Modelagem híbrida multiescala para o crescimento tumoral

• Autor(a) principal: Rocha, Heber Lima da
• Data de Publicação: 2016
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações do LNCC
• Texto Completo: https://tede.lncc.br/handle/tede/236
• topic: Modelos matemáticos; Cancer; Mathematical models; CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::CANCEROLOGIA; CNPQ::CIENCIAS EXATAS E DA TERRA::MATEMATICA::MATEMATICA APLICADA

Cancer is a huge world health problem, what is expanding researches on a wide variety of subjects associated with its onset, evolution and treatment. In this work, we perfom a detailed study on the tumor growth mechanisms in order to build a model to describe the evolution of tumors at different scales. We develop a multiscale hybrid model for the avascular tumor growth which integrates phenomena that occur at two scales, the cellular and tissue scales. The cellular scale is described through an agent based model, allowing to deal with each cell individually and to describe the cell behavior in the microenvironment. We represent the nutrient transport in the microenvironment at the tissue scale through a reaction-diffusion partial differential equation. The oxygen is considered the only source of nutrients and its uptake rate plays the role of the bridge between scales. The model encompasses tumor and normal cells, but the latter are kept in homeostasis. Phenotypic states differentiate tumor cells (quiescent, proliferative, apoptotic, hypoxic and necrotic), which may change in accordance with microenvironment conditions. The tumor growth dynamics is ruled by phenotypic transitions, which are mainly deterministic. However, the transitions from quiescent to proliferative and apoptotic states are stochastic. Each cell movement is driven by the force balance among cells, according to Newton's second law. By including normal cells, the tumor growth strongly depends on the mechanical interactions in the microenvironment. To describe these effects, we develop a model to represent the compressive stress accumulation within the growing tumor, which acts by inhibiting further cell proliferation. Computational simulations are conducted to demonstrate that the developed model can adequately describe the complex mechanisms of tumor dynamics, including growth arrest in avascular tumors.