Oncogene:p300/CBP抑制剂能够增强前列腺中程序性死亡配体1阻断治疗的效果

2020-04-07 AlexYang MedSci原创

抗体药物的程序性死亡配体1(PD-L1)阻断在癌症治疗中是一种很有前景的治疗方法,而在许多类型癌症的临床响应,包括前列腺癌(PCa)仍旧有限。肿瘤细胞通过外泌体或者剪接变异分泌PD-L1,并且在许多类

抗体药物的程序性死亡配体1(PD-L1)阻断在癌症治疗中是一种很有前景的治疗方法,而在许多类型癌症的临床响应,包括前列腺癌(PCa)仍旧有限。肿瘤细胞通过外泌体或者剪接变异分泌PD-L1,并且在许多类型的癌症中是PD-L1阻断治疗抗性产生的新机制,其中包括了前列腺癌。因此,这也表明了阶段PD-L1的分泌或者表达也许能够改善PCa治疗中PD-L1阻断疗法的响应比例。

最近,有研究人员报道了在一个同系PCa模型中,小分子p300/CBP抑制剂通过阻断内在和IFN-γ诱导的PD-L1表达,能够大幅度的增强PD-L1阻断治疗的效果。同时,p300/CBP能够通过转录因子IRF-1被招募到CD274(编码PD-L1)的启动子上,从而诱导CD274启动子区组蛋白H3的乙酰化作用,进而进行CD274转录。A485(一种p300/CBP抑制剂)能够阻止上述过程并通过阻断CD274的表达来阻断外泌体分泌PD-L1,进一步与PD-L1抗体组合来重新激活T细胞的功能来应对肿瘤的攻击。

最后,研究人员指出,他们的研究报道了癌细胞通过表观因子调控PD-L1表达的新机制,并为增强免疫检查点抑制剂治疗提供了一种新的治疗途径。

原始出处:

Jinghui Liu, Daheng He, Lijun Cheng et al. p300/CBP inhibition enhances the efficacy of programmed death-ligand 1 blockade treatment in prostate cancer. Oncogene. 23 Mar 2020

 

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    2021-03-08 jklm09
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  5. [GetPortalCommentsPageByObjectIdResponse(id=1852323, encodeId=628718523235f, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Mon Mar 08 16:21:49 CST 2021, time=2021-03-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2021174, encodeId=0c8720211e45e, content=<a href='/topic/show?id=8747418129' target=_blank style='color:#2F92EE;'>#CBP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4181, encryptionId=8747418129, topicName=CBP)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f07c2500133, createdName=12498adam40暂无昵称, createdTime=Sat Aug 15 12:21:49 CST 2020, time=2020-08-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1803326, encodeId=a6ab18033268c, content=<a href='/topic/show?id=9a70e52596e' target=_blank style='color:#2F92EE;'>#程序性死亡#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75259, encryptionId=9a70e52596e, topicName=程序性死亡)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b78f2500065, createdName=12498761m56暂无昵称, createdTime=Sun Apr 19 00:21:49 CST 2020, time=2020-04-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1710225, encodeId=b38a1e10225ef, content=<a href='/topic/show?id=7ac59e67604' target=_blank style='color:#2F92EE;'>#阻断#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97676, encryptionId=7ac59e67604, topicName=阻断)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b5ca31824852, createdName=41514497@qq.com, createdTime=Wed Nov 25 17:21:49 CST 2020, time=2020-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2049285, encodeId=99e120492858e, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Tue Feb 02 14:21:49 CST 2021, time=2021-02-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558186, encodeId=ff0e15581866f, content=<a href='/topic/show?id=2f1c13349e7' target=_blank style='color:#2F92EE;'>#Oncogene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13349, encryptionId=2f1c13349e7, topicName=Oncogene)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=154614942533, createdName=zsyan, createdTime=Thu Apr 09 04:21:49 CST 2020, time=2020-04-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1047030, encodeId=6072104e030de, content=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, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=CHANGE, createdTime=Tue Apr 07 16:21:49 CST 2020, time=2020-04-07, status=1, ipAttribution=)]
    2021-02-02 cy0324
  6. [GetPortalCommentsPageByObjectIdResponse(id=1852323, encodeId=628718523235f, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Mon Mar 08 16:21:49 CST 2021, time=2021-03-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2021174, encodeId=0c8720211e45e, content=<a href='/topic/show?id=8747418129' target=_blank style='color:#2F92EE;'>#CBP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4181, encryptionId=8747418129, topicName=CBP)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f07c2500133, createdName=12498adam40暂无昵称, createdTime=Sat Aug 15 12:21:49 CST 2020, time=2020-08-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1803326, encodeId=a6ab18033268c, content=<a href='/topic/show?id=9a70e52596e' target=_blank style='color:#2F92EE;'>#程序性死亡#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75259, encryptionId=9a70e52596e, topicName=程序性死亡)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b78f2500065, createdName=12498761m56暂无昵称, createdTime=Sun Apr 19 00:21:49 CST 2020, time=2020-04-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1710225, encodeId=b38a1e10225ef, content=<a href='/topic/show?id=7ac59e67604' target=_blank style='color:#2F92EE;'>#阻断#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97676, encryptionId=7ac59e67604, topicName=阻断)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b5ca31824852, createdName=41514497@qq.com, createdTime=Wed Nov 25 17:21:49 CST 2020, time=2020-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2049285, encodeId=99e120492858e, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Tue Feb 02 14:21:49 CST 2021, time=2021-02-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558186, encodeId=ff0e15581866f, content=<a href='/topic/show?id=2f1c13349e7' target=_blank style='color:#2F92EE;'>#Oncogene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13349, encryptionId=2f1c13349e7, topicName=Oncogene)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=154614942533, createdName=zsyan, createdTime=Thu Apr 09 04:21:49 CST 2020, time=2020-04-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1047030, encodeId=6072104e030de, content=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, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=CHANGE, createdTime=Tue Apr 07 16:21:49 CST 2020, time=2020-04-07, status=1, ipAttribution=)]
    2020-04-09 zsyan
  7. [GetPortalCommentsPageByObjectIdResponse(id=1852323, encodeId=628718523235f, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Mon Mar 08 16:21:49 CST 2021, time=2021-03-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2021174, encodeId=0c8720211e45e, content=<a href='/topic/show?id=8747418129' target=_blank style='color:#2F92EE;'>#CBP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4181, encryptionId=8747418129, topicName=CBP)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f07c2500133, createdName=12498adam40暂无昵称, createdTime=Sat Aug 15 12:21:49 CST 2020, time=2020-08-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1803326, encodeId=a6ab18033268c, content=<a href='/topic/show?id=9a70e52596e' target=_blank style='color:#2F92EE;'>#程序性死亡#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75259, encryptionId=9a70e52596e, topicName=程序性死亡)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b78f2500065, createdName=12498761m56暂无昵称, createdTime=Sun Apr 19 00:21:49 CST 2020, time=2020-04-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1710225, encodeId=b38a1e10225ef, content=<a href='/topic/show?id=7ac59e67604' target=_blank style='color:#2F92EE;'>#阻断#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97676, encryptionId=7ac59e67604, topicName=阻断)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b5ca31824852, createdName=41514497@qq.com, createdTime=Wed Nov 25 17:21:49 CST 2020, time=2020-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2049285, encodeId=99e120492858e, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Tue Feb 02 14:21:49 CST 2021, time=2021-02-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558186, encodeId=ff0e15581866f, content=<a href='/topic/show?id=2f1c13349e7' target=_blank style='color:#2F92EE;'>#Oncogene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13349, encryptionId=2f1c13349e7, topicName=Oncogene)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=154614942533, createdName=zsyan, createdTime=Thu Apr 09 04:21:49 CST 2020, time=2020-04-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1047030, encodeId=6072104e030de, content=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, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=CHANGE, createdTime=Tue Apr 07 16:21:49 CST 2020, time=2020-04-07, status=1, ipAttribution=)]
    2020-04-07 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

    0

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能量代谢的重组和线粒体的适应被认为影响了前列腺癌的发展和恶化。最近,有研究人员报道了良性/恶性人类前列腺组织样本中,线粒体呼吸、DNA变异和基因表达的情况。