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Functional evaluation of therapeutic response of HCC827 lung cancer to bevacizumab and erlotinib targeted therapy using dynamic contrast-enhanced and diffusion-weighted MRI
This study aimed to investigate the therapeutic responses of lung cancer mice models with adenocarcinoma HCC827 (gefitinib sensitive) and HCC827R (gefitinib resistant) to the epidermal growth factor receptor-tyrosine kinase inhibitor erlotinib alone and in combination with the anti-angiogenesis agen...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679602/ https://www.ncbi.nlm.nih.gov/pubmed/29121075 http://dx.doi.org/10.1371/journal.pone.0187824 |
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author | Chen, Yi-Fang Yuan, Ang Cho, Kuan-Hung Lu, Yi-Chien Kuo, Mark Yen-Ping Chen, Jyh-Horng Chang, Yeun-Chung |
author_facet | Chen, Yi-Fang Yuan, Ang Cho, Kuan-Hung Lu, Yi-Chien Kuo, Mark Yen-Ping Chen, Jyh-Horng Chang, Yeun-Chung |
author_sort | Chen, Yi-Fang |
collection | PubMed |
description | This study aimed to investigate the therapeutic responses of lung cancer mice models with adenocarcinoma HCC827 (gefitinib sensitive) and HCC827R (gefitinib resistant) to the epidermal growth factor receptor-tyrosine kinase inhibitor erlotinib alone and in combination with the anti-angiogenesis agent bevacizumab using dynamic contrast enhanced (DCE) and diffusion-weighted MRI. In the HCC827 model, temporal changes in DCE-MRI derived parameters (K(trans), k(ep), and iAUC(90)) and apparent diffusion coefficient (ADC) were significantly correlated with tumor size. K(trans) and iAUC(90) significantly decreased at week 2 in the groups receiving erlotinib alone and in combination with bevacizumab, whereas k(ep) decreased at week 1 and 2 in both treatment groups. In addition, there was a significant difference in iAUC(90) between the treatment groups at week 1. Compared to the control group of HCC827, there was a significant reduction in microvessel density and increased tumor apoptosis in the two treatment group. ADC value increased in the erlotinib alone group at week 1 and week 2, and in the erlotinib combined with bevacizumab group at week 2. Enlarged areas of central tumor necrosis were associated with a higher ADC value. However, progressive enlargement of the tumors but no significant differences in DCE parameters or ADC were noted in the HCC827R model. These results showed that both erlotinib alone and in combination with bevacizumab could effectively inhibit tumor growth in the gefitinib-sensitive lung cancer mice model, and that this was associated with decreased vascular perfusion, increased ADC percentage, decreased microvessel density, and increased tumor apoptosis with a two-week treatment cycle. |
format | Online Article Text |
id | pubmed-5679602 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-56796022017-11-18 Functional evaluation of therapeutic response of HCC827 lung cancer to bevacizumab and erlotinib targeted therapy using dynamic contrast-enhanced and diffusion-weighted MRI Chen, Yi-Fang Yuan, Ang Cho, Kuan-Hung Lu, Yi-Chien Kuo, Mark Yen-Ping Chen, Jyh-Horng Chang, Yeun-Chung PLoS One Research Article This study aimed to investigate the therapeutic responses of lung cancer mice models with adenocarcinoma HCC827 (gefitinib sensitive) and HCC827R (gefitinib resistant) to the epidermal growth factor receptor-tyrosine kinase inhibitor erlotinib alone and in combination with the anti-angiogenesis agent bevacizumab using dynamic contrast enhanced (DCE) and diffusion-weighted MRI. In the HCC827 model, temporal changes in DCE-MRI derived parameters (K(trans), k(ep), and iAUC(90)) and apparent diffusion coefficient (ADC) were significantly correlated with tumor size. K(trans) and iAUC(90) significantly decreased at week 2 in the groups receiving erlotinib alone and in combination with bevacizumab, whereas k(ep) decreased at week 1 and 2 in both treatment groups. In addition, there was a significant difference in iAUC(90) between the treatment groups at week 1. Compared to the control group of HCC827, there was a significant reduction in microvessel density and increased tumor apoptosis in the two treatment group. ADC value increased in the erlotinib alone group at week 1 and week 2, and in the erlotinib combined with bevacizumab group at week 2. Enlarged areas of central tumor necrosis were associated with a higher ADC value. However, progressive enlargement of the tumors but no significant differences in DCE parameters or ADC were noted in the HCC827R model. These results showed that both erlotinib alone and in combination with bevacizumab could effectively inhibit tumor growth in the gefitinib-sensitive lung cancer mice model, and that this was associated with decreased vascular perfusion, increased ADC percentage, decreased microvessel density, and increased tumor apoptosis with a two-week treatment cycle. Public Library of Science 2017-11-09 /pmc/articles/PMC5679602/ /pubmed/29121075 http://dx.doi.org/10.1371/journal.pone.0187824 Text en © 2017 Chen et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Chen, Yi-Fang Yuan, Ang Cho, Kuan-Hung Lu, Yi-Chien Kuo, Mark Yen-Ping Chen, Jyh-Horng Chang, Yeun-Chung Functional evaluation of therapeutic response of HCC827 lung cancer to bevacizumab and erlotinib targeted therapy using dynamic contrast-enhanced and diffusion-weighted MRI |
title | Functional evaluation of therapeutic response of HCC827 lung cancer to bevacizumab and erlotinib targeted therapy using dynamic contrast-enhanced and diffusion-weighted MRI |
title_full | Functional evaluation of therapeutic response of HCC827 lung cancer to bevacizumab and erlotinib targeted therapy using dynamic contrast-enhanced and diffusion-weighted MRI |
title_fullStr | Functional evaluation of therapeutic response of HCC827 lung cancer to bevacizumab and erlotinib targeted therapy using dynamic contrast-enhanced and diffusion-weighted MRI |
title_full_unstemmed | Functional evaluation of therapeutic response of HCC827 lung cancer to bevacizumab and erlotinib targeted therapy using dynamic contrast-enhanced and diffusion-weighted MRI |
title_short | Functional evaluation of therapeutic response of HCC827 lung cancer to bevacizumab and erlotinib targeted therapy using dynamic contrast-enhanced and diffusion-weighted MRI |
title_sort | functional evaluation of therapeutic response of hcc827 lung cancer to bevacizumab and erlotinib targeted therapy using dynamic contrast-enhanced and diffusion-weighted mri |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679602/ https://www.ncbi.nlm.nih.gov/pubmed/29121075 http://dx.doi.org/10.1371/journal.pone.0187824 |
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