Use of Growth Factors and Other Cytokines for Treatment of Injuries During a Radiation Public Health Emergency

DiCarlo, Andrea L.; Horta, Zulmarie Perez; Aldrich, Jennifer T.; Jakubowski, Ann A.; Skinner, William; Case, Cullen

doi:10.1667/rr15363.1

Cited by 21 publications

(20 citation statements)

References 123 publications

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“…Epidermal growth factor (EGF) promotes epithelial and hematopoietic stem cells regeneration [ 259 ]. Bone marrow-derived hematopoietic stem cells (HSCs) express the EGF receptor in response to radiation and, in turn, EGF promotes HSCs regeneration in vivo.…”

Section: Medical Countermeasuresmentioning

confidence: 99%

“…Bone marrow-derived hematopoietic stem cells (HSCs) express the EGF receptor in response to radiation and, in turn, EGF promotes HSCs regeneration in vivo. Mechanistically, EGF reduced radiation-induced apoptosis through repression of PUMA proapoptotic protein, and EGF receptor signaling was needed for DNA repair and for HSCs regeneration [ 259 , 260 ]. rhNRG-1β is an EGF-like protein that maintained mitochondrial integrity and ATP production in irradiated cardiomyocytes and preserves cardiac function via the ErbB2-ERK-SIRT1 signaling pathway [ 261 ].…”

Section: Medical Countermeasuresmentioning

confidence: 99%

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Nuclear and Radiological Emergencies: Biological Effects, Countermeasures and Biodosimetry

et al. 2022

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Atomic and radiological crises can be caused by accidents, military activities, terrorist assaults involving atomic installations, the explosion of nuclear devices, or the utilization of concealed radiation exposure devices. Direct damage is caused when radiation interacts directly with cellular components. Indirect effects are mainly caused by the generation of reactive oxygen species due to radiolysis of water molecules. Acute and persistent oxidative stress associates to radiation-induced biological damages. Biological impacts of atomic radiation exposure can be deterministic (in a period range a posteriori of the event and because of destructive tissue/organ harm) or stochastic (irregular, for example cell mutation related pathologies and heritable infections). Potential countermeasures according to a specific scenario require considering basic issues, e.g., the type of radiation, people directly affected and first responders, range of doses received and whether the exposure or contamination has affected the total body or is partial. This review focuses on available medical countermeasures (radioprotectors, radiomitigators, radionuclide scavengers), biodosimetry (biological and biophysical techniques that can be quantitatively correlated with the magnitude of the radiation dose received), and strategies to implement the response to an accidental radiation exposure. In the case of large-scale atomic or radiological events, the most ideal choice for triage, dose assessment and victim classification, is the utilization of global biodosimetry networks, in combination with the automation of strategies based on modular platforms.

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Section: Medical Countermeasuresmentioning

confidence: 99%

Section: Medical Countermeasuresmentioning

confidence: 99%

Nuclear and Radiological Emergencies: Biological Effects, Countermeasures and Biodosimetry

et al. 2022

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“…Various NHP studies over the last 25 years have shown the effect of leukocyte GFs on blood counts and survival. These GFs are indicated for treatment of ARS since they trigger expansion, growth and differentiation of radioresistant bone marrow stem cells to generate the various hematopoietic lineages, including neutrophils and megakaryocytes (24). In fact, the body naturally begins production of GFs and cytokines after irradiation (24), and radiation accident victims who experienced life-threatening radiation exposure (e.g., Chernobyl liquidators) exhibited spontaneous recovery of neutrophils and platelets (25).…”

Section: Natural History Of Diseasementioning

confidence: 99%

“…These GFs are indicated for treatment of ARS since they trigger expansion, growth and differentiation of radioresistant bone marrow stem cells to generate the various hematopoietic lineages, including neutrophils and megakaryocytes (24). In fact, the body naturally begins production of GFs and cytokines after irradiation (24), and radiation accident victims who experienced life-threatening radiation exposure (e.g., Chernobyl liquidators) exhibited spontaneous recovery of neutrophils and platelets (25). Similarly, accelerated platelet recovery in NHPs has been observed after administration of recombinant megakaryocyte growth and development factor (a truncated form of thrombopoietin) with and without G-CSF (26).…”

Section: Natural History Of Diseasementioning

confidence: 99%

A Poly-Pharmacy Approach to Mitigate Acute Radiation Syndrome

et al. 2021

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“…). Further and despite the common observation of clinical efficacy, the use of these recombinants to treat heavily irradiated individuals does not by any means guarantee a survival benefit (DiCarlo et al 2019). The complexity of systemic injury due to such intense IR exposures often leads to multi-organ failure and, thus, is beyond the therapeutic capacity of these recombinants to salvage individuals with such clinical conditions.…”

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confidence: 99%

Radiation countermeasures for hematopoietic acute radiation syndrome: growth factors, cytokines and beyond

Singh

Seed²

2021

International Journal of Radiation Biology

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Purpose: The intent of this article is to report the status of some of the pharmaceuticals currently in late stage development for possible use for individuals unwantedly and acutely injured as a result of radiological/nuclear exposures. The two major questions we attempt to address here are: (a) What medicinals are currently deemed by regulatory authorities (US FDA) to be safe and effective and are being stockpiled? (b) What additional agents might be needed to make the federal/ state/local medicinal repositories more robust and useful in effectively managing contingencies involving radiation overexposures? Conclusions: A limited number (precisely four) of medicinals have been deemed safe and effective, and are approved by the US FDA for the 'hematopoietic acute radiation syndrome (H-ARS).' These agents are largely recombinant growth factors (e.g. rhuG-CSF/filgrastim, rhuGM-CSF/sargramostim) that target and stimulate myeloid progenitors within bone marrow. Romiplostim, a small molecular agonist that enhances platelet production via stimulation of bone marrow megakaryocytes, has been recently approved and indicated for H-ARS. It is critical that additional agents for other major sub-syndromes of ARS (gastrointestinal-ARS) be approved. Future success in developing such medicinals will undoubtedly entail some form of a polypharmaceutical strategy, or perhaps novel, bioengineered chimeric agents with multiple, radioprotective/radiomitigative functionalities.

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Use of Growth Factors and Other Cytokines for Treatment of Injuries During a Radiation Public Health Emergency

Cited by 21 publications

References 123 publications

Nuclear and Radiological Emergencies: Biological Effects, Countermeasures and Biodosimetry

Nuclear and Radiological Emergencies: Biological Effects, Countermeasures and Biodosimetry

A Poly-Pharmacy Approach to Mitigate Acute Radiation Syndrome

Radiation countermeasures for hematopoietic acute radiation syndrome: growth factors, cytokines and beyond

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