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监测纳米孔硅芯片上转移性乳腺癌的进展。

Monitoring the progression of metastatic breast cancer on nanoporous silica chips.

机构信息

Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, TX 77030, USA.

出版信息

Philos Trans A Math Phys Eng Sci. 2012 May 28;370(1967):2433-47. doi: 10.1098/rsta.2011.0444.

Abstract

Breast cancer accounted for 15 per cent of total cancer deaths in female patients in 2010. Although significant progress has been made in treating early-stage breast cancer patients, there is still no effective therapy targeting late-stage metastatic breast cancers except for the conventional chemotherapy interventions. Until effective therapy for later-stage cancers emerges, the identification of biomarkers for the early detection of tumour metastasis continues to hold the key to successful management of breast cancer therapy. Our study concentrated on the low molecular weight (LMW) region of the serum protein and the information it contains for identifying biomarkers that could reflect the ongoing physiological state of all tissues. Owing to technical difficulties in harvesting LMW species, studying these proteins/peptides has been challenging until now. In our study, we have recently developed nanoporous chip-based technologies to separate small proteins/peptides from the large proteins in serum. We used nanoporous silica chips, with a highly periodic nanostructure and uniform pore size distribution, to isolate LMW proteins and peptides from the serum of nude mice with MDA-MB-231 human breast cancer lung metastasis. By matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and biostatistical analysis, we were able to identify protein signatures unique to different stages of cancer development. The approach and results reported in this study possess a significant potential for the discovery of proteomic biomarkers that may significantly enhance personalized medicine targeted at metastatic breast cancer.

摘要

2010 年,乳腺癌占女性癌症总死亡人数的 15%。尽管在治疗早期乳腺癌患者方面取得了重大进展,但除了常规化疗干预外,针对晚期转移性乳腺癌的有效治疗方法仍然没有。在针对晚期癌症的有效治疗方法出现之前,寻找用于早期检测肿瘤转移的生物标志物仍然是成功管理乳腺癌治疗的关键。我们的研究集中在血清蛋白质的低分子量(LMW)区域及其包含的信息,以鉴定能够反映所有组织生理状态的生物标志物。由于从技术上难以采集 LMW 物质,因此直到现在研究这些蛋白质/肽一直具有挑战性。在我们的研究中,我们最近开发了基于纳米孔芯片的技术,从血清中分离出小蛋白质/肽。我们使用具有高度周期性纳米结构和均匀孔径分布的纳米孔硅芯片,从带有 MDA-MB-231 人乳腺癌肺转移的裸鼠的血清中分离出 LMW 蛋白质和肽。通过基质辅助激光解吸/电离飞行时间质谱和生物统计学分析,我们能够鉴定出不同癌症发展阶段特有的蛋白质特征。本研究中报告的方法和结果具有发现蛋白质组生物标志物的巨大潜力,这可能会极大地增强针对转移性乳腺癌的个性化医学。

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