Single Circulating Vesicle Analysis for Early Cancer Detection

用于早期癌症检测的单循环囊泡分析

• 批准号: 9913496
• 负责人: RALPH WEISSLEDER, MD, PHD
• 金额: $ 21.92万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-12 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9913496
• 关键词: Address; Age; Bar Codes; Biological Markers; Biology; Cells; Clinical; Clinical Trials; DNA; Detection; Disease; EPHA2 gene; Early Diagnosis; Emerging Technologies; Epidermal Growth Factor Receptor; Evaluation; Funding; Glass; Goals; Gold; Heterogeneity; Individual; Infrastructure; Kinetics; Lesion; Light; MSLN gene; MUC5AC gene; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of pancreas; Measurement; Measures; Methods; Microfluidic Microchips; Mucin 1 protein; Mutate; Operative Surgical Procedures; Patients; Periodicity; Pharmaceutical Preparations; Proteins; Recurrent disease; Reproducibility; Resectable; Residual Tumors; Resolution; Sampling; Screening for cancer; Signal Transduction; Slide; Source; Specimen; Techniques; Technology; Testing; Time; Vesicle; Yang; anticancer research; base; cancer biomarkers; cancer type; clinical practice; cost effective; experimental study; extracellular vesicles; improved; innovation; insight; interest; novel; novel therapeutics; pancreatic cancer patients; patient response; point of care; prospective; protein biomarkers; protein profiling; response; thrombospondin 2; tumor; tumor heterogeneity

Analysis of circulating extracellular vesicles (EV) have advanced over the last several years but challenges remain to reproducibly analyze samples in a clinical setting. If more sensitive and reproducible methods could be established, they would have far reaching applications in early cancer detection, measuring patient response to drugs, understanding tumor heterogeneity and discriminating different diseases. The problem is potentiated in pancreatic cancer (PDAC), where early detection methods are lacking, reproducibility of measurements has been a problem and an understanding of vesicle heterogeneity is missing. Furthermore, most existing technologies rely on bulk measurements which are inherently less sensitive since markers of interest are diluted (Yang et al., 2017, Sci Transl Med, 9). The goal of this proposal is to explore a novel single EV analysis (SEA) method (Lee et al, 2018, ACSnano, in press) to shed light on tumor EV (TEV) biomarker composition in PDAC. Specifically, we propose to i) integrate the method with on-chip microfluidics for improved sample handling while adding a MAb-DNA barcoding step for signal amplification and multiplexing (aim 1) and ii) expand and test the approach for point-of-care analyses of TEV in clinical samples (aim 2). The proposed single vesicle method has the potential to transform PDAC cancer research and clinical practice. It will allow us to discover the make-up of TEV in clinical specimen with far reaching applications for early detection (analysis of rare proteins) and treatment t evaluation in different types of cancers.

循环细胞外小泡(EV)的分析在过去几年中取得了进展，但面临着挑战 留下来在临床环境中重复分析样本。如果更灵敏和可重复性的方法 一旦建立，它们将在癌症早期检测、患者测量方面具有深远的应用 对药物的反应，了解肿瘤的异质性和区分不同的疾病。问题是 在缺乏早期检测方法的胰腺癌(PDAC)中增强，重复性 测量一直是个问题，对囊泡的异质性缺乏了解。此外， 大多数现有技术依赖于批量测量，而批量测量本身就不那么敏感，因为标记 兴趣被稀释(Yang等人，2017，Sci Transl Med，9)。这项提议的目标是探索一首新奇的单曲 EV分析(SEA)方法(Lee等人，2018，ACSnano，正在出版中)揭示肿瘤EV(TEV)生物标记物 PDAC中的作文。具体地说，我们提出了：1)将该方法与片上微流体相结合，以进行改进 样品处理，同时增加用于信号放大和多路传输的单抗-DNA条形码步骤(目标1)和2 扩展和测试临床样本中TEV的护理点分析方法(目标2)。建议的单曲 囊泡法具有转化PDAC肿瘤研究和临床应用的潜力。它会让我们发现 TEV在临床标本中的组成及其在早期检测中的深远应用(稀有蛋白分析) 以及对不同类型癌症的治疗t评价。