Multiscale modeling of tumor growth induced by circadian rhythm disruption in epithelial tissue

Bratsun, Dmitry; Merkuriev, D. V.; Захаров, А.П.; Pismen, L. M.

doi:10.1007/s10867-015-9395-y

Cited by 25 publications

(21 citation statements)

References 69 publications

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“…For example, a majority of the pathways regulated by the core circadian genes Clock and Bmal1 contribute to normal metabolic regulation, and disruption in core clock genes Cry1 ; Cry2 and Bmal1 alters sleep patterns (Ehlen et al, ; Takahashi, Hong, Ko, & McDearmon, ). Circadian rhythms also control cell‐cycle related genes (Matsuo et al, ), and play important roles in tissue homeostasis (Bratsun, Merkuriev, Zakharov, & Pismen, ). In addition, shift work, which causes misalignment of both peripheral circadian clocks and of the master circadian clock from environmental time (Roenneberg & Merrow, ), is associated with abnormal cell growth and tumor formation (Bratsun et al, ; Kubo et al, ; Megdal, Kroenke, Laden, Pukkala, & Schernhammer, ; Sack et al, ; Schernhammer, Kroenke, Laden, & Hankinson, ; Schernhammer et al, ).…”

Section: Circadian Physiologymentioning

confidence: 99%

“…Circadian rhythms also control cell‐cycle related genes (Matsuo et al, ), and play important roles in tissue homeostasis (Bratsun, Merkuriev, Zakharov, & Pismen, ). In addition, shift work, which causes misalignment of both peripheral circadian clocks and of the master circadian clock from environmental time (Roenneberg & Merrow, ), is associated with abnormal cell growth and tumor formation (Bratsun et al, ; Kubo et al, ; Megdal, Kroenke, Laden, Pukkala, & Schernhammer, ; Sack et al, ; Schernhammer, Kroenke, Laden, & Hankinson, ; Schernhammer et al, ). Dysregulation of circadian rhythms may also be involved in the development of a variety of psychiatric and neurological diseases such as depression, posttraumatic stress disorder, and neurodegenerative diseases (Rosenwasser, ; VIdenovic, Lazard, Barker & Overeem, ), metabolic diseases such as diabetes (Marcheva et al, ), and other disorders (Kim & Duffy, ; Abbott, Reid & Zee, ).…”

Section: Circadian Physiologymentioning

confidence: 99%

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Mathematical modeling of circadian rhythms

Asgari-Targhi

Klerman

2018

WIREs Mechanisms of Disease

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Circadian rhythms are endogenous~24-hr oscillations usually entrained to daily environmental cycles of light/dark. Many biological processes and physiological functions including mammalian body temperature, the cell cycle, sleep/wake cycles, neurobehavioral performance, and a wide range of diseases including metabolic, cardiovascular, and psychiatric disorders are impacted by these rhythms. Circadian clocks are present within individual cells and at tissue and organismal levels as emergent properties from the interaction of cellular oscillators. Mathematical models of circadian rhythms have been proposed to provide a better understanding of and to predict aspects of this complex physiological system. These models can be used to: (a) manipulate the system in silico with specificity that cannot be easily achieved using in vivo and in vitro experimental methods and at lower cost, (b) resolve apparently contradictory empirical results, (c) generate hypotheses, (d) design new experiments, and (e) to design interventions for altering circadian rhythms. Mathematical models differ in structure, the underlying assumptions, the number of parameters and variables, and constraints on variables. Models representing circadian rhythms at different physiologic scales and in different species are reviewed to promote understanding of these models and facilitate their use. This article is categorized under: Physiology > Mammalian Physiology in Health and Disease Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models K E Y W O R D S biological oscillators, circadian clock, circadian rhythms, dynamic systems, mathematical modeling, statistical modeling BOX 1 CIRCADIAN MODELINGCircadian clocks are present within individual cells, and communication among multiple cells gives rise to emergent properties at the tissue level. In mammals, both the master circadian clock in the suprachiasmatic nucleus and tissuelevel peripheral clocks have major effects at the organism level on numerous key physiological functions, including sleep/wake cycles, metabolism, cardiovascular function, reproduction, immune function, neurobehavioral performance, and mood. Misalignment between the master clock and peripheral clocks within an organism, or misalignment between an organism's clocks and its external environment, has adverse physiological consequences. When circadian interventions are needed to improve physiological function, a multiscale understanding of circadian rhythmicity therefore is essential to accurately manipulate this complex oscillatory system. Mathematical modeling is an essential tool to study and analyze complex physiological systems. It has been used to provide insight into the circadian system at multiple levels (i.e., organism, multi-cellular, cellular, molecular, genetic), to design new experiments, and to manipulate and control the components of the system in silico with specificity that

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Section: Circadian Physiologymentioning

confidence: 99%

Section: Circadian Physiologymentioning

confidence: 99%

Mathematical modeling of circadian rhythms

Asgari-Targhi

Klerman

2018

WIREs Mechanisms of Disease

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“…Bratsun and coauthors [ 128 ] proposed a minimal multiscale chemo-mechanical model of cancer tumor growth induced by circadian rhythm disruption in epithelial tissue.…”

Section: Introductionmentioning

confidence: 99%

Computational modeling of the cell-autonomous mammalian circadian oscillator

2017

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This review summarizes various mathematical models of cell-autonomous mammalian circadian clock. We present the basics necessary for understanding of the cell-autonomous mammalian circadian oscillator, modern experimental data essential for its reconstruction and some special problems related to the validation of mathematical circadian oscillator models. This work compares existing mathematical models of circadian oscillator and the results of the computational studies of the oscillating systems. Finally, we discuss applications of the mathematical models of mammalian circadian oscillator for solving specific problems in circadian rhythm biology.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-016-0379-8) contains supplementary material, which is available to authorized users.

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“…It can also be viewed and explored as a complex adaptive system [1,35,36]. Another important variable for tumor metastasis is the spatiotemporal characteristic, because a tumor's metastasis and diffusion velocities are significantly varied for different tissues and progression stages.…”

Section: Introductionmentioning

confidence: 99%

Tumor proliferation and diffusion on percolation clusters

et al. 2016

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We study in silico the influence of host tissue inhomogeneity on tumor cell proliferation and diffusion by simulating the mobility of a tumor on percolation clusters with different homogeneities of surrounding tissues. The proliferation and diffusion of a tumor in an inhomogeneous tissue could be characterized in the framework of the percolation theory, which displays similar thresholds (0.54, 0.44, and 0.37, respectively) for tumor proliferation and diffusion in three kinds of lattices with 4, 6, and 8 connecting near neighbors. Our study reveals the existence of a critical transition concerning the survival and diffusion of tumor cells with leaping metastatic diffusion movement in the host tissues. Tumor cells usually flow in the direction of greater pressure variation during their diffusing and infiltrating to a further location in the host tissue. Some specific sites suitable for tumor invasion were observed on the percolation cluster and around these specific sites a tumor can develop into scattered tumors linked by some advantage tunnels that facilitate tumor invasion. We also investigate the manner that tissue inhomogeneity surrounding a tumor may influence the velocity of tumor diffusion and invasion. Our simulation suggested that invasion of a tumor is controlled by the homogeneity of the tumor microenvironment, which is basically consistent with the experimental report by Riching et al. as well as our clinical observation of medical imaging. Both simulation and clinical observation proved that tumor diffusion and invasion into the surrounding host tissue is positively correlated with the homogeneity of the tissue.

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Multiscale modeling of tumor growth induced by circadian rhythm disruption in epithelial tissue

Cited by 25 publications

References 69 publications

Mathematical modeling of circadian rhythms

Mathematical modeling of circadian rhythms

Computational modeling of the cell-autonomous mammalian circadian oscillator

Tumor proliferation and diffusion on percolation clusters

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