加拿大的一項(xiàng)最新研究發(fā)現(xiàn),，通常用于治療新陳代謝紊亂癥的廉價(jià)藥物二氯乙酸鹽可以殺死癌細(xì)胞,，它未來(lái)有望用來(lái)治療某些癌癥,。
加拿大艾伯塔大學(xué)研究人員在新一期美國(guó)《科學(xué)—轉(zhuǎn)化醫(yī)學(xué)》雜志網(wǎng)絡(luò)版上發(fā)表報(bào)告說(shuō)，他們讓5名惡性膠質(zhì)瘤（一種腦癌）患者服用了適量的二氯乙酸鹽,。結(jié)果發(fā)現(xiàn),，在二氯乙酸鹽的作用下，患者腫瘤組織的新陳代謝發(fā)生了變化,，其中4名患者的腫瘤在治療后的15個(gè)月里沒有進(jìn)一步發(fā)展,。對(duì)從這些患者身上提取的癌細(xì)胞的研究顯示，二氯乙酸鹽殺死了癌細(xì)胞,。
研究報(bào)告的主要作者,、加拿大艾伯塔大學(xué)的米切拉基斯說(shuō)，可以初步得出二氯乙酸鹽對(duì)某些患者可能是安全的和有臨床效果的結(jié)論,。他同時(shí)指出,，由于研究規(guī)模很小，還不能得出更多的結(jié)論,。(生物谷Bioon.com)
生物谷推薦原文出處：
Sci Transl Med DOI: 10.1126/scitranslmed.3000677
Metabolic Modulation of Glioblastoma with Dichloroacetate
E. D. Michelakis1,*, G. Sutendra1, P. Dromparis1, L. Webster1, A. Haromy1, E. Niven2, C. Maguire2, T.-L. Gammer1, J. R. Mackey3, D. Fulton3, B. Abdulkarim3, M. S. McMurtry1 and K. C. Petruk4
Solid tumors, including the aggressive primary brain cancer glioblastoma multiforme, develop resistance to cell death, in part as a result of a switch from mitochondrial oxidative phosphorylation to cytoplasmic glycolysis. This metabolic remodeling is accompanied by mitochondrial hyperpolarization. We tested whether the small-molecule and orphan drug dichloroacetate (DCA) can reverse this cancer-specific metabolic and mitochondrial remodeling in glioblastoma. Freshly isolated glioblastomas from 49 patients showed mitochondrial hyperpolarization, which was rapidly reversed by DCA. In a separate experiment with five patients who had glioblastoma, we prospectively secured baseline and serial tumor tissue, developed patient-specific cell lines of glioblastoma and putative glioblastoma stem cells (CD133+, nestin+ cells), and treated each patient with oral DCA for up to 15 months. DCA depolarized mitochondria, increased mitochondrial reactive oxygen species, and induced apoptosis in GBM cells, as well as in putative GBM stem cells, both in vitro and in vivo. DCA therapy also inhibited the hypoxia-inducible factor–1α, promoted p53 activation, and suppressed angiogenesis both in vivo and in vitro. The dose-limiting toxicity was a dose-dependent, reversible peripheral neuropathy, and there was no hematologic, hepatic, renal, or cardiac toxicity. Indications of clinical efficacy were present at a dose that did not cause peripheral neuropathy and at serum concentrations of DCA sufficient to inhibit the target enzyme of DCA, pyruvate dehydrogenase kinase II, which was highly expressed in all glioblastomas. Metabolic modulation may be a viable therapeutic approach in the treatment of glioblastoma.
