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Establishment and genomic characterizations of patient-derived esophageal squamous cell carcinoma xenograft models using biopsies for treatment optimization

BACKGROUND: Squamous cell carcinoma is the dominant type of esophageal cancer in China with many patients initially diagnosed at advanced stage. Patient-derived xenografts (PDX) models have been developed to be an important platform for preclinical research. This study aims to establish and characte...

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Detalles Bibliográficos
Autores principales: Zou, Jianling, Liu, Ying, Wang, Jingyuan, Liu, Zhentao, Lu, Zhihao, Chen, Zuhua, Li, Zhongwu, Dong, Bin, Huang, Wenwen, Li, Yanyan, Gao, Jing, Shen, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785825/
https://www.ncbi.nlm.nih.gov/pubmed/29370817
http://dx.doi.org/10.1186/s12967-018-1379-9
Descripción
Sumario:BACKGROUND: Squamous cell carcinoma is the dominant type of esophageal cancer in China with many patients initially diagnosed at advanced stage. Patient-derived xenografts (PDX) models have been developed to be an important platform for preclinical research. This study aims to establish and characterize PDX models using biopsy tissue from advanced esophageal cancer patients to lay the foundation of preclinical application. METHODS: Fresh endoscopic biopsy tissues were harvested from patients with advanced esophageal cancer and implanted subcutaneously into NOD/SCID mice. Then, the PDXs were serially passaged for up to four generations. Transplantation was analyzed and genomic characteristics of xenografts were profiled using next-generation sequencing. RESULTS: Twenty-five PDX models were established (13.3%, 25/188). The latency period was 75.12 ± 19.87 days (50–120 days) for the first passage and it decreased with increasing passaging. Other than tumor stages, no differences were found between transplantations of xenografts and patient characteristics, irrespective of chemotherapy. Histopathological features and chemosensitivity of PDXs were in great accordance with primary patient tumors. Each PDX was assessed for molecular characteristics including copy number variations, somatic mutations, and signaling pathway abnormalities and these were similar to patient results. CONCLUSIONS: Our PDX models were established from real time biopsies and molecularly profiled. They might be promising for drug development and individualized therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-018-1379-9) contains supplementary material, which is available to authorized users.