Sci Transl Med:重大发现!新研究发现或可有效预防移植物抗宿主病的发生

2015-12-01 MedSci MedSci原创

Sci Transl Med:重大发现!新研究发现或可有效预防移植物抗宿主病的发生来自西雅图儿研所实验室的研究人员发现,使用现有药物可靶向移植物抗宿主病(GVHD)发生的遗传途径,GVHD是骨髓移植常见的也是致命的并发症,该研究成果在线发表于Science Translational Medicine。发生GVHD的患者,骨髓移植来源的T细胞可攻击移植受体。在美国每年有1万多名患者接受骨髓移植来治

来自西雅图儿研所实验室的研究人员发现,使用现有药物可靶向移植物抗宿主病(GVHD)发生的遗传途径,GVHD是骨髓移植常见的也是致命的并发症,该研究成果在线发表于Science Translational Medicine。

发生GVHD的患者,骨髓移植来源的T细胞可攻击移植受体。在美国每年有1万多名患者接受骨髓移植来治疗白血病、其他非恶性血液病以及自身免疫性疾病。约50-70%的骨髓移植患者将发展为GVHD,发展为最严重形式的GVHD患者中最终死亡。

“在骨髓移植上,GVHD困扰了医生数十年,” 该研究第一作者、西雅图儿研所儿科肿瘤专家,Dr. Leslie Kean说道,“我们可以通过骨髓移植来治疗白血病和其他疾病,但是许多患者在移植后发生了GVHD。极端的情况下,这些患者会出现严重的并发症,过程痛苦且持久,甚至很多患者会死于GVHD。”

GVHD可发生在身体的任何部位,肝脏、皮肤和胃肠道组织是GVHD发生最常见也是最严重的部位。

“GVHD是接受骨髓移植治疗患者治愈原有疾病后仍要长期住院的主要原因,” Kean说道,“而这一发现着实令人兴奋,因为我们所研究的药物正在临床试验中,所以我们希望在不久的将来, 可受益于这项研究。”

Kean及其团队所研究的通路是极光激酶A,众所周知,极光激酶A是癌症研究人员所研究的遗传靶点。极光激酶是人类细胞分裂和增殖的重要蛋白。极光激酶基因缺陷会导致细胞过度增殖而导致癌症的发生。Kean所研究的药物与Takeda所生产的药物非常相似,正处于儿童和成人癌症III期临床试验。该药物可抑制极光激酶A信号通路,导致细胞分裂停止。

Dr. Ned Waller表示,迫切需要新的方法来理解GVHD的免疫学并限制其对患者影响,以提高患者的生活质量并增加他们的长期无癌生存率。”

Kean及其团队正在设计一个临床试验,他们希望2016年可启动这个试验以应用这项新的策略,从而使得接受骨髓移植的患者有可能接受极光激酶A抑制剂治疗。

原始出处:

Seattle Children’s Researchers Discover Method to Prevent Lethal Bone Marrow Transplant Complication. newswise, 30-Nov-2015.


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    2016-03-23 bsmagic9140
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  5. 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  6. 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createdName=手留余香, createdTime=Wed Dec 02 16:33:00 CST 2015, time=2015-12-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1606743, encodeId=c2751606e4390, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Wed Dec 02 16:33:00 CST 2015, time=2015-12-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1620683, encodeId=5a3216206833f, content=<a href='/topic/show?id=c0c9e520310' target=_blank style='color:#2F92EE;'>#移植物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75203, 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    2015-12-02 wincls
  7. 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    2015-12-02 Kiste

    希望有所突破

    0

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注射MSCs是治疗激素耐药的急性GVHD的一个可行的治疗方法。迫切需要随机临床试验评估不同治疗方法对激素耐药的急性移植物抗宿主病的效果。

Clin Cancer Res.:JAK抑制剂可能潜在预防急性移植物抗宿主病

目的:免疫介导的移植物抗肿瘤效应(GVT)在同种异体造血干细胞移植(HSCT)后可能发生,但GVT与其主要并发症--移植物抗宿主病(GVHD)紧密联系。本方案的目标是:保留GVT的效果的同时调节移植物抗宿主病,提高移植手术的治愈率。鉴于JAK信号在淋巴组织或骨髓发生增生性疾病时具有调节T细胞分化方面的功能,我们推测JAKs可能是潜在的治疗靶标,并通过药理方法验证。实验设计:在完全MHC不匹配的骨髓