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Support for the hypoxia theory in the pathogenesis of infantile haemangioma.
Janmohamed, S R; Brinkhuizen, T; den Hollander, J C; Madern, G C; de Laat, P C; van Steensel, M A; Oranje, A P.
Afiliación
  • Janmohamed SR; Department of Dermatology, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), Brussels, Belgium.
  • Brinkhuizen T; Department of Paediatric Surgery, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
  • den Hollander JC; Department of Pathology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
  • Madern GC; Department of Paediatrics, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
  • de Laat PC; Department of Paediatric Surgery, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
  • van Steensel MA; Department of Dermatology, Maastricht University Medical Center, Maastricht, the Netherlands.
  • Oranje AP; Department of Pathology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
Clin Exp Dermatol ; 40(4): 431-7, 2015 Jun.
Article en En | MEDLINE | ID: mdl-25511669
BACKGROUND: The pathogenesis of infantile haemangioma (IH) is unknown. Several mechanisms have been proposed, including hypoxia, which triggers upregulation and stabilization of hypoxia-inducible factor (HIF)1α. HIF1α stimulates downstream transcription of target genes that enhance angiogenesis. AIM: To identify possible involvement of hypoxia in the pathogenesis of IH, as hypoxia signalling constitutes a potential therapeutic target. METHODS: IH tissue samples collected during the period 1991-2011 (preserved in paraffin wax) were immunohistochemically analysed for HIF1α and the known HIF1α targets: BCL2/adenovirus E1B kD-interacting protein family member 3 (BNIP3), carbon anhydrase (CA)-IX, glucose transporter (GLUT)-1, phosphorylated protein kinase B (pAKT), phosphorylated S6 protein (pS6) and vascular endothelial growth factor (VEGF). Four observers independently assessed the findings. RESULTS: Of the 10 IH samples, 2 appeared to be in the growth phase. In all samples, GLUT-1, BNIP3, pAKT and VEGF were positive, CA-IX was weakly positive, and HIF1α was negative. pS6 was positive in 9/10 cases and negative in 1/10. CONCLUSIONS: Several factors implicated in hypoxia-induced angiogenesis may be involved in IH development. However, the small sample size and retrospective approach of the study preclude definitive conclusions. Prospective studies are needed to conclusively determine which of the factors involved in the (hypoxia) cascade are required for an IH to grow, and could thus be a possible target of drugs for IH treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndromes Neoplásicos Hereditarios / Hipoxia de la Célula / Hemangioma Capilar / Subunidad alfa del Factor 1 Inducible por Hipoxia / Neovascularización Patológica Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Clin Exp Dermatol Año: 2015 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndromes Neoplásicos Hereditarios / Hipoxia de la Célula / Hemangioma Capilar / Subunidad alfa del Factor 1 Inducible por Hipoxia / Neovascularización Patológica Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Clin Exp Dermatol Año: 2015 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Reino Unido