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EGFR Overexpressed in Colonic Neoplasia Can be Detected on Wide-Field Endoscopic Imaging. | LitMetric

EGFR Overexpressed in Colonic Neoplasia Can be Detected on Wide-Field Endoscopic Imaging.

Clin Transl Gastroenterol

1] Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA [2] Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA [3] Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan, USA.

Published: July 2015

AI Article Synopsis

  • Colorectal cancer often begins as dysplasia, a precancerous state that is difficult to detect with standard endoscopy, highlighting the need for better detection methods.* -
  • The study focused on developing a peptide that specifically targets the epidermal growth factor receptor (EGFR), which is overexpressed in colonic adenomas, to enhance imaging capabilities.* -
  • Through experiments, the researchers confirmed that this peptide binds effectively to EGFR in both mouse models and human tissue samples, showing promise as a contrast agent for identifying dysplastic lesions during endoscopy.*

Article Abstract

Objectives: Colorectal cancer initially lies dormant as dysplasia, a premalignant state that provides an opportunity for early cancer detection. Dysplasia can be flat in morphology, focal in size, and patchy in distribution, and thus it appears "invisible" on conventional wide-field endoscopy.

Aims: We aim to develop and validate a peptide that is specific for epidermal growth factor receptor (EGFR), a cell surface target that is overexpressed in colonic adenomas and is readily accessible for imaging.

Methods: We expressed and purified the extracellular domain of EGFR for use with phage display to identify a peptide QRHKPRE that binds to domain 2 of this target. A near-infrared fluorescence endoscope was used to perform in vivo imaging to validate specific peptide binding to spontaneous colonic adenomas in a mouse model with topical administration. We also validated specific peptide binding to human colonic adenomas on immunohistochemistry and immunofluorescence.

Results: After labeling with Cy5.5, we validated specific peptide binding to EGFR on knockdown and competition studies. Peptide binding to cells occurred within 2.46 min and had an affinity of 50 nm. No downstream signaling was observed. We measured a target-to-background ratio of 4.0±1.7 and 2.7±0.7, for polyps and flat lesions, respectively. On immunofluorescence of human colonic specimens, greater intensity from peptide binding to dysplasia than normal was found with a 19.4-fold difference.

Conclusions: We have selected and validated a peptide that can be used as a specific contrast agent to identify colonic adenomas that overexpress EGFR in vivo on fluorescence endoscopy.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816258PMC
http://dx.doi.org/10.1038/ctg.2015.28DOI Listing

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