The Physi(ologi)cal Microenvironment and its Role in Tumor Invasion and Metastase

这个项目将支持一个多学科的团队，结合数学建模和体内实验 （1）研究肿瘤血管分布、血流、代谢和肿瘤细胞增殖之间的相互作用， 控制微环境中物理参数的表型，以及（2）了解 物理参数（特别是p02和细胞外pH）在肿瘤生长和转移中的作用。实验 工作将在PI实验室以及SAIL小动物成像实验室进行，作为 核心A（成像）。建模工作将在综合数学肿瘤学（IMO）中进行。 程序以及核心B（数学）。在以前的工作中， 肿瘤微环境和细胞表型和行为已经建立在体外肿瘤微环境和细胞表型和行为的基础上，并与体外肿瘤微环境和细胞表型和行为相结合。 和体内实验。然而，目前的模型受到缺乏肿瘤血管动力学的限制 其包括血管生成、血管成熟和衰变以及混乱的血流。为了实现这一目标，我们 实验方法将由生物学上真实的生物学模型指导。符合本 研究策略，所有的数学模型将与实验确定的值参数化， 并且模型预测将使用MRI或背侧皮褶室进行体内测试。的准确性和 从图像中提取信号的限制及其与数学模型的关系也将被 在伽马射线成像中心（CGRI）与Barrett和Kupinski博士合作进行了检查。 其中一些实验将采用一种新的成像技术，将荧光显微镜与 通过一种新的/S *'高分辨率成像

This project will support a mulfidisciplinary team that combines mathematical modeling and in-vivo experiments with the following goals to: (1) investigate the interactions between tumor vascularity, blood flow, metabolic phenotype that govern physical parameters in the microenvironment, and (2) gain understanding on the role of physical parameters (particulariy the p02 and extracellular pH) in tumor growth and metastases. Experimental work will be performed in the PIs laboratory as well as the Small Animal Imaging Laboratory, SAIL, as part of Core A (Imaging). The modeling work will be performed within the Integrative Mathematical Oncology (IMO) program as well as within Core B (Math). In previous work, mathemafical models of the interactions of the tumor microenvironment and cellular phenotype and behavior have been built upon and integrated with in-vitro and in-vivo experiments. However, the current models are limited by the absence of tumor vascular dynamics that incorporate angiogenesis, vessel maturation and decay, and chaofic blood flow. To achieve this, our experimental approach will be guided by biologically realistic mathemafical models. Consistent with this research strategy, all of the mathematical models will be parameterized with experimentally determined values, and model predictions will be tested in-vivo using MRI ora dorsal skin-fold chamber. The accuracy and limitations of signal extraction from images and their relationship to the mathematical models will also be examined in collaboration with Drs. Barrett and Kupinski at the Centerfor Gamma Ray Imaging (CGRI). Some of these experiments will employ a new imaging technology that combines fluorescent microscopy with high (40 micron) resolution imaging through a novel /S*'