TY - JOUR
T1 - Detection of intestinal cancer by local, Topical application of a quenched fluorescence probe for cysteine cathepsins
AU - Segal, Ehud
AU - Prestwood, Tyler R.
AU - Van Der Linden, Wouter A.
AU - Carmi, Yaron
AU - Bhattacharya, Nupur
AU - Withana, Nimali
AU - Verdoes, Martijn
AU - Habtezion, Aida
AU - Engleman, Edgar G.
AU - Bogyo, Matthew
N1 - Funding Information:
The authors would like to thank Yaara Segal for her help with the graphics and illustrations and Tina Oresic Bender for her help with SDS-PAGE gels analysis. This work was supported by National Institutes of Health grants EB005011 (to M.B.), T32GM007365 with additional support from Stanford School of Medicine and its Medical Scientist Training Program (to T.R.P.), and 5 U01 CA141468 and 1 R01 CA163441 (to E.G.E.).
Publisher Copyright:
© 2015 Elsevier Ltd. All rights reserved.
PY - 2015/1/22
Y1 - 2015/1/22
N2 - Early detection of colonic polyps can prevent up to 90% of colorectal cancer deaths. Conventional colonoscopy readily detects the majority of premalignant lesions, which exhibit raised morphology. However, lesions that are flat and depressed are often undetected using this method. Therefore, there is a need for molecular-based contrast agents to improve detection rates over conventional colonoscopy. We evaluated a quenched fluorescent activity-based probe (qABP; BMV109) that targets multiple cysteine cathepsins that are overexpressed in intestinal dysplasia in a genetic model of spontaneous intestinal polyp formation and in a chemically induced model of colorectal carcinoma. We found that the qABP selectively targets cysteine cathepsins, resulting in high sensitivity and specificity for intestinal tumors in mice and humans. Additionally, the qABP can be administered by either intravenous injection or by local delivery to the colon, making it a highly valuable tool for improved detection of colorectal lesions using fluorescence-guided colonoscopy.
AB - Early detection of colonic polyps can prevent up to 90% of colorectal cancer deaths. Conventional colonoscopy readily detects the majority of premalignant lesions, which exhibit raised morphology. However, lesions that are flat and depressed are often undetected using this method. Therefore, there is a need for molecular-based contrast agents to improve detection rates over conventional colonoscopy. We evaluated a quenched fluorescent activity-based probe (qABP; BMV109) that targets multiple cysteine cathepsins that are overexpressed in intestinal dysplasia in a genetic model of spontaneous intestinal polyp formation and in a chemically induced model of colorectal carcinoma. We found that the qABP selectively targets cysteine cathepsins, resulting in high sensitivity and specificity for intestinal tumors in mice and humans. Additionally, the qABP can be administered by either intravenous injection or by local delivery to the colon, making it a highly valuable tool for improved detection of colorectal lesions using fluorescence-guided colonoscopy.
UR - http://www.scopus.com/inward/record.url?scp=84921466095&partnerID=8YFLogxK
U2 - 10.1016/j.chembiol.2014.11.008
DO - 10.1016/j.chembiol.2014.11.008
M3 - Article
C2 - 25579207
AN - SCOPUS:84921466095
SN - 1074-5521
VL - 22
SP - 148
EP - 158
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 1
ER -
