An oral Hemokine TM , α-methylhydrocinnamate, enhances myeloid and neutrophil recovery following irradiation in vivo.

Autor: Faller DV; Cancer Center, Boston University School of Medicine, Boston, MA, United States; Phoenicia BioSciences, Inc., Weston, MA, United States., Castaneda SA; Cancer Center, Boston University School of Medicine, Boston, MA, United States., Zhou D; Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas Medical School, Little Rock, AR, United States., Vedamony M; Armed Forces Radiobiology Research Institute, Bethesda, MD, United States., Newburger PE; Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA, United States., White GL; Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States., Kosanke S; Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States., Plett PA; Indiana University, Indianapolis, IN, United States., Orschell CM; Indiana University, Indianapolis, IN, United States., Boosalis MS; Cancer Center, Boston University School of Medicine, Boston, MA, United States., Perrine SP; Cancer Center, Boston University School of Medicine, Boston, MA, United States; Phoenicia BioSciences, Inc., Weston, MA, United States. Electronic address: sperrine@bu.edu.
Jazyk: angličtina
Zdroj: Blood cells, molecules & diseases [Blood Cells Mol Dis] 2017 Mar; Vol. 63, pp. 1-8. Date of Electronic Publication: 2016 Oct 31.
DOI: 10.1016/j.bcmd.2016.10.021
Abstrakt: 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/mm 3 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.
(Copyright © 2016 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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