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Drug Screening of Human GBM Spheroids in Brain Cancer Chip

Glioblastoma multiforme (GBM), an extremely invasive and high-grade (grade IV) glioma, is the most common and aggressive form of brain cancer. It has a poor prognosis, with a median overall survival of only 11 months in the general GBM population and 14.6 to 21 months in clinical trial participants...

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Autores principales: Akay, Metin, Hite, John, Avci, Naze Gul, Fan, Yantao, Akay, Yasemin, Lu, Guangrong, Zhu, Jay-Jiguang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194126/
https://www.ncbi.nlm.nih.gov/pubmed/30337660
http://dx.doi.org/10.1038/s41598-018-33641-2
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author Akay, Metin
Hite, John
Avci, Naze Gul
Fan, Yantao
Akay, Yasemin
Lu, Guangrong
Zhu, Jay-Jiguang
author_facet Akay, Metin
Hite, John
Avci, Naze Gul
Fan, Yantao
Akay, Yasemin
Lu, Guangrong
Zhu, Jay-Jiguang
author_sort Akay, Metin
collection PubMed
description Glioblastoma multiforme (GBM), an extremely invasive and high-grade (grade IV) glioma, is the most common and aggressive form of brain cancer. It has a poor prognosis, with a median overall survival of only 11 months in the general GBM population and 14.6 to 21 months in clinical trial participants with standard GBM therapies, including maximum safe craniotomy, adjuvant radiation, and chemotherapies. Therefore, new approaches for developing effective treatments, such as a tool for assessing tumor cell drug response before drug treatments are administered, are urgently needed to improve patient survival. To address this issue, we developed an improved brain cancer chip with a diffusion prevention mechanism that blocks drugs crossing from one channel to another. In the current study, we demonstrate that the chip has the ability to culture 3D spheroids from patient tumor specimen-derived GBM cells obtained from three GBM patients. Two clinical drugs used to treat GBM, temozolomide (TMZ) and bevacizumab (Avastin, BEV), were applied and a range of relative concentrations was generated by the microfluidic channels in the brain cancer chip. The results showed that TMZ works more effectively when used in combination with BEV compared to TMZ alone. We believe that this low-cost brain cancer chip could be further developed to generate optimal combination of chemotherapy drugs tailored to individual GBM patients.
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spelling pubmed-61941262018-10-24 Drug Screening of Human GBM Spheroids in Brain Cancer Chip Akay, Metin Hite, John Avci, Naze Gul Fan, Yantao Akay, Yasemin Lu, Guangrong Zhu, Jay-Jiguang Sci Rep Article Glioblastoma multiforme (GBM), an extremely invasive and high-grade (grade IV) glioma, is the most common and aggressive form of brain cancer. It has a poor prognosis, with a median overall survival of only 11 months in the general GBM population and 14.6 to 21 months in clinical trial participants with standard GBM therapies, including maximum safe craniotomy, adjuvant radiation, and chemotherapies. Therefore, new approaches for developing effective treatments, such as a tool for assessing tumor cell drug response before drug treatments are administered, are urgently needed to improve patient survival. To address this issue, we developed an improved brain cancer chip with a diffusion prevention mechanism that blocks drugs crossing from one channel to another. In the current study, we demonstrate that the chip has the ability to culture 3D spheroids from patient tumor specimen-derived GBM cells obtained from three GBM patients. Two clinical drugs used to treat GBM, temozolomide (TMZ) and bevacizumab (Avastin, BEV), were applied and a range of relative concentrations was generated by the microfluidic channels in the brain cancer chip. The results showed that TMZ works more effectively when used in combination with BEV compared to TMZ alone. We believe that this low-cost brain cancer chip could be further developed to generate optimal combination of chemotherapy drugs tailored to individual GBM patients. Nature Publishing Group UK 2018-10-18 /pmc/articles/PMC6194126/ /pubmed/30337660 http://dx.doi.org/10.1038/s41598-018-33641-2 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Akay, Metin
Hite, John
Avci, Naze Gul
Fan, Yantao
Akay, Yasemin
Lu, Guangrong
Zhu, Jay-Jiguang
Drug Screening of Human GBM Spheroids in Brain Cancer Chip
title Drug Screening of Human GBM Spheroids in Brain Cancer Chip
title_full Drug Screening of Human GBM Spheroids in Brain Cancer Chip
title_fullStr Drug Screening of Human GBM Spheroids in Brain Cancer Chip
title_full_unstemmed Drug Screening of Human GBM Spheroids in Brain Cancer Chip
title_short Drug Screening of Human GBM Spheroids in Brain Cancer Chip
title_sort drug screening of human gbm spheroids in brain cancer chip
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194126/
https://www.ncbi.nlm.nih.gov/pubmed/30337660
http://dx.doi.org/10.1038/s41598-018-33641-2
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