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A Strategy to Delay the Development of Cisplatin Resistance by Maintaining a Certain Amount of Cisplatin-Sensitive Cells

Cisplatin (ddp), which is commonly employed in the treatment of many advanced cancers, often results in initial therapeutic success; however, rapid progression of ddp-resistant cells remains the main reason for treatment failure. Facd with such a problem, we investigated the fitness differences betw...

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Autores principales: Duan, Guihua, Tang, Qianyuan, Yan, Hongli, Xie, Lijuan, Wang, Yun, Zheng, Xi Emily, Zhuge, Yuzheng, Shen, Shanshan, Zhang, Bin, Zhang, Xiaoqi, Wang, Jun, Wang, Wei, Zou, Xiaoping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428423/
https://www.ncbi.nlm.nih.gov/pubmed/28348367
http://dx.doi.org/10.1038/s41598-017-00422-2
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author Duan, Guihua
Tang, Qianyuan
Yan, Hongli
Xie, Lijuan
Wang, Yun
Zheng, Xi Emily
Zhuge, Yuzheng
Shen, Shanshan
Zhang, Bin
Zhang, Xiaoqi
Wang, Jun
Wang, Wei
Zou, Xiaoping
author_facet Duan, Guihua
Tang, Qianyuan
Yan, Hongli
Xie, Lijuan
Wang, Yun
Zheng, Xi Emily
Zhuge, Yuzheng
Shen, Shanshan
Zhang, Bin
Zhang, Xiaoqi
Wang, Jun
Wang, Wei
Zou, Xiaoping
author_sort Duan, Guihua
collection PubMed
description Cisplatin (ddp), which is commonly employed in the treatment of many advanced cancers, often results in initial therapeutic success; however, rapid progression of ddp-resistant cells remains the main reason for treatment failure. Facd with such a problem, we investigated the fitness differences between ddp-sensitive and ddp-resistant cell lines. We found that the growth of ddp-resistant cells was significantly slower than that of sensitive cells due to elevated ROS levels, which suggested that the ddp resistance mechanisms may have negative impacts on the growth of resistant cells. Furthermore, we observed that, when mixed with ddp-sensitive cells, ddp-resistant cells failed to compete, and the growth of ddp-resistant cells could therefore be suppressed by treatment in vivo. We propose a mathematical model parameterized based on in vivo experiments to describe the allometric growth of tumors consisting of two competing subclones. According to our model, a quantitative strategy with a variant drug-dosing interval is proposed to control tumor growth. Taking advantage of intratumoral competition, our strategy with appropriate dosing intervals could remarkably delay the development of ddp resistance and prolong overall survival. Maintaining a certain number of ddp-sensitive cells rather than eradicating the tumor with continuous treatment is feasible for future tumor treatment.
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spelling pubmed-54284232017-05-15 A Strategy to Delay the Development of Cisplatin Resistance by Maintaining a Certain Amount of Cisplatin-Sensitive Cells Duan, Guihua Tang, Qianyuan Yan, Hongli Xie, Lijuan Wang, Yun Zheng, Xi Emily Zhuge, Yuzheng Shen, Shanshan Zhang, Bin Zhang, Xiaoqi Wang, Jun Wang, Wei Zou, Xiaoping Sci Rep Article Cisplatin (ddp), which is commonly employed in the treatment of many advanced cancers, often results in initial therapeutic success; however, rapid progression of ddp-resistant cells remains the main reason for treatment failure. Facd with such a problem, we investigated the fitness differences between ddp-sensitive and ddp-resistant cell lines. We found that the growth of ddp-resistant cells was significantly slower than that of sensitive cells due to elevated ROS levels, which suggested that the ddp resistance mechanisms may have negative impacts on the growth of resistant cells. Furthermore, we observed that, when mixed with ddp-sensitive cells, ddp-resistant cells failed to compete, and the growth of ddp-resistant cells could therefore be suppressed by treatment in vivo. We propose a mathematical model parameterized based on in vivo experiments to describe the allometric growth of tumors consisting of two competing subclones. According to our model, a quantitative strategy with a variant drug-dosing interval is proposed to control tumor growth. Taking advantage of intratumoral competition, our strategy with appropriate dosing intervals could remarkably delay the development of ddp resistance and prolong overall survival. Maintaining a certain number of ddp-sensitive cells rather than eradicating the tumor with continuous treatment is feasible for future tumor treatment. Nature Publishing Group UK 2017-03-27 /pmc/articles/PMC5428423/ /pubmed/28348367 http://dx.doi.org/10.1038/s41598-017-00422-2 Text en © The Author(s) 2017 This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Duan, Guihua
Tang, Qianyuan
Yan, Hongli
Xie, Lijuan
Wang, Yun
Zheng, Xi Emily
Zhuge, Yuzheng
Shen, Shanshan
Zhang, Bin
Zhang, Xiaoqi
Wang, Jun
Wang, Wei
Zou, Xiaoping
A Strategy to Delay the Development of Cisplatin Resistance by Maintaining a Certain Amount of Cisplatin-Sensitive Cells
title A Strategy to Delay the Development of Cisplatin Resistance by Maintaining a Certain Amount of Cisplatin-Sensitive Cells
title_full A Strategy to Delay the Development of Cisplatin Resistance by Maintaining a Certain Amount of Cisplatin-Sensitive Cells
title_fullStr A Strategy to Delay the Development of Cisplatin Resistance by Maintaining a Certain Amount of Cisplatin-Sensitive Cells
title_full_unstemmed A Strategy to Delay the Development of Cisplatin Resistance by Maintaining a Certain Amount of Cisplatin-Sensitive Cells
title_short A Strategy to Delay the Development of Cisplatin Resistance by Maintaining a Certain Amount of Cisplatin-Sensitive Cells
title_sort strategy to delay the development of cisplatin resistance by maintaining a certain amount of cisplatin-sensitive cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428423/
https://www.ncbi.nlm.nih.gov/pubmed/28348367
http://dx.doi.org/10.1038/s41598-017-00422-2
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