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TO START AT THE BEGINNING. “To develop cancer chronotherapy, the first crucial step is to understand the roles of clock genes in cancer. The mammalian circadian machinery is controlled by two main transcriptional/translational auto-regulatory feedback loops that involve 14 core clock genes.” https://lnkd.in/dT2NKaY View in LinkedIn

NEW WAY FORWARD. “Cancer chronotherapy appears to offer the potential to improve current cancer treatments and to refine the development of new anti-cancer drugs.” https://lnkd.in/dT2NKaY View in LinkedIn

CLOCK GENE DYSFUNCTION. “We sought to systematically investigate the contributions of circadian rhythm disruption and impaired molecular clockworks to tumorigenesis. Several thousand genes lost their correlation to clock genes in tumor samples. We also found that correlation among core clock genes was reduced significantly.” https://lnkd.in/dT2NKaY View in LinkedIn

CELL LINE STUDIES. “To further investigate the potential effects of clock genes on drug sensitivity, we examined the correlation between transcriptional expression of clock genes in the Cancer Cell Line Encyclopedia dataset and drug sensitivity in the CTRP dataset.” https://lnkd.in/dT2NKaY View in LinkedIn

POWERFUL REGULATOR. “DNA methylation regulates gene expression in cancer. We examined the promoter DNA methylation patterns of clock genes across different cancer types and observed an overall negative correlation between DNA methylation and gene expression (Figure S3A). We further observed multiple small alterations with a few genes showing differentially methylated patterns.” https://lnkd.in/dT2NKaY View in LinkedIn

GENES AND MEDICINES. “For drugs with known targeted genes, we further estimated the correlations between targeted genes and clock genes.” https://lnkd.in/dT2NKaY View in LinkedIn

CLOCK GENES AND CANCER. “These results suggest that genetic alterations of clock genes play functional roles in cancer.” https://lnkd.in/dT2NKaY View in LinkedIn

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MUTATED CLOCK GENES. “To further determine genetic alterations of clock genes in human cancer, we analyzed non-silent mutations of clock genes across cancer types. We observed that mutation frequency is relatively low for core clock genes, with fewer than five mutations in the majority of samples (Figure 3B). However, mutations of core clock genes were associated with patients' overall survival.” https://lnkd.in/dT2NKaY View in LinkedIn

Ancient pentagon skewed by street constraints, not fully corrected by internal editing. View in LinkedIn