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【bio-news】分享资料：新模型：有希望取代万能模
新模型：有希望取代万能模型时代
By Anette Breindl
Science Editor
Cancer cures in mice are like Mark Twain's observation that "quitting smoking is easy - I've done it a hundred times." The frequent successes that are reported in the scientific literature are a particularly frustrating form of easy come, easy go; the chance that a given cancer-fighting compound will progress from Phase I to FDA approval is less than 5 percent, not to mention the attrition from preclinical.
Part of the problem is that the mouse models simply are not very good. Cheryl Marks, program director of the National Cancer Institute's Mouse Models for Human Cancers Consortium, told BioWorld Today that the most common cancer model - the xenograft - is "not really a mouse cancer model. It is a human tumor model in an immunoincompetent animal."
在老鼠身上治愈癌症就像马克吐温体会到的那样＂戒烟很容易，我做了一百次了＂．人们对科学文献上频繁报道抗癌成功已失去信心，因为它们来的快去的也快．抗癌化合物从临床试验第1期到ＦＤＡ批准成功概率小于５％，这还没包括临床前的淘汰．部分原因仅仅是老鼠病理模型不是很好，国际人类癌症老鼠病理模型研究协会的计划主管Cheryl Marks告诉《今日生物世界》：“异种移植物是最常用的癌症模型，但不应由老鼠来做癌症模型－因为老鼠是无人类样免疫能力的动物”．
And what's wrong with that? Well, any number of things.
问题出在哪里呢？这应该包括很多方面．
The implanted cells are often derived from a single tumor; they have been grown on plastic for generations to decades before being implanted into mouse flanks, which is not the organ in which the original tumor developed; and the animals have a severely altered immune system. All of that makes the conditions under which the xenografts grow even more unrealistic, since, as Marks pointed out, the immune system plays "an enormous role" in how cancer originates, develops and spreads. ．
被植入的细胞通常取自单一性瘤，在植入老鼠体内之前，它们放在一种塑料管中培养了十几代，而不是在原生肿瘤中生长；并且动物的免疫系统改变也巨大．所有这些使得植入物的生长不切事实情况。所以就像Mark指出的，免疫系统在癌细胞的起源、发展和延伸中扮演＂一个很重要的角色＂．
But researchers are developing new forms of mouse and, to some degree, rat models that will improve their predictive powers for human disease. The models, which mostly consist of inducible knockouts or transgenes in the cell types and pathways that go awry in human cancers, "are rodents - they are not us," Marks said. "But the gene similarities are remarkable."
但是研究员们正在开发一种老鼠新模型，这种模型在一定的程度上可能预测药物在人上的疗效．因为它由可诱导的或人类癌细胞在细胞种类或路径上发生变异而组成的．Marks说＂它们是啮齿动物与我们人类相差很大，但我们基因有惊人的相似性。＂
In general, Marks said, there's bad news and good news about new transgenic mouse models. The bad news is that "we do a very bad job of curing cancer in these animals." The good news is that this is because the transgenics "are really good mimics of the response in the clinic - unlike the xenografts, which often show gangbuster responses to things that don't pan out in the clinic."
Marks认为，一般来说，关于转基因老鼠模型有好消息也有坏消息，坏的是＂我们在这些动物身上做癌症治疗成功病倒很少＂，好的是＂这些转基因很好地反映临床疗效，不像异种移植法在动物实验中很成功但在临床实验中无疗效。
The push to develop such models started about eight years ago, when National Institutes of Health in Bethesda, Md., took stock of cancer research efforts and decided that "we were not learning, nor were the pharmaceutical and biotech companies learning, what we needed to know about human disease" from the available mouse models. And the newest example of the effort appears in the April 24, 2006, issue of the Proceedings of the National Academy of Sciences.
这种模型开始于８年前，是国家健康协会在整理癌症研究成果后决定的。＂我们没有在研究，制药和生物技术公司也没研究，但我们需要从改变的老鼠模型中反映人类的治疗效果＂．最近的模型在２００６年４月２４日的国家科学院学报上发表。
The paper described a mouse model for the pediatric brain cancer medulloblastoma. The authors of the paper, from Harvard Medical School, compared two strains of mice that had different genes knocked out specifically in neural progenitor cells. 神经原细胞
论文描述该老鼠模型适用于小儿脑部肿瘤成神经管细胞癌．论文的作者（来自哈佛大学）比较了同样被破坏神经原细胞的两组具有不同基因的老鼠．
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作者:admin@医学,生命科学 2011-08-06 05:14
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