Chronobiology and Chronomedicine

Royal Society of Chemistry eBooks, Год журнала: 2024, Номер unknown

Опубликована: Янв. 23, 2024

Circadian rhythms have been shown to be ubiquitous and critically important in the experimental laboratory, accounting for difference between life death response identical stimulus. The partly endogenous nature of circadian has well documented methods their characterisation developed enabling cellular molecular mechanisms understood. Chronobiology Chronomedicine aims provide a review these underlying illustrate role brain’s suprachiasmatic nuclei ‘pace-making’ process effects caused by ‘clock genes’ present almost all cells. Beyond involved, book discusses relationship body systems, disease, proper function; particular, how disruption rhythm is associated with ill health disease status from observations made at organismic level. organised an ideal introduction postgraduate various fields, reviewing developments outlining show depth breadth chronobiology chronomedicine, as invaluable companion researchers healthcare professionals working field interest developing novel therapeutic approaches.

Язык: Английский

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Circadian rhythms and cancers: the intrinsic links and therapeutic potentials

Journal of Hematology & Oncology, Год журнала: 2022, Номер 15(1)

Опубликована: Март 4, 2022

The circadian rhythm is an evolutionarily conserved time-keeping system that comprises a wide variety of processes including sleep-wake cycles, eating-fasting and activity-rest coordinating the behavior physiology all organs for whole-body homeostasis. Acute disruption may lead to transient discomfort, whereas long-term irregular will result in dysfunction organism, therefore increasing risks numerous diseases especially cancers. Indeed, both epidemiological experimental evidence has demonstrated intrinsic link between dysregulated cancer. Accordingly, rapidly understanding molecular mechanisms rhythms opening new options cancer therapy, possibly by modulating clock. In this review, we first describe general regulators their functions on addition, provide insights into underlying how several types (including sleep-wake, eating-fasting, activity-rest) can drive progression, which expand our development from clock perspective. Moreover, also summarize potential applications treatment, optional therapeutic strategy patients.

Язык: Английский

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Toxicity and efficacy of chronomodulated chemotherapy: a systematic review

The Lancet Oncology, Год журнала: 2022, Номер 23(3), С. e129 - e143

Опубликована: Фев. 28, 2022

Язык: Английский

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Rhythm is essential: Unraveling the relation between the circadian clock and cancer

Critical Reviews in Oncology/Hematology, Год журнала: 2025, Номер unknown, С. 104632 - 104632

Опубликована: Янв. 1, 2025

Язык: Английский

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Wearable technology and systems modeling for personalized chronotherapy

Current Opinion in Systems Biology, Год журнала: 2020, Номер 21, С. 9 - 15

Опубликована: Июнь 1, 2020

Chronotherapy is a pharmaceutical intervention that considers the patient's internal circadian time to adjust dosing time. Although it can dramatically improve drug efficacy and reduce toxicity, large variability in across within individuals has prevented chronotherapies from progressing beyond clinical trials. To translate chronotherapy developments into real-world outpatient scenario, personalized characterization analysis of essential. Here, we describe recent advances wearable technology enable real-time high-resolution tracking ultradian rhythms. We discuss how integrating data platforms including systems modeling machine learning pave way toward adaptive chronotherapy.

Язык: Английский

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A mathematical model of the circadian clock and drug pharmacology to optimize irinotecan administration timing in colorectal cancer

Computational and Structural Biotechnology Journal, Год журнала: 2021, Номер 19, С. 5170 - 5183

Опубликована: Янв. 1, 2021

Scheduling anticancer drug administration over 24 h may critically impact treatment success in a patient-specific manner. Here, we address personalization of timing using novel mathematical model irinotecan cellular pharmacokinetics and –dynamics linked to representation the core clock predict toxicity colorectal cancer (CRC) model. The is fitted three different scenarios: mouse liver, where metabolism mainly occurs, two human cell lines representing an vitro experimental system for progression. Our successfully recapitulates quantitative circadian datasets mRNA protein expression together with timing-dependent cytotoxicity data. also discriminates time-dependent between cells, suggesting that can be optimized according their clock. results show degradation mediating activation, as well oscillation death rate play important role variations toxicity. In future, this used support personalized scheduling by predicting optimal based on patient's gene profile.

Язык: Английский

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Shaping the future of precision oncology: Integrating circadian medicine and mathematical models for personalized cancer treatment

Current Opinion in Systems Biology, Год журнала: 2024, Номер 37, С. 100506 - 100506

Опубликована: Фев. 29, 2024

The growing numbers of cancer cases represent a medical and societal burden worldwide. More than half all patients are treated with chemotherapy. Yet, chemotherapeutic drugs kill not only cells, but also healthy tissue, causing massive adverse side effects. Recent research on circadian medicine suggests that side-effects can be reduced, treatment efficacy increased, by considering the biological clock patients. Integrating profiles molecular markers in personalized mathematical models simulate individual dynamics drug uptake, action cellular response to This requires advanced computational tools balance prediction quality overfitting. Personalized will eventually lead an optimal alignment timing inner patient, reducing effects, increasing enhancing patient well-being.

Язык: Английский

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Radiation chronotherapy—clinical impact of treatment time-of-day: a systematic review

Journal of Neuro-Oncology, Год журнала: 2019, Номер 145(3), С. 415 - 427

Опубликована: Ноя. 15, 2019

Язык: Английский

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Modeling the Circadian Control of the Cell Cycle and Its Consequences for Cancer Chronotherapy

Biology, Год журнала: 2023, Номер 12(4), С. 612 - 612

Опубликована: Апрель 18, 2023

The mammalian cell cycle is governed by a network of cyclin/Cdk complexes which signal the progression into successive phases division cycle. Once coupled to circadian clock, this produces oscillations with 24 h period such that each phase synchronized day-night Here, we use computational model for clock control investigate entrainment in population cells characterized some variability kinetic parameters. Our numerical simulations showed successful and synchronization are only possible sufficient amplitude an autonomous close h. Cellular heterogeneity, however, introduces cells. Many cancer have disrupted or compromised control. In these conditions, runs independently leading lack When coupling weak, largely impacted, but maintain tendency divide at specific times day. These differential features between healthy can be exploited optimize timing anti-cancer drug administration order minimize their toxicity maximize efficacy. We then used our simulate chronotherapeutic treatments predict optimal drugs targeting Although qualitative, highlights need better characterize cellular heterogeneity populations as well consequences design chronopharmacological protocols.

Язык: Английский

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Personalized Chronomodulated 5‐Fluorouracil Treatment: A Physiologically‐Based Pharmacokinetic Precision Dosing Approach for Optimizing Cancer Therapy

Clinical Pharmacology & Therapeutics, Год журнала: 2024, Номер 115(6), С. 1282 - 1292

Опубликована: Янв. 24, 2024

The discovery of circadian clock genes greatly amplified the study diurnal variations impacting cancer therapy, transforming it into a rapidly growing field research. Especially, use chronomodulated treatment with 5‐fluorouracil (5‐FU) has gained significance. Studies indicate high interindividual variability (IIV) in dihydropyrimidine dehydrogenase (DPD) activity – key enzyme for 5‐FU metabolism. However, influence individual DPD chronotypes on therapy remains unclear and warrants further investigation. To optimize precision dosing 5‐FU, this aims to: (i) build physiologically‐based pharmacokinetic (PBPK) models uracil, their metabolites, (ii) assess impact variation activity, (iii) estimate chronotypes, (iv) personalize infusion rates based patient's chronotype. Whole‐body PBPK were developed PK‐Sim (R) MoBi . Sinusoidal functions used to incorporate as well from DPYD mRNA expression or enzymatic activity. Four whole‐body metabolites established utilizing data 41 10 publicly available uracil studies. IIV was assessed personalized administrations achieve comparable peak plasma concentrations, exposure, constant levels via “noise cancellation” infusion. capture extent can help investigate individualized through testing alternative strategies.

Язык: Английский

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