10,904 research outputs found
Why one-size-fits-all vaso-modulatory interventions fail to control glioma invasion: in silico insights
There is an ongoing debate on the therapeutic potential of vaso-modulatory
interventions against glioma invasion. Prominent vasculature-targeting
therapies involve functional tumour-associated blood vessel deterioration and
normalisation. The former aims at tumour infarction and nutrient deprivation
medi- ated by vascular targeting agents that induce occlusion/collapse of
tumour blood vessels. In contrast, the therapeutic intention of normalising the
abnormal structure and function of tumour vascular net- works, e.g. via
alleviating stress-induced vaso-occlusion, is to improve chemo-, immuno- and
radiation therapy efficacy. Although both strategies have shown therapeutic
potential, it remains unclear why they often fail to control glioma invasion
into the surrounding healthy brain tissue. To shed light on this issue, we
propose a mathematical model of glioma invasion focusing on the interplay
between the mi- gration/proliferation dichotomy (Go-or-Grow) of glioma cells
and modulations of the functional tumour vasculature. Vaso-modulatory
interventions are modelled by varying the degree of vaso-occlusion. We
discovered the existence of a critical cell proliferation/diffusion ratio that
separates glioma invasion re- sponses to vaso-modulatory interventions into two
distinct regimes. While for tumours, belonging to one regime, vascular
modulations reduce the tumour front speed and increase the infiltration width,
for those in the other regime the invasion speed increases and infiltration
width decreases. We show how these in silico findings can be used to guide
individualised approaches of vaso-modulatory treatment strategies and thereby
improve success rates
Activation of effector immune cells promotes tumor stochastic extinction: A homotopy analysis approach
In this article we provide homotopy solutions of a cancer nonlinear model
describing the dynamics of tumor cells in interaction with healthy and effector
immune cells. We apply a semi-analytic technique for solving strongly nonlinear
systems - the Step Homotopy Analysis Method (SHAM). This algorithm, based on a
modification of the standard homotopy analysis method (HAM), allows to obtain a
one-parameter family of explicit series solutions. By using the homotopy
solutions, we first investigate the dynamical effect of the activation of the
effector immune cells in the deterministic dynamics, showing that an increased
activation makes the system to enter into chaotic dynamics via a
period-doubling bifurcation scenario. Then, by adding demographic stochasticity
into the homotopy solutions, we show, as a difference from the deterministic
dynamics, that an increased activation of the immune cells facilitates cancer
clearance involving tumor cells extinction and healthy cells persistence. Our
results highlight the importance of therapies activating the effector immune
cells at early stages of cancer progression
Multiscale model for the effects of adaptive immunity suppression on the viral therapy of cancer
Oncolytic virotherapy - the use of viruses that specifically kill tumor cells
- is an innovative and highly promising route for treating cancer. However, its
therapeutic outcomes are mainly impaired by the host immune response to the
viral infection. In the present work, we propose a multiscale mathematical
model to study how the immune response interferes with the viral oncolytic
activity. The model assumes that cytotoxic T cells can induce apoptosis in
infected cancer cells and that free viruses can be inactivated by neutralizing
antibodies or cleared at a constant rate by the innate immune response. Our
simulations suggest that reprogramming the immune microenvironment in tumors
could substantially enhance the oncolytic virotherapy in immune-competent
hosts. Viable routes to such reprogramming are either in situ virus-mediated
impairing of CD T cells motility or blockade of B and T lymphocytes
recruitment. Our theoretical results can shed light on the design of viral
vectors or new protocols with neat potential impacts on the clinical practice.Comment: 14 pages, 4 figure
An Ag-Dependent Approach Based on Adaptive Mechanisms for Investigating the Regulation of the Memory B Cell Reservoir
In fact, it is well-known that the soluble antibody population is one of the essential mechanisms of immunological response regulation [23-25]. However, despite the pioneering work of Lagreca et al. (2001) in developing a coupled map for studying the behavior of the mammalian immune system, their model did not consider these populations [1-6], which makes the model incomplete with respect to the regulation of the immune response by adaptive mechanisms. This omission opens up the possibility of extending their work by taking the soluble antibody populations into account. We have performed that work and present our immunological modeling and simulation findings in this paper
Mathematical Modeling and Analysis of Leukemia: Effect of External Engineered T Cells Infusion
In this paper, a nonlinear model is proposed and analyzed to study the spread of Leukemia by considering the effect of genetically engineered patients T cells to attack cancer cells. The model is governed by four dependent variables namely; naive or susceptible blood cells, infected or dysfunctional blood cells, cancer cells and immune cells. The model is analyzed by using the stability theory of differential equations and numerical simulation. We have observed that the system is stable in the local and global sense if antigenicity rate or rate of stimulation of immune cells is greater than a threshold value dependent on the density of immune cells. Further, external infusion of T cells (immune cells) reduces the concentration of cancer cells and infected cells in the blood. It is observed that the infected cells decrease with the increase in antigenicity rate or stimulation rate of immune response due to abnormal cancer cells present in the blood. This indicates that immune cells kill cancer cells on being stimulated and as antigenicity rate increases rate of destruction of cancer cells also increase leading to decrease in the concentration of cancer cells in the body. This decrease in cancer cells further causes decrease in the concentration of infected or dysfunctional cells in the body
- …