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; 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.

检测导管内乳头状粘液性肿瘤（IPMN），胰腺癌的癌性病变是 由于高分辨率横截面成像的使用增加而增加。这些囊性肿瘤已经 证明会从低级发育不良发展到高级发育不良，再到侵入性癌，被认为是 占所有胰腺癌的20-30％。具有某些形式IPMN的患者的管理 有争议的是因为当前的技术无法可靠地区分低风险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 该建议的是开发和测试一种超敏感的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）开发和验证与IPMN相关的新标记集 以前所未有的敏感性（目标1）和ii）进行扩展和严格测试护理方法的进展 对前瞻性收集的临床样本进行分析（AIM 2）。我们假设高度敏感的EV分析将 在IPMN中为生物标志物组成提供了宝贵的灯光，这是确定高风险病变和的必要先决条件 早期PDAC。提出的DEST方法有可能改变IPMN/早期PDAC癌症研究和 临床实践。