| |  Online-Ressource |
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| Verfasst von: | Dao Trong, Huy Philip [VerfasserIn]  |
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| | Jungwirth, Gerhard [VerfasserIn] |
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| | Yu, Tao [VerfasserIn] |
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| | Pusch, Stefan [VerfasserIn] |
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| | Unterberg, Andreas [VerfasserIn] |
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| | Herold-Mende, Christel [VerfasserIn] |
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| | Warta, Rolf [VerfasserIn] |
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| Titel: | Large-scale drug screening in patient-derived IDHmut glioma stem cells identifies several efficient drugs among FDA-approved antineoplastic agents |
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| Verf.angabe: | Philip Dao Trong, Gerhard Jungwirth, Tao Yu, Stefan Pusch, Andreas Unterberg, Christel Herold-Mende and Rolf Warta |
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| E-Jahr: | 2020 |
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| Jahr: | 3 June 2020 |
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| Teil: | volume:9 |
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| | year:2020 |
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| | number:6 |
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| Fussnoten: | Im Titel ist "mut" in IDHmut hochgestellt ; Gesehen am 26.08.2020 |
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| Titel Quelle: | Enthalten in: Cells |
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| Ort Quelle: | Basel : MDPI, 2012 |
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| Jahr Quelle: | 2020 |
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| Band/Heft Quelle: | 9(2020,6) Artikel-Nummer 1389, 15 Seiten |
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| ISSN Quelle: | 2073-4409 |
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| Abstract: | The discovery of the isocitrate dehydrogenase (IDH) mutation in glioma led to a paradigm shift on how we see glioma biology. Difficulties in cultivating IDH mutant glioma stem cells (IDHmut GSCs) resulted in a paucity of preclinical models in IDHmut glioma, limiting the discovery of new effective chemotherapeutic agents. To fill this gap, we used six recently developed patient-derived IDHmut GSC lines and performed a large-scale drug screening with 147 Food and Drug Administration (FDA)-approved anticancer drugs. GSCs were subjected to the test compounds for 72 h in concentrations ranging from 0.0001 to 1 µM. Cell viability was assessed by CellTiterGlo and the induction of apoptosis by flow cytometry with Annexin V/propidium iodide staining. The initial screen was performed with two IDHmut GSC lines and identified seven drugs (bortezomib, carfilzomib, daunorubicin, doxorubicin, epirubicin, omacetaxine, plicamycin) with a substantial antiproliferative activity, as reflected by half maximal inhibitory concentrations (IC50) below 1 µM and maximum inhibitory effects (Emax) below 25%. These findings were validated in an additional four IDHmut GSC lines. The candidate drugs, of which plicamycin and omacetaxine are known to cross the blood brain barrier, were used for subsequent cell death analyses. A significant induction of apoptosis was observed at IC50 values of the respective drugs. In summary, we were able to identify seven FDA-approved drugs that should be further taken into clinical investigations for the treatment of IDHmut gliomas. |
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| DOI: | doi:10.3390/cells9061389 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.3390/cells9061389 |
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| | Volltext: https://www.mdpi.com/2073-4409/9/6/1389 |
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| | DOI: https://doi.org/10.3390/cells9061389 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | bortezomib |
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| | carfilzomib |
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| | daunorubicin |
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| | doxorubicin |
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| | drug screen |
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| | epirubicin |
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| | isocitrate dehydrogenase (IDH) mutant glioma stem cells |
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| | lower grade glioma |
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| | omacetaxine |
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| | plicamycin |
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| K10plus-PPN: | 1727831705 |
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| Verknüpfungen: | → Zeitschrift |
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Large-scale drug screening in patient-derived IDHmut glioma stem cells identifies several efficient drugs among FDA-approved antineoplastic agents / Dao Trong, Huy Philip [VerfasserIn]; 3 June 2020 (Online-Ressource)
