Br J Cancer:缺氧能够增加胶质母细胞瘤的进化速度

2020-08-30 QQY MedSci原创

众所周知,肿瘤微环境由多种影响肿瘤细胞适应性的元素组成,而氧气作为肿瘤微环境中的一个关键元素,其在患者的预后中起着至关重要的作用。临床研究发现,缺氧肿瘤组织在治疗上明显差于富氧肿瘤组织,然而氧气作为已

众所周知,肿瘤微环境由多种影响肿瘤细胞适应性的元素组成,而氧气作为肿瘤微环境中的一个关键元素,其在患者的预后中起着至关重要的作用。临床研究发现,缺氧肿瘤组织在治疗上明显差于富氧肿瘤组织,然而氧气作为已知的一种选择性压力,这种压力却有利于某些能够耐受恶劣环境且能够从原生处转移的侵略性癌细胞类型。


既往研究显示,缺氧与肿瘤的转移性相关,尽管已提出了多种机制来解释这一现象,但目前还无法知晓该现象是某一种确切的机制作为关键原因还是多种机制共同作用的结果。

肿瘤进化不仅能够通过遗传和表观遗传上的突变,还能够通过肿瘤细胞、正常细胞和物理微环境之间的相互作用的选择来促进癌症的发生发展和提高对于肿瘤治疗的抵抗力。


在该研究中,研究人员主要采用了数学模型和组织学相结合的方法,通过模拟不同氧气利用率情况下的细胞增殖能力,来分析相对于常氧区域而言缺氧区域对于细胞克隆形成的影响,且分析肿瘤细胞应力增加是否会加快肿瘤进化速度。同时与来自胶质母细胞瘤患者的组织样本相比,通过染色的方式来阐明组织中坏死区域和TP53表达区域的异质性。


研究结果显示,在低氧环境中的细胞分裂水平被有效地上调,说明低氧环境为肿瘤细胞的扩散提供了途径。同样的人组织数据分析表明,在缺氧条件下,细胞分裂能力并未减少,与上述结果一致。研究人员表明低氧条件可能有效的影响肿瘤的进化速度,从而提高出现关键突变的可能性。

综上所述,重要的肿瘤微环境(如低氧状态)可能会改变肿瘤进化的速度,驱动肿瘤突变的产生并加剧肿瘤的异质性。

原始出处:

Grimes, D.R., Jansen, M., Macauley, R.J. et al. Evidence for hypoxia increasing the tempo of evolution in glioblastoma. Br J Cancer (27 August 2020).

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    2020-08-31 ms9000001488433317

    学习

    0

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    2020-08-30 金黎明

    怎能预防缺氧?

    2

    展开2条回复
  6. [GetPortalCommentsPageByObjectIdResponse(id=1772363, encodeId=056c1e723632a, content=<a href='/topic/show?id=c38963544cc' target=_blank style='color:#2F92EE;'>#母细胞瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=63544, encryptionId=c38963544cc, topicName=母细胞瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b07438375157, createdName=huperzia, createdTime=Tue Feb 09 12:14:17 CST 2021, time=2021-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2052934, encodeId=1ac3205293456, content=<a href='/topic/show?id=ae848406335' target=_blank style='color:#2F92EE;'>#胶质母细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84063, encryptionId=ae848406335, topicName=胶质母细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a691420, createdName=30397604, createdTime=Thu Jun 03 22:14:17 CST 2021, time=2021-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1476094, encodeId=c37514e609427, content=<a href='/topic/show?id=2bcee797732' target=_blank style='color:#2F92EE;'>#细胞瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77977, encryptionId=2bcee797732, topicName=细胞瘤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf5e7252474, createdName=spoonycyy, createdTime=Tue Sep 01 07:14:17 CST 2020, time=2020-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=881308, encodeId=f80688130894, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=34125414512, createdName=ms9000001488433317, createdTime=Mon Aug 31 10:52:00 CST 2020, time=2020-08-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=881019, encodeId=35268810198e, content=怎能预防缺氧?, beContent=null, objectType=article, channel=null, level=null, likeNumber=89, replyNumber=2, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a5af5325692, createdName=金黎明, createdTime=Sun Aug 30 19:20:37 CST 2020, time=2020-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=881022, encodeId=9c73881022c2, content=重要的<a href='/topic/show?id=f0838291817' target=_blank style='color:#2F92EE;'>#肿瘤微环境#</a>(如低氧状态)可能会改变肿瘤进化的速度,驱动肿瘤突变的产生并加剧<a href='/topic/show?id=d3e3829103f' target=_blank style='color:#2F92EE;'>#肿瘤异质性#</a>。事实上,乏氧状态下,肿瘤处于无氧代谢,会产生大量的<a href='/topic/show?id=7dc98629006' target=_blank style='color:#2F92EE;'>#自由基#</a>ROS,这些自由基会打断DNA链,从而诱发各种各样的突变,有些突变则有利于肿瘤在<a href='/topic/show?id=41db10385131' target=_blank style='color:#2F92EE;'>#乏氧状态#</a>下存活,于是建立新的优势突变株。, beContent=null, objectType=article, channel=null, level=null, likeNumber=186, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82918, encryptionId=f0838291817, topicName=肿瘤微环境), TopicDto(id=82910, encryptionId=d3e3829103f, topicName=肿瘤异质性), TopicDto(id=86290, encryptionId=7dc98629006, topicName=自由基), TopicDto(id=103851, encryptionId=41db10385131, topicName=乏氧状态)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Sun Aug 30 19:30:24 CST 2020, time=2020-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=880999, encodeId=23a5880999f3, content=了解, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuOgo3iaicb1Imgk1yIfnvr6oXzibcAFB6puAyNJXbzWhNuLqaFYBVRWjh7rghkvFLPxMAfD5ib3nXwVD/0, createdBy=bed21972958, createdName=wxl882001, createdTime=Sun Aug 30 17:43:58 CST 2020, time=2020-08-30, status=1, ipAttribution=)]
    2020-08-30 lovetcm

    重要的#肿瘤微环境#(如低氧状态)可能会改变肿瘤进化的速度,驱动肿瘤突变的产生并加剧#肿瘤异质性#。事实上,乏氧状态下,肿瘤处于无氧代谢,会产生大量的#自由基#ROS,这些自由基会打断DNA链,从而诱发各种各样的突变,有些突变则有利于肿瘤在#乏氧状态#下存活,于是建立新的优势突变株。

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1772363, encodeId=056c1e723632a, content=<a href='/topic/show?id=c38963544cc' target=_blank style='color:#2F92EE;'>#母细胞瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=63544, encryptionId=c38963544cc, topicName=母细胞瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b07438375157, createdName=huperzia, createdTime=Tue Feb 09 12:14:17 CST 2021, time=2021-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2052934, encodeId=1ac3205293456, content=<a href='/topic/show?id=ae848406335' target=_blank style='color:#2F92EE;'>#胶质母细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84063, encryptionId=ae848406335, topicName=胶质母细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a691420, createdName=30397604, createdTime=Thu Jun 03 22:14:17 CST 2021, time=2021-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1476094, encodeId=c37514e609427, content=<a href='/topic/show?id=2bcee797732' target=_blank style='color:#2F92EE;'>#细胞瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77977, encryptionId=2bcee797732, topicName=细胞瘤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf5e7252474, createdName=spoonycyy, createdTime=Tue Sep 01 07:14:17 CST 2020, time=2020-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=881308, encodeId=f80688130894, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=34125414512, createdName=ms9000001488433317, createdTime=Mon Aug 31 10:52:00 CST 2020, time=2020-08-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=881019, encodeId=35268810198e, content=怎能预防缺氧?, beContent=null, objectType=article, channel=null, level=null, likeNumber=89, replyNumber=2, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a5af5325692, createdName=金黎明, createdTime=Sun Aug 30 19:20:37 CST 2020, time=2020-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=881022, encodeId=9c73881022c2, content=重要的<a href='/topic/show?id=f0838291817' target=_blank style='color:#2F92EE;'>#肿瘤微环境#</a>(如低氧状态)可能会改变肿瘤进化的速度,驱动肿瘤突变的产生并加剧<a href='/topic/show?id=d3e3829103f' target=_blank style='color:#2F92EE;'>#肿瘤异质性#</a>。事实上,乏氧状态下,肿瘤处于无氧代谢,会产生大量的<a href='/topic/show?id=7dc98629006' target=_blank style='color:#2F92EE;'>#自由基#</a>ROS,这些自由基会打断DNA链,从而诱发各种各样的突变,有些突变则有利于肿瘤在<a href='/topic/show?id=41db10385131' target=_blank style='color:#2F92EE;'>#乏氧状态#</a>下存活,于是建立新的优势突变株。, beContent=null, objectType=article, channel=null, level=null, likeNumber=186, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82918, encryptionId=f0838291817, topicName=肿瘤微环境), TopicDto(id=82910, encryptionId=d3e3829103f, topicName=肿瘤异质性), TopicDto(id=86290, encryptionId=7dc98629006, topicName=自由基), TopicDto(id=103851, encryptionId=41db10385131, topicName=乏氧状态)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Sun Aug 30 19:30:24 CST 2020, time=2020-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=880999, encodeId=23a5880999f3, content=了解, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuOgo3iaicb1Imgk1yIfnvr6oXzibcAFB6puAyNJXbzWhNuLqaFYBVRWjh7rghkvFLPxMAfD5ib3nXwVD/0, createdBy=bed21972958, createdName=wxl882001, createdTime=Sun Aug 30 17:43:58 CST 2020, time=2020-08-30, status=1, ipAttribution=)]
    2020-08-30 wxl882001

    了解

    0

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