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3. Artigo de Periódico

Type:	Artigo de Periódico
Title:	First insights for targeted therapies in odontogenic myxoma
Authors:	Núbia Braga Pereira Vanessa Fátima Bernardes Adriana Abalen Martins Dias Ricardo Santiago Gomez Carolina Cavalieri Gomes Victor Coutinho Bastos Juliana Cristina de Souza Marina Gonçalves Diniz Jéssica Gardone Vitório Gregory Thomas Kitten Luciana de Oliveira Andrade Gleide Fernandes de Avelar Wagner Henriques de Castro
Abstract:	Objective: Odontogenic myxoma (OM) occasionally responds poorly to surgical treatment. The MAPK pathway is constitutively activated in several neoplasms and we aimed to test if the MAPK pathway is activated in OM, in order to pave the way for an alternative therapy for aggressive and recurrent cases. Materials and methods: The immunoexpression of phosphorylated ERK1/2 (pERK1/2) was assessed in OM. We established a 3D organotypic culture model for the in vitro study and patient-derived xenografts (PDX) in mice for the in vivo study. The MEK inhibitor U0126 was used to inhibit phosphorylation of ERK1/2 in the in vitro and in vivo models. Results: All OM showed strong pERK1/2 immunoexpression, consistent with MAPK pathway activation. Treatment of the 3D culture with U0126 resulted in a reduced pERK1/2/ERK1/2 ratio. Consistent with the in vitro results, all PDX of animals treated with U0126 showed a decreased volume fold change compared with controls. Conclusions: The MAPK pathway is activated in OM and its inhibition leads to tumor shrinkage in PDX and cell culture models. Clinical relevance: Our results offer a pre-clinical frame for OM-targeted therapy. Further work is needed to determine if this initial finding holds clinical promise.
Subject:	Cell culture techniques, three dimensional Mitogen-activated protein kinase kinases Extracellular signal-regulated MAP kinases MAP kinase signaling system MAP kinase kinase kinases Odontogenic tumors Heterografts Therapeutics
language:	eng
metadata.dc.publisher.country:	Brasil
Publisher:	Universidade Federal de Minas Gerais
Publisher Initials:	UFMG
metadata.dc.publisher.department:	FAO - DEPARTAMENTO DE CLÍNICA ICB - DEPARTAMENTO DE MORFOLOGIA ICB - DEPARTAMENTO DE PATOLOGIA
Rights:	Acesso Restrito
metadata.dc.identifier.doi:	https://doi.org/10.1007/s00784-019-03107-4
URI:	http://hdl.handle.net/1843/82633
Issue Date:	Jul-2020
metadata.dc.url.externa:	https://link.springer.com/article/10.1007/s00784-019-03107-4
metadata.dc.relation.ispartof:	Clinical Oral Investigations
Appears in Collections:	Artigo de Periódico

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