Application of Pharmacometrics of 5-Fluorouracil to Personalized Medicine: A Tool for Predicting Pharmacokinetic–Pharmacodynamic/Toxicodynamic Responses

Anticancer Research, Год журнала: 2020, Номер 40(12), С. 6585 - 6597

Опубликована: Дек. 1, 2020

Recently, therapeutic drug monitoring of 5-fluorouracil (5-FU), the key chemotherapeutic for colorectal cancer, has been applied in daily clinical practice and contributed towards improving outcomes. However, current dose modifications are based only on values area under plasma concentration–time profile, which simply calculated from 5-FU concentrations infusion periods. When dose-limiting toxicities occur, dosing is empirically reduced or discontinued, leading to treatment failure. To prevent this predictable failure obtain better outcomes, rational dosage-based strategies required 5-FU. Combining with a mathematical approach using pharmacokinetic– pharmacodynamic/toxicodynamic model expected help simulate time-course profiles efficacy drugs degree toxicity, thereby contributing setting individual patients. Therefore, facilitate pharmacometric modelling simulation techniques optimising oncology therapies, review focuses pharmacometrics approaches personalizing 5-FU-based chemotherapy.

Язык: Английский

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Understanding the significance of biological clock and its impact on cancer incidence

Cancer Letters, Год журнала: 2021, Номер 527, С. 80 - 94

Опубликована: Дек. 11, 2021

Язык: Английский

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An Overview of the Circadian Clock in the Frame of Chronotherapy: From Bench to Bedside

Pharmaceutics, Год журнала: 2022, Номер 14(7), С. 1424 - 1424

Опубликована: Июль 6, 2022

Most living organisms in both the plant and animal kingdoms have evolved processes to stay tune with alternation of day night, optimize their physiology as a function light supply. In mammals, circadian clock relying on feedback loops between key transcription factors will thus control temporally regulated pattern expression most genes. Modern ways life highly altered synchronization human activities clocks. This review discusses links an rise pathologies. We then sum up proofs concept advocating for integration considerations chronotherapy health care, medicine, pharmacotherapy. Finally, we discuss current challenges that biology must face tools address them.

Язык: Английский

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Inflammasome-independent NLRP3 function enforces ATM activity in response to genotoxic stress

Life Science Alliance, Год журнала: 2023, Номер 6(4), С. e202201494 - e202201494

Опубликована: Фев. 6, 2023

NLRP3 is a pattern recognition receptor with well-documented role in inducing inflammasome assembly response to cellular stress. Deregulation of its activity leads many inflammatory disorders including gouty arthritis, Alzheimer disease, and cancer. Whereas the context cancer has been mostly explored immune compartment, whether exerts functions unrelated immunity development remains unexplored. Here, we demonstrate that interacts ATM kinase control activation DNA damage response, independently activity. down-regulation both broncho- mammary human epithelial cells significantly impairs pathway activation, leading lower p53 provides ability resist apoptosis induced by acute genotoxic Interestingly, expression down-regulated non-small cell lung cancers breast cancers, positively correlates patient overall survival. Our findings identify novel non-immune function for maintaining genome integrity strengthen concept functional link between innate sensing pathways maintain integrity.

Язык: Английский

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Coupling between the cell cycle and the circadian clock: Lessons from computational modelling and consequences for cancer chronotherapy

Current Opinion in Systems Biology, Год журнала: 2024, Номер 37, С. 100507 - 100507

Опубликована: Фев. 2, 2024

Язык: Английский

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