Cdc42 is a member of the Rho subfamily of Ras-related proteins, which were among the first oncogenic proteins to be identified as playing a sig-nificant role in a variety of cellular events [Barbacaid, 1987, Ann. Rev....Cdc42 is a member of the Rho subfamily of Ras-related proteins, which were among the first oncogenic proteins to be identified as playing a sig-nificant role in a variety of cellular events [Barbacaid, 1987, Ann. Rev. Biochem]. Equally important, Protein-Protein Interactions [PPIs] involving Cdc42 continue to highlight the role of Ras-related proteins’ relevance to cancer. As these proteins have been considered incapable of being “druggable”, due to a perceived lack of binding surface[s] that are amenable to small molecule targeting, there remains limited development of therapies to tackle diseased states caused by Cdc42-stimulated hyperactivity. Thusly, it has become important to characterize molecular details, including dynamics, of PPIs involving Cdc42 that may lend themselves as potential targets for therapeutic approaches. Recently, two small molecules, ZCL278 and AZA197, have shown promise in directly targeting Cdc42 to influence PPIs that are capable of causing Cdc42-stimulated abnormal signaling. In this editorial, we highlight recent studies that show case how these two small molecules may influence Cdc42-protein interactions.展开更多
目的:探讨与分析高通量测序平台研究非小细胞肺癌热点基因突变情况。方法:选择2019年11月-2020年11月在本院肿瘤科诊治的非小细胞肺癌患者110例作为肺癌组,同期选择健康体检者110例作为对照组,提取血浆组织,采用高通量测序平台分析基因...目的:探讨与分析高通量测序平台研究非小细胞肺癌热点基因突变情况。方法:选择2019年11月-2020年11月在本院肿瘤科诊治的非小细胞肺癌患者110例作为肺癌组,同期选择健康体检者110例作为对照组,提取血浆组织,采用高通量测序平台分析基因表达差异情况,重点检测热点基因突变情况。结果:两组所有入选者DNA提取体积>40μl,浓度>1ng/μl,总量>55ng,<200nt比例<5%,都符合质控要求,两组对比差异无统计学意义(P>0.05)。两组筛选出显著差异表达的基因共1245个,其中肺癌组表达上调652个,表达下调593个。基因测序与实时荧光定量PCR显示肺癌组的鼠肉瘤病毒致癌基因(Kirsten rat sarcoma viral oncogene,KRAS)、磷脂酰肌醇-3-激酶催化亚基α基因(Phosphoinositide-3-kinase,catalytic,alpha gene,PIK3CA)、肿瘤蛋白P53(Tumor protein P53,TP53)表达水平都高于对照组(P<0.05)。基因测序显示肺癌组的KRAS、PIK3CA、TP53基因突变率分别为30.0%、22.7%、17.3%,高于对照组的3.6%、1.8%和0.9%(P<0.05)。结论:高通量测序平台能有效检出非小细胞肺癌热点基因突变情况,具有很好的应用可行性,值得推广应用。展开更多
文摘Cdc42 is a member of the Rho subfamily of Ras-related proteins, which were among the first oncogenic proteins to be identified as playing a sig-nificant role in a variety of cellular events [Barbacaid, 1987, Ann. Rev. Biochem]. Equally important, Protein-Protein Interactions [PPIs] involving Cdc42 continue to highlight the role of Ras-related proteins’ relevance to cancer. As these proteins have been considered incapable of being “druggable”, due to a perceived lack of binding surface[s] that are amenable to small molecule targeting, there remains limited development of therapies to tackle diseased states caused by Cdc42-stimulated hyperactivity. Thusly, it has become important to characterize molecular details, including dynamics, of PPIs involving Cdc42 that may lend themselves as potential targets for therapeutic approaches. Recently, two small molecules, ZCL278 and AZA197, have shown promise in directly targeting Cdc42 to influence PPIs that are capable of causing Cdc42-stimulated abnormal signaling. In this editorial, we highlight recent studies that show case how these two small molecules may influence Cdc42-protein interactions.
文摘目的:探讨与分析高通量测序平台研究非小细胞肺癌热点基因突变情况。方法:选择2019年11月-2020年11月在本院肿瘤科诊治的非小细胞肺癌患者110例作为肺癌组,同期选择健康体检者110例作为对照组,提取血浆组织,采用高通量测序平台分析基因表达差异情况,重点检测热点基因突变情况。结果:两组所有入选者DNA提取体积>40μl,浓度>1ng/μl,总量>55ng,<200nt比例<5%,都符合质控要求,两组对比差异无统计学意义(P>0.05)。两组筛选出显著差异表达的基因共1245个,其中肺癌组表达上调652个,表达下调593个。基因测序与实时荧光定量PCR显示肺癌组的鼠肉瘤病毒致癌基因(Kirsten rat sarcoma viral oncogene,KRAS)、磷脂酰肌醇-3-激酶催化亚基α基因(Phosphoinositide-3-kinase,catalytic,alpha gene,PIK3CA)、肿瘤蛋白P53(Tumor protein P53,TP53)表达水平都高于对照组(P<0.05)。基因测序显示肺癌组的KRAS、PIK3CA、TP53基因突变率分别为30.0%、22.7%、17.3%,高于对照组的3.6%、1.8%和0.9%(P<0.05)。结论:高通量测序平台能有效检出非小细胞肺癌热点基因突变情况,具有很好的应用可行性,值得推广应用。
