非小细胞肺癌抗血管生成治疗中微环境正常化及其对化疗药物输运影响的生物力学研究

项目名称： 非小细胞肺癌抗血管生成治疗中微环境正常化及其对化疗药物输运影响的生物力学研究

项目编号： No.11302050

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 数理科学和化学

项目作者： 蔡彦

作者单位： 东南大学

项目金额： 26万元

中文摘要： 抗血管生成联合化疗是目前治疗非鳞癌的非小细胞肺癌（NSCLC）的新型热点方案之一，其基本原理是以抗血管生成药物使得癌组织微环境各因素"正常化"，从而促进化疗药物输运以提高疗效。然而，对联合治疗中微环境因素间的耦合作用以及正常化对药物输运乃至癌组织生长的影响作用，仍未能建立完善的动态耦合体系加以定量研究。本项目将结合数学建模、数值模拟、动物实验检测及DCE-MRI临床影像学检测等手段，建立一套行之有效的研究方法，（1）研究非鳞癌NSCLC的癌组织及微血管网的病理发展，以及相应病理状态下微循环血液灌注信息；（2）研究抗血管生成治疗引起的微环境正常化后癌组织、微血管网及血液灌注的一系列响应变化，及其对化疗药物输运的动态影响；（3）探讨联合治疗中微血管网形态及功能变化影响癌组织的生物力学机理，为临床优化联合治疗疗程提供一定参考信息。

中文关键词： 数学建模；抗血管生成联合化疗；微环境；正常化；生物力学

英文摘要： Anti-angiogenic agents in combination with chemotherapy is one of the new strategies in patients with non-small cell lung cancer and non squamous cell carcinoma. The "normalization" of factors in microenvironment caused by the anti-angiogenic agents can promote the drug delivery to improve the efficacy of chemotherapy. However, a dynamic coupling system has not established yet for quantitative research about the coupling effects of microenvironmental factors in combination therapy and the influence of the normalization on the drug delivery and cancer growth. The project will establish a set of effective reaseach methods, including mathematical modeling, numerical simulation, animal experiment and clinical DCE-MRI imaging detection, to study (1) the pathological development of non squamous cell carcinoma NSCLC and the microvascular network, and the corresponding blood perfusion information; (2) a series changes of cancer tissue, microvascular network and blood perfusion in response to the normalization of microenvironment due to the anti-angiogenic agents, and the dynamic effects of eht changes on the drug delivery; (3) the biomechanical mechanism of the response of cancer to the functional influence of microvascular network, and the reference information for the optimization of combined treatment in clinical res

英文关键词： mathematical modeling；anti-angiogenic therapy in combination with chemot；microenvironment；normalization；biomechanics