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    An oral HemokineTM, alpha-methylhydrocinnamate, enhances myeloid and neutrophil recovery following irradiation in vivo

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    Authors
    Faller, Douglas V.
    Castaneda, Serguei A.
    Zhou, Daohong
    Vedamony, Merriline
    Newburger, Peter E.
    White, Gary L.
    Kosanke, Stanley
    Plett, P. Artur
    Orschell, Christie M.
    Boosalis, Michael S.
    Perrine, Susan P.
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    UMass Chan Affiliations
    Department of Pediatrics, Division of Hematology/Oncology
    Document Type
    Journal Article
    Publication Date
    2017-02-28
    Keywords
    Cell Biology
    Hematology
    Hemic and Lymphatic Diseases
    
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    Link to Full Text
    https://doi.org/10.1016/j.bcmd.2016.10.021
    Abstract
    An oral therapeutic which reduces duration of cytopenias and is active following accidental radiation exposures is an unmet need in radiation countermeasures. Alpha methylhydrocinnamate (ST7) prolongs STAT-5 phosphorylation, reduces growth-factor dependency of multi-lineage cell lines, and stimulates erythropoiesis. Here, ST7 and its isomers were studied for their effects on myeloid progenitors and hematopoietic stem cells (HSCs) following radiation, in nonhuman primates, and murine irradiation models. Addition of ST7 or ST7-S increased CFU-GM production by 1.7-fold (p<0.001), reduced neutrophil apoptosis comparable to G-CSF, and enhanced HSC survival post-radiation by 2-fold, (p=0.028). ST7 and ST7-S administered in normal baboons increased ANC and platelet counts by 50-400%. In sub-lethally-irradiated mice, ANC nadir remained > 200/mm3 and neutropenia recovered in 6days with ST7 treatment and 18days in controls (p<0.05). In lethally-irradiated mice, marrow pathology at 15days was hypocellular (10% cellularity) in controls, but normal (55-75% cellularity) with complete neutrophil maturation with ST7-S treatment. Following lethal irradiation, ST7, given orally for 4days, reduced mortality, with 30% survival in ST7-animals vs 8% in controls, (p<0.05). Collectively, the studies indicate that ST7 and ST7-S enhance myeloid recovery post-radiation and merit further evaluation to accelerate hematologic recovery in conditions of radiation-related and other marrow hypoplasias.
    Source
    Blood Cells Mol Dis. 2017 Mar;63:1-8. doi: 10.1016/j.bcmd.2016.10.021. Epub 2016 Oct 31. Link to article on publisher's site
    DOI
    10.1016/j.bcmd.2016.10.021
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/43566
    PubMed ID
    27888688
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.bcmd.2016.10.021
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