Preclinical transgenic and patient-derived xenograft models recapitulate the radiological features of human adamantinomatous craniopharyngioma.
Brain Pathol
; 28(4): 475-483, 2018 07.
Article
em En
| MEDLINE
| ID: mdl-28481062
To assess the clinical relevance of transgenic and patient-derived xenograft models of adamantinomatous craniopharyngioma (ACP) using serial magnetic resonance imaging (MRI) and high resolution post-mortem microcomputed tomography (µ-CT), with correlation with histology and human ACP imaging. The growth patterns and radiological features of tumors arising in Hesx1Cre/+ ;Ctnnb1lox(ex3)/+ transgenic mice, and of patient-derived ACP xenografts implanted in the cerebral cortex, were monitored longitudinally in vivo with anatomical and functional MRI, and by ex vivo µ-CT at study end. Pathological correlates with hematoxylin and eosin stained sections were investigated. Early enlargement and heterogeneity of Hesx1Cre/+ ;Ctnnb1lox(ex3)/+ mouse pituitaries was evident at initial imaging at 8 weeks, which was followed by enlargement of a solid tumor, and development of cysts and hemorrhage. Tumors demonstrated MRI features that recapitulated those of human ACP, specifically, T1 -weighted signal enhancement in the solid tumor component following Gd-DTPA administration, and in some animals, hyperintense cysts on FLAIR and T1 -weighted images. Ex vivo µ-CT correlated with MRI findings and identified smaller cysts, which were confirmed by histology. Characteristic histological features, including wet keratin and calcification, were visible on µ-CT and verified by histological sections of patient-derived ACP xenografts. The Hesx1Cre/+ ;Ctnnb1lox(ex3)/+ transgenic mouse model and cerebral patient-derived ACP xenografts recapitulate a number of the key radiological features of the human disease and provide promising foundations for in vivo trials of novel therapeutics for the treatment of these tumors.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Craniofaringioma
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Modelos Animais de Doenças
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Brain Pathol
Assunto da revista:
CEREBRO
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PATOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article