| |  Online-Ressource |
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| Verfasst von: | Müller, Michael [VerfasserIn]  |
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| | Rösch, Lisa [VerfasserIn] |
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| | Najafi, Sara [VerfasserIn] |
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| | Gatzweiler, Charlotte [VerfasserIn] |
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| | Ridinger, Johannes [VerfasserIn] |
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| | Gerloff, Xenia F. [VerfasserIn] |
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| | Jones, David T. W. [VerfasserIn] |
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| | Baßler, Jochen [VerfasserIn] |
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| | Kreth, Sina [VerfasserIn] |
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| | Stainczyk, Sabine [VerfasserIn] |
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| | Frese, Karen S. [VerfasserIn] |
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| | Meder, Benjamin [VerfasserIn] |
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| | Westermann, Frank [VerfasserIn] |
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| | Milde, Till [VerfasserIn] |
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| | Peterziel, Heike [VerfasserIn] |
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| | Witt, Olaf [VerfasserIn] |
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| | Oehme, Ina [VerfasserIn] |
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| Titel: | Combining APR-246 and HDAC-inhibitors |
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| Titelzusatz: | a novel targeted treatment option for neuroblastoma |
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| Verf.angabe: | Michael Müller, Lisa Rösch, Sara Najafi, Charlotte Gatzweiler, Johannes Ridinger, Xenia F. Gerloff, David T. W. Jones, Jochen Baßler, Sina Kreth, Sabine Stainczyk, Karen Frese, Benjamin Meder, Frank Westermann, Till Milde, Heike Peterziel, Olaf Witt and Ina Oehme |
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| E-Jahr: | 2021 |
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| Jahr: | 5 September 2021 |
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| Umfang: | 23 S. |
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| Fussnoten: | Gesehen am 22.10.2021 |
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| Titel Quelle: | Enthalten in: Cancers |
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| Ort Quelle: | Basel : MDPI, 2009 |
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| Jahr Quelle: | 2021 |
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| Band/Heft Quelle: | 13(2021), 17, Artikel-ID 4476, Seite 1-23 |
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| ISSN Quelle: | 2072-6694 |
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| Abstract: | APR-246 (Eprenetapopt/PRIMA-1Met) is a very potent anti-cancer drug in clinical trials and was initially developed as a p53 refolding agent. As an alternative mode of action, the elevation of reactive oxygen species (ROS) has been proposed. Through an in silico analysis, we investigated the responses of approximately 800 cancer cell lines (50 entities; Cancer Therapeutics Response Portal, CTRP) to APR-246 treatment. In particular, neuroblastoma, lymphoma and acute lymphocytic leukemia cells were highly responsive. With gene expression data from the Cancer Cell Line Encyclopedia (CCLE; n = 883) and patient samples (n = 1643) from the INFORM registry study, we confirmed that these entities express low levels of SLC7A11, a previously described predictive biomarker for APR-246 responsiveness. Combining the CTRP drug response data with the respective CCLE gene expression profiles, we defined a novel gene signature, predicting the effectiveness of APR-246 treatment with a sensitivity of 90% and a specificity of 94%. We confirmed the predicted APR-246 sensitivity in 8/10 cell lines and in ex vivo cultures of patient samples. Moreover, the combination of ROS detoxification-impeding APR-246 with approved HDAC-inhibitors, known to elevate ROS, substantially increased APR-246 sensitivity in cell cultures and in vivo in two zebrafish neuroblastoma xenograft models. These data provide evidence that APR-246, in combination with HDAC-inhibitors, displays a novel potent targeted treatment option for neuroblastoma patients. |
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| DOI: | doi:10.3390/cancers13174476 |
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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/cancers13174476 |
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| | Volltext: https://www.mdpi.com/2072-6694/13/17/4476 |
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| | DOI: https://doi.org/10.3390/cancers13174476 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | histone deacetylases |
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| | pediatric tumors of the nervous system |
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| | precision medicine |
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| | response prediction biomarker |
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| | ROS |
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| | small molecule inhibitors |
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| | TP53 |
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| K10plus-PPN: | 1774761661 |
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| Verknüpfungen: | → Zeitschrift |
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Combining APR-246 and HDAC-inhibitors / Müller, Michael [VerfasserIn]; 5 September 2021 (Online-Ressource)
