逆转某些类型肿瘤的创新方式.doc

Revolutionary New Way of Reversing Certain CancersScienceDaily (Sep. 29, 2010) Australian and American scientists have found a way of shrinking tumours in certain cancers - a finding that provides hope for new treatments.The cancers in question are those caused by a new class of genes known as microRNAs, produced by parts of the genome that, until recently, were dismissed as junk DNA. While much is still unknown about microRNAs, it is clear that they can interfere with how our genes are read.The current finding identifies one particular microRNA (microRNA 380) that appears to disable the king of tumour suppressors, the p53 gene. So important is p53, that it is known as the guardian of the genome. In order for a cell to become cancerous, p53 must either be mutated or otherwise disabled.Dr Alex Swarbrick, from Sydneys Garvan Institute of Medical Research, Dr Susan Woods from Brisbanes Queensland Institute of Medical Research and Dr Andrei Goga from The University of California San Francisco chose to study neuroblastoma, a childhood cancer of the nervous system in which 99% of patients do not have mutations of the p53 gene.The researchers found instead that neuroblastomas disable p53 by over-producing microRNA 380. When they blocked the microRNA, p53 production resumed, cancer cells died and tumours became much smaller. Their results are reported in the journal Nature Medicine.The revolutionary thing about this finding is that its the first time anyone has blocked the growth of a primary tumour by the simple delivery of a microRNA inhibitor, said Swarbrick.By that, I mean we delivered the microRNA inhibitor in a way we might give it to a person - as a twice-weekly injection - not using some genetic trick. Its the closest thing to a clinical result thats yet been published.That, of course, makes this microRNA a potential therapeutic target for all cancers that depend on it.The other good news is that you dont find this microRNA in normal adult cells. Its very active while we are developing embryos, when cells need to divide very quickly, but after that it appears to get switched off. So by blocking it, youre effectively returning cells to normal.We still dont know why it gets switched on again in certain cancers. Apart from neuroblastomas, we often see it in brain tumours and in melanomas that dont have mutations in p53.So how exactly does it work?When a gene is transcribed or read, in this case p53, a copy of the gene is made in RNA. In a normal cell, that p53 RNA carries the instructions to make p53 proteins, which in turn carry out the tumour suppressor function in cells.MicroRNAs act to control the production of proteins - the molecules that do the work in cells, explained Swarbrick.In the cancers we are discussing, our microRNA binds with p53 RNA, preventing it from making proteins. That effectively reduces the number of p53 proteins in a cell and allows the tumour to grow.Understanding that certain cancers appear to be regulated like this gives us a new avenue to explore in their treatment.While this finding is at an early research stage, it holds much promise for the future treatment of early childhood neuroblastomas and other microRNA- induced cancers.=Revolutionary New Way of Reversing Certain Cancers逆转某些类型肿瘤的创新方式 译者：Docofsoul ScienceDaily (Sep. 29, 2010) Australian and American scientists have found a way of shrinking tumours in certain cancers - a finding that provides hope for new treatments.每日科学2010年9月29日报道 澳大利亚与美国科学家已经发现一种使某些种类癌症中肿瘤萎缩的方式，这一发现为新的疗法提供了希望。The cancers in question are those caused by a new class of genes known as microRNAs, produced by parts of the genome that, until recently, were dismissed as junk DNA. While much is still unknown about microRNAs, it is clear that they can interfere with how our genes are read.这里所说的肿瘤是指那些由耳熟能详的“microRNAs”这种新一类基因导致的肿瘤。microRNAs由基因组的一部分所生产，直到最近（几年）microRNAs仍被斥责为“垃圾DNA”。虽然（科学家）对microRNAs的了解仍然非常有限，但对microRNAs能够干预我们的基因被“阅读”的方式却很清楚。The current finding identifies one particular microRNA (microRNA 380) that appears to disable the king of tumour suppressors, the p53 gene. So important is p53, that it is known as the guardian of the genome. In order for a cell to become cancerous, p53 must either be mutated or otherwise disabled.目前的发现证实了：特定的microRNA（microRNA 380）看来能让抑癌之王p53基因失效。P53极为重要，有“基因组守护神”之誉。要让一个细胞变成肿瘤，就必须搬开p53这块“绊脚石”，让其变异或失效。Dr Alex Swarbrick, from Sydneys Garvan Institute of Medical Research, Dr Susan Woods from Brisbanes Queensland Institute of Medical Research and Dr Andrei Goga from The University of California San Francisco chose to study neuroblastoma, a childhood cancer of the nervous system in which 99% of patients do not have mutations of the p53 gene.来自悉尼Garvan医学研究院的Alex Swarbrick博士、布里斯班昆士兰医学研究院的Susan Woods博士与加州大学旧金山分校的Dr Andrei Goga博士选择了对神经母细胞瘤的研究。神经母细胞瘤是儿童神经系统肿瘤，99%的患者，其p53基因并不存在变异。The researchers found instead that neuroblastomas disable p53 by over-producing microRNA 380. When they blocked the microRNA, p53 production resumed, cancer cells died and tumours became much smaller. Their results are reported in the journal Nature Medicine.但是研究者却发现：神经母细胞瘤通过过度生产microRNA380使p53失效。当他们阻断microRNA380时，p53又重新产生、癌细胞则凋亡、同时肿瘤也大为缩小。他们的研究结果发表于Nature Medicine杂志。The revolutionary thing about this finding is that its the first time anyone has blocked the growth of a primary tumour by the simple delivery of a microRNA inhibitor, said Swarbrick.Swarbrick对此评论说：“这一发现的创新意义在于：通过简单传递一种microRNA抑制剂，首次能让任何人阻断一种原发肿瘤的生长。” By that, I mean we delivered the microRNA inhibitor in a way we might give it to a person - as a twice-weekly injection - not using some genetic trick. Its the closest thing to a clinical result thats yet been published.“我的意思是说，我们以一种很平常的方式来传递microRNA抑制剂（比如一周注射两次），而不必依赖某种特殊的遗传学技巧， 这样就与一种已发表的临床结果很接近。”That, of course, makes this microRNA a potential therapeutic target for all cancers that depend on it.“当然，这让microRNA成为一种对其有依赖的所有肿瘤的潜在治疗靶点。”The other good news is that you dont find this microRNA in normal adult cells. Its very active while we are developing embryos, when cells need to divide very quickly, but after that it appears to get switched off. So by blocking it, youre effectively returning cells to normal.“其它好消息是在正常的成熟细胞中不会发现microRNA。胚胎发育阶段microRNA十分活跃，因为这个时候细胞需要极为快速地分化，但此后看来被关闭了。因此阻止microRNA是使细胞正常化的卓有成效的方式。”We still dont know why it gets switched on again in certain cancers. Apart from neuroblastomas, we often see it in brain tumours and in melanomas that dont have mutations in p53.“我们仍然不知道microRNA在某些肿瘤中会被再次打开开关的原因，.除了神经母细胞瘤，我们也经常在大脑肿瘤与黑素瘤中见到其身影，而p53并未出现突变。”So how exactly does it work?那么它究竟是如何运作的呢？When a gene is transcribed or read, in this case p53, a copy of the gene is made in RNA. In a normal cell, that p53 RNA carries the instructions to make p53 proteins, which in turn carry out the tumour suppressor function in cells.MicroRNAs act to control the production of proteins - the molecules that do the work in cells, explained Swarbrick.当一个基因被转录或被“阅读”的时候（这里是指p53基因），在RNA中会产生一份该基因的拷贝。在一个正常细胞内，该p53 RNA携带着生产p53蛋白的指令， 而p53蛋白则转而发挥了细胞肿瘤抑制剂的功能。Swarbrick解释说：“MicroRNAs起着控制蛋白生产的作用，这些蛋白正是在细胞中做这项工作的分子。”In the cancers we are discussing, our microRNA binds with p53 RNA, preventing it from making proteins. That effectively reduces the number of p53 proteins in a cell and allows the tumour to grow.“对我们正在讨论的肿瘤而言，microRNA与p53RNA结合，防止p53RNA产生蛋白质。这样就有效减少了一个细胞中的p53蛋白的数量并允许肿瘤生长。”Understanding that certain cancers appear to be regulated like this gives us a new avenue to explore in their treatment.“理解了某些肿瘤看来被这个过程所调节（的事实），就意味着我们在相关治疗中获得了一种新的探索方法。”While this finding is at an early research stage, it holds much promise for the future treatment of early childhood neuroblastomas and other microRNA- induced cancers.虽然本发现尚属研究的早期阶段， 但它为未来治疗儿童早期神经母细胞瘤与治疗microRNA诱导的其它肿瘤提供了很大的希望。参考文献：Alexander Swarbrick, Susan L Woods, Alexander Shaw, Asha Balakrishnan, Yuwei Phua, Akira Nguyen, Yvan Chanthery, Lionel Lim, Lesley J Ashton, Robert L Judson, Noelle Huskey, Robert Blelloch, Michelle Haber, Murray D Norris, Peter Lengyel, Christopher S Hackett, Thomas Preiss, Albert Chetcuti, Christopher S Sullivan, Eric G Marcusson, William Weiss, Noelle LEtoile, Andrei Goga. miR-380-5p represses p53 to control cellular survival and is associated with poor outcome in MYCN-amplified neuroblastoma. Nature Medicine, 2010; DOI: 10.1038/nm.2227（Docofsoul 译于 2010-09-29） Docofsoul edited on 2010-09-30 12:24 The world cannot weigh you down when youre standing on the top of it. 举报论文翻译不用愁2010-09-30 11:32 得票5 逆转某些类型肿瘤的创新方式 译者：Docofsoul 每日科学2010年9月29日报道 澳大利亚与美国科学家已经发现一种使某些种类癌症中肿瘤萎缩的方式，这一发现为新的疗法提供了希望。这里所说的肿瘤是指那些由耳熟能详的“microRNAs”这种新一类基因导致的肿瘤。microRNAs由基因组的一部分所生产，直到最近（几年）microRNAs仍被斥责为“垃圾DNA”。虽然（科学家）对microRNAs的了解仍然非常有限，但对microRNAs能够干预基因被“阅读”的方式则很清楚。目前的发现证实了：特定的microRNA（microRNA 380）看来能让抑癌之王p53基因失效。p53极为重要，有“基因组守护神”之誉。要让一个细胞变成肿瘤，就必须搬开p53这块“绊脚石”，让其变异或失效。来自悉尼Garvan医学研究院的Alex Swarbrick博士、布里斯班昆士兰医学研究院的Susan Woods博士与加州大学旧金山分校的Dr Andrei Goga博士选择了对神经母细胞瘤的研究。神经母细胞瘤是儿童神经系统肿瘤，99%的患者，其p53基因并不存在变异。但是研究者却发现：神经母细胞瘤通过过度生产microRNA380使p53失效。当他们阻断microRNA380时，p53又重新产生、癌细胞则凋亡、同时肿瘤也大为缩小。他们的研究结果发表于Nature Medicine杂志。Swarbrick对此评论说：“这一发现的创新意义在于：通过简单传递一种microRNA抑制剂，首次能让任何人阻断一种原发肿瘤的生长。” “我的意思是说，我们以一种很平常的方式（比如一周注射两次）来传递microRNA抑制剂，而不必依赖某种特殊的遗传学技巧， 这样就与一项已发表的临床结果很接近。”“当然，这让microRNA成为一种对其有依赖的所有肿瘤的潜在治疗靶点。”“其它好消息是在正常的成熟细胞中不会发现microRNA。胚胎发育阶段microRNA十分活跃，因为这个时候细胞需要极为快速地分化，但此后看来被关闭了。因此阻止microRNA是使细胞