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Oxygen supply maps for hypoxic microenvironment visualization in prostate cancer

BACKGROUND: Intratumoral hypoxia plays an important role with regard to tumor biology and susceptibility to radio- and chemotherapy. For further investigation of hypoxia-related changes, areas of certain hypoxia must be reliably detected within cancer tissues. Pimonidazole, a 2-nitroimindazole, accu...

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Autores principales: Rupp, Niels J., Schüffler, Peter J., Zhong, Qing, Falkner, Florian, Rechsteiner, Markus, Rüschoff, Jan H., Fankhauser, Christian, Drach, Matthias, Largo, Remo, Tremp, Mathias, Poyet, Cedric, Sulser, Tullio, Kristiansen, Glen, Moch, Holger, Buhmann, Joachim, Müntener, Michael, Wild, Peter J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763504/
https://www.ncbi.nlm.nih.gov/pubmed/26955501
http://dx.doi.org/10.4103/2153-3539.175376
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author Rupp, Niels J.
Schüffler, Peter J.
Zhong, Qing
Falkner, Florian
Rechsteiner, Markus
Rüschoff, Jan H.
Fankhauser, Christian
Drach, Matthias
Largo, Remo
Tremp, Mathias
Poyet, Cedric
Sulser, Tullio
Kristiansen, Glen
Moch, Holger
Buhmann, Joachim
Müntener, Michael
Wild, Peter J.
author_facet Rupp, Niels J.
Schüffler, Peter J.
Zhong, Qing
Falkner, Florian
Rechsteiner, Markus
Rüschoff, Jan H.
Fankhauser, Christian
Drach, Matthias
Largo, Remo
Tremp, Mathias
Poyet, Cedric
Sulser, Tullio
Kristiansen, Glen
Moch, Holger
Buhmann, Joachim
Müntener, Michael
Wild, Peter J.
author_sort Rupp, Niels J.
collection PubMed
description BACKGROUND: Intratumoral hypoxia plays an important role with regard to tumor biology and susceptibility to radio- and chemotherapy. For further investigation of hypoxia-related changes, areas of certain hypoxia must be reliably detected within cancer tissues. Pimonidazole, a 2-nitroimindazole, accumulates in hypoxic tissue and can be easily visualized using immunohistochemistry. MATERIALS AND METHODS: To improve detection of highly hypoxic versus normoxic areas in prostate cancer, immunoreactivity of pimonidazole and a combination of known hypoxia-related proteins was used to create computational oxygen supply maps of prostate cancer. Pimonidazole was intravenously administered before radical prostatectomy in n = 15 patients, using the da Vinci robot-assisted surgical system. Prostatectomy specimens were immediately transferred into buffered formaldehyde, fixed overnight, and completely embedded in paraffin. Pimonidazole accumulation and hypoxia-related protein expression were visualized by immunohistochemistry. Oxygen supply maps were created using the normalized information from pimonidazole and hypoxia-related proteins. RESULTS: Based on pimonidazole staining and other hypoxia.related proteins (osteopontin, hypoxia-inducible factor 1-alpha, and glucose transporter member 1) oxygen supply maps in prostate cancer were created. Overall, oxygen supply maps consisting of information from all hypoxia-related proteins showed high correlation and mutual information to the golden standard of pimonidazole. Here, we describe an improved computer-based ex vivo model for an accurate detection of oxygen supply in human prostate cancer tissue. CONCLUSIONS: This platform can be used for precise colocalization of novel candidate hypoxia-related proteins in a representative number of prostate cancer cases, and improve issues of single marker correlations. Furthermore, this study provides a source for further in situ tests and biochemical investigations
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spelling pubmed-47635042016-03-07 Oxygen supply maps for hypoxic microenvironment visualization in prostate cancer Rupp, Niels J. Schüffler, Peter J. Zhong, Qing Falkner, Florian Rechsteiner, Markus Rüschoff, Jan H. Fankhauser, Christian Drach, Matthias Largo, Remo Tremp, Mathias Poyet, Cedric Sulser, Tullio Kristiansen, Glen Moch, Holger Buhmann, Joachim Müntener, Michael Wild, Peter J. J Pathol Inform Technical Note BACKGROUND: Intratumoral hypoxia plays an important role with regard to tumor biology and susceptibility to radio- and chemotherapy. For further investigation of hypoxia-related changes, areas of certain hypoxia must be reliably detected within cancer tissues. Pimonidazole, a 2-nitroimindazole, accumulates in hypoxic tissue and can be easily visualized using immunohistochemistry. MATERIALS AND METHODS: To improve detection of highly hypoxic versus normoxic areas in prostate cancer, immunoreactivity of pimonidazole and a combination of known hypoxia-related proteins was used to create computational oxygen supply maps of prostate cancer. Pimonidazole was intravenously administered before radical prostatectomy in n = 15 patients, using the da Vinci robot-assisted surgical system. Prostatectomy specimens were immediately transferred into buffered formaldehyde, fixed overnight, and completely embedded in paraffin. Pimonidazole accumulation and hypoxia-related protein expression were visualized by immunohistochemistry. Oxygen supply maps were created using the normalized information from pimonidazole and hypoxia-related proteins. RESULTS: Based on pimonidazole staining and other hypoxia.related proteins (osteopontin, hypoxia-inducible factor 1-alpha, and glucose transporter member 1) oxygen supply maps in prostate cancer were created. Overall, oxygen supply maps consisting of information from all hypoxia-related proteins showed high correlation and mutual information to the golden standard of pimonidazole. Here, we describe an improved computer-based ex vivo model for an accurate detection of oxygen supply in human prostate cancer tissue. CONCLUSIONS: This platform can be used for precise colocalization of novel candidate hypoxia-related proteins in a representative number of prostate cancer cases, and improve issues of single marker correlations. Furthermore, this study provides a source for further in situ tests and biochemical investigations Medknow Publications & Media Pvt Ltd 2016-01-29 /pmc/articles/PMC4763504/ /pubmed/26955501 http://dx.doi.org/10.4103/2153-3539.175376 Text en Copyright: © 2016 Journal of Pathology Informatics http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
spellingShingle Technical Note
Rupp, Niels J.
Schüffler, Peter J.
Zhong, Qing
Falkner, Florian
Rechsteiner, Markus
Rüschoff, Jan H.
Fankhauser, Christian
Drach, Matthias
Largo, Remo
Tremp, Mathias
Poyet, Cedric
Sulser, Tullio
Kristiansen, Glen
Moch, Holger
Buhmann, Joachim
Müntener, Michael
Wild, Peter J.
Oxygen supply maps for hypoxic microenvironment visualization in prostate cancer
title Oxygen supply maps for hypoxic microenvironment visualization in prostate cancer
title_full Oxygen supply maps for hypoxic microenvironment visualization in prostate cancer
title_fullStr Oxygen supply maps for hypoxic microenvironment visualization in prostate cancer
title_full_unstemmed Oxygen supply maps for hypoxic microenvironment visualization in prostate cancer
title_short Oxygen supply maps for hypoxic microenvironment visualization in prostate cancer
title_sort oxygen supply maps for hypoxic microenvironment visualization in prostate cancer
topic Technical Note
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763504/
https://www.ncbi.nlm.nih.gov/pubmed/26955501
http://dx.doi.org/10.4103/2153-3539.175376
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