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【medical-news】阻断致癌基因可改善放疗效果
Blocking Cancer-Causing Gene Improves Radiation Effectiveness, Jefferson Researchers Find
Inhibiting a particular cancer-causing gene can enhance the cell-killing effects of radiation, a team of radiation oncologists and cancer biologists at the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia has found.
Adam Dicker, M.D., Ph.D., professor of radiation oncology at Jefferson Medical College and his co-workers used an increasingly common animal model, the zebrafish, and antisense technology to show that the drug flavopiridol works by blocking the activity of the gene, cyclin D1, which is made in excessive amounts in about half of all breast cancers. Using similar techniques in the future, the scientists say, may enable researchers to better gauge the effects of drugs.
According to Dr. Dicker, flavopiridol was found to inhibit cyclins, a family of genes vital to cell functioning. When it was initially tested in clinical trials, it was found to be toxic in humans. But in the laboratory, it added to the cell-killing effects of ionizing radiation, which is used to treat cancer. No one was sure why.
To find out, Dr. Dicker and his group turned to zebrafish. If they understood how the drug was causing toxicity, they or someone else could potentially design molecular copycat drugs that worked just as well, but were less toxic.
"Zebrafish enabled us to add a vertebrate system to examine both efficacy and toxicity issues," he notes. They reported their findings November 7, 2006 at the annual meeting of the American Society for Therapeutic Radiology and Oncology in Philadelphia.
In the work, Dr. Dicker and his co-workers first showed that flavopiridol-treated zebrafish embryos were much more sensitive than normal zebrafish to the effects of radiation. Then, believing that this effect stemmed from the drug's ability to block cyclin D, they used antisense technology to "knock down" - reduce the expression of - several cyclin genes, including cyclin D1.
Antisense DNA drugs work by binding to RNA messages from a target gene. The genetic code in the RNA cannot be read, essentially turning off the gene.
"We think that the radiosensitization is primarily due to cyclin D1," Dr. Dicker says. "We were able to genetically reduce the amount of cyclin D1 through the antisense technology, and when compared to embryos treated with radiation and flavopiridol, we saw that the effects were essentially identical. This shows the power of the system. Flavopiridol hits five or six cyclins and this allows us to find which cyclins are responsible for the radiosensitive effects.
"Theoretically, if we had a drug that inhibited several cyclins, we could understand the effect of inhibiting each cyclin by knocking it down with antisense," he says. "The technique helps explain drug function." 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 杰弗逊研究员发现阻断致癌基因可改善放疗效果
来自费城托马斯杰弗逊大学克墨癌症中心的一些放射肿瘤学家和肿瘤生物学家已经发现抑制特定的致癌基因可以提高放疗对细胞的杀灭效果。
亚当.狄克（临床专业学位、科学学位获得者，放射肿瘤学教授）和他的同事用一种
常用的动物模型—斑马鱼和反义技术来研究一种黄酮类药物，这种药物可阻断细胞周期蛋白D1基因的活性，据了解，这种基因在大约半数的乳腺癌患者中有过量表达。科学家声称，运用相同的技术可以使研究者更好的评价药物的效果。
根据狄克博士的研究，这种黄酮类药物能够抑制一类对细胞功能极其重要的细胞周期蛋白。当在临床实验中第一次检测到细胞周期蛋白时，对人体是有害的。但在实验中，它能增加电离放射的的细胞杀伤作用，可用来治疗癌症。还没有人知道究竟是什么原因。
为探讨究竟，狄克博士和他的团队转向斑马鱼的研究，如果他知道这种药物是怎样导致毒性的，他们或者其他人可以设计分子类药物，从而起到一样的效果，并具有更低的毒性。
“斑马鱼为我们提供了用脊椎动物系统检查效能和毒性问题的模型”他解释说。2006年7月，他们在费城举行的美国放射治疗学和肿瘤学年会上发表了他们的成果。
在这个工作中，狄克和他的同事第一次展示了经黄酮类药物处理的斑马鱼胚胎比正常斑马鱼对放射治疗具有更好的敏感性。他们认为这是因为药物阻断了细胞周期蛋白的表达。反义技术可以敲除一些细胞周期蛋白基因的表达，包括细胞周期蛋白D1。
反义DNA 药物通过与目的基因mRNA结合而起作用，使RNA上的遗传密码不能读取，本质上就等于基因沉默。
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作者:admin@医学,生命科学 2010-09-24 05:11
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