Chest:西罗莫司和羟氯喹治疗淋巴管肌瘤病的代谢变化

2022-05-11 xiangting MedSci原创

这项研究数据表明雷帕霉素和羟氯喹合用靶向多胺代谢途径,导致LAM患者血浆和LAM患者来源细胞中的MTA和精氨酸上调。

淋巴管肌瘤病(LAM)是一种主要影响女性的破坏性肺病,由TSC1或TSC2的功能丧失突变引起,导致机械/哺乳动物雷帕霉素靶蛋白1(mTORC1)的过度活化。雷帕霉素(西罗莫司)可以抑制mTORC1,但也诱导自噬,从而促进TSC2缺陷细胞的存活。基于同时抑制mTORC1和自噬将限制利用关键营养素和抑制LAM细胞的假设,研究人员进行了西罗莫司和羟氯喹治疗LAM的I期临床试验。这里报告了临床试验中血浆代谢组学谱的分析。

研究人员使用单因素统计模型和机器学习方法分析了西罗莫司和羟氯喹治疗前、中、后6个月获取样品的血浆代谢组学。在LAM患者来源TSC2缺陷细胞中验证代谢物和代谢途径。单细胞RNA-Seq用于评估来自LAM肺早期传代培养物中的代谢酶。

代谢组学分析揭示了治疗期间多胺代谢的变化,其中5'-甲硫腺苷(MTA)和精氨酸是上调最多的代谢物。在LAM患者来源的TSC2缺陷细胞中也观察到类似结果。原代LAM培养细胞的单细胞转录组学分析显示抑制mTORC1上调多胺代谢途径中的关键酶,其中包括腺苷甲硫氨酸脱羧酶1(AMD1)。

这项研究数据表明雷帕霉素和羟氯喹合用靶向多胺代谢途径,导致LAM患者血浆和LAM患者来源细胞中的MTA和精氨酸上调,并揭示了疗效的新候选生物标志物。

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  5. [GetPortalCommentsPageByObjectIdResponse(id=2051773, encodeId=1eba2051e736a, content=<a href='/topic/show?id=95f8e042dd' target=_blank style='color:#2F92EE;'>#EST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7042, encryptionId=95f8e042dd, topicName=EST)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e9a6357, createdName=xiangyuzhou971, createdTime=Fri Sep 20 20:18:00 CST 2019, time=2019-09-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1667861, encodeId=1621166e86177, content=<a href='/topic/show?id=c0ed65982c2' target=_blank style='color:#2F92EE;'>#淋巴管肌瘤病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65982, encryptionId=c0ed65982c2, topicName=淋巴管肌瘤病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5d8626187223, createdName=d830381, createdTime=Sat Nov 16 05:18:00 CST 2019, time=2019-11-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2055112, encodeId=9d5920551121f, content=<a href='/topic/show?id=5986809543a' target=_blank style='color:#2F92EE;'>#肌瘤病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80954, encryptionId=5986809543a, topicName=肌瘤病)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/C4Qhy5XHSe503Qbjzc1UtDR83BCv66o6P2XRedX9ohsNGa3uEVicFFk2qkuX5zBSmpicepFySBrwoYknhqMdKmtw/132, createdBy=1aca2500179, createdName=12498d2fm51(暂无昵称), createdTime=Tue Aug 06 13:18:00 CST 2019, time=2019-08-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1951971, encodeId=dcfc19519e1d6, content=<a href='/topic/show?id=90a1254194a' target=_blank style='color:#2F92EE;'>#代谢变化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=25419, encryptionId=90a1254194a, topicName=代谢变化)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=74c2229, createdName=tcm99hq, createdTime=Sun Nov 17 22:18:00 CST 2019, time=2019-11-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1929691, encodeId=87e11929691ed, content=<a href='/topic/show?id=9e604625ab' target=_blank style='color:#2F92EE;'>#Chest#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4625, encryptionId=9e604625ab, topicName=Chest)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c48a270, createdName=Smile2680, createdTime=Sat Jul 27 13:18:00 CST 2019, time=2019-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1340058, encodeId=1ac41340058fe, content=<a href='/topic/show?id=8c519053e85' target=_blank style='color:#2F92EE;'>#西罗莫司#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=90537, encryptionId=8c519053e85, topicName=西罗莫司)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/JHX80Wpw3cstP6RtQ1pO8asyNiah0uIJwh7hmKm1emARpicBibTeQrj1SN7YwGSwibOrIL2kZ9WHmRiaznSnuHhUJUg/132, createdBy=c7de2500155, createdName=ms3415360956839622, createdTime=Sat Jul 13 03:18:00 CST 2019, time=2019-07-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1529384, encodeId=6f50152938483, content=<a href='/topic/show?id=4735659e3cf' target=_blank style='color:#2F92EE;'>#淋巴管#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65973, encryptionId=4735659e3cf, topicName=淋巴管)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee7311933759, createdName=amyloid, createdTime=Sat Jul 13 03:18:00 CST 2019, time=2019-07-13, status=1, ipAttribution=)]
    2019-07-27 Smile2680
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  7. [GetPortalCommentsPageByObjectIdResponse(id=2051773, encodeId=1eba2051e736a, content=<a href='/topic/show?id=95f8e042dd' target=_blank style='color:#2F92EE;'>#EST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7042, encryptionId=95f8e042dd, topicName=EST)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e9a6357, createdName=xiangyuzhou971, createdTime=Fri Sep 20 20:18:00 CST 2019, time=2019-09-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1667861, encodeId=1621166e86177, content=<a href='/topic/show?id=c0ed65982c2' target=_blank style='color:#2F92EE;'>#淋巴管肌瘤病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65982, encryptionId=c0ed65982c2, topicName=淋巴管肌瘤病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5d8626187223, createdName=d830381, createdTime=Sat Nov 16 05:18:00 CST 2019, time=2019-11-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2055112, encodeId=9d5920551121f, content=<a href='/topic/show?id=5986809543a' target=_blank style='color:#2F92EE;'>#肌瘤病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80954, encryptionId=5986809543a, topicName=肌瘤病)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/C4Qhy5XHSe503Qbjzc1UtDR83BCv66o6P2XRedX9ohsNGa3uEVicFFk2qkuX5zBSmpicepFySBrwoYknhqMdKmtw/132, createdBy=1aca2500179, createdName=12498d2fm51(暂无昵称), createdTime=Tue Aug 06 13:18:00 CST 2019, time=2019-08-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1951971, encodeId=dcfc19519e1d6, content=<a href='/topic/show?id=90a1254194a' target=_blank style='color:#2F92EE;'>#代谢变化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=25419, encryptionId=90a1254194a, topicName=代谢变化)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=74c2229, createdName=tcm99hq, createdTime=Sun Nov 17 22:18:00 CST 2019, time=2019-11-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1929691, encodeId=87e11929691ed, content=<a href='/topic/show?id=9e604625ab' target=_blank style='color:#2F92EE;'>#Chest#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4625, encryptionId=9e604625ab, topicName=Chest)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c48a270, createdName=Smile2680, createdTime=Sat Jul 27 13:18:00 CST 2019, time=2019-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1340058, encodeId=1ac41340058fe, content=<a href='/topic/show?id=8c519053e85' target=_blank style='color:#2F92EE;'>#西罗莫司#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=90537, encryptionId=8c519053e85, topicName=西罗莫司)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/JHX80Wpw3cstP6RtQ1pO8asyNiah0uIJwh7hmKm1emARpicBibTeQrj1SN7YwGSwibOrIL2kZ9WHmRiaznSnuHhUJUg/132, createdBy=c7de2500155, createdName=ms3415360956839622, createdTime=Sat Jul 13 03:18:00 CST 2019, time=2019-07-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1529384, encodeId=6f50152938483, content=<a href='/topic/show?id=4735659e3cf' target=_blank style='color:#2F92EE;'>#淋巴管#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65973, encryptionId=4735659e3cf, topicName=淋巴管)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee7311933759, createdName=amyloid, createdTime=Sat Jul 13 03:18:00 CST 2019, time=2019-07-13, status=1, ipAttribution=)]
    2019-07-13 amyloid

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