Title |
Cell-intrinsic, Bmal1-dependent Circadian Regulation of Temozolomide Sensitivity in Glioblastoma
|
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Published in |
Journal of Biological Rhythms, March 2017
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DOI | 10.1177/0748730417696788 |
Pubmed ID | |
Authors |
Emily A. Slat, Jasmin Sponagel, Luciano Marpegan, Tatiana Simon, Najla Kfoury, Albert Kim, Andrea Binz, Erik D. Herzog, Joshua B. Rubin |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 33% |
Portugal | 1 | 33% |
Unknown | 1 | 33% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 67% |
Practitioners (doctors, other healthcare professionals) | 1 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 51 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Bachelor | 9 | 18% |
Student > Ph. D. Student | 8 | 16% |
Researcher | 8 | 16% |
Student > Doctoral Student | 3 | 6% |
Professor | 2 | 4% |
Other | 7 | 14% |
Unknown | 14 | 27% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 12 | 24% |
Neuroscience | 6 | 12% |
Medicine and Dentistry | 6 | 12% |
Agricultural and Biological Sciences | 3 | 6% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 4% |
Other | 6 | 12% |
Unknown | 16 | 31% |