Cellular physical properties in relation to cancer

动物肿瘤在使用抗血管/血管生成（AVA）药物或使用切断其血液供应的转基因细胞载体治疗时会缩小。然而，由于影响AVA的细胞因素不易测量，这些有希望的策略的临床实施受到阻碍。为了帮助预测和监测候选疗法的AVA潜力，该项目将开发一种检测可能参与AVA行为的细胞物理特性表达的方法。我们将首先关注血管相关细胞，如内皮细胞和其他类型。内皮细胞表达的几种物理特性被怀疑会影响它们的血管生成潜能，包括：(1)与基质的粘附；(2)细胞变形能力；(3)机械传导过程。这些特性都是由特定分子介导的，这些分子可能是AVA治疗的有用靶点，可以用PI和合作者已经使用和/或开发的工具进行评估。拟议的项目将开发流式细胞术检测（FCMA，美国专利正在申请中），这是标准流式细胞术的一种新型“前端”，将测量与血管生成和致瘤潜能相关的关键物理特性。在第一阶段，我们将使用各种细胞系，结合基因操作和由研究人员和商业供应商提供的AVA药物来测试该系统。项目终点将是FCMA概念的证明。拟议的商业应用：最终产品FCMA将成为标准细胞仪的方便接口，可用于研究人员筛选潜在的抗血管生成药物或遗传载体，并可用于临床医生活检标本。FCMA也将普遍适用于与其他几种疾病相关的细胞细胞力学，包括心血管疾病。因此，该设备的潜在市场是巨大的。该项目将扩大和加强目前悬而未决的专利保护。

Animal tumors shrink when treated with anti-vascular/angiogenic (AVA) drugs, or with genetically modified cellular vectors, that cut-off their blood supplies. Clinical implementation of these promising strategies is impeded however, since the cellular factors that influence AVA are not easily measured. To help predict and monitor the AVA potential of candidate therapies, this project will develop an assay for the expression of cellular physical properties that may be involved in AVA behavior. We will focus initially on vascular-related cells, such as endothelial and other types. Several physical properties expressed by endothelial cells are suspected to influence their angiogenic potential, including: (1) adhesion to matrix; (2) cellular deformability; and (3) mechanotransduction processes. Each of these properties is mediated by specific molecules that may be useful targets of AVA therapy and can be assessed with tools that have been used and/or developed by the PI and collaborators. The proposed project will develop flow cytomechanical assay (FCMA; U.S. patent pending), a novel "front end" to standard flow cytometry, that will measure key physical properties relating to angiogenic and tumorigenic potential. During Phase I we will test the system using various cell lines, in combination with genetic manipulations and AVA drugs provided by researchers and commercial suppliers. Endpoint of the project will be proof of the FCMA concept. PROPOSED COMMERCIAL APPLICATIONS: The end product, FCMA, will be a convenient interface to standard cytometers that will be useful for researchers screening potential anti- angiogenic drugs or genetic vectors, and for clinicians to biopsy specimens. FCMA will also have general applicability to cell cytomechanics relating to several other diseases, including cardiovascular. Thus the potential market for the device is large. Patent protection currently pending will be broadened and strengthened by this project.