Nat commun:缺氧和雄激素相互作用控制一个代谢开关从而给予对雄激素/AR靶向治疗的抗性

2018-12-13 AlexYang MedSci原创

最近的进展表明雄激素/雄激素受体(AR)靶向治疗对患有转移性前列腺癌的治疗作用有限,这种情况部分是由于前列腺癌可以适应性的变换到不依赖于雄激素/AR途径来进行生存和生长,从而产生治疗抗性。肿瘤缺氧被认为是治疗抗性产生的一个主要起因。然而,精确的机制仍旧不清楚。最近,有研究人员报道了在缺氧条件下的长期的雄激素阻断治疗(ADT)能够诱导适应性的不依赖雄激素/AR,从而产生对雄激素/AR靶向治疗的抗性,

最近的进展表明雄激素/雄激素受体(AR)靶向治疗对患有转移性前列腺癌的治疗作用有限,这种情况部分是由于前列腺癌可以适应性的变换到不依赖于雄激素/AR途径来进行生存和生长,从而产生治疗抗性。肿瘤缺氧被认为是治疗抗性产生的一个主要起因。然而,精确的机制仍旧不清楚。

最近,有研究人员报道了在缺氧条件下的长期的雄激素阻断治疗(ADT)能够诱导适应性的不依赖雄激素/AR,从而产生对雄激素/AR靶向治疗的抗性,比如恩杂鲁胺。另外,上述调控机制由葡萄糖-6-磷酸异构酶(GPI)调控,GPI在缺氧条件下被AR在转录水平上抑制,但是在AR受抑制的情况下恢复并增加。反过来,GPI能够在缺氧条件下维持葡萄糖代谢和能量平衡,具体是通过将葡萄糖从雄激素/AR依赖的磷酸戊糖途径(PPP)转向到缺氧诱导的糖酵解途径,从而减少对恩杂鲁胺产生的生长抑制效应。

最后,研究人员指出,抑制GPI能够克服体外缺氧条件下的治疗抗性,并且增加体内恩杂鲁胺治疗的效果。

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    2019-03-28 liuli5079
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    2019-07-21 yige2012
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    2019-03-27 kafei

    学习学习谢谢

    0

  4. 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encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Fri May 10 05:58:00 CST 2019, time=2019-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1909273, encodeId=912719092e3ad, content=<a href='/topic/show?id=8039e2512e8' target=_blank style='color:#2F92EE;'>#相互作用#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72512, encryptionId=8039e2512e8, topicName=相互作用)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f73a255, createdName=medscijoin, createdTime=Sun Dec 16 06:58:00 CST 2018, time=2018-12-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=355695, encodeId=a8b1355695e0, content=看看, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0aa31415219, createdName=orangesking, createdTime=Mon Dec 17 23:43:51 CST 2018, time=2018-12-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=355616, encodeId=86b53556165f, content=谢谢分享学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Sun Dec 16 23:50:19 CST 2018, time=2018-12-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1471623, encodeId=2add14e1623cd, content=<a href='/topic/show?id=c0132410554' target=_blank style='color:#2F92EE;'>#互作#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24105, encryptionId=c0132410554, topicName=互作)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dc87121468, createdName=ylz8405, createdTime=Sat Dec 15 12:58:00 CST 2018, time=2018-12-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=355390, encodeId=ca1e355390b1, content=认真学习,不断进步,把经验分享给同好。点赞了!, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=d85d1636106, createdName=lietome2, createdTime=Fri Dec 14 12:00:36 CST 2018, time=2018-12-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=355345, encodeId=4f2d35534599, content=了解一下,谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Thu Dec 13 22:22:17 CST 2018, time=2018-12-13, status=1, ipAttribution=)]
    2019-05-10 liye789132251
  5. 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likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24105, encryptionId=c0132410554, topicName=互作)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dc87121468, createdName=ylz8405, createdTime=Sat Dec 15 12:58:00 CST 2018, time=2018-12-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=355390, encodeId=ca1e355390b1, content=认真学习,不断进步,把经验分享给同好。点赞了!, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=d85d1636106, createdName=lietome2, createdTime=Fri Dec 14 12:00:36 CST 2018, time=2018-12-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=355345, encodeId=4f2d35534599, content=了解一下,谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Thu Dec 13 22:22:17 CST 2018, time=2018-12-13, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=2087481, encodeId=bf1c208e481d5, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Thu Mar 28 07:58:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1665967, encodeId=b238166596eac, content=<a href='/topic/show?id=6f7d553159c' target=_blank style='color:#2F92EE;'>#抗性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55315, encryptionId=6f7d553159c, topicName=抗性)], attachment=null, authenticateStatus=null, createdAvatar=null, 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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0aa31415219, createdName=orangesking, createdTime=Mon Dec 17 23:43:51 CST 2018, time=2018-12-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=355616, encodeId=86b53556165f, content=谢谢分享学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Sun Dec 16 23:50:19 CST 2018, time=2018-12-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1471623, encodeId=2add14e1623cd, content=<a href='/topic/show?id=c0132410554' target=_blank style='color:#2F92EE;'>#互作#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24105, encryptionId=c0132410554, topicName=互作)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dc87121468, createdName=ylz8405, createdTime=Sat Dec 15 12:58:00 CST 2018, time=2018-12-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=355390, encodeId=ca1e355390b1, content=认真学习,不断进步,把经验分享给同好。点赞了!, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=d85d1636106, createdName=lietome2, createdTime=Fri Dec 14 12:00:36 CST 2018, time=2018-12-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=355345, encodeId=4f2d35534599, content=了解一下,谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Thu Dec 13 22:22:17 CST 2018, time=2018-12-13, status=1, ipAttribution=)]
    2018-12-17 orangesking

    看看

    0

  7. 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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0aa31415219, createdName=orangesking, createdTime=Mon Dec 17 23:43:51 CST 2018, time=2018-12-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=355616, encodeId=86b53556165f, content=谢谢分享学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Sun Dec 16 23:50:19 CST 2018, time=2018-12-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1471623, encodeId=2add14e1623cd, content=<a href='/topic/show?id=c0132410554' target=_blank style='color:#2F92EE;'>#互作#</a>, beContent=null, objectType=article, channel=null, level=null, 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objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Thu Dec 13 22:22:17 CST 2018, time=2018-12-13, status=1, ipAttribution=)]
    2018-12-16 清风拂面

    谢谢分享学习

    0

  8. 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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0aa31415219, createdName=orangesking, createdTime=Mon Dec 17 23:43:51 CST 2018, time=2018-12-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=355616, encodeId=86b53556165f, content=谢谢分享学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Sun Dec 16 23:50:19 CST 2018, time=2018-12-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1471623, encodeId=2add14e1623cd, content=<a href='/topic/show?id=c0132410554' target=_blank style='color:#2F92EE;'>#互作#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24105, encryptionId=c0132410554, topicName=互作)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dc87121468, createdName=ylz8405, createdTime=Sat Dec 15 12:58:00 CST 2018, time=2018-12-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=355390, encodeId=ca1e355390b1, content=认真学习,不断进步,把经验分享给同好。点赞了!, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=d85d1636106, createdName=lietome2, createdTime=Fri Dec 14 12:00:36 CST 2018, time=2018-12-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=355345, encodeId=4f2d35534599, content=了解一下,谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Thu Dec 13 22:22:17 CST 2018, time=2018-12-13, status=1, ipAttribution=)]
    2018-12-15 ylz8405
  9. [GetPortalCommentsPageByObjectIdResponse(id=2087481, encodeId=bf1c208e481d5, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Thu Mar 28 07:58:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1665967, encodeId=b238166596eac, content=<a href='/topic/show?id=6f7d553159c' target=_blank style='color:#2F92EE;'>#抗性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55315, encryptionId=6f7d553159c, topicName=抗性)], attachment=null, authenticateStatus=null, createdAvatar=null, 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objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Thu Dec 13 22:22:17 CST 2018, time=2018-12-13, status=1, ipAttribution=)]
    2018-12-14 lietome2

    认真学习,不断进步,把经验分享给同好。点赞了!

    0

  10. 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objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Thu Dec 13 22:22:17 CST 2018, time=2018-12-13, status=1, ipAttribution=)]
    2018-12-13 天地飞扬

    了解一下,谢谢分享!

    0

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Nat Commun:重磅!转移性前列腺癌新靶点被发现!

此次发现的关键分子称为组蛋白甲基转移酶核受体结合SET结构域蛋白2(NSD2)是,它一种组蛋白甲基转移酶,在基因表达的表观遗传控制中起关键作用。由Alvaro Aytes博士和Katia Ruggero博士领导的Bellvitge生物医学研究所(IDIBELL)团队的研究表明,前列腺肿瘤在进展和治疗期间,它的NSD2水平会不断增加,因此NSD2可能是前列腺癌转移的驱动因素,通过大量实验,研究人员证

Nature Metabolism:雄激素受体驱使的前列腺癌中,线粒体丙酮酸盐输入是代谢的一个弱点

雄激素受体(AR)驱使的前列腺恶性肿瘤(PCa)的生长的特异性代谢基础仍旧大部分未知,当激素治疗失败的时候,阻碍了使用该疾病的代谢依赖性开发治疗策略途径的发展。最近,有研究人员指出,线粒体丙酮酸盐载体(MPC),一个关键的能够联系细胞质代谢和线粒体代谢的代谢途径关键因子,可以由AR进行转录水平上的调控。试验中对MPC的抑制能够限制细胞增殖和三羧酸循环(TCA)的代谢输出,包括了AR驱使PCa模型中

Nature Medicine:ONECUT2是致死性前列腺癌的一个靶向主调控因子,且能够调控雄激素轴

通过对雄激素的抑制对前列腺癌(PC)的治疗能够促进恶性变异的产生,并且不依赖于雄激素受体(AR)。最近,有研究人员鉴定了转录因子ONECUT2(OC2)在转移性去势难治性前列腺癌(mCRPC)中是AR网络中的一个主要调控因子。OC2在mCRPC模型中可以作为一个生存因子通过直接调控AR靶基因和AR许可因子FOXA1来抑制AR转录过程,并能够激活能导致致死疾病的神经分化与进展相关的基因。另外,OC2

Sci Rep:肉盘菌内酯能够抑制STAT/AR信号途径和抑制恩杂鲁胺抗性前列腺癌

大多数前列腺癌患者会在雄激素阻断治疗后恶化发展到去势抵抗性(CRPC)状态,尽管新的有效的抗雄激素药物的开发,比如恩杂鲁胺(ENZ)能够延长CRPC患者的生存,但是ENZ抗性会很快产生。雄激素受体(AR)的重新激活是抗性产生的一个主要机制。最近,有研究人员通过其体内来源的ENZ抗性模型,发现STAT3转录因子不仅在核定位中增加,同时能够结合和促进AR活性。研究人员观察到了在ENZ抗性细胞中STAT

Sci Rep:前列腺癌恶化过程中G蛋白信号2(RGS2)调控子的表达和功能分析

前列腺癌(PC)是男性第二大致死性癌症,因此,早期对恶性和良性肿瘤的区分的生物标记是需要的。之前的研究表明,G蛋白信号2(RGS2)调控因子在PC中下调,然而,潜在的机制还没有研究清楚。另外,RGS2表达的异常在其他阳性和阴性诊断的恶性肿瘤中存在。最近,有研究人员在PC恶化过程中评估了RGS2的表达,并考虑了对肿瘤表型的调控和影响,还评估了它的预后值。研究发现,RGS2在早期PC中的下调是由缺氧引