Blood:Pan-SRC激酶抑制剂可阻断非霍奇金淋巴瘤的B细胞受体致瘤信号转导

2018-03-24 MedSci MedSci原创

中心点:抑制对依鲁替尼耐药的患者的BTK,可改变信号肿瘤依赖性,并促进上调MYC。LYN、FYN和BLK多重靶点抑制对独立于其分子亚型的DLBCL患者治疗效果显著。摘要:对于弥漫性大B细胞淋巴瘤(DLBCL),激活B细胞受体(BCR)可促进多种对肿瘤增殖至关重要的致瘤信号。抑制Bruton'酪氨酸激酶(BTK),BCR的下游靶点,仅用于治疗DLBCL患者亚群时效果显著。Elena Battiste

中心点:

抑制对依鲁替尼耐药的患者的BTK,可改变信号肿瘤依赖性,并促进上调MYC。

LYN、FYN和BLK多重靶点抑制对独立于其分子亚型的DLBCL患者治疗效果显著。

摘要:

对于弥漫性大B细胞淋巴瘤(DLBCL),激活B细胞受体(BCR)可促进多种对肿瘤增殖至关重要的致瘤信号。抑制Bruton'酪氨酸激酶(BTK),BCR的下游靶点,仅用于治疗DLBCL患者亚群时效果显著。

Elena Battistello等人利用从DLBCL患者体内分离的淋巴细胞来检测针对BCR信号的靶向治疗的效果并预测其反应。在对BTK抑制耐药的淋巴瘤中,研究人员发现阻滞BTK活性可改变BCR的下游的致瘤信号,进而增强肿瘤的依赖性,并集中于上调MYC表达。

为彻底消除BCR活性,研究人员利用遗传学和药理学手段抑制传导BCR信号的SRC激酶LYN、FYN和BLK的活性。抑制上述激酶活性可显著减缓独立于其分子亚型的DLBCL患者来源的移植瘤和细胞系的生长速度,从而促进相关治疗靶点广泛用于不同亚型的DLBCL患者。

原始出处:

Elena Battistello,et al. Pan-SRC kinase inhibition blocks B-cell receptor oncogenic signaling in non-Hodgkin lymphoma.Blood  2018  :blood-2017-10-809210;  doi: https://doi.org/10.1182/blood-2017-10-809210

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    2018-10-05 zhangxingru
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    2018-12-05 jklm09
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    2018-06-06 1e145228m78(暂无匿称)

    学习了.谢谢作者分享!

    0

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  7. [GetPortalCommentsPageByObjectIdResponse(id=2039881, encodeId=6de92039881f1, content=<a href='/topic/show?id=f7526685963' target=_blank style='color:#2F92EE;'>#激酶抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66859, encryptionId=f7526685963, topicName=激酶抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e76f39, createdName=smartjoy, createdTime=Fri Nov 02 04:45:00 CST 2018, time=2018-11-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1668773, encodeId=e6f71668e73a8, content=<a href='/topic/show?id=2ef9166e565' target=_blank style='color:#2F92EE;'>#SRC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16675, encryptionId=2ef9166e565, topicName=SRC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6e7c26414300, createdName=zhangxingru, createdTime=Fri Oct 05 04:45:00 CST 2018, time=2018-10-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851675, encodeId=b59e18516e580, 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=34, 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 Dec 05 16:45:00 CST 2018, time=2018-12-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1710125, encodeId=24911e1012551, content=<a href='/topic/show?id=7ac59e67604' target=_blank style='color:#2F92EE;'>#阻断#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, 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 Jul 11 08:45:00 CST 2018, time=2018-07-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=322028, encodeId=5bba32202875, content=学习了.谢谢作者分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xJXLtMtt5B40XXuPjn9xn1rBhrM6fHLkX1hI86ZoWoPJkgDkZuJNKkBfBHOcRd1fAdezg7JlHNOokohdAp3WkI/0, createdBy=32c81964262, createdName=1e145228m78(暂无匿称), createdTime=Wed Jun 06 22:27:19 CST 2018, time=2018-06-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1273236, encodeId=e93612e3236f2, content=<a href='/topic/show?id=310d383ef5' target=_blank style='color:#2F92EE;'>#B细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3837, encryptionId=310d383ef5, topicName=B细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6eba113, createdName=xiaoyeshuang, createdTime=Mon Mar 26 03:45:00 CST 2018, time=2018-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1496011, encodeId=c05114960119d, content=<a href='/topic/show?id=9c516685eea' target=_blank style='color:#2F92EE;'>#激酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66857, encryptionId=9c516685eea, topicName=激酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=73449239400, createdName=redcrab, createdTime=Mon Mar 26 03:45:00 CST 2018, time=2018-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=299297, encodeId=438f29929e74, content=学习一下谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zSn0GqHrsfLGSUSR8zwnWWLT4FMl5XH8S58HuZslVkLsAPbXDXaliagK7TOxQfmngKibG1yrDonepCLDkcxGk8hS/0, createdBy=b8282062892, createdName=changjiu, createdTime=Sat Mar 24 17:00:18 CST 2018, time=2018-03-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=299285, encodeId=8fdf299285a7, content=学习一下谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzaiabIFicf63hKvVMjL6aJlx4yX4UcXmzX9DyibCRcicq0QtCRWMaQKh8MYjE1D3EKUBopgiaGWYuqbeR/0, createdBy=0c2b1999806, createdName=三生有幸9135, createdTime=Sat Mar 24 15:54:25 CST 2018, time=2018-03-24, status=1, ipAttribution=)]
    2018-03-26 redcrab
  8. [GetPortalCommentsPageByObjectIdResponse(id=2039881, encodeId=6de92039881f1, content=<a href='/topic/show?id=f7526685963' target=_blank style='color:#2F92EE;'>#激酶抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66859, encryptionId=f7526685963, topicName=激酶抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e76f39, createdName=smartjoy, createdTime=Fri Nov 02 04:45:00 CST 2018, time=2018-11-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1668773, encodeId=e6f71668e73a8, content=<a href='/topic/show?id=2ef9166e565' target=_blank style='color:#2F92EE;'>#SRC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16675, encryptionId=2ef9166e565, topicName=SRC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6e7c26414300, createdName=zhangxingru, createdTime=Fri Oct 05 04:45:00 CST 2018, time=2018-10-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851675, encodeId=b59e18516e580, 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=34, 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 Dec 05 16:45:00 CST 2018, time=2018-12-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1710125, encodeId=24911e1012551, content=<a href='/topic/show?id=7ac59e67604' target=_blank style='color:#2F92EE;'>#阻断#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, 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 Jul 11 08:45:00 CST 2018, time=2018-07-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=322028, encodeId=5bba32202875, content=学习了.谢谢作者分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xJXLtMtt5B40XXuPjn9xn1rBhrM6fHLkX1hI86ZoWoPJkgDkZuJNKkBfBHOcRd1fAdezg7JlHNOokohdAp3WkI/0, createdBy=32c81964262, createdName=1e145228m78(暂无匿称), createdTime=Wed Jun 06 22:27:19 CST 2018, time=2018-06-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1273236, encodeId=e93612e3236f2, content=<a href='/topic/show?id=310d383ef5' target=_blank style='color:#2F92EE;'>#B细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3837, encryptionId=310d383ef5, topicName=B细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6eba113, createdName=xiaoyeshuang, createdTime=Mon Mar 26 03:45:00 CST 2018, time=2018-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1496011, encodeId=c05114960119d, content=<a href='/topic/show?id=9c516685eea' target=_blank style='color:#2F92EE;'>#激酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66857, encryptionId=9c516685eea, topicName=激酶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=73449239400, createdName=redcrab, createdTime=Mon Mar 26 03:45:00 CST 2018, time=2018-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=299297, encodeId=438f29929e74, content=学习一下谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zSn0GqHrsfLGSUSR8zwnWWLT4FMl5XH8S58HuZslVkLsAPbXDXaliagK7TOxQfmngKibG1yrDonepCLDkcxGk8hS/0, createdBy=b8282062892, createdName=changjiu, createdTime=Sat Mar 24 17:00:18 CST 2018, time=2018-03-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=299285, encodeId=8fdf299285a7, content=学习一下谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzaiabIFicf63hKvVMjL6aJlx4yX4UcXmzX9DyibCRcicq0QtCRWMaQKh8MYjE1D3EKUBopgiaGWYuqbeR/0, createdBy=0c2b1999806, createdName=三生有幸9135, createdTime=Sat Mar 24 15:54:25 CST 2018, time=2018-03-24, status=1, ipAttribution=)]
    2018-03-24 changjiu

    学习一下谢谢

    0

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    2018-03-24 三生有幸9135

    学习一下谢谢分享

    0

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高剂量的利妥昔联合化疗+自体干细胞移植可延长弥漫性大B细胞淋巴瘤的高风险年轻患者2年生存期,但患者5年总生存期未得到改善

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中心点:EBV诱导的弥漫性大B细胞淋巴瘤(DLBLs)的特点是Rho通路的基因和转录改变。用ROCK抑制剂,法舒地尔(fasudil)靶向Rho通路,可显着减缓EBV+-DLBLs患者来源的移植瘤(PDX)模式动物的肿瘤的生长速度。摘要:EB病毒(EBV)阳性的弥漫性大B细胞淋巴瘤(EV+-DLBLs)往往发生于免疫功能不全的患者,如老年人或进行固体器官移植的患者。目前,由于缺乏可用的人类样本和缺

Blood:对于限制期DLBCL患者,R-CHOP化疗联合放射治疗的效果并不优于单纯R-CHOP化疗。

限制期弥漫性大B细胞淋巴瘤(DLBCL)化疗后进行放射治疗(RT)的效果尚存在争议。现研究人员招募无大体积肿瘤的(肿瘤大小<7cm)限制期DLBCL患者进行随机试验,来评估用R-CHOP方案化疗后进行RT的效果。

Blood:依鲁替尼联合R-ICE用于复发性/难治性弥漫性大B细胞淋巴瘤患者的I期研究结果

中心点:依鲁替尼联合R-ICE(利妥昔单抗、异环磷酰胺、卡铂和依托泊苷),用于DLBCL患者,安全可耐受,而且不影响造血干血细胞进行自体移植。所有可评估的rel/ref 非-GC DLBCL患者均获得代谢性环境。摘要:在利妥昔单抗时代,大约一半的复发性/难治性(rel/ref)弥漫性大B细胞淋巴瘤(DLBCL)患者对标准补救治疗不能获得化疗敏感反应,因此不能继续进行自体干细胞移植(ASCT)。Br

2018 ILROG指南:复发/难治性弥漫性大B细胞淋巴瘤患者放射治疗的作用

大约30%-40%的弥漫性大B细胞淋巴瘤(DLBCL)患者有原发性难治性疾病或化疗后复发。本文回顾了复发/难治性DLBCL患者放疗的适应证,并针对优化放疗时机,剂量分割方案以及特殊情况下的治疗提出建议。

Blood:原发性纵膈大B细胞淋巴瘤的体细胞IL4R突变,激活JAK-STAT信号通路

原发性纵膈大B细胞淋巴瘤(PMBCL)是一种胸腺髓质B细胞起源的弥漫性大B细胞淋巴瘤的一种特殊亚型。目前该疾病的分子机制所潜在的基因突变尚未完全研究清楚。Elena Vigano等人从15例原发性PMBCL病例(总62例,24.2%)和所有PMBCL来源的细胞系中检测出新发的体细胞IL4R突变。大多数突变(11/21;52%)是在8号外显子的热点单核苷酸突变,导致跨膜区的I242N核苷酸改变。功能