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Journal of Cancer Research and Clinical Oncology

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01-11-2019 | Gastric Cancer | Original Article – Cancer Research

Malignant ascites-derived organoid (MADO) cultures for gastric cancer in vitro modelling and drug screening

Authors: Jie Li, Huawei Xu, Lixing Zhang, Lele Song, Dan Feng, Xiaobo Peng, Meihong Wu, Yang Zou, Bin Wang, Lixing Zhan, Guoqiang Hua, Xianbao Zhan

Published in: Journal of Cancer Research and Clinical Oncology | Issue 11/2019

Abstract

Purpose

Malignant ascites (MA) is a common manifestation in advanced gastric cancer with peritoneal carcinomatosis and usually indicates a poor prognosis. However, lack of in vitro models that can faithfully recapitulate the characteristics of tumour cells in ascites hinders related researches. Tumour organoids have emerged as a robust in vitro model for tumour research and drug screening. Hence, we aimed to generate a 3-D in vitro organoid cultures from malignant ascites of gastric cancer for disease modelling and drug screening.

Methods

Eleven MADOs were generated from the MA tumour cells of gastric cancer patients. We made comparisons between MADOs and original MA tumour cells in histopathology by immunohistochemistry and genomics by whole-exome sequencing. In order to evaluate MADOs as functional in vitro disease models, we tested whether MADOs could be used for drug sensitivity screens.

Results

Eleven MADO cultures from human gastric cancer were established. MADOs demonstrated divergent growth characteristics and morphologies. MADO cultures preserve the histological architecture, genomic landscape of the corresponding MA tumour cells. MADOs exhibited heterogeneous responses to standard-of-care chemotherapeutics.

Conclusions

We generated MADOs modelling characteristics and mutated genes of MA tumour cells. A broad range of intrinsic MADO response to conventional chemotherapeutics suggests MADOs are amenable to drug screening.

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Title: Malignant ascites-derived organoid (MADO) cultures for gastric cancer in vitro modelling and drug screening
Authors: Jie Li
Huawei Xu
Lixing Zhang
Lele Song
Dan Feng
Xiaobo Peng
Meihong Wu
Yang Zou
Bin Wang
Lixing Zhan
Guoqiang Hua
Xianbao Zhan
Publication date: 01-11-2019
Publisher: Springer Berlin Heidelberg
Keywords: Gastric Cancer
Ascites
Gastric Cancer
Culture
Published in: Journal of Cancer Research and Clinical Oncology / Issue 11/2019
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-019-03004-z

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Abstract

Purpose

Methods

Results

Conclusions

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