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心律失常老药胺碘酮可能抑制肝癌的发生和生长

2015-10-18 MedSci MedSci原创

台湾成功大学医学院研究团队揭开乙型肝炎引发肝癌癌化之谜,更经动物实验,找出心律失常老药胺碘酮(Amiodarone)可抑制约50%的肝肿瘤生长;此药1颗仅8元且毒性不高,未来可望成为晚期肝癌病人在已无其他治疗选项时的另一新契机。老药新用的新发现,起于成大医学院微生物及免疫学研究所特聘教授刘校生带领团队,针对46位罹患乙肝的肝癌病人,研究其体内“自噬小体”与致癌的“微小RNA-224”两个细胞因子,

台湾成功大学医学院研究团队揭开乙型肝炎引发肝癌癌化之谜,更经动物实验,找出心律失常老药胺碘酮(Amiodarone)可抑制约50%的肝肿瘤生长;此药1颗仅8元且毒性不高,未来可望成为晚期肝癌病人在已无其他治疗选项时的另一新契机。


老药新用的新发现,起于成大医学院微生物及免疫学研究所特聘教授刘校生带领团队,针对46位罹患乙肝的肝癌病人,研究其体内“自噬小体”与致癌的“微小RNA-224”两个细胞因子,在肝癌形成过程中的关联。

刘校生指出,境外已有研究发现,临床肝癌病人体内的自噬反应低落、微小RNA-224异常过量,且自噬反应缺失的转殖小鼠,特别容易在肝脏中形成肿瘤,但文献皆尚未找出两者的关联性。
成大研究团队找出93位罹患乙肝或丙肝的肝癌病人,发现其中46位乙肝患者细胞中自噬反应与微小RNA-224大量表现,两者有显著关联,且两因子同时缺失的肝癌病人,术后4年内存活率由80%降到50%以下;丙肝的肝癌病人则无显著关联。

研究进一步以乙肝病毒的基因转殖老鼠,印证乙肝癌化成肝癌的过程中,确实有细胞自噬能力下降与微小RNA-224大量表现,也揭开了乙肝癌化的机制。

刘校生解释,自噬反应主要由细胞内的双层膜胞器“自噬小体”主导,它像清道夫一样,能选择性清除细胞内的垃圾;当微小RNA-224过度生长、累积,会产生致癌因子,也成为自噬小体的清除对象,自噬小体会利用它的双层膜,将微小RNA-224包裹起来,并将之分解。

团队根据以往研究,从3584种小分子药物中,找出心律失常用药Amiodarone可有效增强大鼠细胞的自噬反应,同时分解致癌微小RNA-224,抑制约50%肝肿瘤生长。

刘校生指出,一般治疗肝癌末期患者的标靶药物,1个月至少花费5至10余万新台币不等,Amiodarone 1颗仅8元,且动物实验用量低、用药时间短(约1个月内),未来可望使用于已无其他治疗选择的晚期肝癌病人。

MedSci小编研究:

MedSci小编也是好事者,研究了一下发现早在2001年,国际上一个团队在肝癌研究中,就应用过Amiodarone,主要原因是因为Amiodarone是K+通道抑制剂,它可能抑制肿瘤细胞增殖,或与化疗药物使用,具有增效作用,并进行过相关研究。然而,在2011年一项小型RCT研究中发现,在肝癌者进行碘油TACE中,一组采用Amiodarone+吡柔比星,另一组单独采用阿霉素,并没有看到两组差异。当然,那是一项超小型研究,结果还需要进一步验证。而这项台湾学者的研究,从另一重机制上观察到Amiodarone可能增加了肝癌治疗的可能。但是,基础研究能否转化到临床,还是未知数。

原始出处:

Lan SH, Wu SY, Zuchini R, Lin XZ, Su IJ, Tsai TF, Lin YJ, Wu CT, Liu HS.Autophagy suppresses tumorigenesis of hepatitis B virus-associated hepatocellular carcinomathrough degradation of microRNA-224.Hepatology. 2014 Feb;59(2):505-17.

Lan SH, Wu SY, Zuchini R, Lin XZ, Su IJ, Tsai TF, Lin YJ, Wu CT, Liu HS. Autophagy-preferential degradation of MIR224 participates in hepatocellular carcinomatumorigenesis. Autophagy. 2014 Sep;10(9):1687-9

Boulin M, Ciboulet A, Guiu B, Maillard E, Bonnetain F, Minello A, Gagnaire A, Lepage C, Krause D, Hillon P, Bedenne L, Cercueil JP, Chauffert B, Jouve JL.Randomised controlled trial of lipiodol transarterial chemoembolisation with or without amiodaronefor unresectable hepatocellular carcinoma.Dig Liver Dis. 2011 Nov;43(11):905-11

Favoulet P, Cercueil JP, Faure P, Osmak L, Isambert N, Beltramo JL, Cognet F, Krause D, Bedenne L, Chauffert B.Increased cytotoxicity and stability of Lipiodol-pirarubicin emulsion compared to classical doxorubicin-Lipiodol: potential advantage for chemoembolization of unresectable hepatocellular carcinoma. Anticancer Drugs. 2001 Nov;12(10):801-6.

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  1. [GetPortalCommentsPageByObjectIdResponse(id=1297744, encodeId=7e27129e74460, content=<a href='/topic/show?id=f6a484255be' target=_blank style='color:#2F92EE;'>#胺碘酮#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84255, encryptionId=f6a484255be, topicName=胺碘酮)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Tue Oct 20 01:21:00 CST 2015, time=2015-10-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=39414, encodeId=7d8a3941422, content=赞一个~, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/05/26/5e1df344d663496bdfd43c465d409e2c.jpg, createdBy=bce679058, createdName=sunlong28, createdTime=Mon Oct 19 06:27:00 CST 2015, time=2015-10-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=39415, encodeId=e9db3941574, content=谢谢分享~, beContent=null, objectType=article, channel=null, level=null, likeNumber=160, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/05/26/5e1df344d663496bdfd43c465d409e2c.jpg, createdBy=bce679058, createdName=sunlong28, createdTime=Mon Oct 19 06:27:00 CST 2015, time=2015-10-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=39416, encodeId=468a39416eb, content=为了积分我也是拼了~, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/05/26/5e1df344d663496bdfd43c465d409e2c.jpg, createdBy=bce679058, createdName=sunlong28, createdTime=Mon Oct 19 06:27:00 CST 2015, time=2015-10-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=39045, encodeId=341839045ab, content=这个评论比较不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=111, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96871613250, createdName=medcardio, createdTime=Sun Oct 18 10:42:00 CST 2015, time=2015-10-18, status=1, ipAttribution=)]
  2. [GetPortalCommentsPageByObjectIdResponse(id=1297744, encodeId=7e27129e74460, content=<a href='/topic/show?id=f6a484255be' target=_blank style='color:#2F92EE;'>#胺碘酮#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84255, encryptionId=f6a484255be, topicName=胺碘酮)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Tue Oct 20 01:21:00 CST 2015, time=2015-10-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=39414, encodeId=7d8a3941422, content=赞一个~, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/05/26/5e1df344d663496bdfd43c465d409e2c.jpg, createdBy=bce679058, createdName=sunlong28, createdTime=Mon Oct 19 06:27:00 CST 2015, time=2015-10-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=39415, encodeId=e9db3941574, content=谢谢分享~, beContent=null, objectType=article, channel=null, level=null, likeNumber=160, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/05/26/5e1df344d663496bdfd43c465d409e2c.jpg, createdBy=bce679058, createdName=sunlong28, createdTime=Mon Oct 19 06:27:00 CST 2015, time=2015-10-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=39416, encodeId=468a39416eb, content=为了积分我也是拼了~, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/05/26/5e1df344d663496bdfd43c465d409e2c.jpg, createdBy=bce679058, createdName=sunlong28, createdTime=Mon Oct 19 06:27:00 CST 2015, time=2015-10-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=39045, encodeId=341839045ab, content=这个评论比较不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=111, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96871613250, createdName=medcardio, createdTime=Sun Oct 18 10:42:00 CST 2015, time=2015-10-18, status=1, ipAttribution=)]
    2015-10-19 sunlong28

    赞一个~

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1297744, encodeId=7e27129e74460, content=<a href='/topic/show?id=f6a484255be' target=_blank style='color:#2F92EE;'>#胺碘酮#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84255, encryptionId=f6a484255be, topicName=胺碘酮)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Tue Oct 20 01:21:00 CST 2015, time=2015-10-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=39414, encodeId=7d8a3941422, content=赞一个~, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/05/26/5e1df344d663496bdfd43c465d409e2c.jpg, createdBy=bce679058, createdName=sunlong28, createdTime=Mon Oct 19 06:27:00 CST 2015, time=2015-10-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=39415, encodeId=e9db3941574, content=谢谢分享~, beContent=null, objectType=article, channel=null, level=null, likeNumber=160, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/05/26/5e1df344d663496bdfd43c465d409e2c.jpg, createdBy=bce679058, createdName=sunlong28, createdTime=Mon Oct 19 06:27:00 CST 2015, time=2015-10-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=39416, encodeId=468a39416eb, content=为了积分我也是拼了~, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/05/26/5e1df344d663496bdfd43c465d409e2c.jpg, createdBy=bce679058, createdName=sunlong28, createdTime=Mon Oct 19 06:27:00 CST 2015, time=2015-10-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=39045, encodeId=341839045ab, content=这个评论比较不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=111, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96871613250, createdName=medcardio, createdTime=Sun Oct 18 10:42:00 CST 2015, time=2015-10-18, status=1, ipAttribution=)]
    2015-10-19 sunlong28

    谢谢分享~

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1297744, encodeId=7e27129e74460, content=<a href='/topic/show?id=f6a484255be' target=_blank style='color:#2F92EE;'>#胺碘酮#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84255, encryptionId=f6a484255be, topicName=胺碘酮)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Tue Oct 20 01:21:00 CST 2015, time=2015-10-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=39414, encodeId=7d8a3941422, content=赞一个~, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/05/26/5e1df344d663496bdfd43c465d409e2c.jpg, createdBy=bce679058, createdName=sunlong28, createdTime=Mon Oct 19 06:27:00 CST 2015, time=2015-10-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=39415, encodeId=e9db3941574, content=谢谢分享~, beContent=null, objectType=article, channel=null, level=null, likeNumber=160, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/05/26/5e1df344d663496bdfd43c465d409e2c.jpg, createdBy=bce679058, createdName=sunlong28, createdTime=Mon Oct 19 06:27:00 CST 2015, time=2015-10-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=39416, encodeId=468a39416eb, content=为了积分我也是拼了~, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/05/26/5e1df344d663496bdfd43c465d409e2c.jpg, createdBy=bce679058, createdName=sunlong28, createdTime=Mon Oct 19 06:27:00 CST 2015, time=2015-10-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=39045, encodeId=341839045ab, content=这个评论比较不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=111, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96871613250, createdName=medcardio, createdTime=Sun Oct 18 10:42:00 CST 2015, time=2015-10-18, status=1, ipAttribution=)]
    2015-10-19 sunlong28

    为了积分我也是拼了~

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1297744, encodeId=7e27129e74460, content=<a href='/topic/show?id=f6a484255be' target=_blank style='color:#2F92EE;'>#胺碘酮#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84255, encryptionId=f6a484255be, topicName=胺碘酮)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Tue Oct 20 01:21:00 CST 2015, time=2015-10-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=39414, encodeId=7d8a3941422, content=赞一个~, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/05/26/5e1df344d663496bdfd43c465d409e2c.jpg, createdBy=bce679058, createdName=sunlong28, createdTime=Mon Oct 19 06:27:00 CST 2015, time=2015-10-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=39415, encodeId=e9db3941574, content=谢谢分享~, beContent=null, objectType=article, channel=null, level=null, likeNumber=160, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/05/26/5e1df344d663496bdfd43c465d409e2c.jpg, createdBy=bce679058, createdName=sunlong28, createdTime=Mon Oct 19 06:27:00 CST 2015, time=2015-10-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=39416, encodeId=468a39416eb, content=为了积分我也是拼了~, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/05/26/5e1df344d663496bdfd43c465d409e2c.jpg, createdBy=bce679058, createdName=sunlong28, createdTime=Mon Oct 19 06:27:00 CST 2015, time=2015-10-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=39045, encodeId=341839045ab, content=这个评论比较不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=111, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96871613250, createdName=medcardio, createdTime=Sun Oct 18 10:42:00 CST 2015, time=2015-10-18, status=1, ipAttribution=)]
    2015-10-18 medcardio

    这个评论比较不错

    0

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JACC:心肺适能可预测肥胖房颤患者心律失常复发

肥胖会引发房颤(AF)。尽管心肺健康可预防肥胖者发生AF,但其对房颤复发或增加心肺健康益处的效果是未知的。本研究旨在评估心肺健康状况和心肺功能改善增加的益处对患有AF的肥胖者的作用。该研究纳入了连续1415例房颤患者,825例患者的BMI≥27kg/m2,而且研究人员提供给这些患者风险因素管理,并参与了为他们量身定制的运动计划。经过排除,308例患者被纳入分析。研究人员对患者进行运动负荷试验,以确

JAHA:科学家鉴别出引发罕见心律失常的遗传原因

刊登在国际杂志Journal of the American Heart Association上的一篇研究论文中,来自俄亥俄州大学的研究人员通过研究鉴别出了一种罕见的致死形式的遗传性心律失常,同时研究者也开发出了一种方法来治疗这种疾病。心律失常是心脏系统功能失常的一种表现,其往往会引发不规律的心脏跳动,大多数患者会经历心脏乱跳,目前美国大约有400万人患有不同程度的心脏心率失常。研究者Peter

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