title: Topical axitinib suppresses angiogenesis pathways induced by pulsed dye laser.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To determine whether PDL-induced angiogenesis can be suppressed by topical axitinib.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery and Biomedical Engineering, Beckman Laser Institute and Medical Clinic, University of California, Irvine, CA, 92617, U.S.A; Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: L
authors.initials: L
authors.lastname: Gao
authors.forename: D M
authors.initials: DM
authors.lastname: Nadora
authors.forename: S
authors.initials: S
authors.lastname: Phan
authors.forename: M
authors.initials: M
authors.lastname: Chernova
authors.forename: V
authors.initials: V
authors.lastname: Sun
authors.forename: S M O
authors.initials: SM
authors.lastname: Preciado
authors.forename: W
authors.initials: W
authors.lastname: Jia
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.forename: M C
authors.initials: MC
authors.lastname: Mihm
authors.forename: J S
authors.initials: JS
authors.lastname: Nelson
authors.forename: W
authors.initials: W
authors.lastname: Tan
mesh_terms: D000279:Administration, Cutaneous; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000077784:Axitinib; D003131:Combined Modality Therapy; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D007191:Indazoles / Q000008:administration & dosage / Q000494:pharmacology; D054025:Lasers, Dye / Q000009:adverse effects*; D020935:MAP Kinase Signaling System / Q000528:radiation effects; D008297:Male; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D019339:Port-Wine Stain / Q000601:surgery; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D007093:Imidazoles; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D000077784:Axitinib; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D048049:Extracellular Signal-Regulated MAP Kinases