Ultrasenstive vesicle analysis in precancerous pancreatic neoplasm (IPMN)

癌前胰腺肿瘤 (IPMN) 的超灵敏囊泡分析

• 批准号: 10615899
• 负责人: RALPH WEISSLEDER, MD, PHD
• 金额: $ 37.66万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10615899
• 关键词: Age; Assessment tool; Biological Markers; Blinded; Carcinoma; Clinical; Clinical Management; Clinical Trials; Cyst Fluid; Cystic Neoplasm; Data; Detection; Disease; Dysplasia; Early Diagnosis; Emerging Technologies; Enzyme-Linked Immunosorbent Assay; Evaluation; Frequencies; Future; Goals; Guidelines; High grade dysplasia; Image; Imaging technology; Incidental Findings; Individual; Laboratories; Lesion; Magnetic Resonance Imaging; Malignant - descriptor; Malignant neoplasm of pancreas; Measurement; Methods; Mucinous Neoplasm; Pancreas; Pancreatic Cyst; Pancreatic cystic neoplasia; Pancreatitis; Papillary; Pathway interactions; Patients; Periodicals; Plasma; Proteins; Recommendation; Resolution; Risk Assessment; Sampling; Screening for cancer; Source; Specimen; Surface; Techniques; Technology; Testing; Time; Training; Ultracentrifugation; Validation; Vesicle; anticancer research; biobank; biomarker signature; biomarker validation; cancer biomarkers; cancer cell; clinical practice; cost; detection limit; detection method; digital; extracellular vesicles; high risk; improved; innovation; new technology; novel marker; pancreatic neoplasm; peripheral blood; point of care; premalignant; prospective; protein biomarkers; technology validation; tool; tumor progression

The detection of intraductal papillary mucinous neoplasms (IPMN), precancerous lesions of the pancreas, is rising due to the increasing use of high-resolution cross-sectional imaging. These cystic neoplasms have been shown to evolve from low-grade dysplasia to high-grade dysplasia to invasive carcinoma and are believed to account for 20-30% of all pancreatic cancers. The management of patients with some forms of IPMN remains controversial because current technologies are unable to reliably distinguish between low and high risk IPMN. There is therefore a need to develop better tools to facilitate the management of controversial lesions. The goal of this proposal is to develop and test an ultra-sensitive DEST method for profiling circulating extracellular vesicles (EV) shed by high risk IPMN. Specifically, we propose to i) develop and validate new marker sets relevant for IPMN progression at unprecedented sensitivities (aim 1) and ii) expand and rigorously test the approach for point-of-care analyses in prospectively collected clinical samples (aim 2). We hypothesize that highly sensitive EV analysis will shed valuable light on biomarker composition in IPMN, a necessary prerequisite to identify high risk lesions and early PDAC. The proposed DEST method has the potential to transform IPMN/early PDAC cancer research and clinical practice.

胰腺癌前病变导管内乳头状粘液性肿瘤(IPMN)的检测 上升是由于越来越多地使用高分辨率横断面成像。这些囊性肿瘤一直是 从低度不典型增生演变到高度不典型增生再到浸润性癌，据信 占所有胰腺癌的20%-30%。某些形式的IPMN残留物的处理 有争议的是，因为目前的技术无法可靠地区分低风险和高风险的IPMN。 因此，有必要开发更好的工具来促进有争议的病变的管理。目标是 这项建议的目的是开发和测试一种超灵敏的DeST方法来分析循环细胞外小泡 (Ev)由高风险IPMN传播。具体地说，我们建议i)开发和验证与IPMN相关的新标记集 以前所未有的敏感性取得进展(目标1)和目标2)扩展并严格测试护理点方法 前瞻性收集的临床样本的分析(目标2)。我们假设高度敏感的电动汽车分析将 对IPMN中生物标记物的组成有价值的了解，这是识别高危病变和 早期的PDAC。建议的DEST方法有可能转变IPMN/早期PDAC癌症研究和 临床实践。

项目成果

Extracellular vesicle analysis of plasma allows differential diagnosis of atypical pancreatic serous cystadenoma.

• DOI: 10.1038/s41598-023-37966-5
• 发表时间: 2023-07-06
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Yang, Katherine S.;O'Shea, Aileen;Zelga, Piotr;Liss, Andrew S.;Del Castillo, Carlos Fernandez;Weissleder, Ralph
• 通讯作者: Weissleder, Ralph

Plasmonic Sensors for Extracellular Vesicle Analysis: From Scientific Development to Translational Research.

• DOI: 10.1021/acsnano.0c07581
• 发表时间: 2020-11-24
• 期刊: ACS nano
• 影响因子: 17.1
• 作者: Chin LK;Son T;Hong JS;Liu AQ;Skog J;Castro CM;Weissleder R;Lee H;Im H
• 通讯作者: Im H