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Basal Tumor Cell Isolation and Patient-Derived Xenograft Engraftment Identify High-Risk Clinical Bladder Cancers

Strategies to identify tumors at highest risk for treatment failure are currently under investigation for patients with bladder cancer. We demonstrate that flow cytometric detection of poorly differentiated basal tumor cells (BTCs), as defined by the co-expression of CD90, CD44 and CD49f, directly f...

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Autores principales: Skowron, K. B., Pitroda, S. P., Namm, J. P., Balogun, O., Beckett, M. A., Zenner, M. L., Fayanju, O., Huang, X., Fernandez, C., Zheng, W., Qiao, G., Chin, R., Kron, S. J., Khodarev, N. N., Posner, M. C., Steinberg, G. D., Weichselbaum, R. R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075783/
https://www.ncbi.nlm.nih.gov/pubmed/27775025
http://dx.doi.org/10.1038/srep35854
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author Skowron, K. B.
Pitroda, S. P.
Namm, J. P.
Balogun, O.
Beckett, M. A.
Zenner, M. L.
Fayanju, O.
Huang, X.
Fernandez, C.
Zheng, W.
Qiao, G.
Chin, R.
Kron, S. J.
Khodarev, N. N.
Posner, M. C.
Steinberg, G. D.
Weichselbaum, R. R.
author_facet Skowron, K. B.
Pitroda, S. P.
Namm, J. P.
Balogun, O.
Beckett, M. A.
Zenner, M. L.
Fayanju, O.
Huang, X.
Fernandez, C.
Zheng, W.
Qiao, G.
Chin, R.
Kron, S. J.
Khodarev, N. N.
Posner, M. C.
Steinberg, G. D.
Weichselbaum, R. R.
author_sort Skowron, K. B.
collection PubMed
description Strategies to identify tumors at highest risk for treatment failure are currently under investigation for patients with bladder cancer. We demonstrate that flow cytometric detection of poorly differentiated basal tumor cells (BTCs), as defined by the co-expression of CD90, CD44 and CD49f, directly from patients with early stage tumors (T1-T2 and N0) and patient-derived xenograft (PDX) engraftment in locally advanced tumors (T3-T4 or N+) predict poor prognosis in patients with bladder cancer. Comparative transcriptomic analysis of bladder tumor cells isolated from PDXs indicates unique patterns of gene expression during bladder tumor cell differentiation. We found cell division cycle 25C (CDC25C) overexpression in poorly differentiated BTCs and determined that CDC25C expression predicts adverse survival independent of standard clinical and pathologic features in bladder cancer patients. Taken together, our findings support the utility of BTCs and bladder cancer PDX models in the discovery of novel molecular targets and predictive biomarkers for personalizing oncology care for patients.
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spelling pubmed-50757832016-10-28 Basal Tumor Cell Isolation and Patient-Derived Xenograft Engraftment Identify High-Risk Clinical Bladder Cancers Skowron, K. B. Pitroda, S. P. Namm, J. P. Balogun, O. Beckett, M. A. Zenner, M. L. Fayanju, O. Huang, X. Fernandez, C. Zheng, W. Qiao, G. Chin, R. Kron, S. J. Khodarev, N. N. Posner, M. C. Steinberg, G. D. Weichselbaum, R. R. Sci Rep Article Strategies to identify tumors at highest risk for treatment failure are currently under investigation for patients with bladder cancer. We demonstrate that flow cytometric detection of poorly differentiated basal tumor cells (BTCs), as defined by the co-expression of CD90, CD44 and CD49f, directly from patients with early stage tumors (T1-T2 and N0) and patient-derived xenograft (PDX) engraftment in locally advanced tumors (T3-T4 or N+) predict poor prognosis in patients with bladder cancer. Comparative transcriptomic analysis of bladder tumor cells isolated from PDXs indicates unique patterns of gene expression during bladder tumor cell differentiation. We found cell division cycle 25C (CDC25C) overexpression in poorly differentiated BTCs and determined that CDC25C expression predicts adverse survival independent of standard clinical and pathologic features in bladder cancer patients. Taken together, our findings support the utility of BTCs and bladder cancer PDX models in the discovery of novel molecular targets and predictive biomarkers for personalizing oncology care for patients. Nature Publishing Group 2016-10-24 /pmc/articles/PMC5075783/ /pubmed/27775025 http://dx.doi.org/10.1038/srep35854 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Skowron, K. B.
Pitroda, S. P.
Namm, J. P.
Balogun, O.
Beckett, M. A.
Zenner, M. L.
Fayanju, O.
Huang, X.
Fernandez, C.
Zheng, W.
Qiao, G.
Chin, R.
Kron, S. J.
Khodarev, N. N.
Posner, M. C.
Steinberg, G. D.
Weichselbaum, R. R.
Basal Tumor Cell Isolation and Patient-Derived Xenograft Engraftment Identify High-Risk Clinical Bladder Cancers
title Basal Tumor Cell Isolation and Patient-Derived Xenograft Engraftment Identify High-Risk Clinical Bladder Cancers
title_full Basal Tumor Cell Isolation and Patient-Derived Xenograft Engraftment Identify High-Risk Clinical Bladder Cancers
title_fullStr Basal Tumor Cell Isolation and Patient-Derived Xenograft Engraftment Identify High-Risk Clinical Bladder Cancers
title_full_unstemmed Basal Tumor Cell Isolation and Patient-Derived Xenograft Engraftment Identify High-Risk Clinical Bladder Cancers
title_short Basal Tumor Cell Isolation and Patient-Derived Xenograft Engraftment Identify High-Risk Clinical Bladder Cancers
title_sort basal tumor cell isolation and patient-derived xenograft engraftment identify high-risk clinical bladder cancers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075783/
https://www.ncbi.nlm.nih.gov/pubmed/27775025
http://dx.doi.org/10.1038/srep35854
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