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  2. Johannes Gutenberg-Universität Mainz
  3. DFG-491381577-G
Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-9995
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dc.contributor.authorEl Malki, Khalifa-
dc.contributor.authorWehling, Pia-
dc.contributor.authorAlt, Francesca-
dc.contributor.authorSandhoff, Roger-
dc.contributor.authorZahnreich, Sebastian-
dc.contributor.authorUstjanzew, Arsenij-
dc.contributor.authorWilzius, Carolin-
dc.contributor.authorBrockmann, Marc A.-
dc.contributor.authorWingerter, Arthur-
dc.contributor.authorRusso, Alexandra-
dc.contributor.authorBeck, Olaf-
dc.contributor.authorSommer, Clemens-
dc.contributor.authorOttenhausen, Malte-
dc.contributor.authorFrauenknecht, Katrin B. M.-
dc.contributor.authorParet, Claudia-
dc.contributor.authorFaber, Jörg-
dc.date.accessioned2024-02-13T09:18:48Z-
dc.date.available2024-02-13T09:18:48Z-
dc.date.issued2023-
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/10013-
dc.description.abstractH3K27M mutant (mut) diffuse midline glioma (DMG) is a lethal cancer with no effective cure. The glycosphingolipids (GSL) metabolism is altered in these tumors and could be exploited to develop new therapies. We tested the effect of the glucosylceramide synthase inhibitors (GSI) miglustat and eliglustat on cell proliferation, alone or in combination with temozolomide or ionizing radiation. Miglustat was included in the therapy protocol of two pediatric patients. The effect of H3.3K27 trimethylation on GSL composition was analyzed in ependymoma. GSI reduced the expression of the ganglioside GD2 in a concentration and time-dependent manner and increased the expression of ceramide, ceramide 1-phosphate, sphingosine, and sphingomyelin but not of sphingosine 1-phosphate. Miglustat significantly increased the efficacy of irradiation. Treatment with miglustat according to dose recommendations for patients with Niemann–Pick disease was well tolerated with manageable toxicities. One patient showed a mixed response. In ependymoma, a high concentration of GD2 was found only in the presence of the loss of H3.3K27 trimethylation. In conclusion, treatment with miglustat and, in general, targeting GSL metabolism may offer a new therapeutic opportunity and can be administered in close proximity to radiation therapy. Alterations in H3K27 could be useful to identify patients with a deregulated GSL metabolism.en_GB
dc.language.isoengde
dc.rightsCC BY*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subject.ddc610 Medizinde_DE
dc.subject.ddc610 Medical sciencesen_GB
dc.titleGlucosylceramide synthase inhibitors induce ceramide accumulation and sensitize H3K27 mutant diffuse midline glioma to irradiationen_GB
dc.typeZeitschriftenaufsatzde
dc.identifier.doihttp://doi.org/10.25358/openscience-9995-
jgu.type.contenttypeScientific articlede
jgu.type.dinitypearticleen_GB
jgu.type.versionPublished versionde
jgu.type.resourceTextde
jgu.organisation.departmentFB 04 Medizinde
jgu.organisation.number2700-
jgu.organisation.nameJohannes Gutenberg-Universität Mainz-
jgu.rights.accessrightsopenAccess-
jgu.journal.titleInternational journal of molecular sciencesde
jgu.journal.volume24de
jgu.journal.issue12de
jgu.pages.alternative9905de
jgu.publisher.year2023-
jgu.publisher.nameMDPIde
jgu.publisher.placeBaselde
jgu.publisher.issn1422-0067de
jgu.organisation.placeMainz-
jgu.subject.ddccode610de
jgu.publisher.doi10.3390/ijms24129905de
jgu.organisation.rorhttps://ror.org/023b0x485-
jgu.subject.dfgNaturwissenschaftende
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