2012年9月8日 訊 /生物谷BIOON/ --放射治療是用于治療癌癥最普遍的一種療法,，但是這種療法常常會(huì)對(duì)正常組織帶來損傷,，而且容易導(dǎo)致患者的虛弱表現(xiàn)。近日,，刊登在國(guó)際著名雜志Cell Stem Cell上的研究表明,，一種稱為哺乳動(dòng)物雷帕霉素靶蛋白的系列藥物（mTOR）抑制子可以通過保護(hù)用于修復(fù)組織的正常干細(xì)胞,，來阻止小鼠由于輻射誘發(fā)所致的組織損傷。
研究者Silvio表示,，我們的研究發(fā)現(xiàn)為開發(fā)新的預(yù)防療法帶來了幫助,，進(jìn)行發(fā)射治療的癌癥病人經(jīng)常會(huì)發(fā)生嚴(yán)重的疼痛狀況，稱為粘膜炎,，就是口腔的軟組織腫脹,，這就使得病人不能進(jìn)食，他們不得不用阿片樣藥物來鎮(zhèn)痛,。放射療法也會(huì)通過減少用于修復(fù)損傷組織的干細(xì)胞來使患者機(jī)體更加虛弱,。
這項(xiàng)研究中，研究者發(fā)現(xiàn)mTOR抑制劑-雷帕霉素可以保護(hù)正常個(gè)體的口腔上皮干細(xì)胞避免由于放療所引發(fā)的死亡以及DNA損傷,，可以明顯延長(zhǎng)正常干細(xì)胞的存活時(shí)間,。雷帕霉素可以通過阻止有害分子-活性氧的積累來施展這種保護(hù)效應(yīng)。研究表明,，在放療期間接受雷帕霉素的小鼠明顯不會(huì)產(chǎn)生粘膜炎,。
因?yàn)槔着撩顾啬壳耙呀?jīng)得到了FDA的批準(zhǔn)許可，因此其可以用于進(jìn)行臨床試驗(yàn)來抑制和治療多種類型的癌癥,。這項(xiàng)新型研究發(fā)現(xiàn)對(duì)于治療癌癥病人也非常具有指導(dǎo)意義,。粘膜炎的預(yù)防將對(duì)于改善癌癥病人的生活質(zhì)量具有明顯的影響。研究者希望其研究可以快速進(jìn)行臨床應(yīng)用,，以改善患者的生活質(zhì)量,。（生物谷Bioon.com）
編譯自：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.
