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PNAS:付彩云团队首次揭示靶向抑制髓系白血病细胞增殖的分子机制

2019-09-07 酶美 BioArt

靶向抑制髓系白血病细胞增殖分子机制
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白血病是一类常见的严重危害人类健康的造血干祖细胞恶性克隆性疾病，对儿童和青少年的危害尤为严重，在儿童及 35 岁以下成人恶性肿瘤致死率中居第一位。目前，髓系白血病（myeloid leukemia）发生发展的分子机制还有待进一步阐明，髓系白血病治疗的关键技术和新靶点的发掘也有待突破。因此，研发髓系白血病治疗新技术，发掘髓系白血病治疗新靶点，研发更加有效的髓系白血病治疗药物，是当前髓系白血病基础研究

白血病是一类常见的严重危害人类健康的造血干祖细胞恶性克隆性疾病，对儿童和青少年的危害尤为严重，在儿童及 35 岁以下成人恶性肿瘤致死率中居第一位。目前，髓系白血病（myeloid leukemia）发生发展的分子机制还有待进一步阐明，髓系白血病治疗的关键技术和新靶点的发掘也有待突破。因此，研发髓系白血病治疗新技术，发掘髓系白血病治疗新靶点，研发更加有效的髓系白血病治疗药物，是当前髓系白血病基础研究和临床实践中迫切需要解决的科学问题.

近日，浙江理工大学生命科学与医药学院付彩云教授课题组在PNAS在线发表“Neurokinin-1receptor is an effective target for treating leukemia by inducing oxidativestress through mitochondrial calcium overload”研究论文。该论文首次在髓系白血病病人外周血中发现NK-1R呈现显着高表达，且揭示靶向阻断神经激肽受体 1（NK-1R）首先引起了内质网应激反应，进一步通过线粒体钙超载引起的氧化应激来介导髓系白血病细胞发生凋亡的新分子机制。

研发发现NK-1R在髓系白血病病人外周血及髓系白血病细胞系中呈现显着高表达，用NK-1R拮抗剂靶向阻断NK-1R抑制了髓系白血病细胞增殖并诱导髓系白血病细胞发生凋亡，通过转录组学、蛋白质组学、以及细胞分子实验阐明了其分子机制是通过内质网应激反应引起线粒体钙浓度升高，从而引起了氧化应激介导的DNA损伤反应来介导髓系白血病细胞发生凋亡。研究也在体外和在体内进一步评估了NK-1R拮抗剂的抗肿瘤效果及其安全性。同时，研究也发现NK-1R拮抗剂除了诱导髓系白血病细胞凋亡外，在动物水平也具有缓解癌痛的效果。

NK-1R参与了体内多种生理病理过程，NK-1R拮抗剂阿瑞匹坦已被美国FDA批准用于临床化疗后的恶心和呕吐的治疗，该项目的研究结果对于顺利推进NK-1R拮抗剂用于临床髓系白血病的治疗意义重大。后续研究如能在临床证实NK-1R拮抗剂高效的治疗髓系白血病的效果，将为从此新颖分子机制去发现临床新药提供了坚实的基础。

据悉，浙江理工大学生命科学与医药学院付彩云教授为该论文的最后通讯作者（lead contact），浙江理工大学为第一通讯单位，Peter MacCallumCancer Centre和Karolinska Institutet为合作单位。付彩云教授指导的硕士研究生葛晨涛，黄荷淼等为论文共同第一作者。

付彩云教授一直从事肿瘤靶向治疗、多肽及蛋白结构改造和功能研究，以通讯或第一作者共发表SCI论文26篇，其中近3年以最后通讯或第一作者（含共同）在Proc Natl Acad Sci USA、J Am Chem Soc（2018a， 2018b）、Angew Chem Int Ed、Signal Transduct Target Ther杂志发表了5篇高水平学术论文。

原始出处：
Chentao Ge, Hemiao Huang, Feiyan Huang, et al.Neurokinin-1 receptor is an effective target for treating leukemia by inducing oxidative stress through mitochondrial calcium overload.PNAS.published September 5, 2019 https://doi.org/10.1073/pnas.1908998116

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    2020-08-06 drwjr

    #PNAS#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1856337, encodeId=b275185633e13, content=<a href='/topic/show?id=f32014428fc' target=_blank style='color:#2F92EE;'>#PNAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14428, encryptionId=f32014428fc, topicName=PNAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=08e964, createdName=drwjr, createdTime=Thu Aug 06 04:01:00 CST 2020, time=2020-08-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1822096, encodeId=572d18220967e, content=<a href='/topic/show?id=ee4b1021266e' target=_blank style='color:#2F92EE;'>#髓系白血病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102126, encryptionId=ee4b1021266e, topicName=髓系白血病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b79433, createdName=fangcong, createdTime=Wed May 13 04:01:00 CST 2020, time=2020-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1540948, encodeId=cb2e1540948f0, content=<a href='/topic/show?id=ba2ee78630b' target=_blank style='color:#2F92EE;'>#细胞增殖#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77863, encryptionId=ba2ee78630b, topicName=细胞增殖)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f58613291856, createdName=晓辰, createdTime=Mon Sep 09 01:01:00 CST 2019, time=2019-09-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=372398, encodeId=c7613e2398e9, content=从研究到临床，还有很长的路, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/12/20/dafb36f63f4241903de36c3d053babb8.jpg, createdBy=d367105945, createdName=Midas, createdTime=Sat Sep 07 11:00:18 CST 2019, time=2019-09-07, status=1, ipAttribution=)]
    2020-05-13 fangcong

    #髓系白血病#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1856337, encodeId=b275185633e13, content=<a href='/topic/show?id=f32014428fc' target=_blank style='color:#2F92EE;'>#PNAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14428, encryptionId=f32014428fc, topicName=PNAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=08e964, createdName=drwjr, createdTime=Thu Aug 06 04:01:00 CST 2020, time=2020-08-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1822096, encodeId=572d18220967e, content=<a href='/topic/show?id=ee4b1021266e' target=_blank style='color:#2F92EE;'>#髓系白血病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102126, encryptionId=ee4b1021266e, topicName=髓系白血病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b79433, createdName=fangcong, createdTime=Wed May 13 04:01:00 CST 2020, time=2020-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1540948, encodeId=cb2e1540948f0, content=<a href='/topic/show?id=ba2ee78630b' target=_blank style='color:#2F92EE;'>#细胞增殖#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77863, encryptionId=ba2ee78630b, topicName=细胞增殖)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f58613291856, createdName=晓辰, createdTime=Mon Sep 09 01:01:00 CST 2019, time=2019-09-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=372398, encodeId=c7613e2398e9, content=从研究到临床，还有很长的路, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/12/20/dafb36f63f4241903de36c3d053babb8.jpg, createdBy=d367105945, createdName=Midas, createdTime=Sat Sep 07 11:00:18 CST 2019, time=2019-09-07, status=1, ipAttribution=)]
    2019-09-09 晓辰

    #细胞增殖#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1856337, encodeId=b275185633e13, content=<a href='/topic/show?id=f32014428fc' target=_blank style='color:#2F92EE;'>#PNAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14428, encryptionId=f32014428fc, topicName=PNAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=08e964, createdName=drwjr, createdTime=Thu Aug 06 04:01:00 CST 2020, time=2020-08-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1822096, encodeId=572d18220967e, content=<a href='/topic/show?id=ee4b1021266e' target=_blank style='color:#2F92EE;'>#髓系白血病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102126, encryptionId=ee4b1021266e, topicName=髓系白血病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b79433, createdName=fangcong, createdTime=Wed May 13 04:01:00 CST 2020, time=2020-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1540948, encodeId=cb2e1540948f0, content=<a href='/topic/show?id=ba2ee78630b' target=_blank style='color:#2F92EE;'>#细胞增殖#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77863, encryptionId=ba2ee78630b, topicName=细胞增殖)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f58613291856, createdName=晓辰, createdTime=Mon Sep 09 01:01:00 CST 2019, time=2019-09-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=372398, encodeId=c7613e2398e9, content=从研究到临床，还有很长的路, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/12/20/dafb36f63f4241903de36c3d053babb8.jpg, createdBy=d367105945, createdName=Midas, createdTime=Sat Sep 07 11:00:18 CST 2019, time=2019-09-07, status=1, ipAttribution=)]
    2019-09-07 Midas

    从研究到临床，还有很长的路

    0