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Prediction of Sensitivity and Efficacy of Clinical Chemotherapy Using Larval Zebrafish Patient-Derived Xenografts of Gastric Cancer

BACKGROUND: Perioperative chemotherapy has been accepted as one of the most common approaches for locally advanced gastric cancer. However, the efficacy of chemotherapy varies among patients, and there is no effective method to predict the chemotherapy efficacy currently. We previously established t...

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Autores principales: Zhai, Jing, Wu, Jiaqi, Wang, Yaohui, Fan, Ruoyue, Xie, Guiping, Wu, Fangfang, He, Yani, Qian, Sitong, Tan, Aimin, Yao, Xuequan, He, Mingfang, Shen, Lizong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215369/
https://www.ncbi.nlm.nih.gov/pubmed/34164399
http://dx.doi.org/10.3389/fcell.2021.680491
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author Zhai, Jing
Wu, Jiaqi
Wang, Yaohui
Fan, Ruoyue
Xie, Guiping
Wu, Fangfang
He, Yani
Qian, Sitong
Tan, Aimin
Yao, Xuequan
He, Mingfang
Shen, Lizong
author_facet Zhai, Jing
Wu, Jiaqi
Wang, Yaohui
Fan, Ruoyue
Xie, Guiping
Wu, Fangfang
He, Yani
Qian, Sitong
Tan, Aimin
Yao, Xuequan
He, Mingfang
Shen, Lizong
author_sort Zhai, Jing
collection PubMed
description BACKGROUND: Perioperative chemotherapy has been accepted as one of the most common approaches for locally advanced gastric cancer. However, the efficacy of chemotherapy varies among patients, and there is no effective method to predict the chemotherapy efficacy currently. We previously established the first larval zebrafish patient-derived xenografts (zPDXs) of gastric cancer as a platform for the translational research and personalized treatment. The objective of this study was to investigate the feasibility of screening individualized chemotherapeutics using the zPDXs. METHODS: We further optimized this zPDXs platform including administration route, drug dosing, and rhythm to develop a stable and reliable protocol for chemotherapeutics screening. Using the novel platform, we investigated the chemosensitivity of 5-fluorouracil, cisplatin, docetaxel, and doxorubicin for gastric cancer patients. RESULTS: We showed that the engrafted zebrafish retained the original prominent cell components of the corresponding human tumor tissues, and we successfully obtained the results of chemosensitivity of 5-fluorouracil, cisplatin, docetaxel, and doxorubicin for 28 patients with locally advanced gastric cancer. These patients underwent radical gastrectomy for curative intent and 27 cases received postoperative adjuvant chemotherapy. We revealed that the chemosensitivity obtained from zPDXs was consistent with the clinical responses in these patients (P = 0.029). More importantly, the responder drug(s) from zPDXs used or not was the only risk factor for early-stage recurrence in these 27 patients (P = 0.003). CONCLUSION: Our study with the largest sample size so far suggests that larval zPDXs help to predict the chemotherapeutics response and to achieve precise chemotherapy for gastric cancer.
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spelling pubmed-82153692021-06-22 Prediction of Sensitivity and Efficacy of Clinical Chemotherapy Using Larval Zebrafish Patient-Derived Xenografts of Gastric Cancer Zhai, Jing Wu, Jiaqi Wang, Yaohui Fan, Ruoyue Xie, Guiping Wu, Fangfang He, Yani Qian, Sitong Tan, Aimin Yao, Xuequan He, Mingfang Shen, Lizong Front Cell Dev Biol Cell and Developmental Biology BACKGROUND: Perioperative chemotherapy has been accepted as one of the most common approaches for locally advanced gastric cancer. However, the efficacy of chemotherapy varies among patients, and there is no effective method to predict the chemotherapy efficacy currently. We previously established the first larval zebrafish patient-derived xenografts (zPDXs) of gastric cancer as a platform for the translational research and personalized treatment. The objective of this study was to investigate the feasibility of screening individualized chemotherapeutics using the zPDXs. METHODS: We further optimized this zPDXs platform including administration route, drug dosing, and rhythm to develop a stable and reliable protocol for chemotherapeutics screening. Using the novel platform, we investigated the chemosensitivity of 5-fluorouracil, cisplatin, docetaxel, and doxorubicin for gastric cancer patients. RESULTS: We showed that the engrafted zebrafish retained the original prominent cell components of the corresponding human tumor tissues, and we successfully obtained the results of chemosensitivity of 5-fluorouracil, cisplatin, docetaxel, and doxorubicin for 28 patients with locally advanced gastric cancer. These patients underwent radical gastrectomy for curative intent and 27 cases received postoperative adjuvant chemotherapy. We revealed that the chemosensitivity obtained from zPDXs was consistent with the clinical responses in these patients (P = 0.029). More importantly, the responder drug(s) from zPDXs used or not was the only risk factor for early-stage recurrence in these 27 patients (P = 0.003). CONCLUSION: Our study with the largest sample size so far suggests that larval zPDXs help to predict the chemotherapeutics response and to achieve precise chemotherapy for gastric cancer. Frontiers Media S.A. 2021-06-07 /pmc/articles/PMC8215369/ /pubmed/34164399 http://dx.doi.org/10.3389/fcell.2021.680491 Text en Copyright © 2021 Zhai, Wu, Wang, Fan, Xie, Wu, He, Qian, Tan, Yao, He and Shen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Zhai, Jing
Wu, Jiaqi
Wang, Yaohui
Fan, Ruoyue
Xie, Guiping
Wu, Fangfang
He, Yani
Qian, Sitong
Tan, Aimin
Yao, Xuequan
He, Mingfang
Shen, Lizong
Prediction of Sensitivity and Efficacy of Clinical Chemotherapy Using Larval Zebrafish Patient-Derived Xenografts of Gastric Cancer
title Prediction of Sensitivity and Efficacy of Clinical Chemotherapy Using Larval Zebrafish Patient-Derived Xenografts of Gastric Cancer
title_full Prediction of Sensitivity and Efficacy of Clinical Chemotherapy Using Larval Zebrafish Patient-Derived Xenografts of Gastric Cancer
title_fullStr Prediction of Sensitivity and Efficacy of Clinical Chemotherapy Using Larval Zebrafish Patient-Derived Xenografts of Gastric Cancer
title_full_unstemmed Prediction of Sensitivity and Efficacy of Clinical Chemotherapy Using Larval Zebrafish Patient-Derived Xenografts of Gastric Cancer
title_short Prediction of Sensitivity and Efficacy of Clinical Chemotherapy Using Larval Zebrafish Patient-Derived Xenografts of Gastric Cancer
title_sort prediction of sensitivity and efficacy of clinical chemotherapy using larval zebrafish patient-derived xenografts of gastric cancer
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215369/
https://www.ncbi.nlm.nih.gov/pubmed/34164399
http://dx.doi.org/10.3389/fcell.2021.680491
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