Topical axitinib suppresses angiogenesis pathways induced by pulsed dye laser
| Autor: | S. Phan, Victor Sun, Wangcun Jia, Salena Marie Oaxaca Preciado, Lin Gao, J.S. Nelson, Martin C. Mihm, Margarita Chernova, Dawnica Mercado Nadora, Gang Wang, Wenbin Tan |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Indazoles Axitinib MAP Kinase Signaling System Angiogenesis Port-Wine Stain Lasers Dye Angiogenesis Inhibitors Dermatology Biology Administration Cutaneous Rats Sprague-Dawley Neovascularization chemistry.chemical_compound Growth factor receptor Recurrence Internal medicine medicine Animals RNA Messenger Extracellular Signal-Regulated MAP Kinases Protein Kinase Inhibitors Protein kinase B PI3K/AKT/mTOR pathway Neovascularization Pathologic Ribosomal Protein S6 Kinases Imidazoles Combined Modality Therapy Vascular endothelial growth factor Endocrinology chemistry Cancer research medicine.symptom Proto-Oncogene Proteins c-akt Tyrosine kinase medicine.drug |
| Zdroj: | British Journal of Dermatology. 172:669-676 |
| ISSN: | 0007-0963 |
| DOI: | 10.1111/bjd.13439 |
| Popis: | Port-wine stain (PWS) is a congenital, progressive vascular malformation of human skin involving the superficial vascular plexus. PWS occurs in an estimated 3–5 children per 1000 live births.1–3 In childhood, PWSs are flat red macules, but lesions tend to darken progressively to purple and, by middle age, often become raised as a result of the development of vascular nodules.4,5 Recently, a low-frequency allelic mutation (c.548G→A, p.R183Q) in the guanine nucleotide-binding protein G alpha subunit q has been identified in PWS skin.6 We have also found consecutive activation of c-Jun N-terminal kinases and extracellular signal regulated kinases (ERKs) in both infantile and adult PWS.7 Taken together, these studies have begun to elucidate the molecular mechanisms underlying the pathogenesis of PWS. Pulsed dye laser (PDL) is the current treatment of choice for PWS.8,9 However, if the ultimate standard required is complete blanching of the lesion, the degree of PWS blanching achieved following PDL can be variable and unpredictable, with an average treatment success rate below 10% owing to blood vessel recurrence.10–12 The regeneration and revascularization of blood vessels post-PDL treatment is a critical barrier that must be overcome in order to achieve an adequate PWS therapeutic outcome.13 Recent data suggest that activation of angiogenesis pathways induced by PDL in PWS contributes to this process.13 Thus, we hypothesize that a better PWS therapeutic outcome might be achieved with PDL combined with the administration of anti-angiogenesis agents. In our previous studies, we have demonstrated that topical rapamycin (RPM) can suppress the PDL-induced angiogenesis in rodent skin and that systemic administration of RPM post-PDL enhances the blanching response in patients with PWS.13,14 However, multiple signalling pathways are generally activated during PDL-induced angiogenesis; thus, a multitarget inhibitor, such as axitinib, may produce a better anti-angiogenesis effect than RPM, which mainly blocks the protein kinase B (AKT)/mammalian target of rapamycin (mTOR)/ribosomal protein S6 kinase (P70S6K) pathway.15,16 Axitinib, a U.S. Food and Drugs Administration-approved anti-angiogenesis agent for the second-line treatment of patients with advanced renal cell carcinoma, can inhibit many angiogenic tyrosine kinases, including vascular endothelial growth factor (VEGF) receptors (VEGFRs) 1–3, platelet-derived growth factor receptor and stem cell growth factor receptor.17 In this study, we attempted to combine PDL with topical administration of axitinib in order to evaluate its effectiveness in suppressing PDL-induced angiogenesis in rodent skin. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text