Nat Commun：辨色识癌！MIT这种新技术可有效预测化疗药效果

2018-08-09 探索菌生物探索

如何确定癌细胞是否对化疗药物产生反应？相信不仅医生想知道，患者更想知道。8月7日，麻省理工学院官网报道了一种可“辨色识癌”的神奇传感器——通过识别该传感器与体内过氧化氢反应时的颜色就能揭示这些化疗药物的预期效果！

如何确定癌细胞是否对化疗药物产生反应？相信不仅医生想知道，患者更想知道。8月7日，麻省理工学院官网报道了一种可“辨色识癌”的神奇传感器——通过识别该传感器与体内过氧化氢反应时的颜色就能揭示这些化疗药物的预期效果！

同日，《Nature Communications》杂志也以“Monitoring the action of redox-directed cancer therapeutics using a human peroxiredoxin-2-based probe”为题发表了这项新技术。

01.追踪过氧化氢

癌细胞会经常发生突变，导致新陈代谢失常，同时产生异常高的过氧化氢。一旦过氧化氢过量，就会损伤细胞，因此癌细胞变得高度依赖于清除细胞中过氧化氢的抗氧化系统。很多药物研发者会基于抑制抗氧化系统或进一步提高过氧化氢的产量进行新药开发。

但是据通讯作者、麻省理工学院化学工程副教授Hadley Sikes说：“临床试验发现这些药物往往只对一些病人有效，而对其他病人无效。因此需要一种工具高效检测哪些病人对药物产生反应，哪些不会，这样才能提高新药研发速度。”

通讯作者Hadley Sikes教授（图片来源：MIT官方网站）

为了实现这一目标，Sikes着手设计一种传感器，它能够灵敏检测人体细胞内的过氧化氢，使科学家能够测量细胞对这些药物的反应。

这一过氧化氢传感器基于一种提取自微生物的转录因子，当它们与过氧化氢反应时会发出荧光。Sikes及其同事试图在人类细胞中使用这些物质，但很快发现它们对检测的过氧化氢范围不敏感，这导致他们开始寻找能够完成这项任务的人类蛋白质。

通过对随着过氧化氢的增加而被氧化的人类蛋白质网络的研究，科学家们发现了一种过氧化物酶，它控制着大多数人类细胞与该分子的反应。而这种酶的功能之一正是检测过氧化氢水平的变化。

传感器设计（图片来源： Nature Communications）

接下来，主要研究者Troy Langford在酶的两端分别添加绿色和红色两种荧光蛋白分子，研究人员可通过向细胞发出的颜色来检测这种转变是否发生：如果未检测到过氧化氢，则这种光只保持绿色；如果存在过氧化氢（即当抗癌药物/疗法生效），传感器结构会随之改变，使细胞发出红光。

过氧化氢作用下，传感器让细胞发出红光（图片来源： Nature Communications）

02.成功预测

随后，研究人员在两种类型的人类癌细胞中测试了新传感器：一种是他们知道对氧化还原药物荜茇酰胺敏感的，另一种对现有药物耐受。传感器显示，前者细胞中的过氧化氢水平上升（呈现红色），后者依旧保持绿色。

Sikes指出，未来这种传感器有两个主要用途：一是筛选现有药物的文库，或可能用作药物的化合物，以确定它们是否具有增加癌细胞过氧化氢浓度的预期效果；二是在患者接受此类药物之前对其进行筛选，看看这些药物是否能成功治疗每个患者的肿瘤。目前他们正在试验这两种方法。

原始出处：Troy F. Langford, Beijing K. Huang, Joseph B. Lim, et al. Monitoring the action of redox-directed cancer therapeutics using a human peroxiredoxin-2-based probe. Nat Commun. 2018-08-07

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2019-01-25 lsndxfj

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2019-07-01 liuli5079

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39 0
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2018-12-05 gracezdd

#MIT#

44 0
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2018-11-04 liye789132251

#Nat#

38 0
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2019-01-23 仁心济世

#新技术#

0 0
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2018-08-11 柳叶一刀

#化疗药#

33 0
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2018-08-10 kafei

学习了谢谢

61 0
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2018-08-09 CHANGE

疗效只是效果的众多方面之一，还要看对患者的获益，包括生活质量等因素共同决定效果的

45 0
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2018-08-09 1209e435m98(暂无昵称)

学习了，谢谢分享

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