eLife:大肠癌化疗敏感性为何会转变为耐药性?

2017-09-03 MedSci MedSci原创

肿瘤获得性耐药性是阻碍人类恶性肿瘤发病率和死亡率的一大障碍。导致大肠癌由化疗敏感性转变为耐药性之间的确切机制目前尚未清楚。本研究中,研究人员发现LRP16可选择性作用,并激活双链RNA依赖蛋白激酶(PKR),并可有助于PKR和IKKβ三元络合物的形成,延长ADP核糖(PAR)依赖核因子B(NF-κB)的转活,此过程是由DNA损伤剂引起,由此获得药物耐药性。此外,研究人员还发现了一种小分子——MRS

肿瘤获得性耐药性是阻碍人类恶性肿瘤发病率和死亡率的一大障碍。导致大肠癌由化疗敏感性转变为耐药性之间的确切机制目前尚未清楚。

本研究中,研究人员发现LRP16可选择性作用,并激活双链RNA依赖蛋白激酶(PKR),并可有助于PKR和IKKβ三元络合物的形成,延长ADP核糖(PAR)依赖核因子B(NF-κB)的转活,此过程是由DNA损伤剂引起,由此获得药物耐药性。

此外,研究人员还发现了一种小分子——MRS2578,可显著抑制LRP16 与PKR和IKKβ的结合,将LRP16转化成死亡分子并防止结肠肿瘤的发生。使用依托泊苷携带MRS2578,而非依托泊苷单独使用,在异种移植中表现出具有协同抗肿瘤的细胞毒性作用。此组合方法为肿瘤治疗的遗传毒性的疗法引入了一种策略来提高治疗的疗效。

原始出处:

Xiaolei Li, Zhiqiang Wu, et al., Blockade of the LRP16-PKR-NF-κB signaling axis sensitizes colorectal carcinoma cells to DNA-damaging cytotoxic therapy. eLife. 2017; 6: e27301. Published online 2017 Aug 18. doi: 10.7554/eLife.27301.

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    2018-01-02 clmlylxy
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    2018-05-30 膀胱癌
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    2017-09-05 ylzr123

    好文.值得点赞!认真学习了.把经验应用于实践.为患者解除病痛.

    0

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createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib06iaV3D9Tg5Kzuf9u71gZhPYMiajRtENwicoAABeQtfXOlic8ibhYSy6DvJZWUDVtjRvTfqBffr1XJ6JLtFB5kHicthl/0, createdBy=d41c2055892, createdName=184****9840, createdTime=Sun Sep 03 23:21:18 CST 2017, time=2017-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=240138, encodeId=132b24013861, content=肿瘤获得性耐药性是阻碍人类恶性肿瘤发病率和死亡率的一大障碍.导致大肠癌由化疗敏感性转变为耐药性之间的确切机制目前尚未清楚., beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7cJ6ejWUr2nIia8qOvAKNdLHr32Df6G8iaoaOx6pHaoiacwp26DaslxZHCGbibZhhCGven4rvmWP60GahtzgFjgCjR/0, createdBy=6b111703011, createdName=有备才能无患, createdTime=Sun Sep 03 23:12:52 CST 2017, time=2017-09-03, status=1, ipAttribution=)]
    2017-09-04 tanxingdoctor

    学习啦!谢谢分享!

    0

  7. 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    2017-09-04 suibian2007bbb

    学习

    0

  8. 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    2017-09-03 luominglian113

    学习了.谢谢分享

    0

  9. 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    2017-09-03 184****9840

    学习了谢谢分享

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    2017-09-03 有备才能无患

    肿瘤获得性耐药性是阻碍人类恶性肿瘤发病率和死亡率的一大障碍.导致大肠癌由化疗敏感性转变为耐药性之间的确切机制目前尚未清楚.

    0

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