Bifurcation analysis on a hybrid systems model of intermittent hormonal therapy for prostate cancer

Institute of Industrial Science, University of Tokyo, Tokyo 153-8505, Japan; ERATO Aihara Complexity Modelling Project, JST, Tokyo 151-0065, Japan
Physica D Nonlinear Phenomena (Impact Factor: 1.67). 01/2008; DOI: 10.1016/j.physd.2008.03.044

ABSTRACT Hybrid systems are widely used to model dynamical phenomena that are characterized by interplay between continuous dynamics and discrete events. An example of biomedical application is modeling of disease progression of prostate cancer under intermittent hormonal therapy, where continuous tumor dynamics is switched by interruption and reinstitution of medication. In the present paper, we study a hybrid systems model representing intermittent androgen suppression (IAS) therapy for advanced prostate cancer. Intermittent medication with switching between on-treatment and off-treatment periods is intended to possibly prevent a prostatic tumor from developing into a hormone-refractory state and is anticipated as a possible strategy for delaying or hopefully averting a cancer relapse which most patients undergo as a result of long-term hormonal suppression. Clinical efficacy of IAS therapy for prostate cancer is still under investigation but at least worth considering in terms of reduction of side effects and economic costs during off-treatment periods. In the model of IAS therapy, it depends on some clinically controllable parameters whether a relapse of prostate cancer occurs or not. Therefore, we examine nonlinear dynamics and bifurcation structure of the model by exploiting a numerical method to clarify bifurcation sets in the hybrid system. Our results suggest that adjustment of the normal androgen level in combination with appropriate medication scheduling could enhance the possibility of relapse prevention. Moreover, a two-dimensional piecewise-linear system reduced from the original model highlights the origin of nonlinear phenomena specific to the hybrid system.

  • [Show abstract] [Hide abstract]
    ABSTRACT: In hybrid dynamical systems including both continuous and discrete components, an interplay between a continuous trajectory and a discontinuity boundary can trigger a sudden qualitative change in the system dynamics. Grazing phenomena, which occur when a continuous trajectory hits a boundary tangentially, are well known as a representative of such phenomena. We demonstrate that a grazing phenomenon of a chaotic attractor can result in its sudden disappearance and initiate chaotic transients. The mechanism of this grazing-induced crisis is revealed in an illustrative example. Furthermore, we derive a formula to obtain the critical exponent of the power law on the mean duration of chaotic transients.
    Physics Letters A 08/2009; 373(35):3134-3139. · 1.63 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Non-smooth or even abrupt state changes exist during many biological processes, e.g., cell differentiation processes, proliferation processes, or even disease deterioration processes. Such dynamics generally signals the emergence of critical transition phenomena, which result in drastic changes of system states or eventually qualitative changes of phenotypes. Hence, it is of great importance to detect such transitions and further reveal their molecular mechanisms at network level. Here, we review the recent advances on dynamical network biomarkers (DNBs) as well as the related theoretical foundation, which can identify not only early signals of the critical transitions but also their leading networks, which drive the whole system to initiate such transitions. In order to demonstrate the effectiveness of this novel approach, examples of complex diseases are also provided to detect pre-disease stage, for which traditional methods or biomarkers failed.
    Quantitative Biology. 06/2013; 1(2).
  • [Show abstract] [Hide abstract]
    ABSTRACT: The behaviors of system which alternate between Duffing oscillator and van der Pol oscillator are investigated to explore the influence of the switches on dynamical evolutions of system. Switches related to the state and time are introduced, upon which a typical switched model is established. Poincaré map of the whole switched system is defined by suitable local sections and local maps, and the formal expression of its Jacobian matrix is obtained. The location of the fixed point and associated Floquet multipliers are calculated, based on which two-parameter bifurcation sets of the switched system are obtained, dividing the parameter space into several regions corresponding to different types of attractors. It is found that cascading of period-doubling bifurcations may lead the system to chaos, while fold bifurcations determine the transition between period-3 solution and chaotic movement.
    Communications in Nonlinear Science and Numerical Simulation 03/2014; 19(3):750-757. · 2.57 Impact Factor

Full-text (2 Sources)

Available from
May 26, 2014