Translational Assays for Inflammatory Biomarkers for the Risk Stratification of Pancreatic Cystic Lesions

用于胰腺囊性病变风险分层的炎症生物标志物的转化分析

基本信息

批准号：
10697954
负责人：
Daniel Sheik
金额：
$ 39.99万
依托单位：
AMPLIFIED SCIENCES INC
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10697954
关键词：
Address Aliquot Archives Benign Biochemical Biological Assay Biological Markers Biological Sciences Blinded Chemicals Clinical Clinical Distribution Collaborations Confusion Cyst Cyst Fluid Cystic Lesion Decision Making Detection Development Diagnosis Diagnostic Dimensions Disease Dyes Dysplasia Elastases Environment Enzymes Equilibrium Evaluation Excision Fluorescence Freezing High grade dysplasia Image Imaging technology Individual Inflammatory Investigation Label Laboratories Lesion Leukocyte Elastase Liquid substance Magnetic Resonance Imaging Malignant - descriptor Malignant Neoplasms Malignant neoplasm of pancreas Measures Methods Morbidity - disease rate Mucinous Mucous body substance Nature Non-Malignant Operative Surgical Procedures Pancreas Pancreatic Cyst Pancreatic cystic neoplasia Pancreatic enzyme Patients Pepsinogen C Peptide Hydrolases Performance Peroxidases Phase Population Process Proteins Protocols documentation Publications Raman Spectrum Analysis Reporting Resolution Retrospective Studies Rhodamine Risk Sampling Science Sensitivity and Specificity Site Small Business Innovation Research Grant Specimen Standardization Surface Survival Rate Testing Time Translating Unnecessary Surgery Validation Viscosity accurate diagnosis accurate diagnostics activity marker biomarker panel biomarker validation clinical care clinical decision support clinical decision-making clinical diagnosis clinical diagnostics clinical imaging cohort detection method detection platform diagnostic tool diagnostic value dimensional analysis dimer disease diagnosis enzyme activity experience gastricsin improved inflammatory marker molecular marker mortality novel operation pancreatic neoplasm patient safety premalignant prevent prospective risk stratification routine imaging sample collection targeted biomarker technology platform tool trait translation assay tripeptidyl aminopeptidase tumor progression unnecessary treatment

Address Aliquot Archives Benign Biochemical Biological Assay Biological Markers Biological Sciences Blinded Chemicals Clinical Clinical Distribution Collaborations Confusion Cyst Cyst Fluid Cystic Lesion Decision Making Detection Development Diagnosis Diagnostic Dimensions Disease Dyes Dysplasia Elastases Environment Enzymes Equilibrium Evaluation Excision Fluorescence Freezing High grade dysplasia Image Imaging technology Individual Inflammatory Investigation Label Laboratories Lesion Leukocyte Elastase Liquid substance Magnetic Resonance Imaging Malignant - descriptor Malignant Neoplasms Malignant neoplasm of pancreas Measures Methods Morbidity - disease rate Mucinous Mucous body substance Nature Non-Malignant Operative Surgical Procedures Pancreas Pancreatic Cyst Pancreatic cystic neoplasia Pancreatic enzyme Patients Pepsinogen C Peptide Hydrolases Performance Peroxidases Phase Population Process Proteins Protocols documentation Publications Raman Spectrum Analysis Reporting Resolution Retrospective Studies Rhodamine Risk Sampling Science Sensitivity and Specificity Site Small Business Innovation Research Grant Specimen Standardization Surface Survival Rate Testing Time Translating Unnecessary Surgery Validation Viscosity accurate diagnosis accurate diagnostics activity marker biomarker panel biomarker validation clinical care clinical decision support clinical decision-making clinical diagnosis clinical diagnostics clinical imaging cohort detection method detection platform diagnostic tool diagnostic value dimensional analysis dimer disease diagnosis enzyme activity experience gastricsin improved inflammatory marker molecular marker mortality novel operation pancreatic neoplasm patient safety premalignant prevent prospective risk stratification routine imaging sample collection targeted biomarker technology platform tool trait translation assay tripeptidyl aminopeptidase tumor progression unnecessary treatment

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项目摘要

PROJECT SUMMARY Advances in clinical imaging technologies have increased the incidental detection rate of cystic pancreatic lesions. However, patients remain at risk due to the lack of a definitive diagnosis that accurately assesses if these cysts are pre-malignant. In the absence of robust diagnostic indicators, clinicians must balance patient safety due to a cystic lesion's rapid and aggressive progression to a malignant pancreatic tumor with the severe financial and physical morbidity and mortality associated with surgical interventions. Retrospective studies have found almost a quarter of surgical interventions to address a pancreatic cyst are unwarranted. A confounder is that retrospective studies have also revealed that when clinicians use a wait-and-see approach, up to a quarter of patients receive surgical resection too late. The dual-edged nature of this process highlights the need for better early-stage diagnostic tools. There remains an unmet clinical need for diagnostic information that can accurately stratify the risk associated with pre-cancerous, fluid-filled pancreatic lesions that are commonly the first sign of concern. Currently, clinicians can obtain fluid from incidentally detected pancreatic cysts for chemical analysis of disease- associated molecular markers. Pancreatic cyst fluid samples are most often highly viscous, making it difficult to aliquot, and can be very limited in volume depending on the size of cyst. Furthermore, available biomarker assays lack sensitivity, can have long turnaround times, and require high sample volumes. These traits limit the amount and quality of information from single pancreatic cyst fluid samples. Clinicians must rely on their unique experiences when choosing between appropriate analyses, which further confuses attempts at standardization of clinical care. Amplified Sciences has developed a robust assay platform to analyze low-volume (down to 1 µL) clinical pancreatic cyst fluid samples for protease activity to distinguish non-mucinous from mucinous pancreatic cyst populations. In this proposal, Amplified Sciences is expanding the platform to provide higher content diagnostic information about the malignant potential of the mucinous pancreatic cyst population. Amplified Sciences assay and detection platforms are adaptable to new biomarker targets. This proposal aims to create a multidimensional assay panel that accurately determines the risk of pancreatic cysts progression to cancer. A combination of three (3) markers under investigation by collaborators at Alaunus Biosciences and UCSF show promise to stratify the grade of dysplasia in a limited number of clinical mucinous pancreatic cyst samples. This proposal will 1) validate the capacity of these markers to distinguish low- from high-grade dysplasia in retrospective mucinous clinical samples and 2) translate low-volume assays for these markers into CLIA-ready protocols to enable stacking of assays on individual samples. Upon completion, a novel assay panel will be available that uses minimal cyst fluid volumes to quantitate the validated biomarkers, comprising a new method for clinicians to maximize accurate diagnostic information from precious clinical samples with rapid turnaround.

项目摘要临床成像技术的进步提高了囊性胰腺的偶然检测率病变。但是，由于缺乏明确的诊断，患者仍处于危险之中这些囊肿是预防性的。在没有强大诊断指标的情况下，临床医生必须平衡患者由于囊性病变的快速而侵略性而导致的安全性，因此与手术干预相关的财务和身体发病率和死亡率。回顾性研究发现将近四分之一的手术干预措施解决了胰腺囊肿。混杂因素是回顾性研究还表明，当临床医生采用等待方式时，最多四分之一患者接受外科切除术为时已晚。这个过程的双重性质突出了需要更好的早期诊断工具。对诊断信息的临床需求仍未满足，可以准确地分层与癌前，充满液体的胰腺病变相关的风险，这些风险通常是关注的第一个迹象。目前，临床医生可以从偶然被检测到的胰腺囊肿获取液体，以进行疾病的化学分析 - 相关分子标记。胰腺囊肿流体样品通常是高度粘稠的，因此很难等分试样，并且可以非常有限的体积，具体取决于囊肿的大小。此外，可用的生物标志物分析缺乏灵敏度，可能会有很长的周转时间，并且需要较高的样品体积。这些特征限制了金额来自单个胰腺囊肿流体样品的信息质量。临床医生必须依靠他们的独特在适当的分析之间进行选择时的经验，这进一步混淆了标准化的尝试临床护理。放大科学已经开发了一个强大的测定平台来分析小体积（降至1 µL）用于蛋白酶活性的临床胰腺囊肿样品，以区分非粘液和粘液胰腺囊肿种群。在此提案中，放大科学正在扩展平台以提供更高的内容有关粘液胰腺囊肿种群的恶性潜力的诊断信息。放大的科学测定法和检测平台可适应新的生物标志物靶标。该提议的目的创建一个多维测定面板，以准确确定胰腺囊肿的风险癌症。 Alaunus Biosciences和 UCSF显示有望在有限数量的临床粘液胰腺囊肿中分层发育不良等级样品。该提议将1）验证这些标记以区分低级发育不良的能力在回顾性的粘液临床样品中，2）将这些标记的小体积分析转换为可CLIA准备的可以在各个样本上堆叠测定的协议。完成后，一个新颖的测定面板将是可用的使用最少的囊肿液量来定量经过验证的生物标志物，完成了一种新方法让临床医生最大化具有快速周转的宝贵临床样本的准确诊断信息。