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10.18632/oncotarget.7878

http://scihub22266oqcxt.onion/10.18632/oncotarget.7878
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C4991492!4991492!26959112
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suck abstract from ncbi


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pmid26959112      Oncotarget 2016 ; 7 (15): 20788-800
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  • Radiation therapy generates platelet-activating factor agonists #MMPMID26959112
  • Sahu RP; Harrison KA; Weyerbacher J; Murphy RC; Konger RL; Garrett JE; Chin-Sinex HJ; Johnston ME; Dynlacht JR; Mendonca M; McMullen K; Li G; Spandau DF; Travers JB
  • Oncotarget 2016[Apr]; 7 (15): 20788-800 PMID26959112show ga
  • Pro-oxidative stressors can suppress host immunity due to their ability to generate oxidized lipid agonists of the platelet-activating factor-receptor (PAF-R). As radiation therapy also induces reactive oxygen species, the present studies were designed to define whether ionizing radiation could generate PAF-R agonists and if these lipids could subvert host immunity. We demonstrate that radiation exposure of multiple tumor cell lines in-vitro, tumors in-vivo, and human subjects undergoing radiation therapy for skin tumors all generate PAF-R agonists. Structural characterization of radiation-induced PAF-R agonistic activity revealed PAF and multiple oxidized glycerophosphocholines that are produced non-enzymatically. In a murine melanoma tumor model, irradiation of one tumor augmented the growth of the other (non-treated) tumor in a PAF-R-dependent process blocked by a cyclooxygenase-2 inhibitor. These results indicate a novel pathway by which PAF-R agonists produced as a byproduct of radiation therapy could result in tumor treatment failure, and offer important insights into potential therapeutic strategies that could improve the overall antitumor effectiveness of radiation therapy regimens.
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