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Nat Commun:FOXO3a-miRNA负反馈抑制作用影响HER2阳性乳腺癌的赫赛汀耐药性

2021-06-07 xiaozeng MedSci原创

乳腺癌作为全球女性癌症相关死亡的主要原因之一,是一种异质性疾病,目前已被分为几种分子亚型。

乳腺癌作为全球女性癌症相关死亡的主要原因之一,是一种异质性疾病,目前已被分为几种分子亚型。其中HER2阳性乳腺癌的定义为具有扩增和/或过表达状态的HER2(或erbB2)基因的乳腺癌亚型。

既往研究显示,在大约20-25%的乳腺癌患者中观察到了HER2的扩增/过表达,且与患者的不良预后显著相关。赫赛汀Herceptin(或曲妥珠单抗trastuzumab)作为一种人源化抗HER2的单克隆抗体(Ab),是针对早期和转移性HER2阳性乳腺癌的有效HER2靶向疗法。其能够显著提高HER2阳性乳腺癌患者的生存率。

然而,并非所有HER2阳性乳腺癌患者均对基于赫赛汀的治疗方案有反应。大多数有初始反应的患者在一年内会产生耐药性。由于缺乏可预测赫赛汀疗效的有效生物标志物,赫赛汀的耐药性是成功治疗HER2阳性乳腺癌的一个重大挑战。因此,迫切需要制定克服赫赛汀耐药性的新型疗法,以降低转移性HER2阳性乳腺癌患者的死亡率。

IGF2/IGF-1R/IRS1/Akt/mTOR信号通路参与了HER2阳性乳腺癌细胞的赫赛汀耐药

在该研究中,研究人员发现,在赫赛汀敏感的细胞中,FOXO3a能够通过调节特定的miRNA,进而调控IGF2和IRS1的表达,以维持最基础的IGF2/IGF-1R/IRS1信号转导水平。PPP3CB(丝氨酸/苏氨酸蛋白磷酸酶2B的亚基)的表达以及活性的维持能够抑制FOXO3a的磷酸化(p-FOXO3a),而p-FOXO3a能够诱导靶向IGF2和IRS1的miRNA。

PPP3CB/FOXO3a/IRS1信号通路会引起对赫赛汀的较差响应

研究人员发现,在赫赛汀耐药性细胞中,由于PPP3CB的转录受到抑制,导致p-FOXO3a的水平升高,从而破坏了FOXO3a和miRNA形成的负反馈抑制环,最终上调了IGF2和IRS1的表达水平。进一步的研究显示,在对赫赛汀治疗方案反应较差的乳腺癌患者的肿瘤组织和血液中,IGF2和IRS1的表达水平显著升高。


总而言之,该研究结果揭示,通过破坏FOXO3a-miRNA负反馈抑制作用,能够介导赫赛汀耐药性乳腺癌中IGF2/IGF-1R/IRS1信号通路被异常激活。该研究也鉴定了潜在的预测性生物标志物并提出了克服赫赛汀耐药性的有效治疗策略。


原始出处:

Luo, L., Zhang, Z., Qiu, N. et al. Disruption of FOXO3a-miRNA feedback inhibition of IGF2/IGF-1R/IRS1 signaling confers Herceptin resistance in HER2-positive breast cancer. Nat Commun 12, 2699 (11 May 2021).

 

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    2022-04-07 liuli5079
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    2021-11-13 denglimoxiaoran

    学习

    0

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    2021-07-22 hyf028
  4. 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GetPortalCommentsPageByObjectIdResponse(id=2024544, encodeId=1dcd202454410, content=<a href='/topic/show?id=0219e625d1' target=_blank style='color:#2F92EE;'>#FOXO3a#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7625, encryptionId=0219e625d1, topicName=FOXO3a)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7d40148, createdName=hyf028, createdTime=Thu Jul 22 21:48:05 CST 2021, time=2021-07-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1930828, encodeId=a9c31930828be, content=<a href='/topic/show?id=22f61180211' target=_blank style='color:#2F92EE;'>#miR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11802, encryptionId=22f61180211, topicName=miR)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0a27288, createdName=smallant2002, createdTime=Thu Mar 03 14:48:05 CST 2022, time=2022-03-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1635471, encodeId=958a16354e143, content=<a href='/topic/show?id=b099549160a' target=_blank style='color:#2F92EE;'>#抑制作用#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54916, encryptionId=b099549160a, topicName=抑制作用)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6cd322475383, createdName=124987a0m73(暂无昵称), createdTime=Sun Oct 24 03:48:05 CST 2021, time=2021-10-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1885215, encodeId=b58b188521527, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sun Nov 21 06:48:05 CST 2021, time=2021-11-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1308597, encodeId=f478130859e1f, content=<a href='/topic/show?id=240f8e3234' target=_blank style='color:#2F92EE;'>#HER2阳性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8732, encryptionId=240f8e3234, topicName=HER2阳性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8409354, createdName=闆锋旦, createdTime=Wed Jun 09 12:48:05 CST 2021, time=2021-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1312388, encodeId=a06e13123880d, content=<a href='/topic/show?id=e5571193321' target=_blank style='color:#2F92EE;'>#miRNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11933, encryptionId=e5571193321, topicName=miRNA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e87d405, createdName=Homburg, createdTime=Wed Jun 09 12:48:05 CST 2021, time=2021-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1410640, encodeId=598414106406a, content=<a href='/topic/show?id=08ad9264106' target=_blank style='color:#2F92EE;'>#赫赛汀#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92641, encryptionId=08ad9264106, topicName=赫赛汀)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=05462758965, createdName=wrj0122, createdTime=Wed Jun 09 12:48:05 CST 2021, time=2021-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=971808, encodeId=e3349e1808bd, content=嗯, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a09d5516528, createdName=jankin, createdTime=Tue Jun 08 12:51:44 CST 2021, time=2021-06-08, status=1, ipAttribution=)]
    2022-03-03 smallant2002
  5. [GetPortalCommentsPageByObjectIdResponse(id=2088018, encodeId=6dde20880187e, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, 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 Apr 07 13:48:05 CST 2022, time=2022-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1069995, encodeId=b83b1069995c6, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f4f22999147, createdName=denglimoxiaoran, createdTime=Sat Nov 13 22:33:50 CST 2021, time=2021-11-13, status=1, ipAttribution=), 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createdName=smallant2002, createdTime=Thu Mar 03 14:48:05 CST 2022, time=2022-03-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1635471, encodeId=958a16354e143, content=<a href='/topic/show?id=b099549160a' target=_blank style='color:#2F92EE;'>#抑制作用#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54916, encryptionId=b099549160a, topicName=抑制作用)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6cd322475383, createdName=124987a0m73(暂无昵称), createdTime=Sun Oct 24 03:48:05 CST 2021, time=2021-10-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1885215, encodeId=b58b188521527, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sun Nov 21 06:48:05 CST 2021, time=2021-11-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1308597, encodeId=f478130859e1f, content=<a href='/topic/show?id=240f8e3234' target=_blank style='color:#2F92EE;'>#HER2阳性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8732, encryptionId=240f8e3234, topicName=HER2阳性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8409354, createdName=闆锋旦, createdTime=Wed Jun 09 12:48:05 CST 2021, time=2021-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1312388, encodeId=a06e13123880d, content=<a href='/topic/show?id=e5571193321' target=_blank style='color:#2F92EE;'>#miRNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11933, encryptionId=e5571193321, topicName=miRNA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e87d405, createdName=Homburg, createdTime=Wed Jun 09 12:48:05 CST 2021, time=2021-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1410640, encodeId=598414106406a, content=<a href='/topic/show?id=08ad9264106' target=_blank style='color:#2F92EE;'>#赫赛汀#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92641, encryptionId=08ad9264106, topicName=赫赛汀)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=05462758965, createdName=wrj0122, createdTime=Wed Jun 09 12:48:05 CST 2021, time=2021-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=971808, encodeId=e3349e1808bd, content=嗯, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a09d5516528, createdName=jankin, createdTime=Tue Jun 08 12:51:44 CST 2021, time=2021-06-08, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=2088018, encodeId=6dde20880187e, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, 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 Apr 07 13:48:05 CST 2022, time=2022-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1069995, encodeId=b83b1069995c6, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f4f22999147, createdName=denglimoxiaoran, createdTime=Sat Nov 13 22:33:50 CST 2021, time=2021-11-13, status=1, ipAttribution=), 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createdName=smallant2002, createdTime=Thu Mar 03 14:48:05 CST 2022, time=2022-03-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1635471, encodeId=958a16354e143, content=<a href='/topic/show?id=b099549160a' target=_blank style='color:#2F92EE;'>#抑制作用#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54916, encryptionId=b099549160a, topicName=抑制作用)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6cd322475383, createdName=124987a0m73(暂无昵称), createdTime=Sun Oct 24 03:48:05 CST 2021, time=2021-10-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1885215, encodeId=b58b188521527, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sun Nov 21 06:48:05 CST 2021, time=2021-11-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1308597, encodeId=f478130859e1f, content=<a href='/topic/show?id=240f8e3234' target=_blank style='color:#2F92EE;'>#HER2阳性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8732, encryptionId=240f8e3234, topicName=HER2阳性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8409354, createdName=闆锋旦, createdTime=Wed Jun 09 12:48:05 CST 2021, time=2021-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1312388, encodeId=a06e13123880d, content=<a href='/topic/show?id=e5571193321' target=_blank style='color:#2F92EE;'>#miRNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11933, encryptionId=e5571193321, topicName=miRNA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e87d405, createdName=Homburg, createdTime=Wed Jun 09 12:48:05 CST 2021, time=2021-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1410640, encodeId=598414106406a, content=<a href='/topic/show?id=08ad9264106' target=_blank style='color:#2F92EE;'>#赫赛汀#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92641, encryptionId=08ad9264106, topicName=赫赛汀)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=05462758965, createdName=wrj0122, createdTime=Wed Jun 09 12:48:05 CST 2021, time=2021-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=971808, encodeId=e3349e1808bd, content=嗯, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a09d5516528, createdName=jankin, createdTime=Tue Jun 08 12:51:44 CST 2021, time=2021-06-08, status=1, ipAttribution=)]
    2021-11-21 liye789132251
  7. [GetPortalCommentsPageByObjectIdResponse(id=2088018, encodeId=6dde20880187e, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, 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 Apr 07 13:48:05 CST 2022, time=2022-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1069995, encodeId=b83b1069995c6, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f4f22999147, createdName=denglimoxiaoran, createdTime=Sat Nov 13 22:33:50 CST 2021, time=2021-11-13, status=1, ipAttribution=), 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topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sun Nov 21 06:48:05 CST 2021, time=2021-11-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1308597, encodeId=f478130859e1f, content=<a href='/topic/show?id=240f8e3234' target=_blank style='color:#2F92EE;'>#HER2阳性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8732, encryptionId=240f8e3234, topicName=HER2阳性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8409354, createdName=闆锋旦, createdTime=Wed Jun 09 12:48:05 CST 2021, time=2021-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1312388, encodeId=a06e13123880d, content=<a href='/topic/show?id=e5571193321' target=_blank style='color:#2F92EE;'>#miRNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11933, encryptionId=e5571193321, topicName=miRNA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e87d405, createdName=Homburg, createdTime=Wed Jun 09 12:48:05 CST 2021, time=2021-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1410640, encodeId=598414106406a, content=<a href='/topic/show?id=08ad9264106' target=_blank style='color:#2F92EE;'>#赫赛汀#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92641, encryptionId=08ad9264106, topicName=赫赛汀)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=05462758965, createdName=wrj0122, createdTime=Wed Jun 09 12:48:05 CST 2021, time=2021-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=971808, encodeId=e3349e1808bd, content=嗯, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a09d5516528, createdName=jankin, createdTime=Tue Jun 08 12:51:44 CST 2021, time=2021-06-08, status=1, ipAttribution=)]
  8. [GetPortalCommentsPageByObjectIdResponse(id=2088018, encodeId=6dde20880187e, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, 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 Apr 07 13:48:05 CST 2022, time=2022-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1069995, encodeId=b83b1069995c6, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f4f22999147, createdName=denglimoxiaoran, createdTime=Sat Nov 13 22:33:50 CST 2021, time=2021-11-13, status=1, ipAttribution=), 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createdName=smallant2002, createdTime=Thu Mar 03 14:48:05 CST 2022, time=2022-03-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1635471, encodeId=958a16354e143, content=<a href='/topic/show?id=b099549160a' target=_blank style='color:#2F92EE;'>#抑制作用#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54916, encryptionId=b099549160a, topicName=抑制作用)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6cd322475383, createdName=124987a0m73(暂无昵称), createdTime=Sun Oct 24 03:48:05 CST 2021, time=2021-10-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1885215, encodeId=b58b188521527, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sun Nov 21 06:48:05 CST 2021, time=2021-11-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1308597, encodeId=f478130859e1f, content=<a href='/topic/show?id=240f8e3234' target=_blank style='color:#2F92EE;'>#HER2阳性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8732, encryptionId=240f8e3234, topicName=HER2阳性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8409354, createdName=闆锋旦, createdTime=Wed Jun 09 12:48:05 CST 2021, time=2021-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1312388, encodeId=a06e13123880d, content=<a href='/topic/show?id=e5571193321' target=_blank style='color:#2F92EE;'>#miRNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11933, encryptionId=e5571193321, topicName=miRNA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e87d405, createdName=Homburg, createdTime=Wed Jun 09 12:48:05 CST 2021, time=2021-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1410640, encodeId=598414106406a, content=<a href='/topic/show?id=08ad9264106' target=_blank style='color:#2F92EE;'>#赫赛汀#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92641, encryptionId=08ad9264106, topicName=赫赛汀)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=05462758965, createdName=wrj0122, createdTime=Wed Jun 09 12:48:05 CST 2021, time=2021-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=971808, encodeId=e3349e1808bd, content=嗯, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a09d5516528, createdName=jankin, createdTime=Tue Jun 08 12:51:44 CST 2021, time=2021-06-08, status=1, ipAttribution=)]
    2021-06-09 Homburg
  9. [GetPortalCommentsPageByObjectIdResponse(id=2088018, encodeId=6dde20880187e, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, 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 Apr 07 13:48:05 CST 2022, time=2022-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1069995, encodeId=b83b1069995c6, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f4f22999147, createdName=denglimoxiaoran, createdTime=Sat Nov 13 22:33:50 CST 2021, time=2021-11-13, status=1, ipAttribution=), 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topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sun Nov 21 06:48:05 CST 2021, time=2021-11-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1308597, encodeId=f478130859e1f, content=<a href='/topic/show?id=240f8e3234' target=_blank style='color:#2F92EE;'>#HER2阳性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8732, encryptionId=240f8e3234, topicName=HER2阳性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8409354, createdName=闆锋旦, createdTime=Wed Jun 09 12:48:05 CST 2021, time=2021-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1312388, encodeId=a06e13123880d, content=<a href='/topic/show?id=e5571193321' target=_blank style='color:#2F92EE;'>#miRNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11933, encryptionId=e5571193321, topicName=miRNA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e87d405, createdName=Homburg, createdTime=Wed Jun 09 12:48:05 CST 2021, time=2021-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1410640, encodeId=598414106406a, content=<a href='/topic/show?id=08ad9264106' target=_blank style='color:#2F92EE;'>#赫赛汀#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92641, encryptionId=08ad9264106, topicName=赫赛汀)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=05462758965, createdName=wrj0122, createdTime=Wed Jun 09 12:48:05 CST 2021, time=2021-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=971808, encodeId=e3349e1808bd, content=嗯, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a09d5516528, createdName=jankin, createdTime=Tue Jun 08 12:51:44 CST 2021, time=2021-06-08, status=1, ipAttribution=)]
    2021-06-09 wrj0122
  10. [GetPortalCommentsPageByObjectIdResponse(id=2088018, encodeId=6dde20880187e, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, 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 Apr 07 13:48:05 CST 2022, time=2022-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1069995, encodeId=b83b1069995c6, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f4f22999147, createdName=denglimoxiaoran, createdTime=Sat Nov 13 22:33:50 CST 2021, time=2021-11-13, status=1, ipAttribution=), 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createdName=smallant2002, createdTime=Thu Mar 03 14:48:05 CST 2022, time=2022-03-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1635471, encodeId=958a16354e143, content=<a href='/topic/show?id=b099549160a' target=_blank style='color:#2F92EE;'>#抑制作用#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54916, encryptionId=b099549160a, topicName=抑制作用)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6cd322475383, createdName=124987a0m73(暂无昵称), createdTime=Sun Oct 24 03:48:05 CST 2021, time=2021-10-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1885215, encodeId=b58b188521527, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sun Nov 21 06:48:05 CST 2021, time=2021-11-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1308597, encodeId=f478130859e1f, content=<a href='/topic/show?id=240f8e3234' target=_blank style='color:#2F92EE;'>#HER2阳性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8732, encryptionId=240f8e3234, topicName=HER2阳性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8409354, createdName=闆锋旦, createdTime=Wed Jun 09 12:48:05 CST 2021, time=2021-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1312388, encodeId=a06e13123880d, content=<a href='/topic/show?id=e5571193321' target=_blank style='color:#2F92EE;'>#miRNA#</a>, beContent=null, 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    2021-06-08 jankin

    0

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