Peptide-based slides for improving the diagnostic quality of sputum specimens

基于肽的载玻片可提高痰标本的诊断质量

• 批准号: 9253558
• 负责人: Martyn Darby
• 金额: $ 30万
• 依托单位: AFFINERGY, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-16 至 2017-12-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9253558
• 关键词: Area; Aspirate substance; Atypia; Benign; Binding; Biopsy; Bladder; Blood Cells; Cancer Etiology; Cell physiology; Cells; Cessation of life; Clinical; Cost Savings; Cytology; Detection; Development; Diagnosis; Diagnostic; Disease; Disease Outcome; Dose; Epithelial Cells; Equipment; Evaluation; Excision; Genetic; Glass; Goals; Healthcare Systems; Human; Imagery; Incidence; Lead; Lesion; Leukocytes; Life; Lung; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of lung; Methods; Modality; Molecular; Molecular Abnormality; Molecular Analysis; Morbidity - disease rate; Nature; Operative Surgical Procedures; Outcome; Pancreas; Patients; Peptides; Performance; Phage Display; Phase; Phase I Clinical Trials; Population; Preparation; Prevalence; Process; Sampling; Site; Slide; Smoker; Specificity; Specimen; Sputum; Staging; Staining method; Stains; Survival Rate; Techniques; Technology; Testing; Thyroid Gland; Time; Triage; United States; Unnecessary Procedures; Unnecessary Surgery; Visual; Woman; X-Ray Computed Tomography; advanced disease; base; cell type; clinical material; cost; cost effective; curative treatments; high risk; immunocytochemistry; improved; interest; men; mortality; novel; prevent; research clinical testing; screening; success; unnecessary treatment

SUMMARY/ABSTRACT Lung cancer is the leading cause of cancer-related mortality in both men and women in United States with a dismal 5-year survival rate of 15%. While surgery is the only curative option, 70% of the patients are diagnosed with inoperable advanced disease, thus highlighting a lack of effective early screening methods. Typically, low dose computed tomography (LDCT) is used as the primary screening modality, however, 90-95% of suspicious lung lesions identified by LDCT eventually are found to be benign. As a result, such patients undergo medically unnecessary procedures and treatments, resulting in increased cost, time and morbidity. Hence there is an urgent need to develop a non-invasive complementary screening technique which can identify the high-risk population for lung cancer and thus enable detection of lung lesions at an early and potentially curable stage. To this end, cytological and molecular aberrations found in exfoliated bronchial epithelial cells in sputum of smokers have shown a strong correlation to lung cancer incidence. However, these diagnostically important cells represent less than 1% of the cellular composition of sputum, thus making their detection extremely challenging. Hence, it is essential to develop a method which can isolate and capture these scant yet important cells, while removing the other obscuring cells from sputum and thereby improve the clinical utility of these vital biospecimens. The goal of this Phase I application is to develop a novel peptide-coated glass slide, which can selectively capture and retain the epithelial cells of interest in a peptide-modified region, while moving the obscuring cells to a separate region of the slide. Epithelial cell capture on the peptide-modified slides will be first optimized to identify lead peptides for subsequent clinical testing. Thereafter compatibility of the peptide-modified slides with commonly employed clinical staining techniques will be established. Finally, the feasibility of using these peptide-modified slides for capturing cells from human sputum specimens will be validated. Successful completion of this project will not only allow for better visualization of the captured epithelial cells to the clinicians, but also enable further downstream processing of these cells to identify molecular and/or genetic atypia present, because of the non-destructive nature of this technology.

摘要/摘要 肺癌是美国男性和女性与癌症相关死亡率的主要原因 惨淡的5年生存率为15％。虽然手术是唯一的治愈方法，但有70％的患者被诊断出 由于无法获得晚期疾病，因此突出了缺乏有效的早期筛查方法。通常，低 剂量计算机断层扫描（LDCT）用作主要筛查方式，但是，可疑的90-95％ LDCT鉴定出的肺部病变最终被发现是良性的。结果，此类患者接受医学 不必要的程序和治疗，导致成本，时间和发病率增加。因此有一个 迫切需要开发一种可以识别高风险的非侵入性互补筛查技术 肺癌的种群，因此可以在早期且可能可治愈的阶段检测肺部病变。到 在吸烟者痰中的剥落支气管上皮细胞中发现的细胞学和分子像差 与肺癌发生率有很强的相关性。但是，这些诊断重要的细胞 少于痰液的细胞组成的1％，从而使它们的检测极具挑战性。 因此，必须开发一种可以隔离和捕获这些微不足道但重要的细胞的方法，而 从痰液中去除其他模糊的细胞，从而改善这些重要的临床实用性 生物测量。该阶段I应用的目的是开发新型肽涂层的载玻片，可以 在移动肽修饰区域中有选择地捕获并保留了感兴趣的上皮细胞 将细胞掩盖到载玻片的单独区域。肽修饰载玻片上的上皮细胞捕获将首先 优化以鉴定铅肽以进行随后的临床测试。此后，肽修饰的兼容性 将建立具有常用的临床染色技术的幻灯片。最后，使用的可行性 这些用于从人痰标本捕获细胞的肽修饰的载玻片将得到验证。成功的 该项目的完成不仅将使捕获的上皮细胞更好地可视化临床医生， 但同时也能够进一步的下游加工这些细胞，以鉴定存在分子和/或遗传性疾病， 由于该技术的无损性。