Uma abordagem de metodos computacionais para simulação de processos biologicos : simulação tridimensional e metabolica do desenvolvimento tumoral / A computational approach for simulation of biological process : tridimensional simulation of tumor metabolism and development

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

RESUMO

In this work, we created a piece of software and computer models for studying carcinogenesis, in order to answer biological questions related to the treatment of this disease. The computer models were inspired in the theory of Somatic Evolution and Acid Mediated Tumor Invasion, proposed by Gatenby and Gillies, and were implemented in a tool developed by the author under the scope of this thesis, Tissue Simulator (TSim, www.i-genics.com). The theory of Acid Mediated Tumor Invasion proposes that cancer cells are more resistant to toxicity of an acidic environment that they help create by producing excess of lactic acid through anaerobic glycolysis. Acidification of the extra-cellular environment causes death of healthy tissue through acid-induced apoptosis and ultimately facilitates tumor invasion. Experimental studies, from literature, showed that administration of sodium bicarbonate in water to mice bearing tumors reduced the number of metastases, thus supporting the importance of acidity in tumor invasion. In this study a computer model was built to test if an increase in concentration of bicarbonate in blood serum could alter the pH gradient between the tumor (micrometastases) and halthy tissue, as well as to identify the chemical properties of and ideal buffer with this purpose. The theory of Somatic Evolution, proposes that epithelial tumor cells are submitted to environmental barriers and are selected for three main phenotypes: hyperplasia, hyperglycolysis and acid resistance. A second computer model was created in order to identify the minimum values of these phenotypes that allowed a DCIS to change into an invasive tumor. Once the minimum phenotypic values identified, one can study how mutations on specific enzymes can alter the flux of a metabolic pathway, such as glycolysis, to produce the altered phenotype. As an example of this, we performed a comparative study of robustness of glycolytic flux in two different cells: yeast (S. cerevisiae) and pancreatic human beta-cell, whose enzymatic regulatory strategies differ. This computer model was implemented on Matlab and Jarnac. Overall, our results show that the use of computational tools and quantitative data may be used to create theoretical-quantitative models that help adressing theories about biological systems, as well as to extrapolate and tes new hypothesis, integrating the approach of computational modeling in the scientific research process.

ASSUNTO(S)

tumores - crescimento carcinoma intraductal não infiltrante biologia - simulação por computador metabolism noninfiltrating intraductal carcinoma metabolismo biology tumor growth cancer cancer

ACESSO AO ARTIGO

Documentos Relacionados