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lsysxh铁杆木虫 (著名写手)
糖葫芦
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[求助]
翻译急用，一共七句话！！30金币奉上，翻译的好可追加！
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Advanced microscopy solutions for monitoring the kinetics and dynamics of drug–DNA targeting in living cells Abstract Many anticancer drugs require interaction with DNA or chromatin components of tumor cells to achieve therapeutic activity. Quantification and exploration of drug targeting dynamics can be highly informative in the rational development of new therapies and in the drug discovery pipeline. The problems faced include the potential infrequency and transient nature of critical events, the influence of micropharmacokinetics on the drug–target equilibria, the dependence on preserving cell function to demonstrate dynamic processes in situ, the need to map events in functional cells and the confounding effects of cell-to-cell heterogeneity. We demonstrate technological solutions in which we have integrated two-photon laser scanning microscopy (TPLSM) to track drug delivery in subcellular compartments, with the mapping of sites of critical molecular interactions. We address key design concepts for the development of modular tools used to uncover the complexity of drug targeting in single cells. First, we describe the combination of two-photon excitation with fluorescence lifetime imaging microscopy (FLIM) to map the nuclear docking of the anticancer drug topotecan (TPT) at a subset of DNA sites in nuclear structures of live breast tumor cells. Secondly, we demonstrate how we incorporate the smart design of a two-photon “dark” DNA binding probe, such as DRAQ5, as a well-defined quenching probe to uncover sites of drug interaction. Finally, we discuss the future perspectives on introducing these modular kinetic assays in the high-content screening arena and the interlinking of the consequences of drug–target interactions with cellular stress responses. |
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yuanbing0000
至尊木虫 (小有名气)
- 翻译EPI: 21
- 应助: 0 (幼儿园)
- 金币: 13187.7
- 红花: 1
- 帖子: 81
- 在线: 70.3小时
- 虫号: 1143224
- 注册: 2010-11-10
- 性别: MM
- 专业: 传动机械学
【答案】应助回帖
★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★
Mally89(金币+1): 感谢应助！~欢迎常来！~吼吼！~\(^o^)/~ 2012-03-05 13:57:24
lsysxh(金币+30, 翻译EPI+1): ★★★很有帮助 太感谢你了，这几天愁的厉害啊 2012-03-06 13:55:10
Mally89(金币+1): 感谢应助！~欢迎常来！~吼吼！~\(^o^)/~ 2012-03-05 13:57:24
lsysxh(金币+30, 翻译EPI+1): ★★★很有帮助 太感谢你了，这几天愁的厉害啊 2012-03-06 13:55:10
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对该专业背景与术语不甚了解，以下内容仅供参考: 以活体细胞为目标用先进的显微镜方法监控药物和DNA之间的动力学 摘要: 很多抗癌药物需要与DNA或肿瘤细胞的染色质成分相互作用以完成治疗。以动力学为目标对药物进行量化和研究能对新治疗方法的合理发展及药物发现途径方面提供大量资料。面临的问题包括临界事件不多见性及瞬时性，微观药物代谢动力学对均衡药物与目标的影响，为证明动态作用对保持细胞功能的依赖，需要绘制机能细胞活动及细胞对细胞异质性的混合效应。我们演示了双光子激光集成扫描显微镜法以追踪药物在亚细胞空间的传送的技术方法，给出了临界分子相互作用位置图。以单细胞为对象，为揭示药物的复杂性，我们为模块化工具的发展提出重要的设计理念。首先，记录双光子激感与成像显微镜荧光寿命的组合，绘制抗癌药物TPT在活体胸部肿瘤细胞核心结构中DNA场子集的核心存放处；其次，说明我们怎样使双光子模糊约束探针的精确设计具体化，比如DRAQ5，作为定义明确的淬火探针揭示药物相互作用的场所；最后，讨论关于引进这些模块化分析在高满意度的屏蔽领域未来的前景及药物-目标与细胞应力相互作用结果的内部联系. |
2楼2012-03-04 22:58:27
dc121
木虫 (著名写手)
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- 虫号: 1446107
- 注册: 2011-10-16
- 性别: GG
- 专业: 马克思主义
3楼2012-03-05 19:53:26
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