A basic fibroblast growth factor analog for protection and mitigation against acute radiation syndromes.
The effects of fibroblast growth factors and their potential as broad-spectrum agents to treat and mitigate radiation injury have been studied extensively over the past two decades. This report shows that a peptide mimetic of basic fibroblast growth factor (FGF-P) protects and mitigates against acute radiation syndromes. FGF-P attenuates both sepsis and bleeding in a radiation-induced bone marrow syndrome model and reduces the severity of gastrointestinal and cutaneous syndromes; it should also mitigate combined injuries. FGF-2 and FGF-P induce little or no deleterious inflammation or vascular leakage, which distinguishes them from most other growth factors, angiogenic factors, and cytokines. Although recombinant FGFs have proven safe in several ongoing clinical trials, they are expensive to synthesize, can only be produced in limited quantity, and have limited shelf life. FGF-P mimics the advantageous features of FGF-2 without these disadvantages. This paper shows that FGF-P not only has the potential to be a potent yet safe broad-spectrum medical countermeasure that mitigates acute radiotoxicity but also holds promise for thermal burns, ischemic wound healing, tissue engineering, and stem-cell regeneration.
*Department of Radiation Oncology, University of Florida Health Cancer Center, Gainesville, FL; †BioPowerTech, 4734 Bluegrass Pkwy, Tuscaloosa, AL 35406; ‡Department of Pharmaceutics, University of Florida, College of Pharmacy, University of Florida, Gainesville, FL; §DiaCarta, LLC, Hayward, CA 94545.
Kate
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Casey-Sawicki
Mei
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Zhang
Sunghee
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Kim
Amy
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Zhang
Steven B
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Zhang
Zhenhuan
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Zhang
Ravi
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Singh
Shanmin
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Yang
Steven
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Swarts
Sadasivan
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Vidyasagar
Lurong
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Zhang
Aiguo
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Paul
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Okunieff
D054508:Acute Radiation Syndrome / Q000097:blood / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects / Q000528:radiation effects; D001854:Bone Marrow Cells / Q000166:cytology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004355:Drug Stability; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D016222:Fibroblast Growth Factor 2 / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology*; D007928:Lethal Dose 50; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010976:Platelet Count; D011837:Radiation-Protective Agents / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects
D010750:Phosphoproteins; D011837:Radiation-Protective Agents; D016222:Fibroblast Growth Factor 2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3