Modelagem de tumores avasculares: de autômatos celulares a modelos de multiescala
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Data
2007-03-21
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Editor
Universidade Federal de Viçosa
Resumo
A maior parte das terapias anti-câncer clinicamente usadas tem se desenvolvido empiricamente [1] mas a resposta do tumor e do organismo a essas terapias é não-linear. Portanto, modelos matemáticos podem ser ferramentas complementares (e talvez necessárias) para a compreensão da dinâmica da resposta à droga ou terapia no organismo. Nesta dissertação de mestrado alguns desses modelos são estudados. Em particular, propomos uma estratégia para crescer agregados isotrópicos do modelo de Eden na rede, um modelo estocástico básico para o crescimento de tumores avasculares, Os padrões gerados são caracterizados pela largura da interface, que é calculada considerando o centro da rede ou o centro de massa do agregado como referência, e pela diferença entre as probabilidades de crescimento axial e diagonal. Também foi estudado um modelo de multiescala para viroterapia em tumores avasculares em que as concentrações de nutrientes e vírus são descritas por equações de reação-difusão macroscópicas e as ações de células tumorais são governadas por regras estocásticas microscópicas. O objetivo central dessa parte do trabalho é a determinação do diagrama de estados no espaço de parâmetros. A faixa de parâmetros envolvidos foi estimada a partir de dados experimentais e a resposta das células tumorais à injeção viral apresenta quatro comportamentos diferentes, todos observados experimentalmente. Os valores dos parâmetros que geram predominantemente cada um desses comportamentos são determinados.
Despite of the recent progress in cancer diagnosis and treatment, the survival rates of patients with tumors in unresectable locations, recurrent or metastatic tumors are still low. On the quest for alternative treatments, oncolytic virotherapy and encapsulation of chemotherapeutic drugs into nanoscale vehicles emerge as promissing strategies. However, several fundamental process and issues still must be understood in order to enhance the efficacy of these treatments. The nonlinearities and complexities inherent to tumor-oncolytic virus and tumor-drug interactions claim for a mathematical approach. Quantitative models allow to enlarge our understanding of the parameters influencing therapeutic outcomes, guide essays by indicating relevant physiological processes for further investigation, and prevent excessive experimentation. The multiescale models for virotherapy presented and discussed in this thesis suggest the appropriate traits an oncolytic virus must have and the less agressive ways to modulate the antiviral immune response in order to maximize the tumor erradication probability. Concerning the model for treatment with chemotherapeutic drugs encapsulated into nanoparticles, we focused on chimeric polymers attached with the doxorubicin drug, that recently are under active investigation. Using the same parameters that characterize these particles and the experimental protocols commonly used for their administration, our results indicate some of the basic features of these nanoparticles that should be developed in order to maximize the therapy's success.
Despite of the recent progress in cancer diagnosis and treatment, the survival rates of patients with tumors in unresectable locations, recurrent or metastatic tumors are still low. On the quest for alternative treatments, oncolytic virotherapy and encapsulation of chemotherapeutic drugs into nanoscale vehicles emerge as promissing strategies. However, several fundamental process and issues still must be understood in order to enhance the efficacy of these treatments. The nonlinearities and complexities inherent to tumor-oncolytic virus and tumor-drug interactions claim for a mathematical approach. Quantitative models allow to enlarge our understanding of the parameters influencing therapeutic outcomes, guide essays by indicating relevant physiological processes for further investigation, and prevent excessive experimentation. The multiescale models for virotherapy presented and discussed in this thesis suggest the appropriate traits an oncolytic virus must have and the less agressive ways to modulate the antiviral immune response in order to maximize the tumor erradication probability. Concerning the model for treatment with chemotherapeutic drugs encapsulated into nanoparticles, we focused on chimeric polymers attached with the doxorubicin drug, that recently are under active investigation. Using the same parameters that characterize these particles and the experimental protocols commonly used for their administration, our results indicate some of the basic features of these nanoparticles that should be developed in order to maximize the therapy's success.
Descrição
Palavras-chave
Fenômenos de crescimento, Modelos de multiescala, Câncer, Growth phenomena, Multiscale models, Cancer
Citação
PAIVA, Leticia Ribeiro de. Avascular tumor modelling: from celular automata to multiscale models. 2007. 3 f. Dissertação (Mestrado em Física Teórica e Computacional; Preparação e Caracterização de Materiais; Sensores e Dispositivos.) - Universidade Federal de Viçosa, Viçosa, 2007.