A Cellular Automata Model of Oncolytic Virotherapy in Pancreatic Cancer
- PDF / 8,735,563 Bytes
- 25 Pages / 439.37 x 666.142 pts Page_size
- 52 Downloads / 192 Views
A Cellular Automata Model of Oncolytic Virotherapy in Pancreatic Cancer J. Chen1,2
· D. Weihs3 · F. J. Vermolen2,4
Received: 11 March 2020 / Accepted: 16 July 2020 © The Author(s) 2020
Abstract Oncolytic virotherapy is known as a new treatment to employ less virulent viruses to specifically target and damage cancer cells. This work presents a cellular automata model of oncolytic virotherapy with an application to pancreatic cancer. The fundamental biomedical processes (like cell proliferation, mutation, apoptosis) are modeled by the use of probabilistic principles. The migration of injected viruses (as therapy) is modeled by diffusion through the tissue. The resulting diffusion–reaction equation with smoothed point viral sources is discretized by the finite difference method and integrated by the IMEX approach. Furthermore, Monte Carlo simulations are done to quantitatively evaluate the correlations between various input parameters and numerical results. As we expected, our model is able to simulate the pancreatic cancer growth at early stages, which is calibrated with experimental results. In addition, the model can be used to predict and evaluate the therapeutic effect of oncolytic virotherapy. Keywords Cellular automata · Computational modeling · Cancer treatment · Virotherapy · Monte Carlo simulations
1 Introduction Oncolytic virotherapy is a novel cancer treatment where natural or genetically modified viruses infect cancer cells and then self-replicate until the host cancer cells lysis (see Fig. 1). Ruptured cancer cells release chemicals like tumor antigens, which make cancer cells easily recognizable by the immune system. Moreover, the released viruses
B
J. Chen [email protected]
1
Department of Biomedical Engineering and Physics, Amsterdam UMC, Amsterdam, The Netherlands
2
Delft Institute of Applied Mathematics, Delft University of Technology, Delft, The Netherlands
3
Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel
4
Division of Mathematics and Statistics, Faculty of Sciences, Hasselt University, Diepenbeek, Belgium 0123456789().: V,-vol
123
103
Page 2 of 25
J. Chen et al.
Fig. 1 A schematical figure of oncolytic virotherapy. The viruses can specifically infect cancer cells and then replicate themselves until cancer cells rupture. Subsequently, the newborn viruses are released to infect more cancer cells
Fig. 2 Historical milestones in the development of oncolytic virotherapy
can infect more cancer cells to trigger a chain reaction and effectively act as a followup treatment. As early as in 1912, De Pace (1912) observed a tumor regression after inoculation of an attenuated rabies vaccine in a patient with uterine cervical carcinoma. Later on, an animal-based test (Levaditi and Nicolau 1922) and a human trial (Pack 1950) were conducted in 1920 and 1940, respectively, where both experiments yielded an obvious partial tumor regression (Kasuya et al. 2005). In the subsequent decades, more works (Kirn 2001; Gil et al. 2013, 2014) demonstrated that
Data Loading...
