Translating buccal nanocytology for lung cancer screening into clinical practice

将口腔纳米细胞学肺癌筛查转化为临床实践

• 批准号: 10599179
• 负责人: Vadim Backman
• 金额: $ 31.11万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-15 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10599179
• 关键词: Address; Age; American; Architecture; Area; Biological Markers; Biophotonics; Blinded; Boston; Bronchoscopy; Cancer Etiology; Cancer Patient; Cells; Certification; Cessation of life; Cheek structure; Chromatin; Chromatin Structure; Clinical; Clinical Data; Clinical Research; Clinical Trials; Consultations; Data; Death Rate; Development; Diagnosis; Diagnostic; Disease; Early Diagnosis; Electron Microscopy; Eligibility Determination; Ensure; Esophagus; Excision; Gender; Genetic; Goals; Grant; Heterogeneity; Individual; Laboratories; Lead; Lesion; Life; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Marketing; Medical Device; Medical center; Microscopy; Molecular; Mucous Membrane; Nuclear; Operative Surgical Procedures; Optics; Oral mucous membrane structure; Patients; Population; Prevalence; Procedures; Protocols documentation; ROC Curve; Risk; Sampling; Sensitivity and Specificity; Smoke; Smoker; Smoking History; Specificity; Swab; Techniques; Technology; Testing; Time; Translating; Validation; X-Ray Computed Tomography; cancer subtypes; candidate marker; carcinogenesis; case control; clinical practice; computed tomography screening; cost; cost effective; demographics; diagnostic accuracy; diagnostic technologies; disease diagnosis; former smoker; improved; industry partner; instrumentation; interest; low dose computed tomography; lung cancer screening; lung carcinogenesis; minimally invasive; nanoarchitecture; nanocytology; nanoscale; novel; patient stratification; patient subsets; preservation; prevent; primary care setting; risk stratification; screening; technology development; tool; tumor

Project Summary The overarching goal of the Academic Industrial Partnership grant is to develop a population risk-stratification tool that will allow efficacious and cost-effective lung cancer screening. Lung cancer represents an ideal malignancy for screening because of its prevalence, identifiable risk groups (current/former smokers) and ability to surgically cure the disease if diagnosed early. However, there are no robust screening techniques with options such as low-dose CT (LDCT) scans fraught with cost and harm from large numbers of false positives. In order to make lung cancer screening viable, it is imperative to develop a test to pre-screen for LDCT by identifying the subset of patients who are likely to harbor lung cancers and would benefit from LDCT. The test must be sensitive to early disease (e.g. Stage I), low-cost, and able to be carried out in a primary care setting. The goal of this project is to develop such a test. One attractive approach is to exploit field carcinogenesis, the concept that the same genetic/environmental milieu that results in a lesion in one area of the lung will impact upon the entire aero digestive mucosa. The buccal (cheek) mucosa is a “molecular mirror” of lung carcinogenesis, although current techniques are inadequate to translate this phenomenon into a minimally intrusive screening test. The preliminary data show that the alteration of nanoscale architecture in buccal cells is exquisitely sensitive to field carcinogenesis and hence may serve as a robust biomarker for lung cancer. These nano-architectural changes can be detected in a practical and highly accurate fashion via a novel biophotonics technology, partial wave spectroscopic (PWS) microscopy (“nanocytology”). In this study, PWS technology will be refined and a prediction rule developed based on the PWS-detectable nanoscale alterations that is optimized for early stage, curable lung cancer. The goal of the proposed project is to finalize the remaining technology development aspects to translate nanocytology into a practical, accurate, and low- cost test, bring it to the point where it is viable for population screening, and conduct a pre-definitive clinical validation. The team envision that upon completion of this project, nanocytology will be ready for a definitive clinical trial leading to a launch in clinical practice. This novel paradigm could transform the clinical practice of lung cancer screening and thereby mitigate the large toll of this malignancy in Americans.

项目摘要 学术产业伙伴基金的首要目标是发展人口风险分层 这一工具将使肺癌筛查具有效率和成本效益。肺癌代表着一种理想 因其患病率、可识别的危险群体(现任/曾经吸烟者)和 如果及早诊断，有能力通过手术治愈这种疾病。然而，目前还没有可靠的筛查技术 低剂量CT(LDCT)扫描等选项充满了成本和大量虚假数据的危害 积极的一面。为了使肺癌筛查变得可行，开发一种预先筛查肺癌的测试是当务之急。 通过识别可能患有肺癌并将从LDCT中受益的患者子集，进行LDCT。 检测必须对早期疾病敏感(例如，I期)、低成本，并且能够在初级保健中进行 布景。这个项目的目标就是开发这样一种测试。一种有吸引力的方法是开发油田 致癌，即相同的遗传/环境环境导致某一区域的病变的概念 肺部会影响整个航空消化粘膜。颊(颊)黏膜是一面“分子镜子” 尽管目前的技术不足以将这种现象转化为 最小侵入性筛查测试。初步数据表明，纳米尺度结构的改变 颊上皮细胞对野生性癌变极为敏感，因此可作为肺的有力生物标志物。 癌症。这些纳米结构的变化可以通过一种实用且高度准确的方式进行检测 新的生物光子学技术，部分波谱(PWS)显微镜(“纳米细胞学”)。在这项研究中， 将改进PWS技术，并开发基于PWS可检测纳米级的预测规则 为早期、可治愈的肺癌而优化的改变。拟议项目的目标是最终敲定 剩下的技术发展方面，将纳米细胞学转化为实用、准确和低成本- 成本测试，将其带到可以进行人群筛查的点，并进行初步临床试验 验证。该团队设想，在这个项目完成后，纳米细胞学将准备好进行最终的 临床试验导致了临床实践的启动。这一新的范例可能会改变 肺癌筛查，从而减轻这种恶性肿瘤在美国人中造成的巨大伤亡。

项目成果

Early Upper Aerodigestive Tract Cancer Detection Using Electron Microscopy to Reveal Chromatin Packing Alterations in Buccal Mucosa Cells.

• DOI: 10.1017/s1431927621000507
• 发表时间: 2021-08
• 期刊: Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada
• 作者: Bugter O;Li Y;Wolters AHG;Agrawal V;Dravid A;Chang A;Hardillo J;Giepmans BNG;Baatenburg de Jong RJ;Amelink A;Backman V;Robinson DJ
• 通讯作者: Robinson DJ

Physical and data structure of 3D genome

• DOI: 10.1126/sciadv.aay4055
• 发表时间: 2020-01-01
• 期刊: SCIENCE ADVANCES
• 影响因子: 13.6
• 作者: Huang, Kai;Li, Yue;Szleifer, Igal
• 通讯作者: Szleifer, Igal