| Texto completo | |
| Autor(es): Mostrar menos - |
Sahu, Ravi P.
[1, 2]
;
Ocana, Jesus A.
[1, 3]
;
Harrison, Kathleen A.
[4]
;
Ferracini, Matheus
[1]
;
Touloukian, Christopher E.
[5]
;
Al-Hassani, Mohammed
[1]
;
Sun, Louis
[1]
;
Loesch, Mathew
[1]
;
Murphy, Robert C.
[4]
;
Althouse, Sandra K.
[6]
;
Perkins, Susan M.
[6]
;
Speicher, Paul J.
[7]
;
Tyler, Douglas S.
[7]
;
Konger, Raymond L.
[1, 2]
;
Travers, Jeffrey B.
[1, 3, 8]
Número total de Autores: 15
|
| Afiliação do(s) autor(es): | [1] Indiana Univ Sch Med, Dept Dermatol, Indianapolis, IN 46202 - USA
[2] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 - USA
[3] Indiana Univ Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 - USA
[4] Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Aurora, CO - USA
[5] Indiana Univ Sch Med, Dept Surg, Indianapolis, IN 46202 - USA
[6] Indiana Univ Sch Med, Dept Biostat, Indianapolis, IN 46202 - USA
[7] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 - USA
[8] Richard L Roudebush VA Med Ctr, Indianapolis, IN - USA
Número total de Afiliações: 8
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Cancer Research; v. 74, n. 23, p. 7069-7078, DEC 1 2014. |
| Citações Web of Science: | 19 |
| Resumo | |
Oxidative stress suppresses host immunity by generating oxidized lipid agonists of the platelet-activating factor receptor (PAF-R). Because many classical chemotherapeutic drugs induce reactive oxygen species (ROS), we investigated whether these drugs might subvert host immunity by activating PAF-R. Here, we show that PAF-R agonists are produced in melanoma cells by chemotherapy that is administered in vitro, in vivo, or in human subjects. Structural characterization of the PAF-R agonists induced revealed multiple oxidized glycerophosphocholines that are generated nonenzymatically. In a murine model of melanoma, chemotherapeutic administration could augment tumor growth by a PAF-R-dependent process that could be blocked by treatment with antioxidants or COX-2 inhibitors or by depletion of regulatory T cells. Our findings reveal how PAF-R agonists induced by chemotherapy treatment can promote treatment failure. Furthermore, they offer new insights into how to improve the efficacy of chemotherapy by blocking its heretofore unknown impact on PAF-R activation. (C)2014 AACR. (AU) | |
| Processo FAPESP: | 13/00584-2 - Participação das células supressoras derivadas da linhagem mielóide na inibição induzida pelo PAFR da hipersensibilidade de contato |
| Beneficiário: | Matheus Ferracini |
| Modalidade de apoio: | Bolsas no Exterior - Estágio de Pesquisa - Doutorado |