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Sci Transl Med:致命脑癌的“克星”?竟然是这个小分子

2018-08-21 探索菌 生物探索

胶质母细胞瘤是最致命的癌症之一,患者五年生存率低于百分之五。近日,由利兹大学(University of Leeds)领导的一项研究或许有望在未来几年开发出一种对抗胶质母细胞瘤的疗法。研究人员发现,合成的小分子KHS101能够从胶质母细胞瘤中切除肿瘤细胞的能量来源,从而导致肿瘤细胞死亡。

胶质母细胞瘤是最致命的癌症之一,患者五年生存率低于百分之五。近日,由利兹大学(University of Leeds)领导的一项研究或许有望在未来几年开发出一种对抗胶质母细胞瘤的疗法。研究人员发现,合成的小分子KHS101能够从胶质母细胞瘤中切除肿瘤细胞的能量来源,从而导致肿瘤细胞死亡。

研究结果以 “KHS101 disrupts energy metabolism in human glioblastoma cells and reduces tumor growth in mice” 为题发表在《Science Translational Medicine》杂志上。

利兹大学的Heiko Wurdak博士领导了这个国际研究小组,他说:“当我们开始这项研究时,我们认为KHS101可能会减缓胶质母细胞瘤的生长,但我们惊讶地发现,当癌细胞暴露在它面前时,基本上是自毁的。”


显微镜下捕获的自毁性脑肿瘤细胞。这种红色染色来自于细胞“自噬”过程的标记物。来源: Stem Cells and Brain Tumour Group, University of Leeds

具体来说,这种化学物质破坏了癌细胞内的线粒体和新陈代谢,切断了能量供应,导致了癌细胞自我毁灭。

为了测试KHS101是否能穿过哺乳动物的血脑屏障(血脑屏障通常会阻止大部分分子进入大脑,严重限制了治疗的选择),研究人员将癌细胞从人类身上转移到老鼠体内。

结果发现,与服用安慰剂的小鼠相比,KHS101成功地穿过了血脑屏障,显着降低了肿瘤生长(约50%),从而提高了存活率。重要的是,正常的脑细胞不受这种化学物质的影响。

研究小组还回顾了KHS101对肿瘤内细胞和不同患者肿瘤之间的不同基因图谱的有效性。过去,肿瘤的遗传变异使得确定治疗方法的工作变得复杂,但研究小组发现,所有经过检测的胶质母细胞瘤亚型细胞的变异都对现有治疗有反应。

Wurdak博士表示,“虽然这是一个漫长过程的第一步,但我们的发现为药物开发人员铺平了道路,我们希望有一天它将有助于延长人们的生命。”

英国癌症研究中心的脑瘤专家Richard Gilbertson教授没有参与这项研究,他说道:“胶质母细胞瘤的治疗方法几十年来基本没有变化,因此迫切需要进行这样的临床前研究,以识别和鉴定潜在的新药。虽然这些发现令人鼓舞,但作为一种实验性的化学物质,在人类试验开始之前,需要进一步严格检测和改进KHS101。”

对KHS101特性进一步研究,科学家们或许会发现类似的药物,这些药物也会干扰肿瘤细胞的能量来源,从而导致其自我毁灭,进而扩大了对抗脑肿瘤的治疗选择范围。

原始出处:Polson ES, Kuchler VB, Abbosh C, et al. KHS101 disrupts energy metabolism in human glioblastoma cells and reduces tumor growth in mice. Sci Transl Med. 2018 Aug 15;10(454). 

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    2018-12-05 宋威
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    2018-08-23 pingping&Eva

    学习了

    0

  4. 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createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDicHg2ldsSNmib46PmdzpO7CQEmPjuULp1v45zPWwMYhrnXgvl3OtmUCZSQfgITWn96X9moL94nUGA/0, createdBy=28072041016, createdName=131****1460, createdTime=Tue Aug 21 20:32:59 CST 2018, time=2018-08-21, status=1, ipAttribution=)]
  5. 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GetPortalCommentsPageByObjectIdResponse(id=1657055, encodeId=9007165e0552e, content=<a href='/topic/show?id=3ca31e71903' target=_blank style='color:#2F92EE;'>#TRA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17719, encryptionId=3ca31e71903, topicName=TRA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=757b24868428, createdName=bsmagic9140, createdTime=Sat Sep 22 19:28:00 CST 2018, time=2018-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=340123, encodeId=c8c33401237e, content=好消息, beContent=null, objectType=article, channel=null, level=null, likeNumber=159, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/PiajxSqBRaEJpRpQCnUasd6ib9EVicg5OVCucqkFTXtUXjfzic04Q2rkib9vXavQO1IgUhyqD5aWcLic3cic72icVxNhEw/132, createdBy=58112419314, createdName=诸葛正我, createdTime=Wed Aug 22 09:52:00 CST 2018, time=2018-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=340099, encodeId=3cd0340099fb, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=172, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Wed Aug 22 08:06:21 CST 2018, time=2018-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=339986, encodeId=fa69339986f0, content=学习了受益匪浅, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDicHg2ldsSNmib46PmdzpO7CQEmPjuULp1v45zPWwMYhrnXgvl3OtmUCZSQfgITWn96X9moL94nUGA/0, createdBy=28072041016, createdName=131****1460, createdTime=Tue Aug 21 20:32:59 CST 2018, time=2018-08-21, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1914674, encodeId=3d8319146e4c4, content=<a href='/topic/show?id=84d7469559b' target=_blank style='color:#2F92EE;'>#小分子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46955, encryptionId=84d7469559b, topicName=小分子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6105386, createdName=宋威, createdTime=Wed Dec 05 19:28:00 CST 2018, time=2018-12-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2067372, encodeId=ddbe206e37277, content=<a href='/topic/show?id=d0841e75535' target=_blank style='color:#2F92EE;'>#Transl#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17755, encryptionId=d0841e75535, topicName=Transl)], attachment=null, authenticateStatus=null, 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GetPortalCommentsPageByObjectIdResponse(id=1657055, encodeId=9007165e0552e, content=<a href='/topic/show?id=3ca31e71903' target=_blank style='color:#2F92EE;'>#TRA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17719, encryptionId=3ca31e71903, topicName=TRA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=757b24868428, createdName=bsmagic9140, createdTime=Sat Sep 22 19:28:00 CST 2018, time=2018-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=340123, encodeId=c8c33401237e, content=好消息, beContent=null, objectType=article, channel=null, level=null, likeNumber=159, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/PiajxSqBRaEJpRpQCnUasd6ib9EVicg5OVCucqkFTXtUXjfzic04Q2rkib9vXavQO1IgUhyqD5aWcLic3cic72icVxNhEw/132, createdBy=58112419314, createdName=诸葛正我, createdTime=Wed Aug 22 09:52:00 CST 2018, time=2018-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=340099, encodeId=3cd0340099fb, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=172, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Wed Aug 22 08:06:21 CST 2018, time=2018-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=339986, encodeId=fa69339986f0, content=学习了受益匪浅, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDicHg2ldsSNmib46PmdzpO7CQEmPjuULp1v45zPWwMYhrnXgvl3OtmUCZSQfgITWn96X9moL94nUGA/0, createdBy=28072041016, createdName=131****1460, createdTime=Tue Aug 21 20:32:59 CST 2018, time=2018-08-21, status=1, ipAttribution=)]
    2018-09-22 bsmagic9140
  7. [GetPortalCommentsPageByObjectIdResponse(id=1914674, encodeId=3d8319146e4c4, content=<a href='/topic/show?id=84d7469559b' target=_blank style='color:#2F92EE;'>#小分子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46955, encryptionId=84d7469559b, topicName=小分子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6105386, createdName=宋威, createdTime=Wed Dec 05 19:28:00 CST 2018, time=2018-12-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2067372, encodeId=ddbe206e37277, content=<a href='/topic/show?id=d0841e75535' target=_blank style='color:#2F92EE;'>#Transl#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17755, encryptionId=d0841e75535, topicName=Transl)], attachment=null, authenticateStatus=null, 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GetPortalCommentsPageByObjectIdResponse(id=1657055, encodeId=9007165e0552e, content=<a href='/topic/show?id=3ca31e71903' target=_blank style='color:#2F92EE;'>#TRA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17719, encryptionId=3ca31e71903, topicName=TRA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=757b24868428, createdName=bsmagic9140, createdTime=Sat Sep 22 19:28:00 CST 2018, time=2018-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=340123, encodeId=c8c33401237e, content=好消息, beContent=null, objectType=article, channel=null, level=null, likeNumber=159, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/PiajxSqBRaEJpRpQCnUasd6ib9EVicg5OVCucqkFTXtUXjfzic04Q2rkib9vXavQO1IgUhyqD5aWcLic3cic72icVxNhEw/132, createdBy=58112419314, createdName=诸葛正我, createdTime=Wed Aug 22 09:52:00 CST 2018, time=2018-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=340099, encodeId=3cd0340099fb, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=172, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Wed Aug 22 08:06:21 CST 2018, time=2018-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=339986, encodeId=fa69339986f0, content=学习了受益匪浅, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDicHg2ldsSNmib46PmdzpO7CQEmPjuULp1v45zPWwMYhrnXgvl3OtmUCZSQfgITWn96X9moL94nUGA/0, createdBy=28072041016, createdName=131****1460, createdTime=Tue Aug 21 20:32:59 CST 2018, time=2018-08-21, status=1, ipAttribution=)]
    2018-08-22 诸葛正我

    好消息

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1914674, encodeId=3d8319146e4c4, content=<a href='/topic/show?id=84d7469559b' target=_blank style='color:#2F92EE;'>#小分子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46955, encryptionId=84d7469559b, topicName=小分子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6105386, createdName=宋威, createdTime=Wed Dec 05 19:28:00 CST 2018, time=2018-12-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2067372, encodeId=ddbe206e37277, content=<a href='/topic/show?id=d0841e75535' target=_blank style='color:#2F92EE;'>#Transl#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17755, encryptionId=d0841e75535, topicName=Transl)], attachment=null, authenticateStatus=null, 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GetPortalCommentsPageByObjectIdResponse(id=1657055, encodeId=9007165e0552e, content=<a href='/topic/show?id=3ca31e71903' target=_blank style='color:#2F92EE;'>#TRA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17719, encryptionId=3ca31e71903, topicName=TRA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=757b24868428, createdName=bsmagic9140, createdTime=Sat Sep 22 19:28:00 CST 2018, time=2018-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=340123, encodeId=c8c33401237e, content=好消息, beContent=null, objectType=article, channel=null, level=null, likeNumber=159, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/PiajxSqBRaEJpRpQCnUasd6ib9EVicg5OVCucqkFTXtUXjfzic04Q2rkib9vXavQO1IgUhyqD5aWcLic3cic72icVxNhEw/132, createdBy=58112419314, createdName=诸葛正我, createdTime=Wed Aug 22 09:52:00 CST 2018, time=2018-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=340099, encodeId=3cd0340099fb, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=172, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Wed Aug 22 08:06:21 CST 2018, time=2018-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=339986, encodeId=fa69339986f0, content=学习了受益匪浅, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDicHg2ldsSNmib46PmdzpO7CQEmPjuULp1v45zPWwMYhrnXgvl3OtmUCZSQfgITWn96X9moL94nUGA/0, createdBy=28072041016, createdName=131****1460, createdTime=Tue Aug 21 20:32:59 CST 2018, time=2018-08-21, status=1, ipAttribution=)]
    2018-08-22 kafei

    学习了谢谢

    0

  9. 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GetPortalCommentsPageByObjectIdResponse(id=1657055, encodeId=9007165e0552e, content=<a href='/topic/show?id=3ca31e71903' target=_blank style='color:#2F92EE;'>#TRA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17719, encryptionId=3ca31e71903, topicName=TRA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=757b24868428, createdName=bsmagic9140, createdTime=Sat Sep 22 19:28:00 CST 2018, time=2018-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=340123, encodeId=c8c33401237e, content=好消息, beContent=null, objectType=article, channel=null, level=null, likeNumber=159, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/PiajxSqBRaEJpRpQCnUasd6ib9EVicg5OVCucqkFTXtUXjfzic04Q2rkib9vXavQO1IgUhyqD5aWcLic3cic72icVxNhEw/132, createdBy=58112419314, createdName=诸葛正我, createdTime=Wed Aug 22 09:52:00 CST 2018, time=2018-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=340099, encodeId=3cd0340099fb, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=172, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Wed Aug 22 08:06:21 CST 2018, time=2018-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=339986, encodeId=fa69339986f0, content=学习了受益匪浅, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDicHg2ldsSNmib46PmdzpO7CQEmPjuULp1v45zPWwMYhrnXgvl3OtmUCZSQfgITWn96X9moL94nUGA/0, createdBy=28072041016, createdName=131****1460, createdTime=Tue Aug 21 20:32:59 CST 2018, time=2018-08-21, status=1, ipAttribution=)]
    2018-08-21 131****1460

    学习了受益匪浅

    0

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