marrow
dose. Oren Milstein, PhD; Andrey Broisman, PhD; Tamar Nix, MSc; Itzhak Orion, PhD; and Tuvia
Schlesinger, PhD, StemRad Inc, Palo Alto, CA
Introduction: When the human body receives a high dose of ionizing radiation over a short
period of time Acute Radiation Syndrome (ARS) may result. Protracted exposures to gamma radiation
may result in malignancies such as leukemia.
In order to shield as much of the body as possible, existing personal shielding solutions use only thin
layers of inherently heavy radiation-attenuating materials. These types of solutions are ineffective in
blocking energetic gamma radiation. In the case of high-dose exposure, the life-limiting factor at doses
up to 10 Gy is irreversible bone marrow (BM) damage. Notably, radiation doses in past nuclear
catastrophes were largely under 10 Gy. Thus, numerous fatalities in a nuclear catastrophe may be
avoided by preserving BM. Remarkably, due to its extraordinary regenerative potential, to preserve BM
viability it is enough to protect only a small volume. In the case of protracted exposure, BM is also
among the tissues most susceptible to the carcinogenic effects of radiation. Exposure of large areas of
BM to radiation significantly increases the risk of leukemia. Approximately 50% of the of the body’s
active BM is contained within the pelvic region. As such, shielding this region holds great promise.
In this study we present a first-of-its-kind device providing effective shielding of pelvic BM from gamma
radiation. Methods: We performed an exhaustive anatomical study of active BM distribution in the
human skeleton. Based on this and in combination with Monte Carlo simulations, we developed a device
which is able to selectively shield a critical volume of BM in a realistic setting. Using anatomically
accurate human phantoms, we studied the ability of the device to shield against Cs-137 presented as
fallout. Results: BM doses in the presence vs. in the absence of the device were determined. The
shielding provided by the device was significant throughout the pelvis and was especially evident in the
iliac crest. Conclusions: We present a novel device providing effective shielding of BM in humans. This
device may be used for preventing ARS in nuclear catastrophes or as a result of occupational accidents.
Regarding low dose exposures, this device may be used during select procedures to reduce the
cumulative BM dose and therefore the incidence of hematological malignancies among nuclear industry
personnel.
(PS2-77) HemaMax™ (rHuIL-12) increases bone marrow regeneration and moderates radiation
induced upregulation of osteoclasts in lethally irradiated non-human primates. Sarita R. Mendonca;
Zoya Gluzman-Poltorak; Vladimir Vainstein; and Lena Basile, Neumedicines, Inc, Pasadena, CA
TM
HemaMax (recombinant HuIL-12) is currently in advanced development as a frontline biological
drug for the mitigation of the hematopoietic syndrome of acute radiation syndrome (HSARS) in humans.
Our randomized, blinded, placebo-controlled GLP study demonstrated a positive survival effect of a single
subcutaneous injection of rHuIL-12, 24 hours after lethal total body irradiation (700cGy; LD90/60), over a
10-fold dose range (50-500ng/kg), in the NHP model of HSARS, without the use of antibiotics, fluids, blood
178 | P a g e
1β-induced miR-30 expression in CD34+ cells. Thus, our data suggest that DT3 protects human and mouse
cells from radiation damage through suppression of IL-1β-induced NFκB/miR-30 signaling.
(PS2-76) A novel device for preventing Acute Radiation Syndrome and reducing cumulative marrow
dose. Oren Milstein, PhD; Andrey Broisman, PhD; Tamar Nix, MSc; Itzhak Orion, PhD; and Tuvia
Schlesinger, PhD, StemRad Inc, Palo Alto, CA
Introduction: When the human body receives a high dose of ionizing radiation over a short
period of time Acute Radiation Syndrome (ARS) may result. Protracted exposures to gamma radiation
may result in malignancies such as leukemia.
In order to shield as much of the body as possible, existing personal shielding solutions use only thin
layers of inherently heavy radiation-attenuating materials. These types of solutions are ineffective in
blocking energetic gamma radiation. In the case of high-dose exposure, the life-limiting factor at doses
up to 10 Gy is irreversible bone marrow (BM) damage. Notably, radiation doses in past nuclear
catastrophes were largely under 10 Gy. Thus, numerous fatalities in a nuclear catastrophe may be
avoided by preserving BM. Remarkably, due to its extraordinary regenerative potential, to preserve BM
viability it is enough to protect only a small volume. In the case of protracted exposure, BM is also
among the tissues most susceptible to the carcinogenic effects of radiation. Exposure of large areas of
BM to radiation significantly increases the risk of leukemia. Approximately 50% of the of the body’s
active BM is contained within the pelvic region. As such, shielding this region holds great promise.
In this study we present a first-of-its-kind device providing effective shielding of pelvic BM from gamma
radiation. Methods: We performed an exhaustive anatomical study of active BM distribution in the
human skeleton. Based on this and in combination with Monte Carlo simulations, we developed a device
which is able to selectively shield a critical volume of BM in a realistic setting. Using anatomically
accurate human phantoms, we studied the ability of the device to shield against Cs-137 presented as
fallout. Results: BM doses in the presence vs. in the absence of the device were determined. The
shielding provided by the device was significant throughout the pelvis and was especially evident in the
iliac crest. Conclusions: We present a novel device providing effective shielding of BM in humans. This
device may be used for preventing ARS in nuclear catastrophes or as a result of occupational accidents.
Regarding low dose exposures, this device may be used during select procedures to reduce the
cumulative BM dose and therefore the incidence of hematological malignancies among nuclear industry
personnel.
(PS2-77) HemaMax™ (rHuIL-12) increases bone marrow regeneration and moderates radiation
induced upregulation of osteoclasts in lethally irradiated non-human primates. Sarita R. Mendonca;
Zoya Gluzman-Poltorak; Vladimir Vainstein; and Lena Basile, Neumedicines, Inc, Pasadena, CA
TM
HemaMax (recombinant HuIL-12) is currently in advanced development as a frontline biological
drug for the mitigation of the hematopoietic syndrome of acute radiation syndrome (HSARS) in humans.
Our randomized, blinded, placebo-controlled GLP study demonstrated a positive survival effect of a single
subcutaneous injection of rHuIL-12, 24 hours after lethal total body irradiation (700cGy; LD90/60), over a
10-fold dose range (50-500ng/kg), in the NHP model of HSARS, without the use of antibiotics, fluids, blood
178 | P a g e
