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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.

总结