A pharmacologically based multiscale mathematical model of angiogenesis and its use in investigating the efficacy of a new cancer treatment strategy.
RIBBA, Benjamin
Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 [LBBE]
Numerical Medicine [NUMED]
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Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 [LBBE]
Numerical Medicine [NUMED]
RIBBA, Benjamin
Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 [LBBE]
Numerical Medicine [NUMED]
< Leer menos
Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 [LBBE]
Numerical Medicine [NUMED]
Idioma
en
Article de revue
Este ítem está publicado en
Journal of Theoretical Biology. 2009-10-21, vol. 260, n° 4, p. 545-62
Elsevier
Resumen en inglés
Tumor angiogenesis is the process by which new blood vessels are formed and enhance the oxygenation and growth of tumors. As angiogenesis is recognized as being a critical event in cancer development, considerable efforts ...Leer más >
Tumor angiogenesis is the process by which new blood vessels are formed and enhance the oxygenation and growth of tumors. As angiogenesis is recognized as being a critical event in cancer development, considerable efforts have been made to identify inhibitors of this process. Cytostatic treatments that target the molecular events of the angiogenesis process have been developed, and have met with some success. However, it is usually difficult to preclinically assess the effectiveness of targeted therapies, and apparently promising compounds sometimes fail in clinical trials. We have developed a multiscale mathematical model of angiogenesis and tumor growth. At the molecular level, the model focuses on molecular competition between pro- and anti-angiogenic substances modeled on the basis of pharmacological laws. At the tissue scale, the model uses partial differential equations to describe the spatio-temporal changes in cancer cells during three stages of the cell cycle, as well as those of the endothelial cells that constitute the blood vessel walls. This model is used to qualitatively assess how efficient endostatin gene therapy is. Endostatin is an anti-angiogenic endogenous substance. The gene therapy entails overexpressing endostatin in the tumor and in the surrounding tissue. Simulations show that there is a critical treatment dose below which increasing the duration of treatment leads to a loss of efficacy. This theoretical model may be useful to evaluate the efficacy of therapies targeting angiogenesis, and could therefore contribute to designing prospective clinical trials.< Leer menos
Palabras clave en inglés
Multiscale mathematical modeling
Cell cycle
Tumor growth
Angiogenesis
Pharmacological law
Optimization of cancer treatments
Orígen
Importado de HalCentros de investigación