Three dimensional nanoscale nuclear architecture mapping based taxonomy of precursor lesions for predicting colorectal cancer risk

基于三维纳米级核结构映射的前体病变分类法用于预测结直肠癌风险

基本信息

批准号：
10373010
负责人：
Yang Liu
金额：
$ 41.42万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10373010
关键词：
3-Dimensional APC mutation Acceleration Adenomatous Polyps Animal Model ApcMin/+ mice Architecture Archives BRAF gene Benign Biopsy Cell Nucleus Chemopreventive Agent Classification Clinical Clinical Data Clinical Research Colitis Colonoscopy Colorectal Adenoma Colorectal Cancer Data Dependence Detection Development Disease Progression Effectiveness Epithelial Cells Event Evolution Excision Formalin Future Genetically Engineered Mouse Goals Guidelines High-Risk Cancer Image Individual Intestinal Neoplasms Intestines Lesion Malignant Neoplasms Measurement Medical center Microscopic Modeling Molecular Monitor Monitoring for Recurrence Mutation Neoplasms Nuclear Nuclear Structure Optical Coherence Tomography Optics Outcomes Research Paraffin Embedding Pathologic Pathology Report Pathway interactions Patients Persons Polyps Public Health Recording of previous events Recurrence Research Project Grants Resected Risk Sampling Standardization Stratification Surface Taxonomy Testing Tissue Embedding Tissues Universities Validation adenoma base cancer initiation cancer risk carcinogenesis clinical care clinical practice colon cancer progression colorectal cancer progression colorectal cancer risk colorectal cancer screening cost effective density follow-up high risk imaging system individual patient instrument intestinal epithelium intestinal tumorigenesis molecular subtypes mouse model nanoscale novel strategies patient stratification response risk prediction risk stratification screening success theories time interval tool tumor tumor progression tumorigenesis

项目摘要

PROJECT SUMMARY The effectiveness of colorectal cancer (CRC) screening, with a concomitant increased emphasis on detection of even the smallest adenomas, has resulted in a new clinical challenge. An increased number of people are being identified as harboring an adenomatous polyp, the benign precursor to CRC. These patients are recommended to undergo surveillance, or repeated colonoscopy for monitoring for recurrence. The guidelines for surveillance intervals, based on polyp size and pathologic classification, do not accurately reflect individual’s risk for CRC progression. Due to the lack of reliable markers to stratify individual patient’s cancer risk after adenoma resection, surveillance colonoscopy is often improperly applied in clinical practice. Clinicians urgently need cost-effective tests that accurately distinguish high-risk patients in need of more frequent surveillance from low-risk patients for whom surveillance interval can be lengthened. Building on the imaging principle behind Spectral-Domain Optical Coherence Tomography (SD-OCT), we have developed a new approach for 3D nanoscale nuclear architecture mapping (3D-nanoNAM) on tissue biopsies routinely obtained for patients’ clinical care. We have shown that nanoNAM directly quantifies sub-microscopic alterations in the intrinsic 3D structural architecture of cell nuclei in unstained formalin-fixed, paraffin- embedded (FFPE) tissue sections with nanoscale sensitivity. The goal of this project is to develop a reliable risk taxonomy of nanoNAM markers that are associated with CRC progression, and rigorously validate their ability to consistently predict CRC progression risk in the context of colorectal adenoma. We will rigorously validate the carcinogenesis dependence of 3D nanoNAM markers in intestinal tumorigenesis using animal models and characterize their corresponding change during the acceleration and inhibition of tumorigenesis. We will also evaluate the use of nanoNAM markers to predict the recurrence risk of advanced adenomas. Success of this project will validate nanoNAM markers for CRC progression-risk and justify a future, larger- scale clinical study for employing nanoNAM as an objective, personalized stratification tool to guide establishment of the recommended time interval for surveillance colonoscopy.

项目摘要结直肠癌（CRC）筛查的有效性，同时越来越重视检测即使是最小的腺瘤，也引起了新的临床挑战。人数越来越被确定为拥有腺瘤息肉，是CRC的良性前体。这些患者是建议接受监视或重复结肠镜检查以监测复发。指南对于监视间隔，基于息肉的大小和病理分类，无法准确反映个人的CRC进展风险。由于缺乏可靠的标记来分层患者的癌症腺瘤切除后的风险，经常在临床实践中不适当地使用监测结肠镜检查。临床医生迫切需要进行成本效益的测试，以准确区分需要更多的高危患者经常对低风险患者进行监视间隔的监视。建立在光谱域光学相干断层扫描（SD-OCT）背后的成像原理，我们已经开发了一个 3D纳米级核结构映射（3D-Nanonam）的新方法常规为患者的临床护理获得。我们已经表明，纳米纳姆直接量化了亚显微镜未染色的福音，石蜡中细胞核内固有3D结构结构的改变具有纳米级敏感性的嵌入（FFPE）组织切片。该项目的目的是开发可靠的与CRC进展相关的纳米标记的风险分类法，并严格验证其在结直肠腺瘤的背景下，能够始终如一地预测CRC进展风险。我们会严格使用动物验证3D纳米标记在肠道肿瘤中的癌变依赖性模型并表征其在肿瘤发生加速和抑制期间相应的变化。我们还将评估使用纳米标记来预测晚期腺瘤的复发风险。该项目的成功将验证纳米标记CRC进度风险，并证明未来的较大，更大的合理用于使用纳米纳姆作为目标的个性化分层工具的临床研究建立建议的监测结肠镜检查时间间隔。