Cellular physical properties in relation to cancer

与癌症相关的细胞物理特性

• 批准号: 6614717
• 负责人: WILLIAM CRAELIUS
• 金额: $ 2.38万
• 依托单位: NIAN-CRAE, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-20 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6614717
• 关键词: angiogenesis inhibitors; biological signal transduction; cardiovascular pharmacology; cell adhesion; cell line; extracellular matrix; flow cytometry; vascular endothelium

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.

当用抗血管/血管生成（AVA）药物或基因修饰的细胞载体治疗时，动物肿瘤会缩小，这些药物会切断它们的血液供应。然而，这些有前途的策略的临床实施受到阻碍，因为影响AVA的细胞因子不容易测量。为了帮助预测和监测候选疗法的AVA潜力，该项目将开发一种用于表达可能参与AVA行为的细胞物理特性的测定方法。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性质被怀疑影响其血管生成潜力，包括：（1）与基质的粘附;（2）细胞变形性;和（3）机械转导过程。这些特性中的每一个都由可能是AVA治疗的有用靶点的特定分子介导，并且可以使用PI和合作者使用和/或开发的工具进行评估。拟议的项目将开发流式细胞力学分析（FCMA;美国专利申请中），一种新的“前端”标准流式细胞术，将测量与血管生成和致瘤潜力有关的关键物理特性。在第一阶段，我们将使用各种细胞系，结合遗传操作和研究人员和商业供应商提供的AVA药物来测试该系统。该项目的终点将是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便捷接口，这将有助于研究人员筛选潜在的抗血管生成药物或遗传载体，以及临床医生对样本进行活检。FCMA还将具有与包括心血管在内的几种其他疾病相关的细胞细胞力学的一般适用性。因此，该设备的潜在市场很大。该项目将扩大和加强目前尚待实施的专利保护。