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dc.contributor.author
Slat, Emily A.
dc.contributor.author
Sponagel, Jasmin
dc.contributor.author
Marpegan, Luciano
dc.contributor.author
Simon, Tatiana
dc.contributor.author
Kfoury, Najla
dc.contributor.author
Kim, Albert
dc.contributor.author
Binz, Andrea
dc.contributor.author
Herzog, Erik D.
dc.contributor.author
Rubin, Joshua B.
dc.date.available
2018-04-16T21:30:35Z
dc.date.issued
2017-03
dc.identifier.citation
Slat, Emily A.; Sponagel, Jasmin; Marpegan, Luciano; Simon, Tatiana; Kfoury, Najla; et al.; Cell-intrinsic, Bmal1-dependent Circadian Regulation of Temozolomide Sensitivity in Glioblastoma; SAGE Publications; Journal of Biological Rhythms; 32; 2; 3-2017; 121-129
dc.identifier.issn
0748-7304
dc.identifier.uri
http://hdl.handle.net/11336/42222
dc.description.abstract
The safety and efficacy of chemotherapeutics can vary as a function of the time of their delivery during the day. This study aimed to improve the treatment of glioblastoma (GBM), the most common brain cancer, by testing whether the efficacy of the DNA alkylator temozolomide (TMZ) varies with the time of its administration. We found cell-intrinsic, daily rhythms in both human and mouse GBM cells. Circadian time of treatment affected TMZ sensitivity of murine GBM tumor cells in vitro. The maximum TMZ-induced DNA damage response, activation of apoptosis, and growth inhibition occurred near the daily peak in expression of the core clock gene Bmal1. Deletion of Bmal1 (Arntl) abolished circadian rhythms in gene expression and TMZ-induced activation of apoptosis and growth inhibition. These data indicate that tumor cell-intrinsic circadian rhythms are common to GBM tumors and can regulate TMZ cytotoxicity. Optimization of GBM treatment by timing TMZ administration to daily rhythms should be evaluated in prospective clinical trials.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
SAGE Publications
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Bmal1 Gene
dc.subject
Dna Repair
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Gbm
dc.subject
H2ax
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Otras Ciencias Biológicas
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Cell-intrinsic, Bmal1-dependent Circadian Regulation of Temozolomide Sensitivity in Glioblastoma
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-04-04T14:14:05Z
dc.journal.volume
32
dc.journal.number
2
dc.journal.pagination
121-129
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Slat, Emily A.. Washington University in St. Louis; Estados Unidos
dc.description.fil
Fil: Sponagel, Jasmin. Washington University in St. Louis; Estados Unidos
dc.description.fil
Fil: Marpegan, Luciano. Washington University in St. Louis; Estados Unidos. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Simon, Tatiana. Washington University in St. Louis; Estados Unidos
dc.description.fil
Fil: Kfoury, Najla. Washington University in St. Louis; Estados Unidos
dc.description.fil
Fil: Kim, Albert. Washington University in St. Louis; Estados Unidos
dc.description.fil
Fil: Binz, Andrea. Washington University in St. Louis; Estados Unidos
dc.description.fil
Fil: Herzog, Erik D.. Washington University in St. Louis; Estados Unidos
dc.description.fil
Fil: Rubin, Joshua B.. Washington University in St. Louis; Estados Unidos
dc.journal.title
Journal of Biological Rhythms
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1177/0748730417696788
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://journals.sagepub.com/doi/10.1177/0748730417696788