Detection of Colorectal Adenomas Using a Bioactivatable Probe Specific for Matrix Metalloproteinase Activity

Abstract

A significant proportion of colorectal adenomas, in particular those that lack an elevated growth component, continue to escape detection during endoscopic surveillance. Elevation of the activity of matrix metalloproteinases (MMPs), a large family of zinc endopeptidases, in adenomas serves as a biomarker of early tumorigenesis. The goal of this study was to assess the feasibility of using a newly developed near-infrared bioactivatable probe (MMPSense 680) that reports the activity of a broad array of MMP isoforms to detect early colorectal adenomas. Adenomatous polyposis coli (Apc)(+/Min-FCCC) mice that spontaneously develop multiple colorectal adenomas were injected with MMPSense 680, and the colons were imaged in an IVIS Spectrum system ex vivo. Image analyses were correlated with histopathologic findings for all regions of interest (ROIs). The biochemical basis of fluorescent signal was investigated by immunohistochemical staining of MMP-7 and -9. A strong correlation (Kendall = 0.80) was observed between a positive signal and the presence of pathologically confirmed colonic adenomas; 92.9% of the 350 ROIs evaluated were classified correctly. The correlation between two independent observers was 0.87. MMP-7 expression was localized to epithelial cells of adenomas and microadenomas, whereas staining of MMP-9 was found in infiltrating polymorphonuclear leukocytes within the adenomas. MMPSense 680 identifies colorectal adenomas, both polypoid and nonpolypoid, in Apc(+/Min-FCCC) mice with high specificity. Use of this fluorescent probe in combination with colonoscopy could aid in preventing colorectal neoplasias by providing new opportunities for early detection and therapeutic intervention.

Deguelin Analogue SH-1242 Inhibits Hsp90 Activity and Exerts Potent Anticancer Efficacy with Limited Neurotoxicity

“…2A, b; refs. 21,36). Two representative mice showed markedly decreased lung tumor growth by SH-1242 treatment.…”

Fast in vivo bioluminescence tomography using a novel pure optical imaging technique

“…So far, there are some commercial devices to implement the functionality of the tumor location reconstruction. IVIS Imaging System Spectrum is one of widespread application devices, 26,27 and it is also a pure optical 3D imaging system. To further investigate the performance of our POBT technique, we adopted this commercial system to acquire the°uorescence and white light images, and followed the guideline of the IVIS Living Imaging 3.0 software (PerkinElmer, USA) to achieve 3D light source reconstruction.…”

MMP-9 genetic polymorphism may confer susceptibility to COPD

“…COPD is an incurable lung disease characterized by defective tissue repair, resulting in small airways fibrosis or emphysema (Singh et al, 2011;Brandsma et al, 2015). MMPs are a family of zinc-dependent proteins that mediate a variety of biological functions, including cell migration, cellular invasion, cytokine activation, and tissue damage repair (Clapper et al, 2011). MMP-9 is produced by many inflammatory cell types and epithelial cells, including alveolar macrophages, neutrophils, and macrophages.…”