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: 10403494
• 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/10403494
• 关键词: Address; Age; Assessment tool; Biological Markers; Blinded; Carcinoma; Clinical; Clinical Management; Clinical Trials; Cyst Fluid; Cystic Neoplasm; Cytology; Data; Detection; Disease; Dysplasia; Early Diagnosis; Emerging Technologies; Enzyme-Linked Immunosorbent Assay; Evaluation; Frequencies; Future; Goals; Guidelines; High grade dysplasia; Image; Imaging technology; Individual; Laboratories; Lesion; Light; Magnetic Resonance Imaging; Malignant - descriptor; Malignant neoplasm of pancreas; Measurement; Methods; Mucinous Neoplasm; Pancreas; Pancreatic Cyst; Pancreatic cystic neoplasia; Pancreatitis; Papillary; Pathway interactions; Patients; Periodicity; Plasma; Proteins; Resolution; Risk Assessment; Sampling; Screening for cancer; Source; Specimen; Surface; Techniques; Technology; Testing; Time; Training; Ultracentrifugation; Validation; Vesicle; anticancer research; biobank; biomarker signature; cancer biomarkers; cancer cell; clinical practice; cost; detection limit; detection method; digital; extracellular vesicles; high risk; imaging biomarker; improved; innovation; new technology; novel marker; pancreatic neoplasm; peripheral blood; point of care; premalignant; prospective; protein biomarkers; 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.

导管内乳头状粘液性肿瘤 (IPMN)、胰腺癌前病变的检测 由于高分辨率横截面成像的使用不断增加，这一数字不断上升。这些囊性肿瘤已 显示从低度不典型增生演变为高度不典型增生再到浸润性癌，并且被认为 占所有胰腺癌的20-30%。某些形式的 IPMN 患者的管理仍然存在 由于当前技术无法可靠区分低风险和高风险 IPMN，因此存在争议。 因此，需要开发更好的工具来促进有争议的病变的管理。目标 该提案的目的是开发和测试一种超灵敏的 DEST 方法，用于分析循环细胞外囊泡 (EV) 由高风险 IPMN 脱落。具体来说，我们建议 i) 开发并验证与 IPMN 相关的新标记集 以前所未有的敏感性（目标 1）和 ii）扩展并严格测试即时护理方法 对前瞻性收集的临床样本进行分析（目标 2）。我们假设高度灵敏的 EV 分析将 对 IPMN 中的生物标志物组成提供了有价值的启示，这是识别高风险病变和 早期的PDAC。所提出的 DEST 方法有可能改变 IPMN/早期 PDAC 癌症研究和 临床实践。