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BMC Cancer ; 19(1): 970, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31638925

RESUMO

BACKGROUND: Neuroblastoma (NB) is a paediatric tumour of the sympathetic nervous system. Half of all cases are defined high-risk with an overall survival less than 40% at 5 years from diagnosis. The lack of in vitro models able to recapitulate the intrinsic heterogeneity of primary NB tumours has hindered progress in understanding disease pathogenesis and therapy response. METHODS: Here we describe the establishment of 6 patient-derived organoids (PDOs) from cells of NB tumour biopsies capable of self-organising in a structure resembling the tissue of origin. RESULTS: PDOs recapitulate the histological architecture typical of the NB tumour. Moreover, PDOs expressed NB specific markers such as neural cell adhesion molecules, NB84 antigen, synaptophysin (SYP), chromogranin A (CHGA) and neural cell adhesion molecule NCAM (CD56). Analyses of whole genome genotyping array revealed that PDOs maintained patient-specific chromosomal aberrations such as MYCN amplification, deletion of 1p and gain of chromosome 17q. Furthermore, the PDOs showed stemness features and retained cellular heterogeneity reflecting the high heterogeneity of NB tumours. CONCLUSIONS: We were able to create a novel preclinical model for NB exhibiting self-renewal property and allowing to obtain a reservoir of NB patients' biological material useful for the study of NB molecular pathogenesis and to test drugs for personalised treatments.


Assuntos
Doenças do Sistema Nervoso Autônomo/genética , Doenças do Sistema Nervoso Autônomo/patologia , Modelos Biológicos , Neuroblastoma/genética , Neuroblastoma/patologia , Organoides/patologia , Doenças do Sistema Nervoso Autônomo/metabolismo , Biomarcadores Tumorais/metabolismo , Biópsia , Criança , Pré-Escolar , Cromogranina A/metabolismo , Aberrações Cromossômicas , Amplificação de Genes/genética , Humanos , Lactente , Proteína Proto-Oncogênica N-Myc/genética , Neuroblastoma/metabolismo , Organoides/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Sinaptofisina/metabolismo
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