日前,,日本一個研究小組宣布,,他們在動物實驗中發(fā)現(xiàn)一種防止惡性膠質(zhì)瘤復(fù)發(fā)的新方法,相關(guān)論文已經(jīng)刊登在英國《科學(xué)報告》(Scientific Reports)雜志上,。
惡性膠質(zhì)瘤是一種非常難以治療的惡性腦腫瘤,,術(shù)后復(fù)發(fā)率較高。在日本,,它是一種患者人數(shù)最多的惡性腦腫瘤,,發(fā)病率為萬分之一。能夠重新制造癌細胞的“癌干細胞”被認為是導(dǎo)致惡性膠質(zhì)瘤復(fù)發(fā)的原因,。
日本山形大學(xué)和國立癌癥研究中心的聯(lián)合研究小組注意到,,一種被稱為JNK的蛋白激酶對于維持“癌干細胞”的存活必不可少,,于是將美國制藥公司為治療帕金森氏癥而開發(fā)的JNK抑制劑注射到腦內(nèi)移植了惡性膠質(zhì)瘤的實驗鼠體內(nèi)。結(jié)果發(fā)現(xiàn),,腫瘤中的“癌干細胞”減少到原有水平的十分之一以下,。
如果向?qū)嶒炇竽X內(nèi)移植“癌干細胞”,再連續(xù)10天注射這種藥物,,也能夠?qū)?ldquo;癌干細胞”減少到原有水平的十分之一以下甚至百分之一,。藥物對腦功能也沒有影響。
研究小組負責(zé)人,、山形大學(xué)教授北中千史說:“通過手術(shù)清除膠質(zhì)瘤,,再輔以這種藥物,也許就能夠阻止復(fù)發(fā),,讓患者長期存活,。”研究人員已經(jīng)準備開展臨床研究,有望5至7年后實現(xiàn)臨床應(yīng)用,。(生物谷Bioon.com)
doi:10.1038/srep00516
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Targeting JNK for therapeutic depletion of stem-like glioblastoma cells
Ken-ichiro Matsuda; Atsushi Sato; Masashi Okada; Keita Shibuya; Shizuka Seino; Kaori Suzuki; Eriko Watanabe; Yoshitaka Narita; Soichiro Shibui; Takamasa Kayama; Chifumi Kitanaka
Control of the stem-like tumour cell population is considered key to realizing the long-term survival of patients with glioblastoma, one of the most devastating human malignancies. To date, possible therapeutic targets and targeting methods have been described, but none has yet proven to target stem-like glioblastoma cells in the brain to the extent necessary to provide a survival benefit. Here we show that targeting JNK in vivo, the activity of which is required for the maintenance of stem-like glioblastoma cells, via transient, systemic administration of a small-molecule JNK inhibitor depletes the self-renewing and tumour-initiating populations within established tumours, inhibits tumour formation by stem-like glioblastoma cells in the brain, and provide substantial survival benefit without evidence of adverse events. Our findings not only implicate JNK in the maintenance of stem-like glioblastoma cells but also demonstrate that JNK is a viable, clinically relevant therapeutic target in the control of stem-like glioblastoma cells