From Bench to Bedside： Targeting Epigenetics for Cancer Therapy

The initiation and progression of cancer not only involves genetic abnormalities, but also epigenetic alterations, such as DNA methylation and histone modifications. Epigenetics refers to the heritable changes that do not involve any structural changes in the target gene, i.e., DNA sequence and protein sequence. Thus, these epigenetic aberrations are potentially reversible, allowing the malignant cells to revert to a state with more normal characteristics. The use of epigenetics is emerging as an effective and promising approach to treat cancer. Epigenetic drugs, which target two well- known epigenetic pathways, namely, DNA methyltransferases and histone deacetylases, are already being applied for the cancer treatment. In the current study, an overview regarding the under-standing of epigenetic alterations in the development of cancer and the current state of epigenetic drug discovery is provided.

定量监控大肠杆菌主代谢目标蛋白质及中间代谢物

【目的】监控大肠杆菌(Escherichia coli)主代谢通路上蛋白表达状况及中间代谢物变化,为代谢工程改造提供基础性数据及检测方法。【方法】利用Skyline软件靶向设计主代谢(糖酵解途径、磷酸戊糖途径、三羧酸循环、混合酸发酵途径及脂肪酸合成途径)目标蛋白质label-free(MRM)方法对其相对定量监控;在相同质谱平台(Triple Quad 4500)上利用LC-MS/MS(MRM)方法对目标中间代谢物绝对定量监控。【结果】实验表明不同生长时期内(对数生长期、稳定期及衰亡期)大肠杆菌主代谢蛋白质表达表现出4种不同的变化现象,某一代谢通路上的单一蛋白不能反映该通路的表达状态;磷酸戊糖途径、混合酸发酵途径以及三羧酸循环途径中较多的蛋白质在衰亡期表达量最高,但几种目标中间代谢产物(ATP、ADP、AMP、NAD+、NADH、NADP+、NADPH、Co A、acetyl-Co A)的积累量与对数生长期相比,稳定期及衰亡期都相应减少(除了acetylCo A以外)。【结论】该文中使用的检测方法可以有效地反映大肠杆菌体内代谢的基本状况。