The Influence Of The Microenvironment On Solid Tumor Growth:a Numerical Simulation

Tumors pose a great threat to human health and life. It is a serious problem to study the pathological process and the therapeutic strategies of tumors. The micro-environment of tumor includes tissual level, cellular level and gene level, it is very important for tumor growth. In this paper, we construct a multiscale continuous-discrete hybrid On-Lattice model to simulate solid tumor growth which is influenced by the microenvironment including glucose, p27gene and hypoxia. And meanwhile we explore the impact of radiation therapy for tumor growth. Also, the impact of radiation therapy for tumor growth is explored and tested.In modeling, continuity equations were used to describe the change of the concentration of oxygen, extracellular matrix enzymes and glucose, and discrete model was adopted to research on tumor cell evolution dynamics and solid tumor growth, based on single tumor cell cycle, mutation, division, proliferation, invasion and apoptosis.Research including:(1) a vascular tumor growth under different concentration of glucoseThe results indicate that tumor necrosis due to a lack of glucose. With the glucose concentration reduced, the time required for proliferation is increased, the number of proliferation cells is decreased, necrotic core area is enlarged and nominal diameter of tumor changed slowly.(2) effect of P27regulation on avascular tumor growthA multiscale continuous-discrete model based on the effect of p27gene control has been proposed to simulate a vascular tumor growth. By changing the parameters in the equation controlling p27gene expression, the model of this paper has simulated the inhibiting effect of up-regulating p27gene expression, which corresponds to the experimental findings. The inhibiting effects of up-regulating c1and down-regulating c2on tumour growth have been compared, and through this, a primary method of p27-targeted regulation has been proposed from a mathematical perspective.(3) multicellular tumour spheroids growth under hypoxic micro-environmentThe results show the spatial distribution of different phenotypes of tumor cells and associated oxygen concentration distribution under hypoxia, which is coincidence to physiology. We also assess the model system responses to the varied hypoxia conditions by examing the sensitivities to the oxygen thresholds in this model. The results showed that the resistance of tumour cells to hypoxic environment and the number of mutated cells influence the growth of MTS significantly.(4) the efficacy of radiation therapy on solid tumorsThe study included two phases of growth which are avascular stage and vascular stage, the specific work as follows:①to simulate solid tumors growth;②to simulate the radiation therapy of solid tumors, and discussed the impact of the radio sensitivity、the cell cycle and treatment modalities.Major innovations in this study:(1) The simulations of effect of glucose、hypoxic microenvironment and radiation therapy on solid tumor growth have been reported. A combinated model of continuous-discrete and multi-scale hybrid On-Lattice model was used to directly reflect the changes of these factors in tumor morphology, it is rarely seen.(2) It is the first time to numerically simulatethe effect of p27regulation on tumor growth from morphology.(3) Tumor growth and the changing of the oxygen distribution are coupled in tumor vessel period, which is the difficulty of the research. The study of the impact of radiotherapy on the growth of solid tumors in this paperhas initially solved the problem of tumor growth and oxygen distribution coupled.It provides an effective methodology to the in-depth study of such problems.