Document Detail

Distributed delays in a hybrid model of tumor-Immune system interplay.
MedLine Citation:
PMID:  23311361     Owner:  NLM     Status:  In-Data-Review    
A tumor is kinetically characterized by the presence of multiple spatio-temporal scales in which its cells interplay with, for instance, endothelial cells or Immune system effectors, exchanging various chemical signals. By its nature, tumor growth is an ideal object of hybrid modeling where discrete stochastic processes model low-numbers entities, and mean-field equations model abundant chemical signals. Thus, we follow this approach to model tumor cells, effector cells and Interleukin-2, in order to capture the Immune surveillance effect. We here present a hybrid model with a generic delay kernel accounting that, due to many complex phenomena such as chemical transportation and cellular differentiation, the tumor-induced recruitment of effectors exhibits a lag period. This model is a Stochastic Hybrid Automata and its semantics is a Piecewise Deterministic Markov process where a two-dimensional stochastic process is interlinked to a multi-dimensional mean-field system. We instantiate the model with two well-known weak and strong delay kernels and perform simulations by using an algorithm to generate trajectories of this process. Via simulations and parametric sensitivity analysis techniques we (i) relate tumor mass growth with the two kernels, we (ii) measure the strength of the Immune surveillance in terms of probability distribution of the eradication times, and (iii) we prove, in the oscillatory regime, the existence of a stochastic bifurcation resulting in delay-induced tumor eradication.
Giulio Caravagna; Alex Graudenzi; Alberto d'Onofrio
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Mathematical biosciences and engineering : MBE     Volume:  10     ISSN:  1551-0018     ISO Abbreviation:  Math Biosci Eng     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101197794     Medline TA:  Math Biosci Eng     Country:  United States    
Other Details:
Languages:  eng     Pagination:  37-58     Citation Subset:  IM    
Department of Informatics, Systems and Communication, University of Milan Bicocca, Viale Sarca 336, I-20126 Milan, Italy.
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