The Physical Microenvironment in Cancer Biology and Therapy

我们的总体目标是开发一个综合的、多学科的研究计划，应用数学 方法对肿瘤生物学和临床肿瘤学中的问题进行研究。巨大的挑战--两者都 智力和教育-是将生物数据和数学模型集成到概念性的 该框架可以包含肿瘤生物学中可观察到的细胞和细胞外动力学。要实现 这一目标将在规划赠款的有效期内实现以下具体目标： 项目1：摆脱稳态：综合的数学和实验研究 癌变将侧重于肿瘤细胞的启动、促进和进展，尤其是 进化中的肿瘤种群与微环境因素的相互作用。这其中的大部分 相应的实验工作将在体外进行。 项目2：生理微环境及其在肿瘤侵袭和转移中的作用将集中在 癌细胞表型演变与肿瘤微环境的相互作用包括 成纤维细胞、血管和物理参数，如氧气、葡萄糖和H“浓度。 相应的实验研究将主要在体内进行，特别是使用窗口室。 项目3：临床肿瘤成像的环境驱动的数学建模将侧重于挑战 在成像分辨率受限的环境中模拟肿瘤生长和对治疗的反应 到几毫米和时间的变化，只有通过偶尔成像会议才能获得。 在每个项目中，研究将由一组数学家和实验者进行，并将 关注系统动力学，特别是肿瘤表型进化和肿瘤细胞的相互作用。 不断变化的微环境。

Our overall goal is to develop an integrative, multidisciplinary research program that applies mathematical methods to the investigation of problem in tumor biology and clinical oncology. The great challenge - both intellectually and educationally - is to integrate biological data and mathematical models into a conceptual framework that can encompass observable cellular and extracellular dynamics in tumor biology. To achieve this goal the following specific aims will be pursued during the life-time of the planning grant: Proiect 1: Escape from Homeostasis: Integrated mathematical and experimental investigation of carcinogenesis will focus on tumor cell initiation promotion and progression with particular focus on the interactions of the evolving tumor populations with elements of the microenvironment. Most of this corresponding experimental work will be in-vitro. Proiect 2 : The PhysKologpcal Microenvironment and its role in Tumor Invasion and Metastases will focus on the mutual interactions of cancer cell phenotypic evolution with the tumor microenvironment including fibroblasts, blood vessels, and physical parameters such as oxygen, glucose and H" concentrations. The corresponding empirical research will be largely carried out in-vivo particularly using window chambers. Proiect 3: Environment-driven Mathematical modeling for Clinical Cancer imaging will focus on the challenge modeling tumor growth and response to therapy in an environment in which imaging resolution is restricted to a few mm and temporal variations obtainable only through occasional imaging sessions. n each project the research will be carried out by a team of mathematicians and experimentalists and will focus on system dynamics, particularly on the mutually interactions of tumor phenotypic evolution and the changing microenvironment.