5-androstenediol improves survival in clinically unsupported rhesus monkeys with radiation-induced myelosuppression

Stickney, Dwight R.; Dowding, Charles; Authier, Simon; Garsd, Armando; Onizuka-Handa, Nanette; Reading, Christopher L.; Frincke, James M.

doi:10.1016/j.intimp.2006.12.005

Cited by 78 publications

(73 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5-Androstenediol (5-androstene-3␤-17␤-diol, 5-AED) a novel nontoxic radiation countermeasure, enhances survival in mice and monkeys exposed to whole-body ␥-IR Stickney et al, 2006Stickney et al, , 2007 and induces hematopoiesis and hematopoietic growth factor expression (Whitnall et al, 2000;Singh et al, 2005;Stickney et al, 2006Stickney et al, , 2007. 5-AED administration causes increases in circulating granulocytes, monocytes, NK cells, and platelets in irradiated animals (Whitnall et al, 2000;Stickney et al, 2007).…”

mentioning

confidence: 99%

See 1 more Smart Citation

5-Androstenediol Promotes Survival of γ-Irradiated Human Hematopoietic Progenitors through Induction of Nuclear Factor-κB Activation and Granulocyte Colony-Stimulating Factor Expression

et al. 2007

View full text Add to dashboard Cite

5-Androstenediol (5-AED) stimulates hematopoiesis and enhances survival in animals exposed to ionizing radiation (IR), suggesting that this steroid may act on hematopoietic progenitor cells. We used ␥-irradiated primary human CD34 ϩ hematopoietic progenitor cells to show that 5-AED protects hematopoietic cells from IR damage, as shown by enhanced cell survival, clonogenicity, proliferation, and differentiation. Unlike in tumor cells, IR did not induce nuclear factor-B (NFB) activation in primary progenitors. However, IR stimulated IB ␤ release from NFB/IB complexes and caused NFB1 (p50) degradation. 5-AED stabilized NFB1 in irradiated cells and induced NFB gene expression and NFB activation (DNA binding). 5-AED stimulated interleukin-6 and granulocyte colony-stimulating factor (G-CSF) secretion. The survival-enhancing effects of 5-AED on clonogenic cells were abrogated by small interfering RNA inhibition of NFB gene expression and by neutralization of G-CSF with antibody.

show abstract

mentioning

confidence: 99%

“…5-AED administration causes increases in circulating granulocytes, monocytes, NK cells, and platelets in irradiated animals (Whitnall et al, 2000;Stickney et al, 2007). 5-AED also displays beneficial effects after burn injury, trauma, and sepsis (Szalay et al, 2006).…”

mentioning

confidence: 99%

5-Androstenediol Promotes Survival of γ-Irradiated Human Hematopoietic Progenitors through Induction of Nuclear Factor-κB Activation and Granulocyte Colony-Stimulating Factor Expression

et al. 2007

View full text Add to dashboard Cite

show abstract

“…STICKNEY et al reported that the duration of severe thrombocytopenia appeared to correlate with death to a greater extent than the duration of severe neutropenia. 81) Thrombocytopenia appears to be more clinically relevant to survival in ARS than has been previously recognized. A recent study reported that the activation of TPO signaling by DNA damage activated the DNA repair function in hematopoietic stem and progenitor cells.…”

Section: Research Efforts At Hirosaki Universitymentioning

confidence: 90%

Overview of Radiation-protective Agent Research and Prospects for the Future

Kashiwakura

2017

Jpn. J. Health Phys.

View full text Add to dashboard Cite

Since the discovery of X-rays in 1895, radioactivity and its effects on the body have led to the issue of radiation injury. Radiation-related casualties following exposure to a lethal dose of ionizing radiation show severe acute radiation syndromes (ARS) involving bone marrow death and gastrointestinal death. ARS causes a decrease in the peripheral blood cell count and such as severe ARS, the intake of appropriate medications is the most suitable initial treatment. Therefore, the development of effective radiation-protective agent is an important issue against radiological accidents and nuclear threats. In this review, the overview of radiation-protective/mitigative agent development against acute radiation effects (external exposure), as well as our research data, and the prospects for future research have been outlined.

show abstract

“…Promising radiation countermeasures under development for H-ARS have been tested in NHP for efficacy and pharmacokinetics/ pharmacodynamics. Some important radiation countermeasures tested for efficacy in the NHP model include G-CSF (filgrastim, Neupogen) (Farese et al 2013;, PEGylated G-CSF (PEGfilgrastim/Neulasta) (Hankey et al 2015), CBLB502 (Entolimod) (Krivokrysenko et al 2012(Krivokrysenko et al , 2015, interleukin-12 (HemaMax) (Basile et al 2012;GluzmanPoltorak et al 2014aGluzmanPoltorak et al , 2014b, AEOL 10150 (meso-porphyrin mimetic) (Garofalo et al 2014b), 5-Androstenediol (Stickney et al 2006(Stickney et al , 2007, amifostine (WR2721, Ethyol) (Geary et al 1989), B-190 (Vasin et al 2014) and c-tocotrienol (Singh et al 2016a). …”

Section: Nhpmentioning

confidence: 99%

A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: part I. Radiation sub-syndromes, animal models and FDA-approved countermeasures

Singh

Seed²

2017

International Journal of Radiation Biology

144

103

View full text Add to dashboard Cite

Purpose: The increasing global risk of nuclear and radiological accidents or attacks has driven renewed research interest in developing medical countermeasures to potentially injurious exposures to acute irradiation. Clinical symptoms and signs of a developing acute radiation injury, i.e. the acute radiation syndrome, are grouped into three sub-syndromes named after the dominant organ system affected, namely the hematopoietic, gastrointestinal, and neurovascular systems. The availability of safe and effective countermeasures against the above threats currently represents a significant unmet medical need. This is the first article within a three-part series covering the nature of the radiation subsyndromes, various animal models for radiation countermeasure development, and the agents currently approved by the United States Food and Drug Administration for countering the medical consequences of several of these prominent radiation exposure-associated syndromes. Conclusions: From the U.S. and global perspectives, biomedical research concerning medical countermeasure development is quite robust, largely due to increased government funding following the 9/11 incidence and subsequent rise of terrorist-associated threats. A wide spectrum of radiation countermeasures for specific types of radiation injuries is currently under investigation. However, only a few radiation countermeasures have been fully approved by regulatory agencies for human use during radiological/nuclear contingencies. Additional research effort, with additional funding, clearly will be needed in order to fill this significant, unmet medical health problem. ARTICLE HISTORY

show abstract

5-androstenediol improves survival in clinically unsupported rhesus monkeys with radiation-induced myelosuppression

Cited by 78 publications

References 25 publications

5-Androstenediol Promotes Survival of γ-Irradiated Human Hematopoietic Progenitors through Induction of Nuclear Factor-κB Activation and Granulocyte Colony-Stimulating Factor Expression

5-Androstenediol Promotes Survival of γ-Irradiated Human Hematopoietic Progenitors through Induction of Nuclear Factor-κB Activation and Granulocyte Colony-Stimulating Factor Expression

Overview of Radiation-protective Agent Research and Prospects for the Future

A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: part I. Radiation sub-syndromes, animal models and FDA-approved countermeasures

Contact Info

Product

Resources

About