Target spectrum of the BCR-ABL inhibitors imatinib, nilotinib and dasatinib

Following the initial success of imatinib as frontline therapy for chronic myeloid leukemia (CML), several second-generation therapeutics have been developed with increased potency and the ability to inhibit the majority of imatinib-resistant mutations. Here, we review the current knowledge about the target specificity of the two new inhibitors nilotinib and dasatinib in comparison to imatinib, including the recent large-scale chemical proteomics screens.     

应用SELDI-TOF-MS技术筛选肺腺癌患者血清诊断标志物

目的 探讨肺腺癌患者及正常人血清中蛋白质质谱的不同,筛选出肺腺癌血清诊断标志物.方法 用WCX2蛋白芯片结合表面增强激光解吸电离飞行时间质谱(SELDI-TOF-MS)技术,检测24例肺腺癌和10例正常人血清蛋白质谱,筛选出差异表达蛋白质.结果 本实验共检测到86个有效的蛋白质波峰,其中m/z位于分子质量2000～10 000的波峰有78个.筛选出m/z分子质量为8129.55,2022.18,3271.91,3933.44,3504.49,3811.71的6个血清肿瘤标志物.结论 SELDI-TOF-MS技术是寻找肺腺癌血清诊断标志物的有效工具.利用蛋白组学和生物信息学及相关技术,将有利于建立新的疾病诊断模式--蛋白质指纹图谱.     

The proteomics of ageing

Proteomics provides an extremely powerful tool for the study of variations in protein expression between individuals, different disease states and different conditions. One of the major challenges facing the medical profession in the forthcoming decades is to understand the changes that occur in individuals as they become older and to attempt to develop means to improve the quality of life for the otherwise healthy ageing population. The present study describes the first phase of such an investigation in which the andaged protein composition of human skeletal muscle sample from young and aged subjects are compared. These results provide the beginning of a Human Aged Skeletal Muscle Profile reference map which is an essential first step to further investigations. This revised version was published online in July 2006 with corrections to the Cover Date.     

Proteomics approaches to uncover the repertoire of circulating biomarkers for breast cancer

There is substantial interest in applying proteomics to cancer biomarker discovery. Proteomics is particularly suited for profiling biological fluids and uncovering circulating markers and is currently being applied to the identification of novel biomarkers for breast cancer. Novel proteomic approaches include direct profiling of serum using mass spectrometry, application of a variety of strategies to harness immunity for cancer diagnosis, protein tagging to capture subproteomes rich in diagnostic markers, the use of protein microarrays, and the use of multidimensional liquid protein separation technologies for comprehensive profiling of serum and other biological fluids. It is likely that the application of a wide range of proteomics tools to breast cancer will yield a panel of markers that have utility for breast cancer diagnosis.     

视网膜蛋白质组的研究进展

蛋白质组学是对由一个基因组,或一个细胞、组织表达的所有蛋白质视为一个整体进行研究,是后基因时代的生命科学研究的重心。蛋白质组学技术为研究视网膜生理活动规律和疾病病变机制提供了一个新的研究平台。我们就蛋白质组学在视网膜领域的应用作一综述。     

Contributions of advanced proteomics technologies to cancer diagnosis

The ability of Medicine to effectively treat and cure cancer is directly dependent on their capability to detect cancers at their earliest stages. The advent of proteomics has brought with it the hope of discovering novel biomarkers in the early phases of tumorigenesis that can be used to diagnose diseases, predict susceptibility, and monitor progression. This discipline incorporates technologies that can be applied to complex biosystems such as serum and tissue in order to characterize the content of, and changes in, the proteome induced by physiological changes, benign or pathologic. These tools include 2-DE, 2D-DIGE, ICAT, protein arrays, MudPIT and mass spectrometries including SELDI-TOF. The application of these tools has assisted to uncover molecular mechanisms associated with cancer at the global level and may lead to new diagnostic tests and improvements in therapeutics. In this review these approaches are evaluated in the context of their contribution to cancer biomarker discovery. Particular attention is paid to the promising contribution of the ProteinChip/SELDI-TOF platform as a revolutionary approach in proteomic patterns analysis that can be applied at the bedside for discovering protein profiles that distinguish disease and disease-free states with high sensitivity and specificity. Understanding the basic concepts and tools used will illustrate how best to apply these technologies for patient benefit for the early cancer detection and improved patient care. Supported by an unrestricted educational grant from AstraZeneca.     

复方丹参片对冠心病患者血浆蛋白影响的蛋白质组学研究

目的:用蛋白质组学技术考察复方丹参片对冠心病患者血浆蛋白的影响,在分子水平上探讨复方丹参片活血化瘀的作用机制。方法:收集正常、冠心病患者和复方丹参片用药病人组的血浆,用二向电泳、图像分析、质谱鉴定等蛋白质组学技术测定复方丹参片对冠心病患者血浆中有影响的蛋白质。结果:蛋白质组学研究发现,冠心病病人血浆与正常相比有3个蛋白质下调和6个蛋白质上调,复方丹参片可使这些改变的蛋白质水平有所恢复。胶内酶切提取蛋白进行质谱鉴定,其中冠心病病人血浆与正常相比升高的蛋白质有免疫球蛋白、纤维蛋白原、粒酶,冠心病病人血浆与正常相比降低的蛋白质有细胞表面糖蛋白(CD44SP)。冠心病病人服用复方丹参片后可降低免疫球蛋白、纤维蛋白原、粒酶。结论:复方丹参片可以降低冠心病患者血浆中的纤维蛋白原和粒酶,其可能通过抑制单核细胞黏附、平滑肌细胞增殖和迁移、减轻炎症而治疗冠状动脉粥样硬化。     

蛋白质组学研究技术及其在烷化剂引起的细胞应答反应研究中的应用

蛋白质组学是后基因组时代的一个新兴领域,其理论和技术的发展为化学致癌物致突变的分子机制的研究提供了新的思维方式.本文回顾了蛋白质组学的研究技术,包括双向凝胶电泳、质谱和生物信息学近年的主要进展,并介绍了本实验室利用蛋白质组学的技术,研究低浓度烷化剂引起的细胞应答反应所取得的初步结果.