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CANCER CELL：慢性炎症致癌机制揭开

2012-12-04 CANCER CELL CANCER CELL

慢性炎症癌症
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　　据EurekAlert!网站近日报道，虽然以往的科研证实，慢性炎症有可能导致癌症，但这是如何发生的，科学家并不知晓。而美国俄亥俄州立大学综合癌症中心进行的一项新研究显示，人体制造的一种类似于激素的炎症促进物质在处于高水平时，能够引发一种恶性血癌的产生。相关研究报告发表在近期出版的《癌细胞》杂志上。 　　这项研究表明，仅高水平的白细胞介素15（IL-15）一项就可在动物模型中导致大颗粒淋巴细胞

　　据EurekAlert!网站近日报道，虽然以往的科研证实，慢性炎症有可能导致癌症，但这是如何发生的，科学家并不知晓。而美国俄亥俄州立大学综合癌症中心进行的一项新研究显示，人体制造的一种类似于激素的炎症促进物质在处于高水平时，能够引发一种恶性血癌的产生。相关研究报告发表在近期出版的《癌细胞》杂志上。

　　这项研究表明，仅高水平的白细胞介素15（IL-15）一项就可在动物模型中导致大颗粒淋巴细胞白血病的发生，这是一种罕见却常常致命的癌症。科研人员发现，IL-15在患有大颗粒淋巴细胞白血病的患者体内处于过度表达状态，也是它导致了类似的细胞变化。通常，体内会释放IL-15来刺激天然杀手细胞，即可破坏癌细胞和被病毒感染细胞的免疫细胞的发育、生存和增殖。这一研究证实，当IL-15在体内长期以高量水平存在时，例如在病人患有慢性炎症期间，其可能导致名为大颗粒淋巴细胞的特定免疫细胞转变成为癌细胞。

　　这种癌变开始于IL-15与正常的人类大颗粒淋巴细胞表面上的受体结合时，这一事件会提升细胞内部的致癌蛋白质Myc的水平。而高水平的Myc反过来也会带来相关变化，引起染色体的不稳定和额外的基因突变。同时，其还会激活DNA甲基化过程，这个过程将关闭各种各样的基因，其中就包括会抑制癌症生长的重要基因。

　　研究负责人、综合癌症中心的主任迈克尔·卡利朱里博士谈到：“我们知道炎症可以导致癌症，但却不知道其准确的机制。这次的研究展示了恶性白血病可能发生的一种方式，当我们了解它的产生原因时，就可能开发出相应疗法，干扰这个过程，并最终治愈癌症。”

　　该校药剂学和药物化学教授罗伯特·李就根据研究获取的信息，开发出了一种蛋白酶体抑制剂硼替佐米的脂质体剂型。它能关闭致癌路径，有可能治愈这种恶性疾病。




Highlights
A single pro-inflammatory cytokine, IL-15, can initiate malignant transformation
IL-15-mediated induction of Myc is central to the genesis of leukemia
Targeting miR-29b with a single therapeutic induces long-term remission of leukemia

Summary
How inflammation causes cancer is unclear. Interleukin-15 (IL-15) is a pro-inflammatory cytokine elevated in human large granular lymphocyte (LGL) leukemia. Mice overexpressing IL-15 develop LGL leukemia. Here, we show that prolonged in vitro exposure of wild-type (WT) LGL to IL-15 results in Myc-mediated upregulation of aurora kinases, centrosome aberrancies, and aneuploidy. Simultaneously, IL-15 represses miR-29b via induction of Myc/NF-κBp65/Hdac-1, resulting in Dnmt3b overexpression and DNA hypermethylation. All this is validated in human LGL leukemia. Adoptive transfer of WT LGL cultured with IL-15 led to malignant transformation in vivo. Drug targeting that reverses miR-29b repression cures otherwise fatal LGL leukemia. We show how excessive IL-15 initiates cancer and demonstrate effective drug targeting for potential therapy of human LGL leukemia.
    

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    2013-06-02 zhaozhouchifen

    #Cell#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1868602, encodeId=f5a0186860287, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sun Jun 02 16:12:00 CST 2013, time=2013-06-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1780595, encodeId=81b41e8059524, content=<a href='/topic/show?id=517a4016ac' target=_blank style='color:#2F92EE;'>#cancer cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4016, encryptionId=517a4016ac, topicName=cancer cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=96f62500201, createdName=12498e67m28暂无昵称, createdTime=Tue Aug 13 06:12:00 CST 2013, time=2013-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1958835, encodeId=0fec1958835df, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Sun Apr 28 11:12:00 CST 2013, time=2013-04-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1370771, encodeId=397f13e077136, content=<a href='/topic/show?id=9c39864991e' target=_blank style='color:#2F92EE;'>#致癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86499, encryptionId=9c39864991e, topicName=致癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2c25323, createdName=jambiya, createdTime=Thu Dec 06 02:12:00 CST 2012, time=2012-12-06, status=1, ipAttribution=)]
    2013-08-13 12498e67m28暂无昵称

    #cancer cell#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1868602, encodeId=f5a0186860287, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sun Jun 02 16:12:00 CST 2013, time=2013-06-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1780595, encodeId=81b41e8059524, content=<a href='/topic/show?id=517a4016ac' target=_blank style='color:#2F92EE;'>#cancer cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4016, encryptionId=517a4016ac, topicName=cancer cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=96f62500201, createdName=12498e67m28暂无昵称, createdTime=Tue Aug 13 06:12:00 CST 2013, time=2013-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1958835, encodeId=0fec1958835df, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Sun Apr 28 11:12:00 CST 2013, time=2013-04-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1370771, encodeId=397f13e077136, content=<a href='/topic/show?id=9c39864991e' target=_blank style='color:#2F92EE;'>#致癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86499, encryptionId=9c39864991e, topicName=致癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2c25323, createdName=jambiya, createdTime=Thu Dec 06 02:12:00 CST 2012, time=2012-12-06, status=1, ipAttribution=)]
    2013-04-28 维他命

    #CEL#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1868602, encodeId=f5a0186860287, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sun Jun 02 16:12:00 CST 2013, time=2013-06-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1780595, encodeId=81b41e8059524, content=<a href='/topic/show?id=517a4016ac' target=_blank style='color:#2F92EE;'>#cancer cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4016, encryptionId=517a4016ac, topicName=cancer cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=96f62500201, createdName=12498e67m28暂无昵称, createdTime=Tue Aug 13 06:12:00 CST 2013, time=2013-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1958835, encodeId=0fec1958835df, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Sun Apr 28 11:12:00 CST 2013, time=2013-04-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1370771, encodeId=397f13e077136, content=<a href='/topic/show?id=9c39864991e' target=_blank style='color:#2F92EE;'>#致癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86499, encryptionId=9c39864991e, topicName=致癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2c25323, createdName=jambiya, createdTime=Thu Dec 06 02:12:00 CST 2012, time=2012-12-06, status=1, ipAttribution=)]
    2012-12-06 jambiya

    #致癌#

    0

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