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Establishment of a patient-derived xenograft mouse model of pleomorphic leiomyosarcoma
Soft tissue sarcomas are difficult to treat using chemotherapy owing to a current deficiency in candidate drugs for specific targets. Screening candidate compounds and analyzing therapeutic targets in sarcomas is insufficient, given the lack of an appropriate human sarcoma animal model to accurately...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Japanese Society of Toxicologic Pathology
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890165/ https://www.ncbi.nlm.nih.gov/pubmed/33627948 http://dx.doi.org/10.1293/tox.2020-0061 |
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author | Shimada, Yasuhiro Naito, Tomoharu Hayashi, Takuo Saito, Tsuyoshi Suehara, Yoshiyuki Kakinuma, Chihaya Nozaki, Yuji Takagi, Hisayoshi Yao, Takashi |
author_facet | Shimada, Yasuhiro Naito, Tomoharu Hayashi, Takuo Saito, Tsuyoshi Suehara, Yoshiyuki Kakinuma, Chihaya Nozaki, Yuji Takagi, Hisayoshi Yao, Takashi |
author_sort | Shimada, Yasuhiro |
collection | PubMed |
description | Soft tissue sarcomas are difficult to treat using chemotherapy owing to a current deficiency in candidate drugs for specific targets. Screening candidate compounds and analyzing therapeutic targets in sarcomas is insufficient, given the lack of an appropriate human sarcoma animal model to accurately evaluate their efficacy, as well as the lack of an adequate technical protocol for efficient transplantation and engraftment of sarcoma specimens in patient-derived xenograft (PDX) models. Accordingly, in this study, we sought to identify the optimal type of sarcoma and develop a protocol for generating a PDX model. We characterized a PDX mouse model using histopathological and immunohistochemical analyses to determine whether it would show pathological characteristics similar to those of human sarcomas. We achieved engraftment of one of the 10 transplanted sarcoma specimens, the xenografted tumor of which exhibited massive proliferation. Histologically, the engrafted sarcoma foci resembled a primary tumor of pleomorphic leiomyosarcoma and maintained their histological structure in all passages. Moreover, immunohistochemical analysis revealed the expression of specific markers of differentiation to smooth muscle, which is consistent with the features of leiomyosarcoma. We thus demonstrated that our pleomorphic leiomyosarcoma PDX mouse model mimics at least one aspect of human sarcomas, and we believe that this model will facilitate the development of novel therapies for sarcomas. |
format | Online Article Text |
id | pubmed-7890165 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Japanese Society of Toxicologic Pathology |
record_format | MEDLINE/PubMed |
spelling | pubmed-78901652021-02-23 Establishment of a patient-derived xenograft mouse model of pleomorphic leiomyosarcoma Shimada, Yasuhiro Naito, Tomoharu Hayashi, Takuo Saito, Tsuyoshi Suehara, Yoshiyuki Kakinuma, Chihaya Nozaki, Yuji Takagi, Hisayoshi Yao, Takashi J Toxicol Pathol Original Article Soft tissue sarcomas are difficult to treat using chemotherapy owing to a current deficiency in candidate drugs for specific targets. Screening candidate compounds and analyzing therapeutic targets in sarcomas is insufficient, given the lack of an appropriate human sarcoma animal model to accurately evaluate their efficacy, as well as the lack of an adequate technical protocol for efficient transplantation and engraftment of sarcoma specimens in patient-derived xenograft (PDX) models. Accordingly, in this study, we sought to identify the optimal type of sarcoma and develop a protocol for generating a PDX model. We characterized a PDX mouse model using histopathological and immunohistochemical analyses to determine whether it would show pathological characteristics similar to those of human sarcomas. We achieved engraftment of one of the 10 transplanted sarcoma specimens, the xenografted tumor of which exhibited massive proliferation. Histologically, the engrafted sarcoma foci resembled a primary tumor of pleomorphic leiomyosarcoma and maintained their histological structure in all passages. Moreover, immunohistochemical analysis revealed the expression of specific markers of differentiation to smooth muscle, which is consistent with the features of leiomyosarcoma. We thus demonstrated that our pleomorphic leiomyosarcoma PDX mouse model mimics at least one aspect of human sarcomas, and we believe that this model will facilitate the development of novel therapies for sarcomas. Japanese Society of Toxicologic Pathology 2020-12-12 2021-01 /pmc/articles/PMC7890165/ /pubmed/33627948 http://dx.doi.org/10.1293/tox.2020-0061 Text en ©2021 The Japanese Society of Toxicologic Pathology This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. (CC-BY-NC-ND 4.0: https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Shimada, Yasuhiro Naito, Tomoharu Hayashi, Takuo Saito, Tsuyoshi Suehara, Yoshiyuki Kakinuma, Chihaya Nozaki, Yuji Takagi, Hisayoshi Yao, Takashi Establishment of a patient-derived xenograft mouse model of pleomorphic leiomyosarcoma |
title | Establishment of a patient-derived xenograft mouse model of pleomorphic
leiomyosarcoma |
title_full | Establishment of a patient-derived xenograft mouse model of pleomorphic
leiomyosarcoma |
title_fullStr | Establishment of a patient-derived xenograft mouse model of pleomorphic
leiomyosarcoma |
title_full_unstemmed | Establishment of a patient-derived xenograft mouse model of pleomorphic
leiomyosarcoma |
title_short | Establishment of a patient-derived xenograft mouse model of pleomorphic
leiomyosarcoma |
title_sort | establishment of a patient-derived xenograft mouse model of pleomorphic
leiomyosarcoma |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890165/ https://www.ncbi.nlm.nih.gov/pubmed/33627948 http://dx.doi.org/10.1293/tox.2020-0061 |
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