Temozolomide in Combination With NF-κB Inhibitor Significantly Disrupts the Glioblastoma Multiforme Spheroid Formation
Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, accounting for 50% of all cases. GBM patients have a five-year survival rate of merely 5.6% and a median overall survival of 14.6 months with the “Stupp” regimen, 20.9 months w...
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IEEE
2020-01-01
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| Series: | IEEE Open Journal of Engineering in Medicine and Biology |
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| Online Access: | https://ieeexplore.ieee.org/document/8945401/ |
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| author | Hui Xia Naze G. Avci Yasemin Akay Yoshua Esquenazi Lisa H. Schmitt Nitin Tandon Jay-Jiguang Zhu Metin Akay |
| author_facet | Hui Xia Naze G. Avci Yasemin Akay Yoshua Esquenazi Lisa H. Schmitt Nitin Tandon Jay-Jiguang Zhu Metin Akay |
| author_sort | Hui Xia |
| collection | DOAJ |
| description | Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, accounting for 50% of all cases. GBM patients have a five-year survival rate of merely 5.6% and a median overall survival of 14.6 months with the “Stupp” regimen, 20.9 months with tumor treatment fields (TTF, OptuneR) in patients who participated in clinical trials, and 11 months for all GBM patients prior to TTF use. <italic>Objective:</italic> Our group recently developed a brain cancer chip which generates tumor spheroids, and provides large-scale assessments on the response of tumor cells to various concentrations and combinations of drugs. This platform could optimize the use of tumor samples derived from GBM patients to provide valuable insight on the tumor growth and responses to drug therapies. To minimize any sample loss <italic>in vitro</italic>, we improved our brain cancer chip system by adding an additional laminar flow distribution layer, which reduces sample loss during cell seeding and prevents spheroids from escaping from the microwells. <italic>Methods:</italic> In this study, we cultured 3D spheroids from GBM cell lines and patient-derived GBM cells <italic>in vitro</italic>, and investigated the effect of the combination of Temozolomide and nuclear factor-κB inhibitor on tumor growth. <italic>Results:</italic> Our study revealed that these drugs have synergistic effects in inhibiting spheroid formation when used in combination. <italic>Conclusions:</italic> These results suggest that the brain cancer chip enables large-scale, inexpensive and sample-effective drug screening to 3D cancer tumors <italic>in vitro</italic>, and could be applied to related tissue engineering drug screening studies. |
| format | Article |
| id | doaj-art-a01514c242e445a584eb20dead0930ca |
| institution | Kabale University |
| issn | 2644-1276 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | IEEE |
| record_format | Article |
| series | IEEE Open Journal of Engineering in Medicine and Biology |
| spelling | doaj-art-a01514c242e445a584eb20dead0930ca2025-08-20T03:33:14ZengIEEEIEEE Open Journal of Engineering in Medicine and Biology2644-12762020-01-01191610.1109/OJEMB.2019.29628018945401Temozolomide in Combination With NF-κB Inhibitor Significantly Disrupts the Glioblastoma Multiforme Spheroid FormationHui Xia0Naze G. Avci1Yasemin Akay2Yoshua Esquenazi3Lisa H. Schmitt4Nitin Tandon5Jay-Jiguang Zhu6Metin Akay7https://orcid.org/0000-0002-2988-4669Biomedical Engineering Department, University of Houston, Houston, TX, USABiomedical Engineering Department, University of Houston, Houston, TX, USABiomedical Engineering Department, University of Houston, Houston, TX, USAMischer Neuroscience Associates and the Vivian L. Smith Department of Neurosurgery, University of Texas Health Science Center in Houston, UTHealth and Memorial Hermann, Houston, TX, USAMischer Neuroscience Associates and the Vivian L. Smith Department of Neurosurgery, University of Texas Health Science Center in Houston, UTHealth and Memorial Hermann, Houston, TX, USAMischer Neuroscience Associates and the Vivian L. Smith Department of Neurosurgery, University of Texas Health Science Center in Houston, UTHealth and Memorial Hermann, Houston, TX, USAMischer Neuroscience Associates and the Vivian L. Smith Department of Neurosurgery, University of Texas Health Science Center in Houston, UTHealth and Memorial Hermann, Houston, TX, USABiomedical Engineering Department, University of Houston, Houston, TX, USAGlioblastoma multiforme (GBM) is the most common malignant primary brain tumor, accounting for 50% of all cases. GBM patients have a five-year survival rate of merely 5.6% and a median overall survival of 14.6 months with the “Stupp” regimen, 20.9 months with tumor treatment fields (TTF, OptuneR) in patients who participated in clinical trials, and 11 months for all GBM patients prior to TTF use. <italic>Objective:</italic> Our group recently developed a brain cancer chip which generates tumor spheroids, and provides large-scale assessments on the response of tumor cells to various concentrations and combinations of drugs. This platform could optimize the use of tumor samples derived from GBM patients to provide valuable insight on the tumor growth and responses to drug therapies. To minimize any sample loss <italic>in vitro</italic>, we improved our brain cancer chip system by adding an additional laminar flow distribution layer, which reduces sample loss during cell seeding and prevents spheroids from escaping from the microwells. <italic>Methods:</italic> In this study, we cultured 3D spheroids from GBM cell lines and patient-derived GBM cells <italic>in vitro</italic>, and investigated the effect of the combination of Temozolomide and nuclear factor-κB inhibitor on tumor growth. <italic>Results:</italic> Our study revealed that these drugs have synergistic effects in inhibiting spheroid formation when used in combination. <italic>Conclusions:</italic> These results suggest that the brain cancer chip enables large-scale, inexpensive and sample-effective drug screening to 3D cancer tumors <italic>in vitro</italic>, and could be applied to related tissue engineering drug screening studies.https://ieeexplore.ieee.org/document/8945401/Drug-screeningglioblastomamicrofluidicPEGDA3D cell culture |
| spellingShingle | Hui Xia Naze G. Avci Yasemin Akay Yoshua Esquenazi Lisa H. Schmitt Nitin Tandon Jay-Jiguang Zhu Metin Akay Temozolomide in Combination With NF-κB Inhibitor Significantly Disrupts the Glioblastoma Multiforme Spheroid Formation IEEE Open Journal of Engineering in Medicine and Biology Drug-screening glioblastoma microfluidic PEGDA 3D cell culture |
| title | Temozolomide in Combination With NF-κB Inhibitor Significantly Disrupts the Glioblastoma Multiforme Spheroid Formation |
| title_full | Temozolomide in Combination With NF-κB Inhibitor Significantly Disrupts the Glioblastoma Multiforme Spheroid Formation |
| title_fullStr | Temozolomide in Combination With NF-κB Inhibitor Significantly Disrupts the Glioblastoma Multiforme Spheroid Formation |
| title_full_unstemmed | Temozolomide in Combination With NF-κB Inhibitor Significantly Disrupts the Glioblastoma Multiforme Spheroid Formation |
| title_short | Temozolomide in Combination With NF-κB Inhibitor Significantly Disrupts the Glioblastoma Multiforme Spheroid Formation |
| title_sort | temozolomide in combination with nf x03ba b inhibitor significantly disrupts the glioblastoma multiforme spheroid formation |
| topic | Drug-screening glioblastoma microfluidic PEGDA 3D cell culture |
| url | https://ieeexplore.ieee.org/document/8945401/ |
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