L Gao1, D M Nadora, S Phan, M Chernova, V Sun, S M O Preciado, W Jia, G Wang, M C Mihm, J S Nelson, W Tan. 1. 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.
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. OBJECTIVES: 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.
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. OBJECTIVES: 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: Markus Guba; Philipp von Breitenbuch; Markus Steinbauer; Gudrun Koehl; Stefanie Flegel; Matthias Hornung; Christiane J Bruns; Carl Zuelke; Stefan Farkas; Matthias Anthuber; Karl-Walter Jauch; Edward K Geissler Journal: Nat Med Date: 2002-02 Impact factor: 53.440
Authors: Wenbin Tan; Margarita Chernova; Lin Gao; Victor Sun; Huaxu Liu; Wangcun Jia; Stephanie Langer; Gang Wang; Martin C Mihm; J Stuart Nelson Journal: J Am Acad Dermatol Date: 2014-08-16 Impact factor: 11.527
Authors: W Tan; J Wang; F Zhou; L Gao; R Yin; H Liu; A Sukanthanag; G Wang; M C Mihm; D-B Chen; J S Nelson Journal: Br J Dermatol Date: 2017-11-16 Impact factor: 11.113
Authors: Rong Yin; Lin Gao; Wenbin Tan; Wei Guo; Tao Zhao; Jhon Stuart Nelson; Gang Wang Journal: Am J Dermatopathol Date: 2017-10 Impact factor: 1.533
Authors: M Ingmar van Raath; Jojanneke E van Amesfoort; Martin Hermann; Yasin Ince; Maurice J Zwart; Agustina V Echague; Yan Chen; Baoyue Ding; Xuan Huang; Gert Storm; Michal Heger Journal: J Clin Transl Res Date: 2019-05-01