PILOT STUDY OF LIQUID CRYSTAL NANO-STRUCTURED SURFACES (LC/NS) ANALYSES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 (摘自CRISP网站) 癌症是人类健康领域之一，技术突破导致在理解疾病的分子基础方面取得了重大进展。对关键信号蛋白在癌症中作用的了解促使人们尝试开发针对信号靶点的抗癌药物，如表皮生长因子受体(EGFR)。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，主要是因为在有限的组织材料上进行相关的分子分析是困难的。由于缺乏对这些药物如何影响EGFR介导的人类肿瘤事件的了解，使得这一领域的临床研究变得极其困难。来自医学院和工程学院的多学科研究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种全新的精密敏感工具类别，该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标本中获得的信息将使医生能够确定哪些调节蛋白通路最有可能对EGFR酪氨酸激酶抑制剂产生反应。这些新工具的创造和使用涉及(1)纳米结构表面的制造，(2)将液晶(LCS)的定向行为用作将特定结合事件与装饰在纳米结构表面上的受体联系起来的一种非常精确的手段，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)开发一种新的方法，使用液晶和纳米结构表面来评估有限的临床标本上EGFR的表达和激活程度；以及2)通过在接受EGFR抑制剂的癌症患者的肿瘤样本中给予酪氨酸激酶导向的抗癌药物后，通过识别EGFR途径中的体内变化来验证Aim 1中开发的分子分析工具。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. (from CRISP website) 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 were 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.