The goal of this project is to develop an integrative/mathematical framework in which the role of nitric oxide (NO) in the tumor pathophysiology can be investigated. Nitric oxide is involved in numerous vascular and hemodynamic processes in solid tumors that depend upon its local concentration. In turn, its production and elimination from the tumor depend on numerous other parameters such as concentrations of nutrients, blood gases, and vascular growth factors, pH, cell type, number and morphology, and so on. Effectively, NO is a highly connected node in a complex network of interactions. Since many of the causes and effects in this network are heterogeneously distributed throughout a tumor, it is natural to consider this a coupled system of reaction-diffusion processes. This project proposes to explore the NO network by generating a relatively simple numerical model of the temporally and spatially varying parameters in the system. Existing data in which simultaneous measurements of several of the relevant variables were taken will be used to develop a robust model of the system. The model is formulated in such a way that it can be readily expanded to incorporate new data as they become available and other substances as they become of interest. A user-friendly form of the model will be made available online to the physiology community for further study. This study promises to yield new insights and quantitative tools to aid in understanding how NO modulates and is modulated by its environment. Such knowledge should be useful for altering tumor angiogenesis, growth and metastasis.
| Baish, James W; Stylianopoulos, Triantafyllos; Lanning, Ryan M et al. (2011) Scaling rules for diffusive drug delivery in tumor and normal tissues. Proc Natl Acad Sci U S A 108:1799-803 |
