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【bio-news】Tuning the body's defence to cancer
Tuning the body's defence to cancer
调整机体对癌症的防御
Turning off our natural killer could help to reduce chemotherapy side effects.
关闭我们自身杀伤细胞能有助于减少化疗的副作用
Lucy Heady
A fundamental shift in our understanding of the body's natural defence mechanism against cancer has revealed an odd trick: turning this weapon off during chemotherapy might actively help to reduce side effects such as hair loss.
关于机体对癌症自然防御机制的认识有了一个基本的变化，这个变化揭示：在化疗过程中关闭机体防御武器可能有助于减少脱发等副作用。
Our cells contain a protein called p53, dubbed 'the guardian of the genome', which regulates the process of DNA replication. It also plays a crucial role in cancer: 50% of human tumours contain a mutation or a deletion in the gene that makes p53.
人体细胞中包含了一种p53的蛋白，又可以称作“基因卫士”，它在DNA的复制过程中起到调节作用。该蛋白在癌症机制中也扮演重要角色：50%的肿瘤中表达p53蛋白的基因都发生了突变或缺失。
p53 does two things: it repairs broken or damaged strands of DNA, and kills off cells containing defective DNA. Both can help to fight against cancer. But the latter can also have negative effects.
P53起两种作用：它修复受损的DNA链；并且杀伤含有缺陷DNA的细胞。这些作用都对癌症的治疗有裨益，但是第2种作用也可能起到负面影响。
When cells suffer massive DNA damage, from a dose of radiation, for example, p53 steps into enthusiastic action. Only about one in a billion damaged cells will contain a mutation likely to cause cancer, but p53 will kill off all damaged cells. "It's like preventing the rise of a potential dictator in a country by killing off the whole population," says Gerard Evan of the University of California, San Francisco, who led the research. This indiscriminate destruction causes the hair loss and extreme nausea experienced by radio- and chemotherapy patients.
当细胞受到一定剂量的辐射作用而使其DNA受到严重伤害时，p53就开始发挥作用。一般10亿个损坏细胞中只包含一个可能导致癌症的突变体，但是p53会杀伤所有缺陷细胞。研究的领导者，sanfrancisco 加利福利亚大学的gerard evan说：“这就好象为了防止***者的出现而杀掉所用的嫌疑犯“。这种“不分青红皂白”的攻击导致了接受放射治疗和化疗的病人出现脱发以及严重呕吐等症状。
The two actions of p53 were thought to be intimately linked, making this overkill an unfortunate but necessary part of how p53 stops the formation of tumours. The results from Evan's lab, however, tell a different story.
P53的两种作用是紧密联系的，它们既对机体造成严重损害却又是p53终止肿瘤形成的必须过程。但是，evan的研究小组的成果，却开辟出了一片新天地。
未完待续 Switched on
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Evan's group developed a pioneering mouse method to try to unlock the function of p53. In this method the gene is not deleted, as in traditional 'knockout' experiments, but is instead mutated so that it can be switched on or off at any stage by injecting the mice with a simple chemical.
evan的团队研究了一种“先锋鼠模型”的方法试图揭示p53的作用。这种方法与传统的基因敲除实验相比不同在于：不删除基因，而用突变基因来替代，这样只需要给予实验鼠简单的化学刺激就能在实验的任意阶段控制基因的开启和关闭。
Three sets of these 'knockin' mice, all with a switchable p53 gene, were blasted with high-intensity radiation similar to that experienced by radiotherapy patients. This causes extensive DNA damage, as well as a type of cancer known as lymphoma.
三批这种带有可变p53基因的“基因钉入”鼠，都用与患者进行放射线治疗相似的射线强度进行辐射。辐射将导致严重的DNA损伤，包括生成淋巴瘤。
Mice that had p53 switched on during the radiation, but turned off immediately afterwards, fared the worst. They suffered massive tissue damage as the p53 responded to DNA damage by killing off cells. And they still formed tumours and died from cancer, to the same extent as mice who had p53 turned off for the entire procedure: mice in both groups lived for a maximum of 300 days.
一部分老鼠在辐射过程中开启p53表达，但是辐射一结束马上关闭。由于DNA损伤杀伤了大量细胞，它们的组织机能也遭到严重破坏。另一部分整个实验过程中始终关闭p53表达的老鼠结果也差不多，它们都形成了肿瘤并死于癌症：各个组的老鼠最多存活300天。
Mice that had p53 turned off during the irradiation, and turned on 8 days after the radiation blast, suffered least. They had no detectable tissue damage, and a vastly reduced number of lymphomas — they lived an average 99 days longer than the other mice. Mice with p53 turned on for the entire procedure — as is the case with human patients — suffered tissue damage but were spared from extensive lymphomas. Although it is impossible to turn genes on and off perfectly with this technique, Evan notes, the data in this case are very clear. They report the results in Nature1.
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作者:admin@医学,生命科学 2011-09-01 05:13
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