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RRx-001 Radioprotection: Enhancement of Survival and Hematopoietic Recovery in Gamma-Irradiated Mice.
Jurgensen, Kimberly J; Skinner, William K J; Oronsky, Bryan; Abrouk, Nacer D; Graff, Andrew E; Landes, Reid D; Culp, William E; Summers, Thomas A; Cary, Lynnette H.
Afiliación
  • Jurgensen KJ; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States.
  • Skinner WKJ; Scientific Research Department, Armed Forces Radiobiology Research Institute, Uniformed Services University, Bethesda, MD, United States.
  • Oronsky B; Department of Radiation Oncology, Walter Reed National Military Medical Center, Bethesda, MD, United States.
  • Abrouk ND; EpicentRx, Inc., San Diego, CA, United States.
  • Graff AE; EpicentRx, Inc., San Diego, CA, United States.
  • Landes RD; Department of Radiation Oncology, Walter Reed National Military Medical Center, Bethesda, MD, United States.
  • Culp WE; Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
  • Summers TA; Director, Biomedical Instrumentation Center, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
  • Cary LH; Department of Pathology, Uniformed Services University, Bethesda, MD, United States.
Front Pharmacol ; 12: 676396, 2021.
Article en En | MEDLINE | ID: mdl-33967816
The present studies evaluate the in vivo prophylactic radioprotective effects of 1-bromoacetyl-3, 3-dinitroazetidine (RRx-001), a phase III anticancer agent that inhibits c-myc and downregulates CD-47, after total body irradiation (TBI), in lethally and sublethally irradiated CD2F1 male mice. A single dose of RRx-001 was administered by intraperitoneal (IP) injection 24 h prior to a lethal or sublethal radiation dose. When irradiated with 9.35 Gy, the dose lethal to 70% of untreated mice at 30 days (LD70/30), only 33% of mice receiving RRx-001 (10 mg/kg) 24 h prior to total body irradiation (TBI) died by day 30, compared to 67% in vehicle-treated mice. The same pretreatment dose of RRx-001 resulted in a significant dose reduction factor of 1.07. In sublethally TBI mice, bone marrow cellularity was increased at day 14 in the RRx-001-treated mice compared to irradiated vehicle-treated animals. In addition, significantly higher numbers of lymphocytes, platelets, percent hematocrit and percent reticulocytes were observed on days 7 and/or 14 in RRx-001-treated mice. These experiments provide proof of principle that systemic administration of RRx-001 prior to TBI significantly improves overall survival and bone marrow regeneration.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Pharmacol Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Pharmacol Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza