3,245
Views
77
CrossRef citations to date
0
Altmetric
Reviews

Radiation countermeasure agents: an update (2011 – 2014)

, PhD, , , &

Bibliography

  • Carter AB, May MM, Perry WJ. The day after: action following a nuclear blast in a U.S. city. Washington Quarterly 2007;30:19-32
  • Benjamin GC, McGeary M, McCutchen SR. Assessing medical preparedness to respond to a terrorist nuclear event: workshop report. The National Academies Press; Washington, DC: 2009
  • Pellmar TC, Rockwell S. Priority list of research areas for radiological nuclear threat countermeasures. Radiat Res 2005;163:115-23
  • Waselenko JK, MacVittie TJ, Blakely WF, et al. Medical management of the acute radiation syndrome: recommendations of the Strategic National Stockpile Radiation Working Group. Ann Intern Med 2004;140:1037-51
  • Hall EJ, Giaccia AJ. Radiobiology for the radiobiologist. 6th edition. Lippincott Williams and Wilkins; Philadelphia, PA: 2006
  • Fliedner TM, Dorr DH, Meineke V. Multi-organ involvement as a pathogenetic principle of the radiation syndromes: a study involving 110 case histories documented in SEARCH and classified as the bases of haematopoietic indicators of effect. Br J Radiol Suppl 2005;27:1-8
  • Hill RP. Radiation effects on the respiratory system. Br J Radiol Suppl 2005;27:75-81
  • Moulder JE, Cohen EP. Radiation-induced multi-organ involvement and failure: the contribution of radiation effects on the renal system. Br J Radiol Suppl 2005;27:82-8
  • Stone HB, Moulder JE, Coleman CN, et al. Models for evaluating agents intended for the prophylaxis, mitigation and treatment of radiation injuries. Report of an NCI Workshop, December 3-4, 2003. Radiat Res 2004;162:711-28
  • Singh VK, Ducey EJ, Brown DS, Whitnall MH. A review of radiation countermeasure work ongoing at the Armed Forces Radiobiology Research Institute. Int J Radiat Biol 2012;88:296-310
  • Singh VK, Beattie LA, Seed TM. Vitamin E: tocopherols and tocotrienols as potential radiation countermeasures. J Radiat Res 2013;54:973-88
  • Koenig KL, Goans RE, Hatchett RJ, et al. Medical treatment of radiological casualties: current concepts. Ann Emer Med 2005;45:643-52
  • Dumont F, Le Roux A, Bischoff P. Radiation countermeasure agents: an update. Expert Opin Ther Pat 2010;20:73-101
  • Seed TM. Radiation protectants: current status and future prospects. Health Phys 2005;89:531-45
  • Whitnall MH, Wilhelmsen CL, McKinney L, et al. Radioprotective efficacy and acute toxicity of 5-androstenediol after subcutaneous or oral administration in mice. Immunopharmacol Immunotoxicol 2002;24:595-626
  • Stickney DR, Dowding C, Garsd A, et al. 5-androstenediol stimulates multilineage hematopoiesis in rhesus monkeys with radiation-induced myelosuppression. Int Immunopharmacol 2006;6:1706-13
  • Stickney DR, Dowding C, Authier S, et al. 5-androstenediol improves survival in clinically unsupported rhesus monkeys with radiation-induced myelosuppression. Int Immunopharmacol 2007;7:500-5
  • Whitnall MH, Villa V, Seed TM, et al. Molecular specificity of 5-androstenediol as a systemic radioprotectant in mice. Immunopharmacol Immunotoxicol 2005;27:1-18
  • Whitnall MH, Elliott TB, Harding RA, et al. Androstenediol stimulates myelopoiesis and enhances resistance to infection in gamma-irradiated mice. Int J Immunopharmacol 2000;22:1-14
  • Loria RM, Conrad DH, Huff T, et al. Androstenetriol and androstenediol. Protection against lethal radiation and restoration of immunity after radiation injury. Ann N Y Acad Sci 2000;917:860-7
  • Whitnall MH, Inal CE, Jackson III WE, et al. In vivo radioprotection by 5-androstenediol: stimulation of the innate immune system. Radiat Res 2001;156:283-93
  • Singh VK, Shafran RL, Inal CE, et al. Effects of whole-body gamma irradiation and 5-androstenediol administration on serum G-CSF. Immunopharmacol Immunotoxicol 2005;27:521-34
  • Grace MB, Singh VK, Rhee JG, et al. 5-AED enhances survival of irradiated mice in a G-CSF-dependent manner, stimulates innate immune cell function, reduces radiation-induced DNA damage and induces genes that modulate cell cycle progression and apoptosis. J Radiat Res 2012;53:840-53
  • Stickney DR, Groothuis JR, Ahlem C, et al. Preliminary clinical findings on NEUMUNE as a potential treatment for acute radiation syndrome. J Radiol Prot 2010;30:687-98
  • Soligenix. 2014. Available from: http://www.soligenix.com/prod_def_sgx202.shtml [Last accessed 25 March 2014]
  • Georges GE, Kuver RP, Jordan R, et al. Post-exposure oral 17,21-beclomethasone dipropionate (BDP) improves survival in a canine gastrointestinal acute radiation syndrome (GI-ARS) model. 58th Annual Meeting of the Radiation Research Society; San Juan, PR; 2012
  • Zenk JL. New therapy for the prevention and prophylactic treatment of acute radiation syndrome. Expert Opin Investig Drugs 2007;16:767-70
  • Valachovicova T, Slivova V, Bergman H, et al. Soy isoflavones suppress invasiveness of breast cancer cells by the inhibition of NF-kappaB/AP-1-dependent and -independent pathways. Int J Oncol 2004;25:1389-95
  • U.S. Secretary Department of Health and Human Services Uniformed Services University of the Health Sciences. Landauer MR, Seed TM, Srinivasan V, et al. Inventor Isoflavones against radiation-induced mortality. EP1767215; 2007
  • Landauer MR, Srinivasan V, Seed TM. Genistein treatment protects mice from ionizing radiation injury. J Appl toxicol 2003;23:379-85
  • Zhou Y, Mi MT. Genistein stimulates hematopoiesis and increases survival in irradiated mice. J Radiat Res 2005;46:425-33
  • Landauer M. Radioprotection by the soy isoflavone genistein. In: Arora R, editor. Herbal radiomodulators: applications in medicine, homeland defense and space. CABI Publishing; Wallingford, England: 2008. p. 163-73
  • Day RM, Barshishat-Kupper M, Mog SR, et al. Genistein protects against biomarkers of delayed lung sequelae in mice surviving high-dose total body irradiation. J Radiat Res 2008;49:361-72
  • Singh VK, Grace MB, Parekh VI, et al. Effects of genistein administration on cytokine induction in whole-body gamma irradiated mice. Int Immunopharmacol 2009;9:1401-10
  • Davis TA, Clarke TK, Mog SR, Landauer MR. Subcutaneous administration of genistein prior to lethal irradiation supports multilineage, hematopoietic progenitor cell recovery and survival. Int J Radiat Biol 2007;83:141-51
  • Davis TA, Mungunsukh O, Zins S, et al. Genistein induces radioprotection by hematopoietic stem cell quiescence. Int J Radiat Biol 2008;84:713-26
  • Day RM, Davis TA, Barshishat-Kupper M, et al. Enhanced hematopoietic protection from radiation by the combination of genistein and captopril. Int Immunopharmacol 2013;15:348-56
  • Humanetics Pharmaceuticals. 2014. Available from: http://www.humaneticscorp.com/ Last accessed 25 January 2014]
  • Ha CT, Li XH, Fu D, et al. Genistein nanoparticles protect mouse hematopoietic system and prevent proinflammatory factors after gamma irradiation. Radiat Res 2013;180:316-25
  • Cleveland Clinic Foundation Gudkov AV, Didonato JA, Krivokrysenko V. Flagellin related polypeptide and uses thereof. WO/2006/069198; 2007
  • Burdelya LG, Krivokrysenko VI, Tallant TC, et al. An agonist of toll-like receptor 5 has radioprotective activity in mouse and primate models. Science 2008;320:226-30
  • Vijay-Kumar M, Aitken JD, Sanders CJ, et al. Flagellin treatment protects against chemicals, bacteria, viruses, and radiation. J Immunol 2008;180:8280-5
  • Krivokrysenko V, Toshov I, Gleiberman AS, et al. Single injection of novel medical radiation countermeasure CBLB502 rescues nonhuman primates within broad time window after lethal irradiation. 56th Annual Meeting of the Radiation Research Society. Maui, Hawaii; 2010
  • Krivokrysenko VI, Shakhov AN, Singh VK, et al. Identification of granulocyte colony-stimulating factor and interleukin-6 as candidate biomarkers of CBLB502 efficacy as a medical radiation countermeasure. J Pharmacol Exp Ther 2012;343:497-508
  • Cleveland BioLabs, Inc. 2014. Available from: http://www.cbiolabs.com/ [Last accessed 2014]
  • Neumedicine. 2014. Available from: http:/www.neumedicines.com/about.shtml [Last accessed 27 March 2014]
  • Colombo MP, Trinchieri G. Interleukin-12 in anti-tumor immunity and immunotherapy. Cytokine Growth Factor Rev 2002;13:155-68
  • Chen T, Burke KA, Zhan Y, et al. IL-12 facilitates both the recovery of endogenous hematopoiesis and the engraftment of stem cells after ionizing radiation. Exp Hematol 2007;35:203-13
  • Basile LA, Gallaher TK, Shibata D, et al. Multilineage hematopoietic recovery with concomitant antitumor effects using low dose Interleukin-12 in myelosuppressed tumor-bearing mice. J Transl Med 2008;6:26
  • Basile LA, Ellefson D, Gluzman-Poltorak Z, et al. HemaMax, a recombinant human interleukin-12, is a potent mitigator of acute radiation injury in mice and non-human primates. PLoS One 2012;7:e30434
  • Xiong GL, Zhao Y, Xing S, et al. Radiation protection effect of rhIL-12 on monkey hematopoietic system. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2013;21:150-4
  • Ellefson D, Galalaher T, Gluzman-Poltorak Z, et al. Mitigation of radiation combined injury (RCI) by interleukin-12. 14th International Congress of Radiation Research; Warsaw, Poland; 2011
  • Farese AM, Cohen MV, Katz BP, et al. Filgrastim improves survival in lethally irradiated nonhuman primates. Radiat Res 2013;179:89-100
  • Gluzman-Poltorak Z, Mendonca SR, Vainstein V, et al. Randomized comparison of single dose of recombinant human IL-12 versus placebo for restoration of hematopoiesis and improved survival in rhesus monkeys exposed to lethal radiation. J Hematol Oncol 2014;7:31
  • Ghosh SP, Perkins MW, Hieber K, et al. Radiation protection by a new chemical entity, Ex-Rad: efficacy and mechanisms. Radiat Res 2009;171:173-9
  • Suman S, Maniar M, Fornace AJ Jr, Datta K. Administration of ON 01210.Na after exposure to ionizing radiation protects bone marrow cells by attenuating DNA damage response. Radiat Oncol 2012;7:6
  • Suman S, Datta K, Doiron K, et al. Radioprotective effects of ON 01210.Na upon oral administration. J Radiat Res 2012;53:368-76
  • Kumar R. Radioprotection and radiomitigation properties of Ex-Rad upon oral administration. 56th Annual Meeting of the Radiation Research Society; Maui, Hawaii; 2010
  • Ghosh SP, Kulkarni S, Perkins MW, et al. Amelioration of radiation-induced hematopoietic and gastrointestinal damage by Ex-RAD(R) in mice. J Radiat Res 2012;53:526-36
  • Kang AD, Cosenza SC, Bonagura M, et al. ON01210.Na (Ex-RAD(R)) mitigates radiation damage through activation of the AKT pathway. PLoS One 2013;8:e58355
  • Onconova Therapeutics, Inc. 2014. Available from: http://www.onconova.com/product-pipeline/recilisib.php [Last accessed 28 March 2014]
  • HHS boosts stockpile of products to treat acute radiation syndrome. 2013. Available from: http://www.hhs.gov/news/press/2013pres/09/20130926a.html [Last accessed 2014]
  • U.S. Food and Drug Administration. FDA Advisory Committee Briefing Document: a Joint Meeting of the Medical Imaging Drugs Advisory Committee and the Oncologic Drugs Advisory Committee. 2013. Available from: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/MedicalImagingDrugsAdvisoryCommittee/UCM350151.pdf [Last accessed 5 February 2014]
  • Hosoi Y, Kurishita A, Ono T, Sakamoto K. Effect of recombinant human granulocyte colony-stimulating factor on survival in lethally irradiated mice. Acta Oncol 1992;31:59-63
  • Sureda A, Kadar E, Valls A, Garcia-Lopez J. Granulocyte colony-stimulating factor administered as a single intraperitoneal injection modifies the lethal dose95/30 in irradiated B6D2F1 mice. Haematologica 1998;83:863-4
  • Patchen ML, MacVittie TJ. Granulocyte colony-stimulating factor and amifostine (Ethyol) synergize to enhance hemopoietic reconstitution and increase survival in irradiated animals. Semin Oncol 1994;21:26-32
  • Tanikawa S, Nose M, Aoki Y, et al. Effects of recombinant human granulocyte colony-stimulating factor on the hematologic recovery and survival of irradiated mice. Blood 1990;76:445-9
  • Mac Vittie TJ, Monroy RL, Farese AM, et al. Cytokine therapy in canine and primate models of radiation-induced marrow aplasia. Behring Inst Mitt 1991;90:1-13
  • Nash RA, Schuening FG, Seidel K, et al. Effect of recombinant canine granulocyte-macrophage colony-stimulating factor on hematopoietic recovery after otherwise lethal total body irradiation. Blood 1994;83:1963-70
  • MacVittie TJ, Monroy RL, Patchen ML, Souza LM. Therapeutic use of recombinant human G-CSF (rhG-CSF) in a canine model of sublethal and lethal whole-body irradiation. Int J Radiat Biol 1990;57:723-36
  • Schuening FG, Appelbaum FR, Deeg HJ, et al. Effects of recombinant canine stem cell factor, a c-kit ligand, and recombinant granulocyte colony-stimulating factor on hematopoietic recovery after otherwise lethal total body irradiation. Blood 1993;81:20-6
  • Schuening FG, Storb R, Goehle S, et al. Effect of recombinant human granulocyte colony-stimulating factor on hematopoiesis of normal dogs and on hematopoietic recovery after otherwise lethal total body irradiation. Blood 1989;74:1308-13
  • Moroni M, Ngudiankama BF, Christensen C, et al. The Gottingen minipig is a model of the hematopoietic acute radiation syndrome: G-colony stimulating factor stimulates hematopoiesis and enhances survival from lethal total-body gamma-irradiation. Int J Radiat Oncol Biol Phys 2013;86:986-92
  • Cary LH, Ngudiankama BF, Salber RE, et al. Efficacy of radiation countermeasures depends on radiation quality. Radiat Res 2012;177:663-75
  • Chua HL, Plett PA, Sampson CH, et al. Survival efficacy of the PEGylated G-CSFs Maxy-G34 and neulasta in a mouse model of lethal H-ARS, and residual bone marrow damage in treated survivors. Health Phys 2014;106:21-38
  • Farese AM, Cohen MV, Stead RB, et al. Pegfilgrastim administered in an abbreviated schedule, significantly improved neutrophil recovery after high-dose radiation-induced myelosuppression in rhesus macaques. Radiat Res 2012;178:403-13
  • Kiang JG, Zhai M, Liao PJ, et al. Pegylated G-CSF inhibits blood cell depletion, increases platelets, blocks splenomegaly, and improves survival after whole-body ionizing irradiation but not after irradiation combined with burn. Oxid Med Cell Longev 2014;2014:481392
  • Atkinson K, Matias C, Guiffre A, et al. In vivo administration of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF, interleukin-1 (IL-1), and IL-4, alone and in combination, after allogeneic murine hematopoietic stem cell transplantation. Blood 1991;77:1376-82
  • Monroy RL, Skelly RR, Taylor P, et al. Recovery from severe hematopoietic suppression using recombinant human granulocyte-macrophage colony-stimulating factor. Exp Hematol 1988;16:344-8
  • Tanikawa S, Nakao I, Tsuneoka K, Nara N. Effects of recombinant granulocyte colony-stimulating factor (rG-CSF) and recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) on acute radiation hematopoietic injury in mice. Exp Hematol 1989;17:883-8
  • Waddick KG, Song CW, Souza L, Uckun FM. Comparative analysis of the in vivo radioprotective effects of recombinant granulocyte colony-stimulating factor (G-CSF), recombinant granulocyte-macrophage CSF, and their combination. Blood 1991;77:2364-71
  • Patchen ML, Fischer R, MacVittie TJ, et al. Mast cell growth factor (C-kit ligand) in combination with granulocyte-macrophage colony-stimulating factor and interleukin-3: in vivo hemopoietic effects in irradiated mice compared to in vitro effects. Biotherapy 1993;7:13-26
  • Nothdurft W, Selig C, Fliedner TM, et al. Haematological effects of rhGM-CSF in dogs exposed to total-body irradiation with a dose of 2.4 Gy. Int J Radiat Biol 1992;61:519-31
  • Selig C, Nothdurft W, Kreja L, Fliedner TM. Influence of combined treatment with interleukin 1 and erythropoietin or GM-CSF and erythropoietin on the regeneration of hemopoiesis in the dog after total body irradiation – a preliminary report. Behring Inst Mitt 1991(90):86-92
  • Farese AM, Williams DE, Seiler FR, MacVittie TJ. Combination protocols of cytokine therapy with interleukin-3 and granulocyte-macrophage colony-stimulating factor in a primate model of radiation-induced marrow aplasia. Blood 1993;82:3012-18
  • Neelis KJ, Hartong SC, Egeland T, et al. The efficacy of single-dose administration of thrombopoietin with coadministration of either granulocyte/macrophage or granulocyte colony-stimulating factor in myelosuppressed rhesus monkeys. Blood 1997;90:2565-73
  • Rasey JS, Spence AM, Badger CC, et al. Specific protection of different normal tissues. Pharmacol Ther 1988;39:33-43
  • Glover D, Fox KR, Weiler C, et al. Clinical trials of WR-2721 prior to alkylating agent chemotherapy and radiotherapy. Pharmacol Ther 1988;39:3-7
  • Weiss JF. Pharmacologic approaches to protection against radiation-induced lethality and other damage. Environ Health Perspect 1997;105(Suppl 6):1473-8
  • MedImmune. 2013. Available from: http://www.medimmune.com/docs/default-source/pdfs/prescribing-information-for-amifostine.pdf [Last accessed 30 September 2013]
  • Culy CR, Spencer CM. Amifostine: an update on its clinical status as a cytoprotectant in patients with cancer receiving chemotherapy or radiotherapy and its potential therapeutic application in myelodysplastic syndrome. Drugs 2001;61:641-84
  • Seed TM, Inal CE, Singh VK. Radioprotection of hematopoietic progenitors by low dose amifostine prophylaxis. Int J Radiat Biol 2014;90:594-604
  • Sen CK, Khanna S, Roy S. Tocotrienols in health and disease: the other half of the natural vitamin E family. Mol Aspects Med 2007;28:692-728
  • Baliarsingh S, Beg ZH, Ahmad J. The therapeutic impacts of tocotrienols in type 2 diabetic patients with hyperlipidemia. Atherosclerosis 2005;182:367-74
  • Qureshi AA, Burger WC, Peterson DM, Elson CE. The structure of an inhibitor of cholesterol biosynthesis isolated from barley. J Biol Chem 1986;261:10544-50
  • Berbee M, Fu Q, Boerma M, et al. Reduction of radiation-induced vascular nitrosative stress by the vitamin E analog gamma-tocotrienol: evidence of a role for tetrahydrobiopterin. Int J Radiat Oncol Biol Phys 2011;79:884-91
  • Berbee M, Fu Q, Boerma M, et al. Gamma-Tocotrienol ameliorates intestinal radiation injury and reduces vascular oxidative stress after total-body irradiation by an HMG-CoA reductase-dependent mechanism. Radiat Res 2009;171:596-605
  • Ghosh SP, Kulkarni S, Hieber K, et al. Gamma-tocotrienol, a tocol antioxidant as a potent radioprotector. Int J Radiat Biol 2009;85:598-606
  • Kulkarni S, Ghosh SP, Satyamitra M, et al. Gamma-tocotrienol protects hematopoietic stem and progenitor cells in mice after total-body irradiation. Radiat Res 2010;173:738-47
  • Kulkarni SS, Cary LH, Gambles K, et al. Gamma-tocotrienol, a radiation prophylaxis agent, induces high levels of granulocyte colony-stimulating factor. Int Immunopharmacol 2012;14:495-503
  • Suman S, Datta K, Chakraborty K, et al. Gamma tocotrienol, a potent radioprotector, preferentially upregulates expression of anti-apoptotic genes to promote intestinal cell survival. Food Chem Toxicol 2013;60:488-96
  • Kulkarni S, Singh PK, Ghosh SP, et al. Granulocyte colony-stimulating factor antibody abrogates radioprotective efficacy of gamma-tocotrienol, a promising radiation countermeasure. Cytokine 2013;62:278-85
  • Li XH, Fu D, Latif NH, et al. Delta-tocotrienol protects mouse and human hematopoietic progenitors from gamma-irradiation through extracellular signal-regulated kinase/mammalian target of rapamycin signaling. Haematologica 2010;95:1996-2004
  • Li XH, Ghosh SP, Ha CT, et al. Delta-tocotrienol protects mice from radiation-induced gastrointestinal injury. Radiat Res 2013;180(6):649-57
  • Satyamitra M, Ney P, Graves J III, et al. Mechanism of radioprotection by delta-tocotrienol: pharmacokinetics, pharmacodynamics and modulation of signalling pathways. Br J Radiol 2012;85:e1093-103
  • Satyamitra MM, Kulkarni S, Ghosh SP, et al. Hematopoietic recovery and amelioration of radiation-induced lethality by the vitamin E isoform delta-tocotrienol. Radiat Res 2011;175:736-45
  • Singh VK, Wise SY, Scott JR, et al. Radioprotective efficacy of delta-tocotrienol, a vitamin E isoform, is mediated through granulocyte colony-stimulating factor. Life Sci 2014;98:113-22
  • Gridley DS, Makinde AY, Luo X, et al. Radiation and a metalloporphyrin radioprotectant in a mouse prostate tumor model. Anticancer Res 2007;27:3101-9
  • Pearlstein RD, Higuchi Y, Moldovan M, et al. Metalloporphyrin antioxidants ameliorate normal tissue radiation damage in rat brain. Int J Radiat Biol 2010;86:145-63
  • Zhang Y, Zhang X, Rabbani ZN, et al. Oxidative stress mediates radiation lung injury by inducing apoptosis. Int J Radiat Oncol Biol Phys 2012;83:740-8
  • Aeolus Pharmaceuticals. 2013. Available from: http://www.aeoluspharma.com/ [Last accessed 30 September 2013]
  • Batinic-Haberle I, Tovmasyan A, Roberts E, et al. SOD therapeutics: Latest insights into their structure-activity relationships and impact upon the cellular redox-based pathways. Antioxid Redox Signal 2014;20(15):2372-415
  • Orrell RW. AEOL-10150 (Aeolus). Curr Opin Investig Drugs 2006;7:70-80
  • Garofalo MC, Ward AA, Farese AM, et al. A Pilot study in rhesus macaques to assess the treatment efficacy of a small molecular weight catalytic metalloporphyrin antioxidant (AEOL 10150) in mitigating radiation-induced lung damage. Health Phys 2014;106:73-83
  • Singh VK, Christensen J, Fatanmi OO, et al. Myeloid Progenitors: a radiation countermeasure that is effective when initiated days after irradiation. Radiat Res 2012;177:781-91
  • Singh VK, Elliott TB, Mandalam R, et al. Myeloid progenitors mitigate radiation injury and improve intestinal integrity after whole-body irradiation. NATO RTO HFM-223 Symposium “Biological effects of ionizing radiation exposure and countermeasures: current status and future perspectives”; 8-10 October 2012; Ljubljana, Slovenia; p. 1-13
  • Cellerant therapeutics. 2013. Available from: http://www.cellerant.com/ [Last accessed 26 September 2013]
  • Satyamitra M, Lombardini E, Graves J III, et al. A TPO receptor agonist, ALXN4100TPO, mitigates radiation-induced lethality and stimulates hematopoiesis in CD2F1 mice. Radiat Res 2011;175:746-58
  • Satyamitra M, Lombardini E, Peng T, et al. Preliminary nonclinical toxicity, pharmacokinetics, and pharmacodynamics of ALXN4100TPO, a thrombopoietin receptor agonist, in CD2F1 mice. Int J Toxicol 2013;32:100-12
  • Cai Y, Wang W, Liang H, et al. Keratinocyte growth factor pretreatment prevents radiation-induced intestinal damage in a mouse model. Scand J Gastroenterol 2013;48:419-26
  • Finch PW, Mark Cross LJ, McAuley DF, Farrell CL. Palifermin for the protection and regeneration of epithelial tissues following injury: new findings in basic research and pre-clinical models. J Cell Mol Med 2013;17:1065-87
  • Vadhan-Raj S, Goldberg JD, Perales MA, et al. Clinical applications of palifermin: amelioration of oral mucositis and other potential indications. J Cell Mol Med 2013;17:1371-84
  • Epperly MW, Bray JA, Krager S, et al. Intratracheal injection of adenovirus containing the human MnSOD transgene protects athymic nude mice from irradiation-induced organizing alveolitis. Int J Radiat Oncol Biol Phys 1999;43:169-81
  • Epperly MW, Sikora CA, DeFilippi SJ, et al. Manganese superoxide dismutase (SOD2) inhibits radiation-induced apoptosis by stabilization of the mitochondrial membrane. Radiat Res 2002;157:568-77
  • Guo H, Seixas-Silva JA Jr, Epperly MW, et al. Prevention of radiation-induced oral cavity mucositis by plasmid/liposome delivery of the human manganese superoxide dismutase (SOD2) transgene. Radiat Res 2003;159:361-70
  • Epperly MW, Wang H, Jones JA, et al. Antioxidant-chemoprevention diet ameliorates late effects of total-body irradiation and supplements radioprotection by MnSOD-plasmid liposome administration. Radiat Res 2011;175:759-65
  • Robbins ME, Diz DI. Pathogenic role of the renin-angiotensin system in modulating radiation-induced late effects. Int J Radiat Oncol Biol Phys 2006;64:6-12
  • Robbins ME, Hopewell JW. Physiological factors effecting renal radiation tolerance: a guide to the treatment of late effects. Br J Cancer Suppl 1986;7:265-7
  • Davis TA, Landauer MR, Mog SR, et al. Timing of captopril administration determines radiation protection or radiation sensitization in a murine model of total body irradiation. Exp Hematol 2010;38:270-81
  • Moulder JE, Cohen EP, Fish BL. Captopril and losartan for mitigation of renal injury caused by single-dose total-body irradiation. Radiat Res 2011;175:29-36
  • Kma L, Gao F, Fish BL, et al. Angiotensin converting enzyme inhibitors mitigate collagen synthesis induced by a single dose of radiation to the whole thorax. J Radiat Res 2012;53:10-17
  • Medhora M, Gao F, Jacobs ER, Moulder JE. Radiation damage to the lung: mitigation by angiotensin-converting enzyme (ACE) inhibitors. Respirology 2012;17:66-71
  • Ghosh SN, Zhang R, Fish BL, et al. Renin-Angiotensin system suppression mitigates experimental radiation pneumonitis. Int J Radiat Oncol Biol Phys 2009;75:1528-36
  • Moulder JE, Cohen EP. Future strategies for mitigation and treatment of chronic radiation-induced normal tissue injury. Semin Radiat Oncol 2007;17:141-8
  • Ward WF, Kim YT, Molteni A, Solliday NH. Radiation-induced pulmonary endothelial dysfunction in rats: modification by an inhibitor of angiotensin converting enzyme. Int J Radiat Oncol Biol Phys 1988;15:135-40
  • Ward WF, Molteni A, Ts’ao C, Hinz JM. The effect of Captopril on benign and malignant reactions in irradiated rat skin. Br J Radiol 1990;63:349-54
  • Cohen EP, Fish BL, Moulder JE. Treatment of radiation nephropathy with captopril. Radiat Res 1992;132:346-50
  • Moulder JE, Cohen EP, Fish BL, Hill P. Prophylaxis of bone marrow transplant nephropathy with captopril, an inhibitor of angiotensin-converting enzyme. Radiat Res 1993;136:404-7
  • Cohen EP, Irving AA, Drobyski WR, et al. Captopril to mitigate chronic renal failure after hematopoietic stem cell transplantation: a randomized controlled trial. Int J Radiat Oncol Biol Phys 2008;70:1546-51
  • Charrier S, Michaud A, Badaoui S, et al. Inhibition of angiotensin I-converting enzyme induces radioprotection by preserving murine hematopoietic short-term reconstituting cells. Blood 2004;104:978-85
  • Aggarwal BB, Ichikawa H. Molecular targets and anticancer potential of indole-3-carbinol and its derivatives. Cell Cycle 2005;4:1201-15
  • Reed GA, Arneson DW, Putnam WC, et al. Single-dose and multiple-dose administration of indole-3-carbinol to women: pharmacokinetics based on 3,3’-diindolylmethane. Cancer Epidemiol Biomarkers Prev 2006;15:2477-81
  • Reed GA, Sunega JM, Sullivan DK, et al. Single-dose pharmacokinetics and tolerability of absorption-enhanced 3,3’-diindolylmethane in healthy subjects. Cancer Epidemiol Biomarkers Prev 2008;17:2619-24
  • Heath EI, Heilbrun LK, Li J, et al. A phase I dose-escalation study of oral BR-DIM (BioResponse 3,3’- Diindolylmethane) in castrate-resistant, non-metastatic prostate cancer. Am J Transl Res 2010;2:402-11
  • Del Priore G, Gudipudi DK, Montemarano N, et al. Oral diindolylmethane (DIM): pilot evaluation of a nonsurgical treatment for cervical dysplasia. Gynecol Oncol 2010;116:464-7
  • Fan S, Meng Q, Xu J, et al. DIM (3,3’-diindolylmethane) confers protection against ionizing radiation by a unique mechanism. Proc Natl Acad Sci USA 2013;110:18650-5
  • Kumar A, Kochar A, Sharma D, et al. Antimutagenic and radioprotective effects of oltipraz. 14th International Congress of Radiation Research; Warsaw, Poland; 2011
  • Kim SG, Nam SY, Kim CW. In vivo radioprotective effects of oltipraz in gamma-irradiated mice. Biochem Pharmacol 1998;55:1585-90
  • Lazo JS, Sharlow ER, Epperly MW, et al. Pharmacologic profiling of phosphoinositide 3-kinase inhibitors as mitigators of ionizing radiation-induced cell death. J Pharmacol Exp Ther 2013;347:669-80
  • Maclachlan T, Narayanan B, Gerlach VL, et al. Human fibroblast growth factor 20 (FGF-20; CG53135-05): a novel cytoprotectant with radioprotective potential. Int J Radiat Biol 2005;81:567-79
  • Okunieff P, Wu T, Huang K, Ding I. Differential radioprotection of three mouse strains by basic or acidic fibroblast growth factor. Br J Cancer Suppl 1996;27:S105-8
  • Casey-Sawicki K, Zhang M, Kim S, et al. A basic fibroblast growth factor analog for protection and mitigation against acute radiation syndromes. Health Phys 2014;106:704-12
  • Ma J, Hou Y, Han D, et al. Fibroblast growth factor-peptide promotes bone marrow recovery after irradiation. Adv Exp Med Biol 2013;765:155-61
  • Bhanja P, Saha S, Kabarriti R, et al. Protective role of R-spondin1, an intestinal stem cell growth factor, against radiation-induced gastrointestinal syndrome in mice. PLoS One 2009;4:e8014
  • Kiss GN, Lee SC, Fells JI, et al. Mitigation of radiation injury by selective stimulation of the LPA(2) receptor. Biochim Biophys Acta 2013;1831:117-25
  • Fu Q, Berbee M, Boerma M, et al. The somatostatin analog SOM230 (pasireotide) ameliorates injury of the intestinal mucosa and increases survival after total-body irradiation by inhibiting exocrine pancreatic secretion. Radiat Res 2009;171:698-707
  • Fu Q, Berbee M, Wang W, et al. Preclinical evaluation of Som230 as a radiation mitigator in a mouse model: postexposure time window and mechanisms of action. Radiat Res 2011;175:728-35
  • Rosenbloom AL. Mecasermin (recombinant human insulin-like growth factor I). Adv Ther 2009;26:40-54
  • Zhou D, Deoliveira D, Kang Y, et al. Insulin-like growth factor 1 mitigates hematopoietic toxicity after lethal total body irradiation. Int J Radiat Oncol Biol Phys 2013;85:1141-8
  • Rotolo J, Stancevic B, Zhang J, et al. Anti-ceramide antibody prevents the radiation gastrointestinal syndrome in mice. J Clin Invest 2012;122:1786-90
  • Miller AC, Cohen S, Stewart M, et al. Radioprotection by the histone deacetylase inhibitor phenylbutyrate. Radiat Environ Biophys 2011;50:585-96
  • Lu X, Nurmemet D, Bolduc DL, et al. Radioprotective effects of oral 17-dimethylaminoethylamino-17-demethoxygeldanamycin in mice: bone marrow and small intestine. Cell Biosci 2013;3:36
  • Gronvall GK, Trent D, Borio L, et al. The FDA animal efficacy rule and biodefense. Nat Biotechnol 2007;25:1084-7
  • Guidance for industry: product developoment under the animal rule. 2014. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM399217.pdf [Last accessed 2014]
  • Augustine AD, Gondre-Lewis T, McBride W, et al. Animal models for radiation injury, protection and therapy. Radiat Res 2005;164:100-9
  • Williams JP, Brown SL, Georges GE, et al. Animal models for medical countermeasures to radiation exposure. Radiat Res 2010;173:557-78
  • Ahlem CN, White SK, Page TM, Frincke JM. Differential metabolism of androst-5-ene-3beta,17beta-diol between rats, canines, monkeys and humans. Steroids 2011;76:669-74
  • Shim S, Jang WS, Lee SJ, et al. Development of a new minipig model to study radiation-induced gastrointestinal syndrome and its application in clinical research. Radiat Res 2014;181:387-95
  • U.S. Food and Drug Administration. About the pandemic and all-hazards preparedness reauthorization Act of 2013 (PAHPRA), emergency preparedness and response. 2014. Available from: http://www.fda.gov/emergencypreparedness/medicalcountermeasures/ucm346195.htm [Last accessed 15 February 2014]
  • Singh VK, Newman VL, Seed TM. Colony-stimulating factors for the treatment of the hematopoietic component of the acute radiation syndrome (H-ARS): a review. Cytokine 2015;71:22-37
  • Ding NH, Li JJ, Sun LQ. Molecular mechanisms and treatment of radiation-induced lung fibrosis. Curr Drug Targets 2013;14:1347-56
  • Reeves G. Overview of use of G-CSF and GM-CSF in the treatment of acute radiation injury. Health Phys 2014;106:699-703
  • International Atomic Energy Agency. The radiological accident in Istanbul. 2000. Available from: http://www-pub.iaea.org/books/IAEABooks/6071/The-Radiological-Accident-in-Istanbul [Last accessed 2014]
  • Dainiak N, Gent RN, Carr Z, et al. First global consensus for evidence-based management of the hematopoietic syndrome resulting from exposure to ionizing radiation. Disaster Med Public Health Prep 2011;5:202-12