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Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors
Peripheral nerve sheath tumors are benign tumors that have the potential to transform into malignant peripheral nerve sheath tumors (MPNSTs). Interleukin-13 receptor alpha 2 (IL13Rα2) is a cancer associated receptor expressed in glioblastoma and other invasive cancers. We analyzed IL13Rα2 expression...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5755733/ https://www.ncbi.nlm.nih.gov/pubmed/29304038 http://dx.doi.org/10.1371/journal.pone.0181529 |
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author | Madhankumar, A. B. Mrowczynski, Oliver D. Slagle-Webb, Becky Ravi, Vagisha Bourcier, Alexandre J. Payne, Russell Harbaugh, Kimberly S. Rizk, Elias Connor, James R. |
author_facet | Madhankumar, A. B. Mrowczynski, Oliver D. Slagle-Webb, Becky Ravi, Vagisha Bourcier, Alexandre J. Payne, Russell Harbaugh, Kimberly S. Rizk, Elias Connor, James R. |
author_sort | Madhankumar, A. B. |
collection | PubMed |
description | Peripheral nerve sheath tumors are benign tumors that have the potential to transform into malignant peripheral nerve sheath tumors (MPNSTs). Interleukin-13 receptor alpha 2 (IL13Rα2) is a cancer associated receptor expressed in glioblastoma and other invasive cancers. We analyzed IL13Rα2 expression in several MPNST cell lines including the STS26T cell line, as well as in several peripheral nerve sheath tumors to utilize the IL13Rα2 receptor as a target for therapy. In our studies, we demonstrated the selective expression of IL13Rα2 in several peripheral nerve sheath tumors by immunohistochemistry (IHC) and immunoblots. We established a sciatic nerve MPNST mouse model in NIH III nude mice using a luciferase transfected STS26T MPNST cell line. Similarly, analysis of the mouse sciatic nerves after tumor induction revealed significant expression of IL13Rα2 by IHC when compared to a normal sciatic nerve. IL13 conjugated liposomal doxorubicin was formulated and shown to bind and internalized in the MPNST cell culture model demonstrating cytotoxic effect. Our subsequent in vivo investigation in the STS26T MPNST sciatic nerve tumor model indicated that IL13 conjugated liposomal doxorubicin (IL13LIPDXR) was more effective in inhibiting tumor progression compared to unconjugated liposomal doxorubicin (LIPDXR). This further supports that IL13 receptor targeted nanoliposomes is a potential approach for treating MPNSTs. |
format | Online Article Text |
id | pubmed-5755733 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-57557332018-01-26 Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors Madhankumar, A. B. Mrowczynski, Oliver D. Slagle-Webb, Becky Ravi, Vagisha Bourcier, Alexandre J. Payne, Russell Harbaugh, Kimberly S. Rizk, Elias Connor, James R. PLoS One Research Article Peripheral nerve sheath tumors are benign tumors that have the potential to transform into malignant peripheral nerve sheath tumors (MPNSTs). Interleukin-13 receptor alpha 2 (IL13Rα2) is a cancer associated receptor expressed in glioblastoma and other invasive cancers. We analyzed IL13Rα2 expression in several MPNST cell lines including the STS26T cell line, as well as in several peripheral nerve sheath tumors to utilize the IL13Rα2 receptor as a target for therapy. In our studies, we demonstrated the selective expression of IL13Rα2 in several peripheral nerve sheath tumors by immunohistochemistry (IHC) and immunoblots. We established a sciatic nerve MPNST mouse model in NIH III nude mice using a luciferase transfected STS26T MPNST cell line. Similarly, analysis of the mouse sciatic nerves after tumor induction revealed significant expression of IL13Rα2 by IHC when compared to a normal sciatic nerve. IL13 conjugated liposomal doxorubicin was formulated and shown to bind and internalized in the MPNST cell culture model demonstrating cytotoxic effect. Our subsequent in vivo investigation in the STS26T MPNST sciatic nerve tumor model indicated that IL13 conjugated liposomal doxorubicin (IL13LIPDXR) was more effective in inhibiting tumor progression compared to unconjugated liposomal doxorubicin (LIPDXR). This further supports that IL13 receptor targeted nanoliposomes is a potential approach for treating MPNSTs. Public Library of Science 2018-01-05 /pmc/articles/PMC5755733/ /pubmed/29304038 http://dx.doi.org/10.1371/journal.pone.0181529 Text en © 2018 Madhankumar 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Madhankumar, A. B. Mrowczynski, Oliver D. Slagle-Webb, Becky Ravi, Vagisha Bourcier, Alexandre J. Payne, Russell Harbaugh, Kimberly S. Rizk, Elias Connor, James R. Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors |
title | Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors |
title_full | Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors |
title_fullStr | Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors |
title_full_unstemmed | Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors |
title_short | Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors |
title_sort | tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5755733/ https://www.ncbi.nlm.nih.gov/pubmed/29304038 http://dx.doi.org/10.1371/journal.pone.0181529 |
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