Daily coordination of cancer growth and circadian clock gene expression

You, Sylvaine; Wood, Patricia A.; Xiong, Yin; Kobayashi, Minoru; Du-Quiton, Jovelyn; Hrushesky, William J. M.

doi:10.1007/s10549-004-6603-z

Cited by 82 publications

(93 citation statements)

References 58 publications

(75 reference statements)

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“…In early-stage mouse sarcoma180, clock gene mRNAs were rhythmic, with peaks occurring near the LD transition for Per1 and Per2 and at late dark/early light for Bmal1 (Koyanagi et al 2003). In a mouse breast cancer model at a more advanced stage of growth (early to late), Per1 and Per2 mRNAs lacked any circadian periodicity, whereas Bmal1 mRNA remained rhythmic, yet with a 13-fold reduction in circadian amplitude (You et al 2005). An elegant study performed in rats with diethylnitrosamine-induced hepatocarcinoma, a very slow growing tumor, further shows that the entrainment properties of Per1 in cancerous liver tissue differ from those of the healthy liver tissue it originates from (Davidson et al 2006).…”

Section: Interactions Between Molecular Clock and Cellular Proliferationmentioning

confidence: 99%

Cross-talks between Circadian Timing System and Cell Division Cycle Determine Cancer Biology and Therapeutics

Lévi

Filipski²,

Iurisci³

et al. 2007

Cold Spring Harbor Symposia on Quantitative Biology

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Section: Interactions Between Molecular Clock and Cellular Proliferationmentioning

confidence: 99%

Cross-talks between Circadian Timing System and Cell Division Cycle Determine Cancer Biology and Therapeutics

Lévi

Filipski²,

Iurisci³

et al. 2007

Cold Spring Harbor Symposia on Quantitative Biology

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“…Areas containing the most viable tumor cells in five consecutive images (300 -400 tumor cells per image) were randomly taken from each section using Â40 objective lens and the AxioCam Digital camera and quantitated as described (14). Values are mean number of mitotic figures per field.…”

Section: -Fu Treatmenttoxicity Parametersmentioning

confidence: 99%

“…Tumor Tissue Array A tissue array instrument (Beecher Instrument, Inc., Sun Prairie, WI) was used to construct tumor tissue array block (14). Multiple 5-Am sections were cut from the array block and mounted on the positively charged glass slides (Surgipath, Richmond, IL) for histopathologic and immunochemical examination.…”

Section: -Fu Treatmenttoxicity Parametersmentioning

confidence: 99%

See 1 more Smart Citation

Circadian clock coordinates cancer cell cycle progression, thymidylate synthase, and 5-fluorouracil therapeutic index

Wood

Du-Quiton

You

et al. 2006

Molecular Cancer Therapeutics

Self Cite

101

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Dysregulated cellular proliferation is a characteristic property of cancer. We show that, despite this fact, cancers maintain high amplitude, circadian rhythms in their growth, DNA synthesis, and mitosis. These patterns are accompanied by the daily traverse of BMAL-1 protein between the cytoplasm, where it is produced, and nucleus, where it influences timing of cancer cell proliferation. This core clock gene product gates cancer cell proliferation by coordinating clock-controlled proteins, thymidylate synthase [thymidylate synthase activity (TSA) cell DNA replication], WEE-1 (cell mitosis), and vascular endothelial growth factor (growth). 5-Fluorouracil (5-FU) -induced host bone marrow and gut toxicity and tumor shrinkage following administration at six equispaced times of day allowed determination of circadian relationships among tumor growth, relevant clock, and clock-controlled proteins and dependence of 5-FU target availability (TSA) in normal and cancer tissues and resultant 5-FU toxic-therapeutic index. The time of day (hours after lights on) of low TSA in each tissue and tumor is respectively associated with greatest toxicity to that tissue and greatest tumor shrinkage. 5-FU treatment near daily awakening results in least damage to bone marrow and gut, greatest antitumor effect, and best survival. This time of day is associated with maximum tumor nuclear BMAL-1 and total cell WEE-1 protein. The described chain of events, for the first time, links cancer cell clock proteins, cancer cell DNA synthesis, proliferation, TSA, and 5-FU toxic-therapeutic index, explaining the dependence of cancer outcome on circadian timing of 5-FU.

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“…through p53, but also cyclin synthesis, apoptosis determinants) by inputs from local circadian clocks [32,229]. One clear molecular connection between the circadian clock and the cell division cycle has been established in [194,239,277], by showing that kinase Wee1, that inhibits the synthesis of the CyclinB −Cdk1 complex, controlling G 2 /M transition, is itself controlled by the circadian clock gene Bmal1. Since normal cell populations seem rather well synchronised with respect to phases of the cell division (undergoing e.g., S phase, more or less all at the same time) and show circadian rhythm in this synchronisation [246], rhythms that are harder to find in tumours [118], one can hypothesize that such synchronisation is due to circadian clock inputs, and that cancer cells have lost this synchrony -that could be necessary to ensure normal control of cell proliferation-by escaping normal control on their division cycle by circadian inputs.…”

Section: Perturbations Of Circadian Clocks: Resulting In Cell Populatmentioning

confidence: 99%

Modelling Physiological and Pharmacological Control on Cell Proliferation to Optimise Cancer Treatments

Clairambault

2009

Math. Model. Nat. Phenom.

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Abstract. This review aims at presenting a synoptic, if not exhaustive, point of view on some of the problems encountered by biologists and physicians who deal with natural cell proliferation and disruptions of its physiological control in cancer disease. It also aims at suggesting how mathematicians are naturally challenged by these questions and how they might help, not only biologists to deal theoretically with biological complexity, but also physicians to optimise therapeutics, on which last point the focus will be set here. To this purpose, mathematical modelling should represent proliferating cell population dynamics with natural built-in control targets (which implies modelling the cell division cycle), together with the distribution of drugs in the organism and their molecular actions on different targets at the cell level on proliferation, i.e., molecular pharmacokinetics-pharmacodynamics of antiproliferative drugs. This should make possible optimal control of drug delivery with constraints to be determined according to the main pharmacological issues encountered in the clinic: unwanted toxic side-effects, occurrence of drug resistance. Mathematical modelling should also take into account physiological determinants of cell and tissue proliferation, such as intervention of the immune system, circadian control on cell cycle checkpoint proteins, and activity of intracellular drug processing enzymes together with individual variations in the activities of these proteins (genetic polymorphism). Taking these points into account will add to the rich scenery of normal or disrupted cell and tissue regulations, and their corrections by drugs, a natural environmental, whole body physiological, frame. It is necessary indeed to consider such a framework if one wants to eventually be actually helpful to clinicians who routinely treat by combinations of drugs living Humans with their complex whole body regulations, often dependent on genotypic variations, and not isolated cells or tissues.Key words: cell proliferation, population dynamics, physiologically structured partial differential equations, pharmacological control, pharmacokinetics-pharmacodynamics, physiological modelling, cancer treatments, therapeutic optimisation, individualised medicine AMS subject classification: 92-02, 92B05 Biological common knowledge on cancerThis section shortly presents the general scenery of cancer evolution and features that must be included in models designed to describe and control it, bearing in mind a more descriptive (physicist's) than a therapeutic (physician's) point of view, only to reverse this perspective in the following sections, in which will be stressed the interest of modelling from the point of view of control, at least if one wants to design models for therapeutic applications. This biological section will be only a short sketch, if one considers that on this subject many books have already been written, e.g. [24,78,96,97,223]. Cancer: a challenging public health problemCardiovascular diseases and cancer are by fa...

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Daily coordination of cancer growth and circadian clock gene expression

Cited by 82 publications

References 58 publications

Cross-talks between Circadian Timing System and Cell Division Cycle Determine Cancer Biology and Therapeutics

Cross-talks between Circadian Timing System and Cell Division Cycle Determine Cancer Biology and Therapeutics

Circadian clock coordinates cancer cell cycle progression, thymidylate synthase, and 5-fluorouracil therapeutic index

Modelling Physiological and Pharmacological Control on Cell Proliferation to Optimise Cancer Treatments

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