ArticleInternational journal of radiation oncology, biology, physics2024
Anti-ceramide Single-Chain Variable Fragment Mitigates Gastrointestinal-Acute Radiation Syndrome and Improves Marrow Reconstitution, Rendering Near-Normal 90-Day Autopsies.
Article in International journal of radiation oncology, biology, physics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- Radiation emergency medical countermeasures: Current formulary, identified gaps, and future approaches.Animal models and experimental medicine · 2025Review
- Advanced Medical Countermeasures and Devices for Use During a Radiological or Nuclear Emergency.Disaster medicine and public health preparedness · 2025Review
- Balancing Regeneration and Resistance: Targeting DCLK1 to Mitigate Gastrointestinal Radiation Injury and Oncogenesis.Cancers · 2025Review
- A comprehensive review of sensors of radiation-induced damage, radiation-induced proximal events, and cell death.Immunological reviews · 2025Review
- Diabetic retinopathy is a ceramidopathy reversible by anti-ceramide immunotherapy.Cell metabolism · 2024Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeAfter September 11, 2001, nuclear threat prompted government agencies to develop medical countermeasures to mitigate two syndromes, the hematopoietic-acute radiation syndrome (H-ARS) and the higher-dose gastrointestinal-acute radiation syndrome (GI-ARS), both lethal within weeks. While repurposing leukemia drugs that enhance bone marrow repopulation successfully treats H-ARS, no mitigator potentially deliverable under mass casualty conditions preserves the GI tract. We recently reported that anti-ceramide single-chain variable fragment (scFv) mitigates GI-ARS lethality, abrogating ongoing small intestinal endothelial apoptosis to rescue Lgr5 METHODS AND MATERIALS: For these studies, C57BL/6J male mice were treated with 15 Gy whole body irradiation, the 90% GI-ARS lethal dose for this mouse strain.
resultsMice irradiated with 15 Gy alone or with 15 Gy + bone marrow transplantation (BMT) or anti-ceramide scFv, succumb to an ARS within 8 to 10 days. Autopsies reveal only mice receiving anti-ceramide scFv at 24 hours post-whole body irradiation display small intestinal rescue. No marrow reconstitution occurs in any group with attendant undetectable circulating blood elements. Mice receiving 15 Gy + BMT + scFv, however, normalize blood counts by day 12, suggesting that scFv also improves marrow reconstitution, a concept for which we provide experimental support. We show that at 14 Gy, the upper limit dose for H-ARS lethality before transition to GI-ARS lethality, anti-ceramide scFv markedly improves marrow take, reducing the quantity of marrow-conferring survival by more than 3-fold. Consistent with these findings, mice receiving 15 Gy + BMT + scFv exhibit prolonged survival. At day 90, before sacrifice, they display normal appearance, behavior, and serum biochemistries, and surprisingly, at full autopsy, near-normal physiology in all 42 tissues examined.
conclusionsAnti-ceramide scFv mitigates GI-ARS lethality and improves marrow reconstitution rendering prolonged survival with near normal autopsies.
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