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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...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2008
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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. |
format | Text |
id | pubmed-2488397 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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