scholarly journals Delay Differential Model for Tumour-Immune Response with Chemoimmunotherapy and Optimal Control

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
F. A. Rihan ◽  
D. H. Abdelrahman ◽  
F. Al-Maskari ◽  
F. Ibrahim ◽  
M. A. Abdeen
Keyword(s):  
Optimal Control ◽  
Immune Response ◽  
Treatment Strategies ◽  
Tumour Cells ◽  
Optimal Controls ◽  
Control Pair ◽  
Differential Model ◽  
Effector Cells ◽  
Days Of Therapy ◽  
Delay Differential

We present a delay differential model with optimal control that describes the interactions of the tumour cells and immune response cells with external therapy. The intracellular delay is incorporated into the model to justify the time required to stimulate the effector cells. The optimal control variables are incorporated to identify the best treatment strategy with minimum side effects by blocking the production of new tumour cells and keeping the number of normal cells above 75% of its carrying capacity. Existence of the optimal control pair and optimality system are established. Pontryagin’s maximum principle is applicable to characterize the optimal controls. The model displays a tumour-free steady state and up to three coexisting steady states. The numerical results show that the optimal treatment strategies reduce the tumour cells load and increase the effector cells after a few days of therapy. The performance of combination therapy protocol of immunochemotherapy is better than the standard protocol of chemotherapy alone.

scholarly journals Delay Differential Model for Tumour-Immune System With Chemo-therapy and Optimal Control

2020 ◽  
Vol 31 ◽  
pp. 04003
Author(s):  
Fathalla A. Rihan ◽  
Bassel F. Rihan
Keyword(s):  
Optimal Control ◽  
Carrying Capacity ◽  
Tumour Cells ◽  
Chemotherapy Treatment ◽  
Control Variables ◽  
Differential Model ◽  
Effector Cells ◽  
Days Of Therapy ◽  
Delay Differential ◽  
Optimal Treatment Strategy

In this paper, we present a mathematical model of tumour-immune interactions in presence of chemotherapy treatment. The model is governed by a system of delay differential equations with optimal control variables. The control variables are included to justify the best strategy of treatments with minimum side effects, by reducing the production of new tumour cells and keeping the number of normal cells above the average of its carrying capacity. Existence of optimality and optimality conditions are also proved. The numerical simulations show that the optimal treatment strategy reduces the load of tumour cells and increases the effector cells after few days of therapy.

scholarly journals Optimal Control of a Delayed HIV Infection Model with Immune Response Using an Efficient Numerical Method

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Khalid Hattaf ◽  
Noura Yousfi
Keyword(s):  
Optimal Control ◽  
Immune Response ◽  
Hiv Infection ◽  
Equation Model ◽  
Difference Approximation ◽  
Infection Model ◽  
Optimal Controls ◽  
Control Pair ◽  
Hiv Infection Model ◽  
Delay Differential

We present a delay-differential equation model with optimal control that describes the interactions between human immunodeficiency virus (HIV), CD4+ T cells, and cell-mediated immune response. Both the treatment and the intracellular delay are incorporated into the model in order to improve therapies to cure HIV infection. The optimal controls represent the efficiency of drug treatment in inhibiting viral production and preventing new infections. Existence for the optimal control pair is established, Pontryagin’s maximum principle is used to characterize these optimal controls, and the optimality system is derived. For the numerical simulation, we propose a new algorithm based on the forward and backward difference approximation.

scholarly journals Optimal control of acute myeloid leukaemia

2018 ◽  
Author(s):  
Jesse A Sharp ◽  
Alexander P Browning ◽  
Tarunendu Mapder ◽  
Kevin Burrage ◽  
Matthew J Simpson
Keyword(s):  
Optimal Control ◽  
Immune Response ◽  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Cell Model ◽  
Control Strategies ◽  
Treatment Strategies ◽  
Numerical Convergence ◽  
Stem Cell Model ◽  
Acute Myeloid

AbstractAcute myeloid leukaemia (AML) is a blood cancer affecting haematopoietic stem cells. AML is routinely treated with chemotherapy, and so it is of great interest to develop optimal chemotherapy treatment strategies. In this work, we incorporate an immune response into a stem cell model of AML, since we find that previous models lacking an immune response are inappropriate for deriving optimal control strategies. Using optimal control theory, we produce continuous controls and bang-bang controls, corresponding to a range of objectives and parameter choices. Through example calculations, we provide a practical approach to applying optimal control using Pontryagin’s Maximum Principle. In particular, we describe and explore factors that have a profound influence on numerical convergence. We find that the convergence behaviour is sensitive to the method of control updating, the nature of the control, and to the relative weighting of terms in the objective function. All codes we use to implement optimal control are made available.

Controlled Lotka-Volterra systems in the modeling of biomedical processes

2021 ◽  
Author(s):  
Evgenii Khailov ◽  
Nikolai Grigorenko ◽  
Ellina Grigorieva ◽  
Anna Klimenkova
Keyword(s):  
Optimal Control ◽  
Optimal Control Problems ◽  
Numerical Study ◽  
Treatment Strategies ◽  
Main Tool ◽  
Necessary Condition ◽  
Control Problems ◽  
Optimal Controls ◽  
Controlled Systems ◽  
Volterra Systems

This book is devoted to a consistent presentation of the recent results obtained by the authors related to controlled systems created based on the Lotka-Volterra competition model, as well as to theoretical and numerical study of the corresponding optimal control problems. These controlled systems describe various modern methods of treating blood cancers, and the optimal control problems stated for such systems, reflect the search for the optimal treatment strategies. The main tool of the theoretical analysis used in this book is the Pontryagin maximum principle - a necessary condition for optimality in optimal control problems. Possible types of the optimal blood cancer treatment - the optimal controls - are obtained as a result of analytical investigations and are confirmed by corresponding numerical calculations. This book can be used as a supplement text in courses of mathematical modeling for upper undergraduate and graduate students. It is our believe that this text will be of interest to all professors teaching such or similar courses as well as for everyone interested in modern optimal control theory and its biomedical applications.

scholarly journals Mathematical Analysis and Optimal Control of Giving up the Smoking Model

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Omar Khyar ◽  
Jaouad Danane ◽  
Karam Allali
Keyword(s):  
Optimal Control ◽  
Mathematical Analysis ◽  
Minimum Principle ◽  
Smoking Behavior ◽  
Difference Approximation ◽  
Optimal Controls ◽  
Pontryagin Minimum Principle ◽  
Control Pair ◽  
Public Areas ◽  
The Government

In this study, we are going to explore mathematically the dynamics of giving up smoking behavior. For this purpose, we will perform a mathematical analysis of a smoking model and suggest some conditions to control this serious burden on public health. The model under consideration describes the interaction between the potential smokers P , the occasional smokers L , the chain smokers S , the temporarily quit smokers Q T , and the permanently quit smokers Q P . Existence, positivity, and boundedness of the proposed problem solutions are proved. Local stability of the equilibria is established by using Routh–Hurwitz conditions. Moreover, the global stability of the same equilibria is fulfilled through using suitable Lyapunov functionals. In order to study the optimal control of our problem, we will take into account a two controls’ strategy. The first control will represent the government prohibition of smoking in public areas which reduces the contact between nonsmokers and smokers, while the second will symbolize the educational campaigns and the increase of cigarette cost which prevents occasional smokers from becoming chain smokers. The existence of the optimal control pair is discussed, and by using Pontryagin minimum principle, these two optimal controls are characterized. The optimality system is derived and solved numerically using the forward and backward difference approximation. Finally, numerical simulations are performed in order to check the equilibria stability, confirm the theoretical findings, and show the role of optimal strategy in controlling the smoking severity.

scholarly journals The role of unconventional T cells in COVID-19

2021 ◽  
Author(s):  
Kristen Orumaa ◽  
Margaret R. Dunne
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Treatment Strategies ◽  
Γδ T Cells ◽  
Protective Role ◽  
T Cell Subsets ◽  
Viral Immunity ◽  
Mait Cells

AbstractCOVID-19 is a respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first documented in late 2019, but within months, a worldwide pandemic was declared due to the easily transmissible nature of the virus. Research to date on the immune response to SARS-CoV-2 has focused largely on conventional B and T lymphocytes. This review examines the emerging role of unconventional T cell subsets, including γδ T cells, invariant natural killer T (iNKT) cells and mucosal associated invariant T (MAIT) cells in human SARS-CoV-2 infection.Some of these T cell subsets have been shown to play protective roles in anti-viral immunity by suppressing viral replication and opsonising virions of SARS-CoV. Here, we explore whether unconventional T cells play a protective role in SARS-CoV-2 infection as well. Unconventional T cells are already under investigation as cell-based immunotherapies for cancer. We discuss the potential use of these cells as therapeutic agents in the COVID-19 setting. Due to the rapidly evolving situation presented by COVID-19, there is an urgent need to understand the pathogenesis of this disease and the mechanisms underlying its immune response. Through this, we may be able to better help those with severe cases and lower the mortality rate by devising more effective vaccines and novel treatment strategies.

scholarly journals Pharmacokinetic modeling of Gadolinium nanoparticles (Gd-NPs) with the sojourn time in vasa vasorum for the contrast enhanced MRI

2020 ◽  
Vol 2020 (1) ◽  
Author(s):  
Angkhana Prommarat ◽  
Farida Chamchod
Keyword(s):  
Sojourn Time ◽  
Vasa Vasorum ◽  
Peripheral Arteries ◽  
Resonance Imaging ◽  
Differential Model ◽  
Transfer Rates ◽  
Dynamical Behaviors ◽  
Contrast Enhanced ◽  
Delay Differential

AbstractDeposition of lipid in the artery wall called atherosclerosis is recognized as a major cause of cardiovascular disease that leads to death worldwide. A better understanding into factors that may influence the delivery of gadolinium nanoparticles (Gd-NPs) that enhances quality of magnetic resonance imaging in diagnosis may provide a vital key for atherosclerotic treatment. In this study, we propose a delay differential model for describing the dynamics of Gd-NPs in bloodstream, peripheral arteries, and vasa vasorum with two phenomena of Gd-NPs during a sojourn in vasa vasorum. We then investigate the dynamical behaviors of Gd-NPs and explore the effects of sojourn time and transfer rates of Gd-NPs on the concentration of Gd-NPs in vasa vasorum at the 12th hour after the administration of gadolinium chelates contrast media and also the maximum concentration of Gd-NPs in peripheral arteries and vasa vasorum. Our results suggest that the sojourn of Gd-NPs in vasa vasorum may lead to complex behaviors of Gd-NPs dynamics, and transfer rates of Gd-NPs may have a significant impact on the concentration of Gd-NPs.

scholarly journals Increased VEGF-A in solid type of lung adenocarcinoma reduces the patients’ survival

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Woon Yong Jung ◽  
Kyueng-Whan Min ◽  
Young Ha Oh
Keyword(s):  
Immune Response ◽  
Survival Analysis ◽  
Lung Adenocarcinoma ◽  
Survival Rates ◽  
Treatment Strategies ◽  
Enrichment Analysis ◽  
Genetic Alterations ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Solid Type

AbstractThe histological classification of lung adenocarcinoma includes 5 types: lepidic, acinar, papillary, micropapillary and solid. The complex gene interactions and anticancer immune response of these types are not well known. The aim of this study was to reveal the survival rates, genetic alterations and immune activities of the five histological types and provide treatment strategies. This study reviewed the histological findings of 517 patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA) database and classified them into five types. We performed gene set enrichment analysis (GSEA) and survival analysis according to the different types. We found six oncogenic gene sets that were higher in lung adenocarcinoma than in normal tissues. In the survival analysis of each type, the acinar type had a favorable prognosis, and the solid subtype had an unfavorable prognosis; however, the survival differences between the other types were not significant. Our study focused on the solid type, which had the poorest prognosis. The solid type was related to adaptive immune resistance associated with elevated CD8 T cells and high CD274 (encoding PD-L1) expression. In the pathway analyses, the solid type was significantly related to high vascular endothelial growth factor (VEGF)-A expression, reflecting tumor angiogenesis. Non-necrosis/low immune response affected by high VEGF-A was associated with worse prognosis. The solid type associated with high VEGF-A expression may contribute to the development of therapeutic strategies for lung adenocarcinoma.

scholarly journals DAP12 Inhibits Pulmonary Immune Responses to Cryptococcus neoformans

2016 ◽  
Vol 84 (6) ◽  
pp. 1879-1886 ◽  
Author(s):  
Lena J. Heung ◽  
Tobias M. Hohl
Keyword(s):  
Immune Response ◽  
Nk Cells ◽  
Cryptococcus Neoformans ◽  
Molecular Mechanisms ◽  
Content Type ◽  
Effector Cells ◽  
Opportunistic Fungal Pathogen ◽  
Efficient Uptake ◽  
Bacteria And Fungi

Cryptococcus neoformansis an opportunistic fungal pathogen that is inhaled into the lungs and can lead to life-threatening meningoencephalitis in immunocompromised patients. Currently, the molecular mechanisms that regulate the mammalian immune response to respiratory cryptococcal challenge remain poorly defined. DAP12, a signaling adapter for multiple pattern recognition receptors in myeloid and natural killer (NK) cells, has been shown to play both activating and inhibitory roles during lung infections by different bacteria and fungi. In this study, we demonstrate that DAP12 plays an important inhibitory role in the immune response toC. neoformans. Infectious outcomes in DAP12−/−mice, including survival and lung fungal burden, are significantly improved compared to those in C57BL/6 wild-type (WT) mice. We find that eosinophils and macrophages are decreased while NK cells are increased in the lungs of infected DAP12−/−mice. In contrast to WT NK cells, DAP12−/−NK cells are able to repressC. neoformansgrowthin vitro. Additionally, DAP12−/−macrophages are more highly activated than WT macrophages, with increased production of tumor necrosis factor (TNF) and CCL5/RANTES and more efficient uptake and killing ofC. neoformans. These findings suggest that DAP12 acts as a brake on the pulmonary immune response toC. neoformansby promoting pulmonary eosinophilia and by inhibiting the activation and antifungal activities of effector cells, including NK cells and macrophages.

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