Characterizing Chemotherapy-Induced Neutropenia and Monocytopenia Through Mathematical Modelling

Cassidy, Tyler; Humphries, A. R.; Craig, Morgan; Mackey, Michael C.

doi:10.1007/s11538-020-00777-0

Cited by 9 publications

(6 citation statements)

References 90 publications

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“…Because the identification of immune mechanisms responsible for divergent disease outcomes can be difficult clinically, and experimental models and longitudinal data are only beginning to emerge, theoretical explorations are ideal [31]. Quantitative approaches combining mechanistic disease modelling and computational strategies are being increasingly leveraged to investigate inter-and intra-patient variability by, for example, developing virtual clinical trials [32][33][34]. Such in silico trials enable the theoretical exploration of how multiple key underlying mechanisms simultaneously impact disease severity [34].…”

Section: Introductionmentioning

confidence: 99%

COVID-19 virtual patient cohort suggests immune mechanisms driving disease outcomes

et al. 2021

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To understand the diversity of immune responses to SARS-CoV-2 and distinguish features that predispose individuals to severe COVID-19, we developed a mechanistic, within-host mathematical model and virtual patient cohort. Our results suggest that virtual patients with low production rates of infected cell derived IFN subsequently experienced highly inflammatory disease phenotypes, compared to those with early and robust IFN responses. In these in silico patients, the maximum concentration of IL-6 was also a major predictor of CD8+ T cell depletion. Our analyses predicted that individuals with severe COVID-19 also have accelerated monocyte-to-macrophage differentiation mediated by increased IL-6 and reduced type I IFN signalling. Together, these findings suggest biomarkers driving the development of severe COVID-19 and support early interventions aimed at reducing inflammation.

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Section: Introductionmentioning

confidence: 99%

COVID-19 virtual patient cohort suggests immune mechanisms driving disease outcomes

et al. 2021

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“…Neutrophils are the most abundant among the white blood cells with a short life span that act as a primary defense response to infections [ 50 ]. Promyelocytes are the earliest recognizable precursors of neutrophils, which actively synthesize DNA and are susceptible to the antimitotic effects of chemotherapy.…”

Section: Bloodstream Infections Originate From the Git Colonizationmentioning

confidence: 99%

The Intestinal Microbiota: Impacts of Antibiotics Therapy, Colonization Resistance, and Diseases

Shah

Baloch

Shah

et al. 2021

IJMS

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Trillions of microbes exist in the human body, particularly the gastrointestinal tract, coevolved with the host in a mutually beneficial relationship. The main role of the intestinal microbiome is the fermentation of non-digestible substrates and increased growth of beneficial microbes that produce key antimicrobial metabolites such as short-chain fatty acids, etc., to inhibit the growth of pathogenic microbes besides other functions. Intestinal microbiota can prevent pathogen colonization through the mechanism of colonization resistance. A wide range of resistomes are present in both beneficial and pathogenic microbes. Giving antibiotic exposure to the intestinal microbiome (both beneficial and hostile) can trigger a resistome response, affecting colonization resistance. The following review provides a mechanistic overview of the intestinal microbiome and the impacts of antibiotic therapy on pathogen colonization and diseases. Further, we also discuss the epidemiology of immunocompromised patients who are at high risk for nosocomial infections, colonization and decolonization of multi-drug resistant organisms in the intestine, and the direct and indirect mechanisms that govern colonization resistance to the pathogens.

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“…The structure variable a in (2) corresponds to chronological cellular age which we use as a cipher for a number of epigenetic factors. It is possible to include specific epigenetic factors by including a non-constant ageing velocity as in other structured models of physiological processes [49,50]. However, it is difficult to determine how these epigenetic factors accumulate throughout a cell's lifespan and during treatment.…”

Section: Bðt; Aþda: ð1þmentioning

confidence: 99%

The role of memory in non-genetic inheritance and its impact on cancer treatment resistance

et al. 2021

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Intra-tumour heterogeneity is a leading cause of treatment failure and disease progression in cancer. While genetic mutations have long been accepted as a primary mechanism of generating this heterogeneity, the role of phenotypic plasticity is becoming increasingly apparent as a driver of intra-tumour heterogeneity. Consequently, understanding the role of this plasticity in treatment resistance and failure is a key component of improving cancer therapy. We develop a mathematical model of stochastic phenotype switching that tracks the evolution of drug-sensitive and drug-tolerant subpopulations to clarify the role of phenotype switching on population growth rates and tumour persistence. By including cytotoxic therapy in the model, we show that, depending on the strategy of the drug-tolerant subpopulation, stochastic phenotype switching can lead to either transient or permanent drug resistance. We study the role of phenotypic heterogeneity in a drug-resistant, genetically homogeneous population of non-small cell lung cancer cells to derive a rational treatment schedule that drives population extinction and avoids competitive release of the drug-tolerant sub-population. This model-informed therapeutic schedule results in increased treatment efficacy when compared against periodic therapy, and, most importantly, sustained tumour decay without the development of resistance.

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Characterizing Chemotherapy-Induced Neutropenia and Monocytopenia Through Mathematical Modelling

Cited by 9 publications

References 90 publications

COVID-19 virtual patient cohort suggests immune mechanisms driving disease outcomes

COVID-19 virtual patient cohort suggests immune mechanisms driving disease outcomes

The Intestinal Microbiota: Impacts of Antibiotics Therapy, Colonization Resistance, and Diseases

The role of memory in non-genetic inheritance and its impact on cancer treatment resistance

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