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Early detection of colorectal cancer in the traditional and serrated pathways

通过传统途径和锯齿状途径早期发现结直肠癌

基本信息

批准号：
10244933
负责人：
Thomas D Wang
金额：
$ 34.52万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
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：
2020-09-01 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10244933
关键词：
Address Affinity Antibodies Appearance Area Binding Biochemical Biological Biological Assay Biological Markers Biopsy Cancer Etiology Cell surface Cells Cessation of life Clinic Clinical Clinical Research Colon Colonoscopy Colorectal Cancer Community Physician Contrast Media DNA Detection Development Devices Dimensions Disease Early Diagnosis Effectiveness Endoscopes Endoscopy Excision Fecal occult blood Fiber Fluorescence Genetic Heterogeneity Heterogeneity Human Image Imaging Device Immunocompromised Host Implant In Vitro Kinetics Label Lesion Ligands Light Lighting Localized Lesion Malignant Neoplasms Medical Methods MicroRNAs Molecular Molecular Target Mucous Membrane Mus Optics Organ Organoids Pathway interactions Patients Peptides Performance Physicians Pre-Clinical Model Primary Care Physician Procedures Protein Fragment Proteins Resected Resolution Scanning Screening for cancer Serrated Adenoma Specificity Specimen Structure Surface Technology Testing Validation Visualization Work adenoma authority base clinically relevant colon cancer screening colorectal cancer screening contrast imaging design detection sensitivity flexibility fluorescence imaging fluorophore hexanoic acid human subject imaging agent imaging biomarker imaging modality improved in vivo in vivo imaging instrument microsystems minimally invasive monomer overexpression patient population peroxiredoxin I premalignant prevent prototype response routine imaging targeted imaging tumor progression

项目摘要

Project Summary/Abstract Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Conventional colonoscopy with white light illumination frequently misses pre-malignant lesions that are either flat or subtle in appearance. CRC arises from either the traditional or serrated pathways in >95% of all known cases. Development of imaging biomarkers expressed in these two pathways can improve methods for early CRC detection. Successful completion of the aims will result in proof-of-concept for a targeted imaging strategy to improve the effectiveness of colonoscopy for early CRC detection. Peptide monomers specific for cMet and peroxiredoxin-1 will be optimized and arranged in a heterodimer configuration. These molecular targets are over expressed by pre-malignant lesions that arise from the traditional and serrated pathways, respectively. IRDye800 will be used as a near-infrared fluorescence label. Specific binding will be validated with cells in vitro and human colon specimens ex vivo using known antibodies. A flexible fiber endoscope accessory will be developed to image the heterodimer in vivo. The scalable optical design scans a low numerical aperture beam at large angles to achieve diffraction-limited resolution over a wide field-of-view. A miniature scanner will be developed based on parametric resonance with mixed stiffness-softening dynamics to deflect the beam at large angles. The compact form factor allows the instrument to be passed forward through the biopsy channel of standard medical endoscopes. Patient-derived organoids will be used to validate specific binding by the peptide heterodimer and verify the flexible fiber endoscope in vivo. These colonoids will be developed from traditional adenomas, sessile serrated adenomas, and normal mucosa, and will be implanted orthotopically in immunocompromised mice. These pre-malignant lesions appear endoscopically with flat and subtle features. Target expression levels and genetic heterogeneity are representative of pre-malignant lesions seen in the clinic. This collaborative work will be led by PI TD Wang, an expert in development and validation of peptide- based imaging agents. KR Oldham is an authority in microsystems-based scanning technologies, and JR Spence is an expert in development of primary human organoid cultures.

项目总结/文摘