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Live Imaging of Cysteine-Cathepsin Activity Reveals Dynamics of Focal Inflammation, Angiogenesis, and Polyp Growth

It has been estimated that up to 30% of detectable polyps in patients regress spontaneously. One major challenge in the evaluation of effective therapy of cancer is the readout for tumor regression and favorable biological response to therapy. Inducible near infra-red (NIR) fluorescent probes were u...

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Autores principales: Gounaris, Elias, Tung, Ching H., Restaino, Clifford, Maehr, René, Kohler, Rainer, Joyce, Johanna A., Plough, Hidde L., Barrett, Terrence A., Weissleder, Ralph, Khazaie, Khashayarsha
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2488397/
https://www.ncbi.nlm.nih.gov/pubmed/18698347
http://dx.doi.org/10.1371/journal.pone.0002916
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author Gounaris, Elias
Tung, Ching H.
Restaino, Clifford
Maehr, René
Kohler, Rainer
Joyce, Johanna A.
Plough, Hidde L.
Barrett, Terrence A.
Weissleder, Ralph
Khazaie, Khashayarsha
author_facet Gounaris, Elias
Tung, Ching H.
Restaino, Clifford
Maehr, René
Kohler, Rainer
Joyce, Johanna A.
Plough, Hidde L.
Barrett, Terrence A.
Weissleder, Ralph
Khazaie, Khashayarsha
author_sort Gounaris, Elias
collection PubMed
description It has been estimated that up to 30% of detectable polyps in patients regress spontaneously. One major challenge in the evaluation of effective therapy of cancer is the readout for tumor regression and favorable biological response to therapy. Inducible near infra-red (NIR) fluorescent probes were utilized to visualize intestinal polyps of mice hemizygous for a novel truncation of the Adenomatous Polyposis coli (APC) gene. Laser Scanning Confocal Microscopy in live mice allowed visualization of cathepsin activity in richly vascularized benign dysplastic lesions. Using biotinylated suicide inhibitors we quantified increased activities of the Cathepsin B & Z in the polyps. More than ¾ of the probe signal was localized in CD11b(+)Gr1(+) myeloid derived suppressor cells (MDSC) and CD11b(+)F4/80(+) macrophages infiltrating the lesions. Polyposis was attenuated through genetic ablation of cathepsin B, and suppressed by neutralization of TNFα in mice. In both cases, diminished probe signal was accounted for by loss of MDSC. Thus, in vivo NIR imaging of focal cathepsin activity reveals inflammatory reactions etiologically linked with cancer progression and is a suitable approach for monitoring response to therapy.
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spelling pubmed-24883972008-08-13 Live Imaging of Cysteine-Cathepsin Activity Reveals Dynamics of Focal Inflammation, Angiogenesis, and Polyp Growth Gounaris, Elias Tung, Ching H. Restaino, Clifford Maehr, René Kohler, Rainer Joyce, Johanna A. Plough, Hidde L. Barrett, Terrence A. Weissleder, Ralph Khazaie, Khashayarsha PLoS One Research Article It has been estimated that up to 30% of detectable polyps in patients regress spontaneously. One major challenge in the evaluation of effective therapy of cancer is the readout for tumor regression and favorable biological response to therapy. Inducible near infra-red (NIR) fluorescent probes were utilized to visualize intestinal polyps of mice hemizygous for a novel truncation of the Adenomatous Polyposis coli (APC) gene. Laser Scanning Confocal Microscopy in live mice allowed visualization of cathepsin activity in richly vascularized benign dysplastic lesions. Using biotinylated suicide inhibitors we quantified increased activities of the Cathepsin B & Z in the polyps. More than ¾ of the probe signal was localized in CD11b(+)Gr1(+) myeloid derived suppressor cells (MDSC) and CD11b(+)F4/80(+) macrophages infiltrating the lesions. Polyposis was attenuated through genetic ablation of cathepsin B, and suppressed by neutralization of TNFα in mice. In both cases, diminished probe signal was accounted for by loss of MDSC. Thus, in vivo NIR imaging of focal cathepsin activity reveals inflammatory reactions etiologically linked with cancer progression and is a suitable approach for monitoring response to therapy. Public Library of Science 2008-08-13 /pmc/articles/PMC2488397/ /pubmed/18698347 http://dx.doi.org/10.1371/journal.pone.0002916 Text en Gounaris et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Gounaris, Elias
Tung, Ching H.
Restaino, Clifford
Maehr, René
Kohler, Rainer
Joyce, Johanna A.
Plough, Hidde L.
Barrett, Terrence A.
Weissleder, Ralph
Khazaie, Khashayarsha
Live Imaging of Cysteine-Cathepsin Activity Reveals Dynamics of Focal Inflammation, Angiogenesis, and Polyp Growth
title Live Imaging of Cysteine-Cathepsin Activity Reveals Dynamics of Focal Inflammation, Angiogenesis, and Polyp Growth
title_full Live Imaging of Cysteine-Cathepsin Activity Reveals Dynamics of Focal Inflammation, Angiogenesis, and Polyp Growth
title_fullStr Live Imaging of Cysteine-Cathepsin Activity Reveals Dynamics of Focal Inflammation, Angiogenesis, and Polyp Growth
title_full_unstemmed Live Imaging of Cysteine-Cathepsin Activity Reveals Dynamics of Focal Inflammation, Angiogenesis, and Polyp Growth
title_short Live Imaging of Cysteine-Cathepsin Activity Reveals Dynamics of Focal Inflammation, Angiogenesis, and Polyp Growth
title_sort live imaging of cysteine-cathepsin activity reveals dynamics of focal inflammation, angiogenesis, and polyp growth
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2488397/
https://www.ncbi.nlm.nih.gov/pubmed/18698347
http://dx.doi.org/10.1371/journal.pone.0002916
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