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Development of a noninvasive, rapid and affordable method for early detection of colorectal cancer

开发一种无创、快速且经济实惠的结直肠癌早期检测方法

基本信息

批准号：
10044350
负责人：
CAROLE A OSKERITZIAN
金额：
$ 20.9万
依托单位：
UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10044350
关键词：
Address Age American ApcMin/+ mice Appearance Azoxymethane Biological Blood Vessels Brightfield Microscopy Cancer Control Carcinogens Cell physiology Cells Cellular biology Clinic Clinical Colon Colonic Polyps Colonoscopy Colorectal Cancer Computer Assisted Computer software DNA analysis Data Data Analyses Descriptor Detection Development Diagnostic Diffusion Magnetic Resonance Imaging Disease Distal Distant Doctor of Medicine Early Diagnosis Endoscopy Ensure Equipment Event Excision FDA approved Family Practice Feces Flexible fiberoptic sigmoidoscopy Genetic Models Gold Health Homeostasis Human Human Resources Image Image Analysis Immune Intervention Intestinal Polyposis Intestines Laboratories Lesion Low income Malignant Neoplasms Master of Public Health Measures Medical Methods Microscopy Modality Modeling Morbidity - disease rate Morphology Mus Patients Performance Physicians Pilot Projects Polyps Population Pre-Clinical Model Precancerous Polyp Prevention Preventive Medicine Primary Health Care Procedures Process Retrieval Sampling Schedule Sentinel Slide Specificity Specimen Stains Standardization Structure Swab Technology Testing Tissues Training Validation Wild Type Mouse adenoma adherence rate base cancer genetics cancer prevention carcinogenesis clinical practice colorectal cancer prevention colorectal cancer screening complex data computer aided detection computer data analysis computerized cost cost effective design dextran sulfate sodium induced colitis digital early onset equipment training human tissue imaging modality improved innovation intestinal epithelium mast cell medical schools minimally invasive mortality mouse model neoplastic pre-clinical preclinical study premalignant preservation prevent primary care setting prisma procedure cost professor programs quantitative imaging rectal sample collection screening tumor progression uptake validation studies

项目摘要

SUMMARY Screening remains the key intervention for colorectal cancer (CRC) control and prevention as detection and removal of premalignant lesions can prevent progression to cancer. Colonoscopy, the gold standard for CRC screening, is an invasive and costly procedure resulting in low compliance in both the general and the under- screened populations, including low-income and early-onset young patients. Feces-screening methods also suffer low compliance rates. Affordable and minimally invasive approaches are urgently warranted to address low screening rates and prevent CRC through early detection. We are proposing to explore the concept of field effect in CRC or simultaneous occurrence of subtle alterations distal from precancerous polyps in the colon, in an innovative way, to develop a new screening modality for CRC. Mast cells (MC) are innate immune cells located close to the intestinal epithelium and blood vessels at homeostasis, whose accumulation is an essential feature of intestinal polyposis in mice and of invasive intestinal lesions. We hypothesized that MC might slough off in the colonic lumen upon precancerous transformation, but not in normal healthy cases, thus being accessible by rectal swabbing, together with other cells. Combining our dual expertise in quantitative imaging and mast cell (MC) biology, we surmise that swab-collected cells might be analyzed on microscopy slides after processing and staining for MC using bright-field microscopy and image analysis software. Our preliminary results using two preclinical models of CRC, the genetic ApcMin/+ mouse model and the azoxymethane/dextran sulfate sodium-induced colitis leading to CRC, indicate the presence of swab MC in polyp carrying but not in healthy polyp-free, inflamed polyp-free, cancer-free or wild type mice. To ensure standardized sample analysis, we propose to develop a computational imaging method for swab MC detection by integrating MC-restricted morphometric descriptors. Further biological and technical validations will be performed. If confirm, our working hypothesis will be tested in a human pilot study.

概括与检测和预防一样，筛查仍然是结直肠癌 (CRC) 控制和预防的关键干预措施。去除癌前病变可以防止进展为癌症。结肠镜检查，结直肠癌的金标准筛查是一种侵入性且昂贵的程序，导致普通和低水平人群的依从性较低。筛查人群，包括低收入和早发的年轻患者。粪便筛查方法遵守率较低。迫切需要经济实惠且微创的方法来解决筛查率低，通过早期检测预防结直肠癌。我们建议探索场的概念 CRC 的影响或结肠癌前息肉远端同时发生的细微改变，一种创新方法，开发一种新的 CRC 筛查方式。肥大细胞（MC）是先天免疫细胞位于稳态时靠近肠上皮和血管，其积累是小鼠肠息肉病和侵袭性肠道病变的基本特征。我们假设 MC 在癌前转化时可能会在结肠腔中脱落，但在正常健康病例中不会脱落，因此可通过直肠拭子与其他细胞一起获取。结合我们在定量方面的双重专业知识成像和肥大细胞（MC）生物学，我们推测拭子收集的细胞可能会在显微镜下进行分析使用明场显微镜和图像分析软件对 MC 进行处理和染色后的载玻片。我们的使用两种 CRC 临床前模型（遗传 ApcMin/+ 小鼠模型和偶氮甲烷/硫酸葡聚糖钠诱导的结肠炎导致 CRC，表明拭子 MC 的存在携带息肉，但健康的无息肉、无发炎的息肉、无癌症或野生型小鼠中不存在。为确保标准化样本分析，我们建议开发一种用于拭子 MC 检测的计算成像方法通过整合 MC 限制的形态测量描述符。进一步的生物学和技术验证将执行。如果得到证实，我们的工作假设将在人体试点研究中得到检验。