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A Novel Chordoma Xenograft Allows In Vivo Drug Testing and Reveals the Importance of NF-κB Signaling in Chordoma Biology

Chordoma is a rare primary bone malignancy that arises in the skull base, spine and sacrum and originates from remnants of the notochord. These tumors are typically resistant to conventional chemotherapy, and to date there are no FDA-approved agents to treat chordoma. The lack of in vivo models of c...

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Autores principales: Trucco, Matteo M., Awad, Ola, Wilky, Breelyn A., Goldstein, Seth D., Huang, Ruili, Walker, Robert L., Shah, Preeti, Katuri, Varalakshmi, Gul, Naheed, Zhu, Yuelin J., McCarthy, Edward F., Paz-Priel, Ido, Meltzer, Paul S., Austin, Christopher P., Xia, Menghang, Loeb, David M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819300/
https://www.ncbi.nlm.nih.gov/pubmed/24223206
http://dx.doi.org/10.1371/journal.pone.0079950
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author Trucco, Matteo M.
Awad, Ola
Wilky, Breelyn A.
Goldstein, Seth D.
Huang, Ruili
Walker, Robert L.
Shah, Preeti
Katuri, Varalakshmi
Gul, Naheed
Zhu, Yuelin J.
McCarthy, Edward F.
Paz-Priel, Ido
Meltzer, Paul S.
Austin, Christopher P.
Xia, Menghang
Loeb, David M.
author_facet Trucco, Matteo M.
Awad, Ola
Wilky, Breelyn A.
Goldstein, Seth D.
Huang, Ruili
Walker, Robert L.
Shah, Preeti
Katuri, Varalakshmi
Gul, Naheed
Zhu, Yuelin J.
McCarthy, Edward F.
Paz-Priel, Ido
Meltzer, Paul S.
Austin, Christopher P.
Xia, Menghang
Loeb, David M.
author_sort Trucco, Matteo M.
collection PubMed
description Chordoma is a rare primary bone malignancy that arises in the skull base, spine and sacrum and originates from remnants of the notochord. These tumors are typically resistant to conventional chemotherapy, and to date there are no FDA-approved agents to treat chordoma. The lack of in vivo models of chordoma has impeded the development of new therapies for this tumor. Primary tumor from a sacral chordoma was xenografted into NOD/SCID/IL-2R γ-null mice. The xenograft is serially transplantable and was characterized by both gene expression analysis and whole genome SNP genotyping. The NIH Chemical Genomics Center performed high-throughput screening of 2,816 compounds using two established chordoma cell lines, U-CH1 and U-CH2B. The screen yielded several compounds that showed activity and two, sunitinib and bortezomib, were tested in the xenograft. Both agents slowed the growth of the xenograft tumor. Sensitivity to an inhibitor of IκB, as well as inhibition of an NF-κB gene expression signature demonstrated the importance of NF-κB signaling for chordoma growth. This serially transplantable chordoma xenograft is thus a practical model to study chordomas and perform in vivo preclinical drug testing.
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spelling pubmed-38193002013-11-12 A Novel Chordoma Xenograft Allows In Vivo Drug Testing and Reveals the Importance of NF-κB Signaling in Chordoma Biology Trucco, Matteo M. Awad, Ola Wilky, Breelyn A. Goldstein, Seth D. Huang, Ruili Walker, Robert L. Shah, Preeti Katuri, Varalakshmi Gul, Naheed Zhu, Yuelin J. McCarthy, Edward F. Paz-Priel, Ido Meltzer, Paul S. Austin, Christopher P. Xia, Menghang Loeb, David M. PLoS One Research Article Chordoma is a rare primary bone malignancy that arises in the skull base, spine and sacrum and originates from remnants of the notochord. These tumors are typically resistant to conventional chemotherapy, and to date there are no FDA-approved agents to treat chordoma. The lack of in vivo models of chordoma has impeded the development of new therapies for this tumor. Primary tumor from a sacral chordoma was xenografted into NOD/SCID/IL-2R γ-null mice. The xenograft is serially transplantable and was characterized by both gene expression analysis and whole genome SNP genotyping. The NIH Chemical Genomics Center performed high-throughput screening of 2,816 compounds using two established chordoma cell lines, U-CH1 and U-CH2B. The screen yielded several compounds that showed activity and two, sunitinib and bortezomib, were tested in the xenograft. Both agents slowed the growth of the xenograft tumor. Sensitivity to an inhibitor of IκB, as well as inhibition of an NF-κB gene expression signature demonstrated the importance of NF-κB signaling for chordoma growth. This serially transplantable chordoma xenograft is thus a practical model to study chordomas and perform in vivo preclinical drug testing. Public Library of Science 2013-11-06 /pmc/articles/PMC3819300/ /pubmed/24223206 http://dx.doi.org/10.1371/journal.pone.0079950 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Trucco, Matteo M.
Awad, Ola
Wilky, Breelyn A.
Goldstein, Seth D.
Huang, Ruili
Walker, Robert L.
Shah, Preeti
Katuri, Varalakshmi
Gul, Naheed
Zhu, Yuelin J.
McCarthy, Edward F.
Paz-Priel, Ido
Meltzer, Paul S.
Austin, Christopher P.
Xia, Menghang
Loeb, David M.
A Novel Chordoma Xenograft Allows In Vivo Drug Testing and Reveals the Importance of NF-κB Signaling in Chordoma Biology
title A Novel Chordoma Xenograft Allows In Vivo Drug Testing and Reveals the Importance of NF-κB Signaling in Chordoma Biology
title_full A Novel Chordoma Xenograft Allows In Vivo Drug Testing and Reveals the Importance of NF-κB Signaling in Chordoma Biology
title_fullStr A Novel Chordoma Xenograft Allows In Vivo Drug Testing and Reveals the Importance of NF-κB Signaling in Chordoma Biology
title_full_unstemmed A Novel Chordoma Xenograft Allows In Vivo Drug Testing and Reveals the Importance of NF-κB Signaling in Chordoma Biology
title_short A Novel Chordoma Xenograft Allows In Vivo Drug Testing and Reveals the Importance of NF-κB Signaling in Chordoma Biology
title_sort novel chordoma xenograft allows in vivo drug testing and reveals the importance of nf-κb signaling in chordoma biology
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819300/
https://www.ncbi.nlm.nih.gov/pubmed/24223206
http://dx.doi.org/10.1371/journal.pone.0079950
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