BACKGROUND/AIMS: Early tumor detection is crucial for the prevention of colon cancer. Near-infrared fluorescence (NIRF) imaging using a target-activatable probe may permit earlier disease detection. Matrix metalloproteinases (MMPs) participate in tumorigenesis and tumor growth. The aim of this study was to determine whether NIRF imaging using an MMP-activatable probe can detect colon tumors at early stages. METHODS: WE UTILIZED TWO MURINE COLON CANCER MODELS: a sporadic colon cancer model induced by azoxymethane (AOM), and a colitis-associated cancer model induced by a combination of AOM and dextran sodium sulfate (DSS). Colonic lesions were analyzed by histologic examination, Western blotting, immunohistochemical staining, and NIRF imaging using an MMP-activatable probe. RESULTS: Multiple variable-sized tumors developed in both models and progressed from adenomas to adenocarcinomas over time. At the early stage of the AOM/DSS model, diffuse inflammation was observed within the tumors. MMP expression increased progressively through normal, inflammation, adenoma, and adenocarcionoma stages. NIRF signal intensities were strongly correlated with each tumor stage from adenoma to adenocarcinoma. NIRF imaging also distinguished tumors from inflamed mucosa. CONCLUSIONS: NIRF imaging using a protease-activatable probe may be a useful tool for early tumor detection. This approach could translate to improve the endoscopic detection of colon tumors, especially in patients with inflammatory bowel disease.
BACKGROUND/AIMS: Early tumor detection is crucial for the prevention of colon cancer. Near-infrared fluorescence (NIRF) imaging using a target-activatable probe may permit earlier disease detection. Matrix metalloproteinases (MMPs) participate in tumorigenesis and tumor growth. The aim of this study was to determine whether NIRF imaging using an MMP-activatable probe can detect colon tumors at early stages. METHODS: WE UTILIZED TWO MURINECOLON CANCER MODELS: a sporadic colon cancer model induced by azoxymethane (AOM), and a colitis-associated cancer model induced by a combination of AOM and dextran sodium sulfate (DSS). Colonic lesions were analyzed by histologic examination, Western blotting, immunohistochemical staining, and NIRF imaging using an MMP-activatable probe. RESULTS: Multiple variable-sized tumors developed in both models and progressed from adenomas to adenocarcinomas over time. At the early stage of the AOM/DSS model, diffuse inflammation was observed within the tumors. MMP expression increased progressively through normal, inflammation, adenoma, and adenocarcionoma stages. NIRF signal intensities were strongly correlated with each tumor stage from adenoma to adenocarcinoma. NIRF imaging also distinguished tumors from inflamed mucosa. CONCLUSIONS: NIRF imaging using a protease-activatable probe may be a useful tool for early tumor detection. This approach could translate to improve the endoscopic detection of colon tumors, especially in patients with inflammatory bowel disease.
Authors: László Herszényi; Ferenc Sipos; Orsolya Galamb; Norbert Solymosi; István Hritz; Pál Miheller; Lajos Berczi; Béla Molnár; Zsolt Tulassay Journal: Pathol Oncol Res Date: 2008-03-18 Impact factor: 3.201
Authors: Wilhelm J Lubbe; Zengyi Y Zhou; Weili Fu; David Zuzga; Stephanie Schulz; Rafael Fridman; Ruth J Muschel; Scott A Waldman; Giovanni M Pitari Journal: Clin Cancer Res Date: 2006-03-15 Impact factor: 12.531
Authors: Herlen Alencar; Martin A Funovics; Jose Figueiredo; Heloisa Sawaya; Ralph Weissleder; Umar Mahmood Journal: Radiology Date: 2007-05-16 Impact factor: 11.105
Authors: Giulia Marelli; Roberta Avigni; Paola Allavena; Cecilia Garlanda; Alberto Mantovani; Andrea Doni; Marco Erreni Journal: Oncotarget Date: 2018-07-31