CSC:雷帕霉素可阻止癌症病人放疗副作用

放射治疗是用于治疗癌症最普遍的一种疗法，但是这种疗法常常会对正常组织带来损伤，而且容易导致患者的虚弱表现。近日，刊登在国际著名杂志Cell Stem Cell上的研究表明，一种称为哺乳动物雷帕霉素靶蛋白的系列药物（mTOR）抑制子可以通过保护用于修复组织的正常干细胞，来阻止小鼠由于辐射诱发所致的组织损伤。

研究者Silvio表示，我们的研究发现为开发新的预防疗法带来了帮助，进行发射治疗的癌症病人经常会发生严重的疼痛状况，称为粘膜炎，就是口腔的软组织肿胀，这就使得病人不能进食，他们不得不用阿片样药物来镇痛。放射疗法也会通过减少用于修复损伤组织的干细胞来使患者机体更加虚弱。

这项研究中，研究者发现mTOR抑制剂-雷帕霉素可以保护正常个体的口腔上皮干细胞避免由于放疗所引发的死亡以及DNA损伤，可以明显延长正常干细胞的存活时间。雷帕霉素可以通过阻止有害分子-活性氧的积累来施展这种保护效应。研究表明，在放疗期间接受雷帕霉素的小鼠明显不会产生粘膜炎。

因为雷帕霉素目前已经得到了FDA的批准许可，因此其可以用于进行临床试验来抑制和治疗多种类型的癌症。这项新型研究发现对于治疗癌症病人也非常具有指导意义。粘膜炎的预防将对于改善癌症病人的生活质量具有明显的影响。研究者希望其研究可以快速进行临床应用，以改善患者的生活质量。

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编译自：Stem-Cell-Protecting Drug Could Prevent the Harmful Side Effects of Radiation Therapy

doi:10.1016/j.stem.2012.06.007
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mTOR Inhibition Prevents Epithelial Stem Cell Senescence and Protects from Radiation-Induced Mucositis

Ramiro Iglesias-Bartolome, Vyomesh Patel, Ana Cotrim, Kantima Leelahavanichkul, Alfredo A. Molinolo, James B. Mitchell, J. Silvio Gutkind

The integrity of the epidermis and mucosal epithelia is highly dependent on resident self-renewing stem cells, which makes them vulnerable to physical and chemical insults compromising the repopulating capacity of the epithelial stem cell compartment. This is frequently the case in cancer patients receiving radiation or chemotherapy, many of whom develop mucositis, a debilitating condition involving painful and deep mucosal ulcerations. Here, we show that inhibiting the mammalian target of rapamycin (mTOR) with rapamycin increases the clonogenic capacity of primary human oral keratinocytes and their resident self-renewing cells by preventing stem cell senescence. This protective effect of rapamycin is mediated by the increase in expression of mitochondrial superoxide dismutase (MnSOD), and the consequent inhibition of ROS formation and oxidative stress. mTOR inhibition also protects from the loss of proliferative basal epithelial stem cells upon ionizing radiation in vivo, thereby preserving the integrity of the oral mucosa and protecting from radiation-induced mucositis.

doi:10.1016/j.stem.2012.08.003
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Relief with Rapamycin: mTOR Inhibition Protects against Radiation-Induced Mucositis

Toren Finkel

In this issue of Cell Stem Cell, Iglesias-Bartolome et al., 2012 show that mTOR inhibition with rapamycin protects against mucositis in mice, suggesting potential treatment strategies against this harmful side effect of anticancer therapies. In normal tissues, rapamycin prevents epithelial stem cell senescence by reducing oxidative stress through increased MnSOD.