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lsysxh鐵桿木蟲 (著名寫手)
糖葫蘆
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[求助]
翻譯急用，一共七句話！！30金幣奉上，翻譯的好可追加！
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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
至尊木蟲 (小有名氣)
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【答案】應(yīng)助回帖
★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★
Mally89(金幣+1): 感謝應(yīng)助！~歡迎常來！~吼吼！~\(^o^)/~ 2012-03-05 13:57:24
lsysxh(金幣+30, 翻譯EPI+1): ★★★很有幫助 太感謝你了，這幾天愁的厲害啊 2012-03-06 13:55:10
Mally89(金幣+1): 感謝應(yīng)助！~歡迎常來！~吼吼！~\(^o^)/~ 2012-03-05 13:57:24
lsysxh(金幣+30, 翻譯EPI+1): ★★★很有幫助 太感謝你了，這幾天愁的厲害啊 2012-03-06 13:55:10
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對(duì)該專業(yè)背景與術(shù)語不甚了解，以下內(nèi)容僅供參考: 以活體細(xì)胞為目標(biāo)用先進(jìn)的顯微鏡方法監(jiān)控藥物和DNA之間的動(dòng)力學(xué) 摘要: 很多抗癌藥物需要與DNA或腫瘤細(xì)胞的染色質(zhì)成分相互作用以完成治療。以動(dòng)力學(xué)為目標(biāo)對(duì)藥物進(jìn)行量化和研究能對(duì)新治療方法的合理發(fā)展及藥物發(fā)現(xiàn)途徑方面提供大量資料。面臨的問題包括臨界事件不多見性及瞬時(shí)性，微觀藥物代謝動(dòng)力學(xué)對(duì)均衡藥物與目標(biāo)的影響，為證明動(dòng)態(tài)作用對(duì)保持細(xì)胞功能的依賴，需要繪制機(jī)能細(xì)胞活動(dòng)及細(xì)胞對(duì)細(xì)胞異質(zhì)性的混合效應(yīng)。我們演示了雙光子激光集成掃描顯微鏡法以追蹤藥物在亞細(xì)胞空間的傳送的技術(shù)方法，給出了臨界分子相互作用位置圖。以單細(xì)胞為對(duì)象，為揭示藥物的復(fù)雜性，我們?yōu)槟K化工具的發(fā)展提出重要的設(shè)計(jì)理念。首先，記錄雙光子激感與成像顯微鏡熒光壽命的組合，繪制抗癌藥物TPT在活體胸部腫瘤細(xì)胞核心結(jié)構(gòu)中DNA場(chǎng)子集的核心存放處；其次，說明我們?cè)鯓邮闺p光子模糊約束探針的精確設(shè)計(jì)具體化，比如DRAQ5，作為定義明確的淬火探針揭示藥物相互作用的場(chǎng)所；最后，討論關(guān)于引進(jìn)這些模塊化分析在高滿意度的屏蔽領(lǐng)域未來的前景及藥物-目標(biāo)與細(xì)胞應(yīng)力相互作用結(jié)果的內(nèi)部聯(lián)系. |
2樓2012-03-04 22:58:27
dc121
木蟲 (著名寫手)
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- 專業(yè): 馬克思主義
3樓2012-03-05 19:53:26
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