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Clin Cancer Res：MEK抑制剂单独或联合mTOR抑制剂对头颈部鳞状细胞癌的抗肿瘤作用

2015-05-17 范伟译 MedSci原创

PD-0325901PF-5212384头颈部鳞状细胞癌抗肿瘤作用
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目的：头颈部鳞状细胞癌对PI3K(磷酸肌醇3-激酶)/ mTOR(哺乳动物雷帕霉素)信号通路表现出不同的敏感性，这个癌症基因组类型中有重要靶标基因的改变。MEK(促分裂原活化的蛋白激酶激酶)/ERK(胞外信号调节激酶)/ AP-1(激活蛋白1)和NF-κB(核因子-κB)信号通路也经常被共同激活，但它们在PI3K / mTOR抵抗机制中的角色以及头颈部鳞状细

目的：头颈部鳞状细胞癌对PI3K(磷酸肌醇3-激酶)/ mTOR(哺乳动物雷帕霉素)信号通路表现出不同的敏感性，这个癌症基因组类型中有重要靶标基因的改变。MEK(促分裂原活化的蛋白激酶激酶)/ERK(胞外信号调节激酶)/ AP-1(激活蛋白1)和NF-κB(核因子-κB)信号通路也经常被共同激活，但它们在PI3K / mTOR抵抗机制中的角色以及头颈部鳞状细胞癌HNSCC中的治疗靶标目前并不清楚。

实验设计：我们测定双重PI3K/mTOR抑制剂PF-05212384(PF-384)的IC50值，通过对14个PI3K /Akt/mTOR级联变化的HNSCC细胞系进行XTT测定。在两个耐药模型中，我们进一步观察PF- 384和MEK抑制剂PD - 0325901(PD-901)对细胞的在体影响。

结果：在14个PIK3CA过表达或者突变的HNSCC细胞系中，PF-384的IC50值在0.75 nM-133nM之间变化，敏感性与增加的磷酸化-AKT(T308/S473)相关。在耐药UMSCC-1和46模型中，PF-384增加G0/G1期的积累但较弱的诱导sub-G0期的细胞凋亡。PF-384抑制PI3K-mTOR的直接靶标，但在体内不完全减弱的共同激活ERK和UMSCC-1异种移植的增长。PD- 901强烈抑制MEK /ERK靶标，PF-384和PD-901的联合使用抑制下游NF-κB和AP-1 的反向激活以及IL-8和VEGF在体外的产生。PD-901单独或者联合PF384强有力地抑制肿瘤的生长，增强抗-增殖、凋亡和体内抗血管生成活性。

结论：在不同头颈部鳞状细胞癌细胞系伴有不同PIK3C表达和突变状态，PI3K/mTOR抑制剂PF- 384呈现出不同的活性。MEK抑制剂PD-901克服耐药，与PF-384联合使能，能增强体内的抗肿瘤效果。

原始出处：

Mohan S1, Vander Broek R1, Shah S1, Eytan DF1, Pierce M1, Carlson SG1, Coupar JF1, Zhang J1, Cheng H1, Chen Z1, Van Waes C2.MEK inhibitor PD-0325901 overcomes resistance to PI3K/mTOR inhibitor PF5212384 and potentiates antitumor effects in human head and neck squamous cell carcinoma. Clin Cancer Res. 2015 May 14. pii: clincanres.3377.2015.

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    2016-02-04 naiwu77

    #MEK#

    0

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    2016-01-16 qingting

    #细胞癌#

    0

  3. 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content=学习，再学习！, beContent=null, objectType=article, channel=null, level=null, likeNumber=116, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=yydlt, createdTime=Mon May 18 08:17:00 CST 2015, time=2015-05-18, status=1, ipAttribution=)]
    2015-10-07 jklm09

    #抑制剂#

    0

  4. 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createdName=qingting, createdTime=Sat Jan 16 15:05:00 CST 2016, time=2016-01-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851246, encodeId=9ea71851246b1, 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=33, 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=Wed Oct 07 03:05:00 CST 2015, time=2015-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1297673, encodeId=a2ce129e673f0, content=<a href='/topic/show?id=f999444352f' target=_blank style='color:#2F92EE;'>#头颈部鳞状细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44435, encryptionId=f999444352f, topicName=头颈部鳞状细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c48a270, createdName=Smile2680, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1489887, encodeId=f270148988e97, content=<a href='/topic/show?id=df661233631' target=_blank style='color:#2F92EE;'>#mTOR抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12336, encryptionId=df661233631, topicName=mTOR抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7f708628038, createdName=yankaienglish, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1491763, encodeId=572a1491e6340, content=<a href='/topic/show?id=b4f14442346' target=_blank style='color:#2F92EE;'>#头颈部#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44423, encryptionId=b4f14442346, topicName=头颈部)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0b2d8903151, createdName=wshxjq, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1512726, encodeId=47171512e263a, content=<a href='/topic/show?id=c3e91152873' target=_blank style='color:#2F92EE;'>#MEK抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11528, encryptionId=c3e91152873, topicName=MEK抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=318b10497059, createdName=ms2186806800017884, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1589686, encodeId=22631589686d5, content=<a href='/topic/show?id=124d10065220' target=_blank style='color:#2F92EE;'>#颈部#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=100652, encryptionId=124d10065220, topicName=颈部)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c46a17776631, createdName=木头人519, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=24010, encodeId=abd924010e8, content=好好深的研究！, beContent=null, objectType=article, channel=null, level=null, likeNumber=115, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=yydlt, createdTime=Mon May 18 08:18:00 CST 2015, time=2015-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=24009, encodeId=fcea24009ba, content=学习，再学习！, beContent=null, objectType=article, channel=null, level=null, likeNumber=116, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=yydlt, createdTime=Mon May 18 08:17:00 CST 2015, time=2015-05-18, status=1, ipAttribution=)]
    2015-05-19 Smile2680

    #头颈部鳞状细胞癌#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1943879, encodeId=99a119438e9c6, content=<a href='/topic/show?id=d2af1152597' target=_blank style='color:#2F92EE;'>#MEK#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11525, encryptionId=d2af1152597, topicName=MEK)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5b0e350, createdName=naiwu77, createdTime=Thu Feb 04 10:05:00 CST 2016, time=2016-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1978412, encodeId=c11b19e84120e, content=<a href='/topic/show?id=3b90e79787f' target=_blank style='color:#2F92EE;'>#细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77978, encryptionId=3b90e79787f, topicName=细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e457184, createdName=qingting, createdTime=Sat Jan 16 15:05:00 CST 2016, time=2016-01-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851246, encodeId=9ea71851246b1, 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=33, 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=Wed Oct 07 03:05:00 CST 2015, time=2015-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1297673, encodeId=a2ce129e673f0, content=<a href='/topic/show?id=f999444352f' target=_blank style='color:#2F92EE;'>#头颈部鳞状细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44435, encryptionId=f999444352f, topicName=头颈部鳞状细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c48a270, createdName=Smile2680, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1489887, encodeId=f270148988e97, content=<a href='/topic/show?id=df661233631' target=_blank style='color:#2F92EE;'>#mTOR抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12336, encryptionId=df661233631, topicName=mTOR抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7f708628038, createdName=yankaienglish, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1491763, encodeId=572a1491e6340, content=<a href='/topic/show?id=b4f14442346' target=_blank style='color:#2F92EE;'>#头颈部#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44423, encryptionId=b4f14442346, topicName=头颈部)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0b2d8903151, createdName=wshxjq, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1512726, encodeId=47171512e263a, content=<a href='/topic/show?id=c3e91152873' target=_blank style='color:#2F92EE;'>#MEK抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11528, encryptionId=c3e91152873, topicName=MEK抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=318b10497059, createdName=ms2186806800017884, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1589686, encodeId=22631589686d5, content=<a href='/topic/show?id=124d10065220' target=_blank style='color:#2F92EE;'>#颈部#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=100652, encryptionId=124d10065220, topicName=颈部)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c46a17776631, createdName=木头人519, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=24010, encodeId=abd924010e8, content=好好深的研究！, beContent=null, objectType=article, channel=null, level=null, likeNumber=115, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=yydlt, createdTime=Mon May 18 08:18:00 CST 2015, time=2015-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=24009, encodeId=fcea24009ba, content=学习，再学习！, beContent=null, objectType=article, channel=null, level=null, likeNumber=116, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=yydlt, createdTime=Mon May 18 08:17:00 CST 2015, time=2015-05-18, status=1, ipAttribution=)]
    2015-05-19 yankaienglish

    #mTOR抑制剂#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1943879, encodeId=99a119438e9c6, content=<a href='/topic/show?id=d2af1152597' target=_blank style='color:#2F92EE;'>#MEK#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11525, encryptionId=d2af1152597, topicName=MEK)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5b0e350, createdName=naiwu77, createdTime=Thu Feb 04 10:05:00 CST 2016, time=2016-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1978412, encodeId=c11b19e84120e, content=<a href='/topic/show?id=3b90e79787f' target=_blank style='color:#2F92EE;'>#细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77978, encryptionId=3b90e79787f, topicName=细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e457184, createdName=qingting, createdTime=Sat Jan 16 15:05:00 CST 2016, time=2016-01-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851246, encodeId=9ea71851246b1, 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=33, 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=Wed Oct 07 03:05:00 CST 2015, time=2015-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1297673, encodeId=a2ce129e673f0, content=<a href='/topic/show?id=f999444352f' target=_blank style='color:#2F92EE;'>#头颈部鳞状细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44435, encryptionId=f999444352f, topicName=头颈部鳞状细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c48a270, createdName=Smile2680, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1489887, encodeId=f270148988e97, content=<a href='/topic/show?id=df661233631' target=_blank style='color:#2F92EE;'>#mTOR抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12336, encryptionId=df661233631, topicName=mTOR抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7f708628038, createdName=yankaienglish, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1491763, encodeId=572a1491e6340, content=<a href='/topic/show?id=b4f14442346' target=_blank style='color:#2F92EE;'>#头颈部#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44423, encryptionId=b4f14442346, topicName=头颈部)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0b2d8903151, createdName=wshxjq, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1512726, encodeId=47171512e263a, content=<a href='/topic/show?id=c3e91152873' target=_blank style='color:#2F92EE;'>#MEK抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11528, encryptionId=c3e91152873, topicName=MEK抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=318b10497059, createdName=ms2186806800017884, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1589686, encodeId=22631589686d5, content=<a href='/topic/show?id=124d10065220' target=_blank style='color:#2F92EE;'>#颈部#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=100652, encryptionId=124d10065220, topicName=颈部)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c46a17776631, createdName=木头人519, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=24010, encodeId=abd924010e8, content=好好深的研究！, beContent=null, objectType=article, channel=null, level=null, likeNumber=115, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=yydlt, createdTime=Mon May 18 08:18:00 CST 2015, time=2015-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=24009, encodeId=fcea24009ba, content=学习，再学习！, beContent=null, objectType=article, channel=null, level=null, likeNumber=116, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=yydlt, createdTime=Mon May 18 08:17:00 CST 2015, time=2015-05-18, status=1, ipAttribution=)]
    2015-05-19 wshxjq

    #头颈部#

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1943879, encodeId=99a119438e9c6, content=<a href='/topic/show?id=d2af1152597' target=_blank style='color:#2F92EE;'>#MEK#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11525, encryptionId=d2af1152597, topicName=MEK)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5b0e350, createdName=naiwu77, createdTime=Thu Feb 04 10:05:00 CST 2016, time=2016-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1978412, encodeId=c11b19e84120e, content=<a href='/topic/show?id=3b90e79787f' target=_blank style='color:#2F92EE;'>#细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77978, encryptionId=3b90e79787f, topicName=细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e457184, 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encryptionId=f999444352f, topicName=头颈部鳞状细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c48a270, createdName=Smile2680, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1489887, encodeId=f270148988e97, content=<a href='/topic/show?id=df661233631' target=_blank style='color:#2F92EE;'>#mTOR抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12336, encryptionId=df661233631, topicName=mTOR抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7f708628038, createdName=yankaienglish, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1491763, encodeId=572a1491e6340, content=<a href='/topic/show?id=b4f14442346' target=_blank style='color:#2F92EE;'>#头颈部#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44423, encryptionId=b4f14442346, topicName=头颈部)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0b2d8903151, createdName=wshxjq, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1512726, encodeId=47171512e263a, content=<a href='/topic/show?id=c3e91152873' target=_blank style='color:#2F92EE;'>#MEK抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11528, encryptionId=c3e91152873, topicName=MEK抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=318b10497059, createdName=ms2186806800017884, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1589686, encodeId=22631589686d5, content=<a href='/topic/show?id=124d10065220' target=_blank style='color:#2F92EE;'>#颈部#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=100652, encryptionId=124d10065220, topicName=颈部)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c46a17776631, createdName=木头人519, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=24010, encodeId=abd924010e8, content=好好深的研究！, beContent=null, objectType=article, channel=null, level=null, likeNumber=115, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=yydlt, createdTime=Mon May 18 08:18:00 CST 2015, time=2015-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=24009, encodeId=fcea24009ba, content=学习，再学习！, beContent=null, objectType=article, channel=null, level=null, likeNumber=116, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=yydlt, createdTime=Mon May 18 08:17:00 CST 2015, time=2015-05-18, status=1, ipAttribution=)]
    2015-05-19 ms2186806800017884

    #MEK抑制剂#

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1943879, encodeId=99a119438e9c6, content=<a href='/topic/show?id=d2af1152597' target=_blank style='color:#2F92EE;'>#MEK#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11525, encryptionId=d2af1152597, topicName=MEK)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5b0e350, createdName=naiwu77, createdTime=Thu Feb 04 10:05:00 CST 2016, time=2016-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1978412, encodeId=c11b19e84120e, content=<a href='/topic/show?id=3b90e79787f' target=_blank style='color:#2F92EE;'>#细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77978, encryptionId=3b90e79787f, topicName=细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e457184, createdName=qingting, createdTime=Sat Jan 16 15:05:00 CST 2016, time=2016-01-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851246, encodeId=9ea71851246b1, 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=33, 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=Wed Oct 07 03:05:00 CST 2015, time=2015-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1297673, encodeId=a2ce129e673f0, content=<a href='/topic/show?id=f999444352f' target=_blank style='color:#2F92EE;'>#头颈部鳞状细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44435, encryptionId=f999444352f, topicName=头颈部鳞状细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c48a270, createdName=Smile2680, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1489887, encodeId=f270148988e97, content=<a href='/topic/show?id=df661233631' target=_blank style='color:#2F92EE;'>#mTOR抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12336, encryptionId=df661233631, topicName=mTOR抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7f708628038, createdName=yankaienglish, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1491763, encodeId=572a1491e6340, content=<a href='/topic/show?id=b4f14442346' target=_blank style='color:#2F92EE;'>#头颈部#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44423, encryptionId=b4f14442346, topicName=头颈部)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0b2d8903151, createdName=wshxjq, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1512726, encodeId=47171512e263a, content=<a href='/topic/show?id=c3e91152873' target=_blank style='color:#2F92EE;'>#MEK抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11528, encryptionId=c3e91152873, topicName=MEK抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=318b10497059, createdName=ms2186806800017884, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1589686, encodeId=22631589686d5, content=<a href='/topic/show?id=124d10065220' target=_blank style='color:#2F92EE;'>#颈部#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=100652, encryptionId=124d10065220, topicName=颈部)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c46a17776631, createdName=木头人519, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=24010, encodeId=abd924010e8, content=好好深的研究！, beContent=null, objectType=article, channel=null, level=null, likeNumber=115, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=yydlt, createdTime=Mon May 18 08:18:00 CST 2015, time=2015-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=24009, encodeId=fcea24009ba, content=学习，再学习！, beContent=null, objectType=article, channel=null, level=null, likeNumber=116, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=yydlt, createdTime=Mon May 18 08:17:00 CST 2015, time=2015-05-18, status=1, ipAttribution=)]
    2015-05-19 木头人519

    #颈部#

    0

  9. [GetPortalCommentsPageByObjectIdResponse(id=1943879, encodeId=99a119438e9c6, content=<a href='/topic/show?id=d2af1152597' target=_blank style='color:#2F92EE;'>#MEK#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11525, encryptionId=d2af1152597, topicName=MEK)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5b0e350, createdName=naiwu77, createdTime=Thu Feb 04 10:05:00 CST 2016, time=2016-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1978412, encodeId=c11b19e84120e, content=<a href='/topic/show?id=3b90e79787f' target=_blank style='color:#2F92EE;'>#细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77978, encryptionId=3b90e79787f, topicName=细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e457184, createdName=qingting, createdTime=Sat Jan 16 15:05:00 CST 2016, time=2016-01-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851246, encodeId=9ea71851246b1, 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=33, 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=Wed Oct 07 03:05:00 CST 2015, time=2015-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1297673, encodeId=a2ce129e673f0, content=<a href='/topic/show?id=f999444352f' target=_blank style='color:#2F92EE;'>#头颈部鳞状细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44435, encryptionId=f999444352f, topicName=头颈部鳞状细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c48a270, createdName=Smile2680, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1489887, encodeId=f270148988e97, content=<a href='/topic/show?id=df661233631' target=_blank style='color:#2F92EE;'>#mTOR抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12336, encryptionId=df661233631, topicName=mTOR抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7f708628038, createdName=yankaienglish, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1491763, encodeId=572a1491e6340, content=<a href='/topic/show?id=b4f14442346' target=_blank style='color:#2F92EE;'>#头颈部#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44423, encryptionId=b4f14442346, topicName=头颈部)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0b2d8903151, createdName=wshxjq, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1512726, encodeId=47171512e263a, content=<a href='/topic/show?id=c3e91152873' target=_blank style='color:#2F92EE;'>#MEK抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11528, encryptionId=c3e91152873, topicName=MEK抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=318b10497059, createdName=ms2186806800017884, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1589686, encodeId=22631589686d5, content=<a href='/topic/show?id=124d10065220' target=_blank style='color:#2F92EE;'>#颈部#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=100652, encryptionId=124d10065220, topicName=颈部)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c46a17776631, createdName=木头人519, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=24010, encodeId=abd924010e8, content=好好深的研究！, beContent=null, objectType=article, channel=null, level=null, likeNumber=115, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=yydlt, createdTime=Mon May 18 08:18:00 CST 2015, time=2015-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=24009, encodeId=fcea24009ba, content=学习，再学习！, beContent=null, objectType=article, channel=null, level=null, likeNumber=116, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=yydlt, createdTime=Mon May 18 08:17:00 CST 2015, time=2015-05-18, status=1, ipAttribution=)]
    2015-05-18 yydlt

    好好深的研究！

    0

  10. [GetPortalCommentsPageByObjectIdResponse(id=1943879, encodeId=99a119438e9c6, content=<a href='/topic/show?id=d2af1152597' target=_blank style='color:#2F92EE;'>#MEK#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11525, encryptionId=d2af1152597, topicName=MEK)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5b0e350, createdName=naiwu77, createdTime=Thu Feb 04 10:05:00 CST 2016, time=2016-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1978412, encodeId=c11b19e84120e, content=<a href='/topic/show?id=3b90e79787f' target=_blank style='color:#2F92EE;'>#细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77978, encryptionId=3b90e79787f, topicName=细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e457184, createdName=qingting, createdTime=Sat Jan 16 15:05:00 CST 2016, time=2016-01-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851246, encodeId=9ea71851246b1, 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=33, 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=Wed Oct 07 03:05:00 CST 2015, time=2015-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1297673, encodeId=a2ce129e673f0, content=<a href='/topic/show?id=f999444352f' target=_blank style='color:#2F92EE;'>#头颈部鳞状细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44435, 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objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44423, encryptionId=b4f14442346, topicName=头颈部)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0b2d8903151, createdName=wshxjq, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1512726, encodeId=47171512e263a, content=<a href='/topic/show?id=c3e91152873' target=_blank style='color:#2F92EE;'>#MEK抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11528, encryptionId=c3e91152873, topicName=MEK抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=318b10497059, createdName=ms2186806800017884, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1589686, encodeId=22631589686d5, content=<a href='/topic/show?id=124d10065220' target=_blank style='color:#2F92EE;'>#颈部#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=100652, encryptionId=124d10065220, topicName=颈部)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c46a17776631, createdName=木头人519, createdTime=Tue May 19 04:05:00 CST 2015, time=2015-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=24010, encodeId=abd924010e8, content=好好深的研究！, beContent=null, objectType=article, channel=null, level=null, likeNumber=115, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=yydlt, createdTime=Mon May 18 08:18:00 CST 2015, time=2015-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=24009, encodeId=fcea24009ba, content=学习，再学习！, beContent=null, objectType=article, channel=null, level=null, likeNumber=116, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=yydlt, createdTime=Mon May 18 08:17:00 CST 2015, time=2015-05-18, status=1, ipAttribution=)]
    2015-05-18 yydlt

    学习，再学习！

    0

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