PROTEOMICS ALLIANCE FOR CANCER

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。癌症蛋白质组学联盟(PAC)由密歇根生命科学走廊(MLSC)/密歇根经济发展公司支持，隶属于密歇根大学NCRR中心。癌症蛋白质组学联盟汇集了密歇根大学、Van Andel研究所、当地公司、MLSC核心技术联盟和UM NCRR中心在癌症蛋白质组学领域的关键实验室。PAC已经证明，结合我们的三维分离和质谱分析方案，配对临床标本的Cy3/Cy5双标记(治疗前和治疗后，或并发症发生前后)的临床研究是有用的。骨髓移植是一种治疗某些癌症的方法，在移植物抗宿主病方面有了新的发现。PAC是新的Beckman-Coulter PF 2D蛋白质组学设备的测试点，也是新的Agilent免疫亲和柱的几个测试点之一，用于去除血浆/血清中最丰富的六种蛋白质。我们为这些新产品的改进做出了重大贡献，并受益于设备的早期使用。两家公司都已将这些产品投入商业使用。我们的结论是，去除血浆中白蛋白和其他几种高度丰富的蛋白质可以显著提高检测较少丰富蛋白质的分辨率和灵敏度，包括那些可能来自疾病过程起源部位的器官和组织的蛋白质。我们正在追求提高基于液体的分离系统的吞吐量这一具有挑战性的目标。与此同时，我们正在利用现有的LC系统从VAI和UM的肿瘤细胞裂解液中创建2000个组分，用于蛋白质微阵列，这些蛋白质微阵列有望用于诊断应用。Van Andel的Haab实验室和UM的Hanash实验室在前列腺癌和肺癌细胞蛋白质微阵列方面合作取得了实质性进展，用于检测前列腺癌或肺癌患者血清中针对这些蛋白质的循环自身抗体。这些研究有很大的潜力来识别和验证有用的生物标记物，用于这些和其他癌症的早期诊断。

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. The Proteomics Alliance for Cancer (PAC) is supported by the Michigan Life Sciences Corridor (MLSC)/Michigan Economic Development Corporation, and affiliated with the UM NCRR Center The Proteomics Alliance for Cancer has brought together key laboratories in the cancer proteomics domain at the University of Michigan, Van Andel Research Institute, local firms, MLSC Core Technology Alliance, and the UM NCRR Center. The PAC has demonstrated the usefulness for clinical studies of the Cy3/Cy5 double-labeling of paired clinical specimens (before and after treatment, or before and after development of complications), combined with our 3-dimensional fractionation and mass spec analysis scheme. Novel findings were obtained for graft-versus-host disease after bone marrow transplantation, a treatment for certain kinds of cancers. PAC served as the beta-site for the new Beckman-Coulter PF 2D proteomics equipment and as one of several beta-sites for the new Agilent immuno-affinity column for depletion of the six most abundant proteins in plasma/serum. We made major contributions to the improvements of these new products and have had the benefit of early use of the equipment. Both companies have introduced these products commercially. We concluded that depletion of albumin and several other highly abundant proteins in plasma can markedly improve the resolution and sensitivity of detection of less abundant proteins, including those which may be derived from organs and tissues that are sites of origin of disease processes. We are pursuing the challenging aim of enhancing throughput in liquid-based separation systems. At the same time, we are utilizing the existing LC systems to create 2000 fractions from tumor cell lysates for protein microarrays both at VAI and UM that have promise for diagnostic applications. Substantial progress has been made collaboratively in the Haab lab at Van Andel and the Hanash lab at UM on prostate and lung cancer cell protein microarrays for detection of circulating auto-antibodies against these proteins in the sera of patients with prostate cancer or lung cancer, respectively. These studies have major potential to identify and validate useful biomarkers for earlier diagnosis of these and other cancers.