Preclinical transgenic and patient-derived xenograft models recapitulate the radiological features of human adamantinomatous craniopharyngioma

Boult JK, Apps JR, Hölsken A, Hutchinson JC, Carreno G, Danielson LS, Smith LM, Bäuerle T, Buslei R, Buchfelder M, Virasami AK, Koers A, Arthurs OJ, Jacques TS, Chesler L, Martinez-Barbera JP, Robinson SP (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Brain Pathology Wiley-Blackwell

DOI: 10.1111/bpa.12525

Abstract

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 (?-CT), with correlation with histology and human ACP imaging. The growth patterns and radiological features of tumors arising in Hesx1(Cre/+) ;Ctnnb1(lox(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 ?-CT at study end. Pathological correlates with hematoxylin and eosin stained sections were investigated. Early enlargement and heterogeneity of Hesx1(Cre/+) ;Ctnnb1(lox(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 ?-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 ?-CT and verified by histological sections of patient-derived ACP xenografts. The Hesx1(Cre/+) ;Ctnnb1(lox(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.

Authors with CRIS profile

Tobias Bäuerle Professur für Multimodale Bildgebung in der präklinischen Forschung

Involved external institutions

The Institute of Cancer Research (ICR) GB United Kingdom (GB) University College London Hospitals (UCLH) GB United Kingdom (GB)

How to cite

APA:

Boult, J.K., Apps, J.R., Hölsken, A., Hutchinson, J.C., Carreno, G., Danielson, L.S.,... Robinson, S.P. (2017). Preclinical transgenic and patient-derived xenograft models recapitulate the radiological features of human adamantinomatous craniopharyngioma. Brain Pathology. https://doi.org/10.1111/bpa.12525

MLA:

Boult, Jessica K.R., et al. "Preclinical transgenic and patient-derived xenograft models recapitulate the radiological features of human adamantinomatous craniopharyngioma." Brain Pathology (2017).

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