Nano-Structure Surfaces and Liquid Crystal Analysis

纳米结构表面和液晶分析

• 批准号: 6720021
• 负责人: JOAN H SCHILLER
• 金额: $ 12.95万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6720021
• 关键词: antineoplastics; biological signal transduction; biopsy; biosensor device; clinical research; enzyme activity; epidermal growth factor; growth factor receptors; human subject; kinase inhibitor; liquid crystal; lung neoplasms; pharmacokinetics; posttranslational modifications; protein tyrosine kinase; receptor binding; receptor expression; surface property; technology /technique development

DESCRIPTION (provided by applicant): Cancer is one of the areas of human health where technological breakthroughs have resulted in major advances in understanding the molecular basis of disease. Knowledge concerning the role of key signaling proteins in cancer has prompted attempts to develop anti-cancer agents directed against signaling targets such as the epidermal growth factor receptor (EGFR). However, little information is available regarding the precise mechanisms of action of these anti-cancer agents in human tumors, primarily due to the difficulty in performing relevant molecular assays on limited tissue material. This lack of understanding regarding how these agents affect EGFR-mediated events in human tumors has made clinical investigation into this area extremely difficult. This multi-disciplinary team of researchers from the Medical School and the College of Engineering are presently working together to establish an integrated approach, which revolves around the development and utilization of a fundamentally new class of exquisitely sensitive tools that exploit recent advances in nano-scale materials science for molecular analysis. The information derived from minimal amounts of clinical specimens using this new method of analysis will enable physicians to determine which regulatory protein pathways are most likely to respond to EGFR tyrosine kinase inhibitors. The creation and use of these new tools involves (1) the fabrication of nano-structured surfaces, (2) employing the orientational behavior of liquid crystals (LCs) as a powerfully precise means of road-out of specific binding events to receptors decorated on the nanostructured surfaces, and (3) validating these techniques in tumor samples from lung cancer patients receiving EGFR inhibitors. To accomplish these goals, the following specific aims are proposed: 1) Develop a new methodology using LCs and nano-structured surfaces for evaluation of the expression and extent of activation of EGFR on limited clinical specimens; and 2) Validate the molecular analysis tools developed in Aim 1 by identifying in-vivo alterations in the EGFR pathway, following administration of tyrosine kinase-dirocted anticancer drugs in tumor samples from cancer patients receiving EGFR inhibitors.

描述（由申请人提供）：癌症是人类健康领域之一，其中技术突破导致了对疾病分子基础的理解的重大进展。关于关键信号传导蛋白在癌症中的作用的知识促使人们尝试开发针对信号传导靶点如表皮生长因子受体（EGFR）的抗癌剂。然而，关于这些抗癌剂在人类肿瘤中的确切作用机制的信息很少，主要是由于难以对有限的组织材料进行相关的分子测定。缺乏对这些药物如何影响EGFR介导的人类肿瘤事件的了解，使得对该领域的临床研究变得非常困难。来自医学院和工程学院的多学科研究人员团队目前正在共同努力建立一种综合方法，该方法围绕开发和利用一类全新的精密灵敏工具，这些工具利用纳米材料科学的最新进展进行分子分析。使用这种新的分析方法从最少量的临床样本中获得的信息将使医生能够确定哪些调节蛋白途径最有可能对EGFR酪氨酸激酶抑制剂产生反应。这些新工具的创建和使用涉及（1）纳米结构表面的制造，（2）采用液晶（LC）的取向行为作为一种强有力的精确手段，将特异性结合事件排除在修饰在纳米结构表面上的受体之外，以及（3）在接受EGFR抑制剂的肺癌患者的肿瘤样本中验证这些技术。为了实现这些目标，提出了以下具体目标：1）开发使用LC和纳米结构表面的新方法，用于评估有限临床标本上EGFR的表达和活化程度;和2）通过鉴定EGFR途径中的体内改变来验证目标1中开发的分子分析工具，在来自接受EGFR抑制剂的癌症患者的肿瘤样品中给予酪氨酸激酶导向的抗癌药物后。