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Circadian Rhythmicity in Cancer & Treatment: Mechanisms and Future Perspectives

Lanting, G.D. (2014) Circadian Rhythmicity in Cancer & Treatment: Mechanisms and Future Perspectives. Bachelor's Thesis, Biology.

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The circadian clock is a complex biological program that controls a vast variety of bodily functions. Output signals in the form of genes and proteins that are generated by the cellular molecular clock play a major role in the control of cell division and proliferation. Malfunction of this genetic molecular clock might result in the genesis of cancer. The main components of the molecular clock are Bmal1, Clock, Per and Cry. Bmal1 promotes the transcription of other genes by binding to E-boxes in promoter regions and activates p53 by facilitating p21. Bmal1 also induces the transcription of Myc, an important oncogene. Clock has proven to have important acetyltransferase functions, thereby stimulating transcription and translation. Per has a tumour-suppressor effect by activation of the ataxia telangiectasia, and by regulating cyclin D and β-catenin, both important regulators of the cell cycle. Cry has oncogenic effects, which are enhanced in the absence of Per. The mechanism of this is not well known. A complex and delicate balance exist between the circadian clock genes and their actors in the control of expression of genes required for controlled replication and proliferation. Other elements that control the cell cycle and are temporally controlled include Myc, Wee1, Cyclin D and P21. Circadian driven chances in physiology also have major effects on the genesis of tumours. The immune system is an important safeguard in controlling cancer and it is subject to circadian variation. Natural killer cell count appears to be oscillating and directly influence the avoidance of apoptosis. Melatonin is an important circadian endocrine output signal and has significant tumour-suppressor effects through inhibition of the LA-uptake pathway and lowering of PKA activity, ultimately leading a decrease in transcription factors. This mechanism is only proven in nocturnal animals. There is also circadian variation in chemotherapy resistance. The circadian time-dependant therapeutic index is designed because of this and takes into regards pharmacokinetics and pharmacodynamics. What is most important is that a delicate balance exists between clock genes that prevent uncontrolled cell division, proliferation and ultimately the genesis of cancer.

Item Type: Thesis (Bachelor's Thesis)
Degree programme: Biology
Thesis type: Bachelor's Thesis
Language: English
Date Deposited: 15 Feb 2018 07:57
Last Modified: 15 Feb 2018 07:57

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