Format

Send to

Choose Destination
Sci Rep. 2016 Mar 1;6:22172. doi: 10.1038/srep22172.

Establishment and characterisation of patient-derived xenografts as paraclinical models for gastric cancer.

Choi YY1,2, Lee JE1,2, Kim H3, Sim MH1,2, Kim KK4, Lee G4, Kim HI1, An JY1,5, Hyung WJ1, Kim CB1, Noh SH1,6, Kim S4, Cheong JH1,2,6,7,8.

Author information

1
Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.
2
Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul, Korea.
3
Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
4
Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
5
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
6
Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
7
Department of Biochemistry &Molecular Biology, Yonsei University College of Medicine, Seoul, Korea.
8
Open NBI Convergence Technology Research Laboratory of Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.

Abstract

The patient-derived xenograft (PDX) model is emerging as a promising translational platform to duplicate the characteristics of tumours. However, few studies have reported detailed histological and genomic analyses for model fidelity and for factors affecting successful model establishment of gastric cancer. Here, we generated PDX tumours surgically-derived from 62 gastric cancer patients. Fifteen PDX models were successfully established (24.2%, 15/62) and passaged to maintain tumours in immune-compromised mice. Diffuse type and low tumour cell percentage were negatively correlated with success rates (p = 0.005 and p = 0.025, respectively), while reducing ex vivo and overall procedure times were positively correlated with success rates (p = 0.003 and p = 0.01, respectively). The histology and genetic characteristics of PDX tumour models were stable over subsequent passages. Lymphoma transformation occurred in five cases (33.3%, 5/15), and all were in the NOG mouse, with none in the nude mouse. Together, the present study identified Lauren classification, tumour cell percentages, and ex vivo times along with overall procedure times, as key determinants for successful PDX engraftment. Furthermore, genetic and histological characteristics were highly consistent between primary and PDX tumours, which provide realistic paraclinical models, enabling personalised development of treatment options for gastric cancer.

PMID:
26926953
PMCID:
PMC4772087
DOI:
10.1038/srep22172
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center