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Kunitz type protease inhibitor from the canine tapeworm as a potential therapeutic for melanoma

Modulating the tumor microenvironment to promote an effective immune response is critical in managing any type of tumor. Melanoma is an aggressive skin cancer and the incidence rate is increasing worldwide. Potent protease inhibitors have recently been extensively researched as potential therapeutic...

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Autores principales: Ranasinghe, Shiwanthi L., Rivera, Vanessa, Boyle, Glen M., McManus, Donald P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838156/
https://www.ncbi.nlm.nih.gov/pubmed/31700040
http://dx.doi.org/10.1038/s41598-019-52609-4
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author Ranasinghe, Shiwanthi L.
Rivera, Vanessa
Boyle, Glen M.
McManus, Donald P.
author_facet Ranasinghe, Shiwanthi L.
Rivera, Vanessa
Boyle, Glen M.
McManus, Donald P.
author_sort Ranasinghe, Shiwanthi L.
collection PubMed
description Modulating the tumor microenvironment to promote an effective immune response is critical in managing any type of tumor. Melanoma is an aggressive skin cancer and the incidence rate is increasing worldwide. Potent protease inhibitors have recently been extensively researched as potential therapeutic agents against various cancers. EgKI-1 is a potent Kunitz type protease inhibitor identified from the canine tapeworm Echinococcus granulosus that has shown anti-cancer activities in vivo. In this study we show that EgKI-1 significantly reduced the growth of melanoma in the B16-F0 mouse model and was not toxic to normal surrounding tissue. Moreover, EgKI-1 treatment significantly reduced survivin expression levels and increased the CD8+ T cell population in draining axillary lymph nodes. Therefore, EgKI-1 potentially reduces tumor growth by inducing apoptosis and modulating the tumor microenvironment, and has potential for development as an intra-lesional treatment for melanoma.
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spelling pubmed-68381562019-11-14 Kunitz type protease inhibitor from the canine tapeworm as a potential therapeutic for melanoma Ranasinghe, Shiwanthi L. Rivera, Vanessa Boyle, Glen M. McManus, Donald P. Sci Rep Article Modulating the tumor microenvironment to promote an effective immune response is critical in managing any type of tumor. Melanoma is an aggressive skin cancer and the incidence rate is increasing worldwide. Potent protease inhibitors have recently been extensively researched as potential therapeutic agents against various cancers. EgKI-1 is a potent Kunitz type protease inhibitor identified from the canine tapeworm Echinococcus granulosus that has shown anti-cancer activities in vivo. In this study we show that EgKI-1 significantly reduced the growth of melanoma in the B16-F0 mouse model and was not toxic to normal surrounding tissue. Moreover, EgKI-1 treatment significantly reduced survivin expression levels and increased the CD8+ T cell population in draining axillary lymph nodes. Therefore, EgKI-1 potentially reduces tumor growth by inducing apoptosis and modulating the tumor microenvironment, and has potential for development as an intra-lesional treatment for melanoma. Nature Publishing Group UK 2019-11-07 /pmc/articles/PMC6838156/ /pubmed/31700040 http://dx.doi.org/10.1038/s41598-019-52609-4 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ranasinghe, Shiwanthi L.
Rivera, Vanessa
Boyle, Glen M.
McManus, Donald P.
Kunitz type protease inhibitor from the canine tapeworm as a potential therapeutic for melanoma
title Kunitz type protease inhibitor from the canine tapeworm as a potential therapeutic for melanoma
title_full Kunitz type protease inhibitor from the canine tapeworm as a potential therapeutic for melanoma
title_fullStr Kunitz type protease inhibitor from the canine tapeworm as a potential therapeutic for melanoma
title_full_unstemmed Kunitz type protease inhibitor from the canine tapeworm as a potential therapeutic for melanoma
title_short Kunitz type protease inhibitor from the canine tapeworm as a potential therapeutic for melanoma
title_sort kunitz type protease inhibitor from the canine tapeworm as a potential therapeutic for melanoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838156/
https://www.ncbi.nlm.nih.gov/pubmed/31700040
http://dx.doi.org/10.1038/s41598-019-52609-4
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