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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2018

Open Access 01-12-2018 | Research

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

Authors: Jianling Zou, Ying Liu, Jingyuan Wang, Zhentao Liu, Zhihao Lu, Zuhua Chen, Zhongwu Li, Bin Dong, Wenwen Huang, Yanyan Li, Jing Gao, Lin Shen

Published in: Journal of Translational Medicine | Issue 1/2018

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Abstract

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.
Appendix
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Metadata
Title
Establishment and genomic characterizations of patient-derived esophageal squamous cell carcinoma xenograft models using biopsies for treatment optimization
Authors
Jianling Zou
Ying Liu
Jingyuan Wang
Zhentao Liu
Zhihao Lu
Zuhua Chen
Zhongwu Li
Bin Dong
Wenwen Huang
Yanyan Li
Jing Gao
Lin Shen
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2018
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-018-1379-9

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