药物基因组学（徐建凯）3药物蛋白质组学.pptVIP

药物蛋白质组学 Pharmacoproteomics;一、概念和研究内容;运用比较蛋白质组学的策略发现与药物作用相关的蛋白质;二、药物作用靶点研究;药物作用靶点研究策略和方法;通过差异表达谱分析发现药物靶标;2、蛋白质活性表达谱（activity-based protein profiling, ABPP）分析;PNAS August 6, 2002 vol. 99 no. 16 10335–10340;3、亲和色谱法(affinity chromatography) 直接分离活性小分子的结合蛋白;成功的例子;4、酵母三杂交系统鉴定药物靶点 ;成功的例子;三、药物蛋白质学在临床诊断和治疗中的应用;1、发现疾病特异性生物标记物进行诊断及预测疾病的预后及转归;生物标记物（biomarker);;Example;(A) Specific populations of cells were recovered using laser under microscopic observation.;(B) The extracted proteins were labeled with fluorescent dyes and separated by two-dimensional polyacrylamide gel electrophoresis (2D). (C) Evaluation of the reproducibility of 2D-DIGE by scatter graphs.;Results of hierarchical clustering were associated with histological grouping: the seven normal liver tissues, 11 adjacent nontumor tissues, six well-differentiated HCCs, and one moderately-differentiated HCC were grouped together, while the 13 moderately-differentiated HCCs and seven poorly-differentiated HCCs were clustered together forming a separate group (A). Principal component analysis also showed similar results (B);;Among the identified proteins, EB1 is controlled by c-Myc, RhoA and CDC42, which have all been linked toHCC malignancy in previous reports;;;;2、评价药物疗效;Example;3、研究药物毒理机制进行药物毒性生物标志物的监控;四、抗肿瘤药多药耐药机制的蛋白质组学研究;Potential mechanisms of chemoresistance suggestedby various published pharmacoproteomic studies;Proteins identified by the proteomic approach in cancer cell lines resistant to different anti-cancer drugs;五、基于蛋白质组表达谱的抗肿瘤药物化疗敏感性预测;传统药敏检测方法及其存在的问题;The selective pressure exerted by drugs combined with cell heterogeneity (often a result of tumor genomic instability) is the driving force for drug resistance. In addition, tumors can regulate their own microenvironment by remodeling the extracellular matrix, deregulating cell–cell contact and cell–cell interactions with neighboring mesothelial and endothelial cells, and other changes such as increased hypoxia. Factors unrelated to the tumor but contribut