2015年精準醫(yī)學概念提出以來,全球從事生物醫(yī)學研究的科學家,尋找更新更精準的技術(shù),以期對腫瘤進行精準分型,從而尋找最精準的藥物,以達到對腫瘤精準的治療,突破腫瘤治療的瓶頸。
2016年10月份全球最頂級雜志Nature發(fā)表文章,以美國ProteinSimple公司Nanopro1000作為技術(shù)平臺,開發(fā)腫瘤分型診斷的新策略,并指導腫瘤的精準治療。
作者來自于世界最大的私人腫瘤研究中心:美國斯隆—凱特林癌癥研究所,及康奈爾大學醫(yī)學院等世界著名醫(yī)學研究機構(gòu)。
研究者發(fā)現(xiàn),大蛋白復合體的形成,和腫瘤存活及腫瘤對于治療藥物敏感高度相關(guān)。樣本來自于急性髓系白血病病人,作者將HSP90作為研究靶蛋白,使用Nanopro1000作為研究平臺,研究病人機體是否會形成HSP90蛋白復合體。正常HSP90等電點在4.9,如果形成的HSP90蛋白復合體等電點大于4.9,命名為“一型”腫瘤,HSP90蛋白復合體等電點小于4.9,則命名為“二型”腫瘤。研究發(fā)現(xiàn)“一型”腫瘤對于HSP90抑制劑治療敏感,“二型”腫瘤對于HSP90抑制劑不敏感,故需要選擇其他治療方法。
原文閱讀:
HSP90 focused primarily as a single species at the predicted isoelectric point (pI) of 4.9. However, cancer cell lines analysed by this method contained a complex mixture of HSP90 species spanning a pI range of 4.5 to 6; HSP90α and HSP90β isoforms were part of these complexes. Furthermore, although all cancer cell lines contained a number of HSP90 complexes with pI < 4.9, a subset was enriched in HSP90 complexes with the unusual pI of ≥5, herein referred to as ‘type 1’ cells. We refer to cancer cell lines that contained mainly complexes with pI < 4.9 as ‘type 2’ cells.
Nanopro1000超靈敏蛋白質(zhì)免疫檢測系統(tǒng),可以直接使用來自病人的微量臨床穿刺樣本,進行蛋白質(zhì)天然結(jié)構(gòu)等電聚焦分離及免疫定量,繪制病人蛋白質(zhì)結(jié)構(gòu)變化,翻譯后修飾改變,氨基酸突變等帶來的圖譜變化。根據(jù)蛋白質(zhì)圖譜變化,繪制疾病相關(guān)診斷圖譜,精準制導治療。已經(jīng)在Nature, Nature Medicine, Cell Stem cell等眾多頂尖雜志發(fā)表了診斷白血病,淋巴瘤,脂肪肝等的分子分型標準,對于重新認識疾病,精準診斷,精準治療帶來了新的策略。原文閱讀:
To identify and separate chaperome complexes in tumours, and to overcome the limitations of classical protein chromatography methods for resolving complexes of similar composition and size, we took advantage of a capillary-based platform that combines isoelectric focusing (IEF) with immunoblotting capabilities. This methodology uses an immobilized pH gradient to separate native multimeric protein complexes based on their isoelectric point (pI), and allows for subsequent probing of immobilized complexes with specific antibodies. The method uses only minute amounts of sample, thus enabling the interrogation of primary specimens.
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