上海 2012年8月11日 訊 /生物谷BIOON/ --腫瘤熱療，或稱加溫治癌,、溫?zé)嶂伟?、高溫治癌等，是用加熱方法治療腫瘤,，近20年來獲迅速發(fā)展,，在臨床上已顯出很好的效果。大量的臨床研究表明,，熱療合并放療或/和化療的效果,，有明顯的互補(bǔ)和增效作用；腫瘤熱療若使用得當(dāng),，對(duì)某些腫瘤治療的全消率可提高一倍左右，且無毒副作用,，遠(yuǎn)期療效也很可觀,。雖然熱療正越來越廣泛的應(yīng)用，但其中基本分子機(jī)制目前仍不清楚,。
近日,，班戈大學(xué)的研究人員確定了細(xì)胞中存在一種“開關(guān)”可以幫助熱殺死腫瘤。該開關(guān)機(jī)制可以有效的將熱量和一種破壞基因的抗癌藥物結(jié)合起來治療前列腺癌等,。這種新療法的背后機(jī)制是熱量關(guān)閉細(xì)胞的基本生存能力,。
這項(xiàng)最新研究發(fā)表在Journal of Cell Science雜志上,，研究發(fā)現(xiàn)熱量通過促進(jìn)產(chǎn)生一種新的蛋白質(zhì)調(diào)節(jié)細(xì)胞的生存系統(tǒng)。有趣的是,，這種蛋白質(zhì)只在溫度升高激活一種基因時(shí)才會(huì)生成,。（生物谷：Bioon.com）
編譯自：How heat helps to treat cancer
doi:10.1242/jcs.104075
PMC:
PMID:
Heat induction of a novel Rad9 variant from a cryptic translation initiation site reduces mitotic commitment
Simon Janes, Ulrike Schmidt, Karim Ashour Garrido, Nadja Ney, et al.
Exposure of human cells to heat switches DNA damage signaling from genotoxic to temperature stress. This change reduces mitotic commitment at the expense of DNA break repair. The thermal alterations behind this switch remain elusive despite the successful use of heat to sensitize cancer cells to DNA breaks. Rad9 is a highly conserved subunit of the Rad9-Rad1-Hus1 (9-1-1) checkpoint-clamp that is loaded by Rad17 onto damaged chromatin. At the DNA, Rad9 activates the checkpoint kinases Rad3ATR and Chk1 to arrest cells in G2. Using Schizosaccharomyces pombe as a model eukaryote, we discovered a new variant of Rad9, Rad9-M50, expression of which is specifically induced by heat. High temperatures promote alternative translation from a cryptic initiation codon at methionine-50. This process is restricted to cycling cells and independent of the temperature-sensing MAP kinase pathway. While full-length Rad9 delays mitosis in the presence of DNA lesions, Rad9-M50 functions in a remodeled checkpoint pathway to reduce mitotic commitment at elevated temperatures. This remodeled pathway still relies on Rad1 and Hus1, but acts independently of Rad17. Heat-induction of Rad9-M50 ensures that Chk1 kinase remains in a hypo-phosphorylated state. Elevated temperatures specifically reverse the DNA damage-induced modification of Chk1 in a manner dependent on Rad9-M50. Taken together, heat reprograms the DNA damage checkpoint at the level of Chk1 by inducing a Rad9 variant that can act outside of the canonical 9-1-1 complex.
