肿瘤科

订阅

MedSci主页 / 所有栏目 / 肿瘤科

Clin Cancer Res:抗衰老蛋白可能成为老年黑色素瘤患者的潜在治疗靶点

2017-02-26 MedSci MedSci原创

Klotho蛋白老年黑色素瘤rosiglitazone
关注

衰老是黑色素瘤的不良预后因素。前期的研究表明，处于衰老微环境中的黑色素瘤细胞比处于年轻微环境中的相同细胞，对靶向治疗抵抗作用更强，这归因于衰老相关分泌因子。Klotho是一种衰老相关蛋白，40岁以后，在血清中表达水平剧烈下降。目前，Klotho蛋白在肿瘤中的研究，主要集中在不同肿瘤细胞的表达情况。Weeraratna教授课题组以往研究表明，Wnt5A驱动黑色素瘤的转移和靶向治疗抵抗性，而外源性Kl

衰老是黑色素瘤的不良预后因素。前期的研究表明，处于衰老微环境中的黑色素瘤细胞比处于年轻微环境中的相同细胞，对靶向治疗抵抗作用更强，这归因于衰老相关分泌因子。Klotho是一种衰老相关蛋白，40岁以后，在血清中表达水平剧烈下降。目前，Klotho蛋白在肿瘤中的研究，主要集中在不同肿瘤细胞的表达情况。

Weeraratna教授课题组以往研究表明，Wnt5A驱动黑色素瘤的转移和靶向治疗抵抗性，而外源性Klotho抑制Wnt5A的内化和信号传导。该课题组最新发表在Clin Cancer Res的文章，旨在探究在衰老微环境中增加Klotho蛋白，是否是一个治疗黑色素瘤的有效策略。

在该研究中，Weeraratna团队利用人工皮肤构建模型去重建黑色素瘤细胞与年轻微环境或者衰老微环境的相互作用。他们观察到Klotho，Wnt5A，黑素瘤细胞和肿瘤微环境之间存在错综复杂的相互调节；同时表明，抗糖尿病药物rosiglitazone可以促进Klotho的表达，进而抑制Wnt5A的表达，减少衰老老鼠治疗抵抗性黑色素瘤的生长，但在年轻小鼠中不起作用；重要的是，rosiglitazone与靶向治疗联合使用可减少年轻和衰老临床前模型中的肿瘤生长，但是单独使用rosiglitazone可加速年轻模型中的肿瘤生长，抑制老年模型中的肿瘤生长。

该项研究为老年黑色素瘤患者佐剂治疗的发展奠定了基础。未来还需要更多的研究验证其在人类受试者中的益处。Klotho是一种分泌蛋白，可以直接在血清中检测到，这将有助于确认rosiglitazone治疗的获益人群。

原始出处：

Reeti Behera， Amanpreet Kaur， Marie R Webster，et al. Inhibition of age-related therapy resistance in melanoma by rosiglitazone-mediated induction of Klotho.Clinical Cancer Research， 2017 Feb 23. doi：10.1158/1078-0432.CCR-17-0201
https：//www.sciencedaily.com/releases/2017/02/170223114744.htm

本文系梅斯医学（MedSci）原创编译整理，转载需授权！



版权声明：
本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料，版权均属于梅斯医学所有。非经授权，任何媒体、网站或个人不得转载，授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章，或“梅斯号”自媒体发布的文章，仅系出于传递更多信息之目的，本站仅负责审核内容合规，其内容不代表本站立场，本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系，我们将立即进行删除处理。
在此留言
评论区 (5)
#插入话题
  1. [GetPortalCommentsPageByObjectIdResponse(id=1895326, encodeId=2f011895326c6, content=<a href='/topic/show?id=18ae64e21d3' target=_blank style='color:#2F92EE;'>#治疗靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64721, encryptionId=18ae64e21d3, topicName=治疗靶点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80c5136, createdName=drj2003, createdTime=Sat Dec 09 04:30:00 CST 2017, time=2017-12-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1680382, encodeId=7a1a168038205, content=<a href='/topic/show?id=9e5c86e0712' target=_blank style='color:#2F92EE;'>#色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86707, encryptionId=9e5c86e0712, topicName=色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=343027846633, createdName=sunylz, createdTime=Mon Aug 28 14:30:00 CST 2017, time=2017-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558788, encodeId=2c1f1558e887b, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Tue Feb 28 07:30:00 CST 2017, time=2017-02-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1564797, encodeId=7a381564e9719, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Tue Feb 28 07:30:00 CST 2017, time=2017-02-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=178132, encodeId=d8081e813218, content=希望总在不断出现, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo5gJeAA33pg8XSpMyoXQLg4TTWfCC26g4ibkFFUdQVBtofBwAITTWib8S4f1bKDLaYsKVz2KtVfhLQJoia5mISjlibk/0, createdBy=28331949612, createdName=1e10eabem79(暂无匿称), createdTime=Tue Feb 28 00:20:58 CST 2017, time=2017-02-28, status=1, ipAttribution=)]
    2017-12-09 drj2003

    #治疗靶点#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1895326, encodeId=2f011895326c6, content=<a href='/topic/show?id=18ae64e21d3' target=_blank style='color:#2F92EE;'>#治疗靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64721, encryptionId=18ae64e21d3, topicName=治疗靶点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80c5136, createdName=drj2003, createdTime=Sat Dec 09 04:30:00 CST 2017, time=2017-12-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1680382, encodeId=7a1a168038205, content=<a href='/topic/show?id=9e5c86e0712' target=_blank style='color:#2F92EE;'>#色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86707, encryptionId=9e5c86e0712, topicName=色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=343027846633, createdName=sunylz, createdTime=Mon Aug 28 14:30:00 CST 2017, time=2017-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558788, encodeId=2c1f1558e887b, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Tue Feb 28 07:30:00 CST 2017, time=2017-02-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1564797, encodeId=7a381564e9719, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Tue Feb 28 07:30:00 CST 2017, time=2017-02-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=178132, encodeId=d8081e813218, content=希望总在不断出现, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo5gJeAA33pg8XSpMyoXQLg4TTWfCC26g4ibkFFUdQVBtofBwAITTWib8S4f1bKDLaYsKVz2KtVfhLQJoia5mISjlibk/0, createdBy=28331949612, createdName=1e10eabem79(暂无匿称), createdTime=Tue Feb 28 00:20:58 CST 2017, time=2017-02-28, status=1, ipAttribution=)]
    2017-08-28 sunylz

    #色素#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1895326, encodeId=2f011895326c6, content=<a href='/topic/show?id=18ae64e21d3' target=_blank style='color:#2F92EE;'>#治疗靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64721, encryptionId=18ae64e21d3, topicName=治疗靶点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80c5136, createdName=drj2003, createdTime=Sat Dec 09 04:30:00 CST 2017, time=2017-12-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1680382, encodeId=7a1a168038205, content=<a href='/topic/show?id=9e5c86e0712' target=_blank style='color:#2F92EE;'>#色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86707, encryptionId=9e5c86e0712, topicName=色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=343027846633, createdName=sunylz, createdTime=Mon Aug 28 14:30:00 CST 2017, time=2017-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558788, encodeId=2c1f1558e887b, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Tue Feb 28 07:30:00 CST 2017, time=2017-02-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1564797, encodeId=7a381564e9719, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Tue Feb 28 07:30:00 CST 2017, time=2017-02-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=178132, encodeId=d8081e813218, content=希望总在不断出现, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo5gJeAA33pg8XSpMyoXQLg4TTWfCC26g4ibkFFUdQVBtofBwAITTWib8S4f1bKDLaYsKVz2KtVfhLQJoia5mISjlibk/0, createdBy=28331949612, createdName=1e10eabem79(暂无匿称), createdTime=Tue Feb 28 00:20:58 CST 2017, time=2017-02-28, status=1, ipAttribution=)]
    2017-02-28 cqlidoudou

    #黑色素#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1895326, encodeId=2f011895326c6, content=<a href='/topic/show?id=18ae64e21d3' target=_blank style='color:#2F92EE;'>#治疗靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64721, encryptionId=18ae64e21d3, topicName=治疗靶点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80c5136, createdName=drj2003, createdTime=Sat Dec 09 04:30:00 CST 2017, time=2017-12-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1680382, encodeId=7a1a168038205, content=<a href='/topic/show?id=9e5c86e0712' target=_blank style='color:#2F92EE;'>#色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86707, encryptionId=9e5c86e0712, topicName=色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=343027846633, createdName=sunylz, createdTime=Mon Aug 28 14:30:00 CST 2017, time=2017-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558788, encodeId=2c1f1558e887b, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Tue Feb 28 07:30:00 CST 2017, time=2017-02-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1564797, encodeId=7a381564e9719, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Tue Feb 28 07:30:00 CST 2017, time=2017-02-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=178132, encodeId=d8081e813218, content=希望总在不断出现, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo5gJeAA33pg8XSpMyoXQLg4TTWfCC26g4ibkFFUdQVBtofBwAITTWib8S4f1bKDLaYsKVz2KtVfhLQJoia5mISjlibk/0, createdBy=28331949612, createdName=1e10eabem79(暂无匿称), createdTime=Tue Feb 28 00:20:58 CST 2017, time=2017-02-28, status=1, ipAttribution=)]
    2017-02-28 cqlidoudou

    #黑色素#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1895326, encodeId=2f011895326c6, content=<a href='/topic/show?id=18ae64e21d3' target=_blank style='color:#2F92EE;'>#治疗靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64721, encryptionId=18ae64e21d3, topicName=治疗靶点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80c5136, createdName=drj2003, createdTime=Sat Dec 09 04:30:00 CST 2017, time=2017-12-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1680382, encodeId=7a1a168038205, content=<a href='/topic/show?id=9e5c86e0712' target=_blank style='color:#2F92EE;'>#色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86707, encryptionId=9e5c86e0712, topicName=色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=343027846633, createdName=sunylz, createdTime=Mon Aug 28 14:30:00 CST 2017, time=2017-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558788, encodeId=2c1f1558e887b, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Tue Feb 28 07:30:00 CST 2017, time=2017-02-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1564797, encodeId=7a381564e9719, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Tue Feb 28 07:30:00 CST 2017, time=2017-02-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=178132, encodeId=d8081e813218, content=希望总在不断出现, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo5gJeAA33pg8XSpMyoXQLg4TTWfCC26g4ibkFFUdQVBtofBwAITTWib8S4f1bKDLaYsKVz2KtVfhLQJoia5mISjlibk/0, createdBy=28331949612, createdName=1e10eabem79(暂无匿称), createdTime=Tue Feb 28 00:20:58 CST 2017, time=2017-02-28, status=1, ipAttribution=)]
    2017-02-28 1e10eabem79(暂无匿称)

    希望总在不断出现

    0