Jie Li1, Huawei Xu1, Lixing Zhang2, Lele Song1, Dan Feng1, Xiaobo Peng1, Meihong Wu1, Yang Zou3, Bin Wang1, Lixing Zhan4, Guoqiang Hua5, Xianbao Zhan6. 1. Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. 2. Research and Early Development, Shanghai 121Biomed Inc, Shanghai, 200235, China. 3. Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, Institute of Biomedical Sciences, East China Normal University, Shanghai, 200241, China. 4. CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China. 5. Institute of Radiation Medicine and Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 230032, China. guoqianghua@fudan.edu.cn. 6. Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. zhan.xianbao@smmu.edu.cn.
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.
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 MAtumour cells of gastric cancerpatients. We made comparisons between MADOs and original MAtumour 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 humangastric cancer were established. MADOs demonstrated divergent growth characteristics and morphologies. MADO cultures preserve the histological architecture, genomic landscape of the corresponding MAtumour cells. MADOs exhibited heterogeneous responses to standard-of-care chemotherapeutics. CONCLUSIONS: We generated MADOs modelling characteristics and mutated genes of MAtumour cells. A broad range of intrinsic MADO response to conventional chemotherapeutics suggests MADOs are amenable to drug screening.
Entities:
Keywords:
Drug screening; Gastric cancer; Malignant ascites; Organoid; Personalised medicine
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