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Application of a Patient Derived Xenograft Model for Predicative Study of Uterine Fibroid Disease
Human uterine fibroids, benign tumors derived from the smooth muscle layers of the uterus, impose a major health burden to up to 50% of premenopausal women in their daily life. To improve our understanding of this disease, we developed and characterized a patient-derived xenograft model by subcutane...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4654507/ https://www.ncbi.nlm.nih.gov/pubmed/26588841 http://dx.doi.org/10.1371/journal.pone.0142429 |
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author | Fritsch, Martin Schmidt, Nicole Gröticke, Ina Frisk, Anna-Lena Keator, Christopher S. Koch, Markus Slayden, Ov D. |
author_facet | Fritsch, Martin Schmidt, Nicole Gröticke, Ina Frisk, Anna-Lena Keator, Christopher S. Koch, Markus Slayden, Ov D. |
author_sort | Fritsch, Martin |
collection | PubMed |
description | Human uterine fibroids, benign tumors derived from the smooth muscle layers of the uterus, impose a major health burden to up to 50% of premenopausal women in their daily life. To improve our understanding of this disease, we developed and characterized a patient-derived xenograft model by subcutaneous transplantation of pieces of human uterine fibroid tissue into three different strains of severe combined immunodeficient mice. Engrafted uterine fibroid tissue preserved the classical morphology with interwoven bundles of smooth muscle cells and an abundant deposition of collagenous matrix, similar to uterine fibroids in situ. The grafts expressed both estrogen receptor 1 and progesterone receptor. Additionally, both receptors were up-regulated by estrogen treatment. Growth of the fibroid grafts was dependent on 17β-estradiol and progesterone supplementation at levels similar to women with the disease and was studied for up to 60 days at maximum. Co-treatment with the antiprogestin mifepristone reduced graft growth (four independent donors, p<0.0001 two-sided t-test), as did treatment with the mTOR inhibitor rapamycin (three independent donors, p<0.0001 two-sided t-test). This in vivo animal model preserves the main histological and functional characteristics of human uterine fibroids, is amenable to intervention by pharmacological treatment, and can thus serve as an adequate model for the development of novel therapies. |
format | Online Article Text |
id | pubmed-4654507 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-46545072015-11-25 Application of a Patient Derived Xenograft Model for Predicative Study of Uterine Fibroid Disease Fritsch, Martin Schmidt, Nicole Gröticke, Ina Frisk, Anna-Lena Keator, Christopher S. Koch, Markus Slayden, Ov D. PLoS One Research Article Human uterine fibroids, benign tumors derived from the smooth muscle layers of the uterus, impose a major health burden to up to 50% of premenopausal women in their daily life. To improve our understanding of this disease, we developed and characterized a patient-derived xenograft model by subcutaneous transplantation of pieces of human uterine fibroid tissue into three different strains of severe combined immunodeficient mice. Engrafted uterine fibroid tissue preserved the classical morphology with interwoven bundles of smooth muscle cells and an abundant deposition of collagenous matrix, similar to uterine fibroids in situ. The grafts expressed both estrogen receptor 1 and progesterone receptor. Additionally, both receptors were up-regulated by estrogen treatment. Growth of the fibroid grafts was dependent on 17β-estradiol and progesterone supplementation at levels similar to women with the disease and was studied for up to 60 days at maximum. Co-treatment with the antiprogestin mifepristone reduced graft growth (four independent donors, p<0.0001 two-sided t-test), as did treatment with the mTOR inhibitor rapamycin (three independent donors, p<0.0001 two-sided t-test). This in vivo animal model preserves the main histological and functional characteristics of human uterine fibroids, is amenable to intervention by pharmacological treatment, and can thus serve as an adequate model for the development of novel therapies. Public Library of Science 2015-11-20 /pmc/articles/PMC4654507/ /pubmed/26588841 http://dx.doi.org/10.1371/journal.pone.0142429 Text en © 2015 Fritsch 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Fritsch, Martin Schmidt, Nicole Gröticke, Ina Frisk, Anna-Lena Keator, Christopher S. Koch, Markus Slayden, Ov D. Application of a Patient Derived Xenograft Model for Predicative Study of Uterine Fibroid Disease |
title | Application of a Patient Derived Xenograft Model for Predicative Study of Uterine Fibroid Disease |
title_full | Application of a Patient Derived Xenograft Model for Predicative Study of Uterine Fibroid Disease |
title_fullStr | Application of a Patient Derived Xenograft Model for Predicative Study of Uterine Fibroid Disease |
title_full_unstemmed | Application of a Patient Derived Xenograft Model for Predicative Study of Uterine Fibroid Disease |
title_short | Application of a Patient Derived Xenograft Model for Predicative Study of Uterine Fibroid Disease |
title_sort | application of a patient derived xenograft model for predicative study of uterine fibroid disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4654507/ https://www.ncbi.nlm.nih.gov/pubmed/26588841 http://dx.doi.org/10.1371/journal.pone.0142429 |
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