Topical axitinib suppresses angiogenesis pathways induced by pulsed dye laser.
Topical axitinib suppresses angiogenesis pathways induced by pulsed dye laser.
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DOI:
10.1111/bjd.13439
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发表时间:
2015-03
期刊:
影响因子:
--
通讯作者:
Tan W
中科院分区:
文献类型:
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作者:
Gao L;Nadora DM;Phan S;Chernova M;Sun V;Preciado SM;Jia W;Wang G;Mihm MC Jr;Nelson JS;Tan W
The recurrence of port-wine stain (PWS) blood vessels by pulsed dye laser (PDL)-induced angiogenesis is a critical barrier that must be overcome to achieve a better therapeutic outcome. To determine whether PDL-induced angiogenesis can be suppressed by topical axitinib. The mRNA expression profiles of 86 angiogenic genes and phosphorylation levels of extracellular signal regulated kinases (ERKs), phosphorylated protein kinase B (AKT) and ribosomal protein S6 kinase (p70S6K) in rodent skin were examined with or without topical axitinib administration after PDL exposure. The PDL-induced increased transcriptional levels of angiogenic genes peaked at days 3–7 post-PDL exposure. Topical application of 0.5% axitinib effectively suppressed the PDL-induced increase in mRNA levels of the examined angiogenic genes and activation of AKT, P70S6K and ERK from days 1 to 7 post-PDL exposure. After topical administration, axitinib penetrated into rodent skin to an approximate depth of 929.5 μm. Topical application of 0.5% axitinib can systematically suppress the PDL-induced early stages of angiogenesis via inhibition of the AKT/mammalian target of rapamycin/p70S6K and Src homology 2 domain containing transforming protein-1/mitogen-activated protein kinase kinase/ERK pathway cascades.