XWH - 12 - 1 - 0477 TITLE : Reducing toxicity of radiation treatment of advanced prostate cancer
نویسندگان
چکیده
Bone marrow suppression due to ionizing radiation is a significant clinical problem in radiation therapy andfollowing non-medical radiation exposure. Currently, no small molecule agents that can enhance hematopoieticregeneration following radiation exposure are available. Here, we report the effective mitigation of acutehematopoietic radiation syndrome in mice by the synthetic triterpenoid, RTA 408. The administration of a briefcourse of RTA 408 treatment beginning 24 h after bone marrow lethal doses of radiation significantly increasedoverall survival. Importantly, treatment with RTA 408 led to the full recovery of steady state hematopoiesis withnormalization of the frequency of hematopoietic stem and progenitor cells. Moreover, hematopoietic stem cellsfrom RTA 408-mitigated mice showed lineage-balanced, long-term, multilineage potential in serialtransplantation assays, indicative of their normal self-renewal activity. The potency of RTA 408 in mitigatingradiation-induced bone marrow suppression makes it an attractive candidate for potential clinical use intreating both therapy-related and unanticipated radiation exposure.
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