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Evaluating Changes to Blood-Brain Barrier Integrity in Brain Metastasis over Time and after Radiation Treatment()
INTRODUCTION: The incidence of brain metastasis due to breast cancer is increasing, and prognosis is poor. Treatment is challenging because the blood-brain barrier (BBB) limits efficacy of systemic therapies. In this work, we develop a clinically relevant whole brain radiotherapy (WBRT) plan to inve...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907987/ https://www.ncbi.nlm.nih.gov/pubmed/27267840 http://dx.doi.org/10.1016/j.tranon.2016.04.006 |
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author | Murrell, Donna H. Zarghami, Niloufar Jensen, Michael D. Chambers, Ann F. Wong, Eugene Foster, Paula J. |
author_facet | Murrell, Donna H. Zarghami, Niloufar Jensen, Michael D. Chambers, Ann F. Wong, Eugene Foster, Paula J. |
author_sort | Murrell, Donna H. |
collection | PubMed |
description | INTRODUCTION: The incidence of brain metastasis due to breast cancer is increasing, and prognosis is poor. Treatment is challenging because the blood-brain barrier (BBB) limits efficacy of systemic therapies. In this work, we develop a clinically relevant whole brain radiotherapy (WBRT) plan to investigate the impact of radiation on brain metastasis development and BBB permeability in a murine model. We hypothesize that radiotherapy will decrease tumor burden and increase tumor permeability, which could offer a mechanism to increase drug uptake in brain metastases. METHODS: Contrast-enhanced magnetic resonance imaging (MRI) and high-resolution anatomical MRI were used to evaluate BBB integrity associated with brain metastases due to breast cancer in the MDA-MB-231-BR-HER2 model during their natural development. Novel image-guided microirradiation technology was employed to develop WBRT treatment plans and to investigate if this altered brain metastatic growth or permeability. Histology and immunohistochemistry were performed on whole brain slices corresponding with MRI to validate and further investigate radiological findings. RESULTS: Herein, we show successful implementation of microirradiation technology that can deliver WBRT to small animals. We further report that WBRT following diagnosis of brain metastasis can mitigate, but not eliminate, tumor growth in the MDA-MB-231-BR-HER2 model. Moreover, radiotherapy did not impact BBB permeability associated with metastases. CONCLUSIONS: Clinically relevant WBRT is not curative when delivered after MRI-detectable tumors have developed in this model. A dose of 20 Gy in 2 fractions was not sufficient to increase tumor permeability such that it could be used as a method to increase systemic drug uptake in brain metastasis. |
format | Online Article Text |
id | pubmed-4907987 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-49079872016-06-22 Evaluating Changes to Blood-Brain Barrier Integrity in Brain Metastasis over Time and after Radiation Treatment() Murrell, Donna H. Zarghami, Niloufar Jensen, Michael D. Chambers, Ann F. Wong, Eugene Foster, Paula J. Transl Oncol Original article INTRODUCTION: The incidence of brain metastasis due to breast cancer is increasing, and prognosis is poor. Treatment is challenging because the blood-brain barrier (BBB) limits efficacy of systemic therapies. In this work, we develop a clinically relevant whole brain radiotherapy (WBRT) plan to investigate the impact of radiation on brain metastasis development and BBB permeability in a murine model. We hypothesize that radiotherapy will decrease tumor burden and increase tumor permeability, which could offer a mechanism to increase drug uptake in brain metastases. METHODS: Contrast-enhanced magnetic resonance imaging (MRI) and high-resolution anatomical MRI were used to evaluate BBB integrity associated with brain metastases due to breast cancer in the MDA-MB-231-BR-HER2 model during their natural development. Novel image-guided microirradiation technology was employed to develop WBRT treatment plans and to investigate if this altered brain metastatic growth or permeability. Histology and immunohistochemistry were performed on whole brain slices corresponding with MRI to validate and further investigate radiological findings. RESULTS: Herein, we show successful implementation of microirradiation technology that can deliver WBRT to small animals. We further report that WBRT following diagnosis of brain metastasis can mitigate, but not eliminate, tumor growth in the MDA-MB-231-BR-HER2 model. Moreover, radiotherapy did not impact BBB permeability associated with metastases. CONCLUSIONS: Clinically relevant WBRT is not curative when delivered after MRI-detectable tumors have developed in this model. A dose of 20 Gy in 2 fractions was not sufficient to increase tumor permeability such that it could be used as a method to increase systemic drug uptake in brain metastasis. Neoplasia Press 2016-05-17 /pmc/articles/PMC4907987/ /pubmed/27267840 http://dx.doi.org/10.1016/j.tranon.2016.04.006 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original article Murrell, Donna H. Zarghami, Niloufar Jensen, Michael D. Chambers, Ann F. Wong, Eugene Foster, Paula J. Evaluating Changes to Blood-Brain Barrier Integrity in Brain Metastasis over Time and after Radiation Treatment() |
title | Evaluating Changes to Blood-Brain Barrier Integrity in Brain Metastasis over Time and after Radiation Treatment() |
title_full | Evaluating Changes to Blood-Brain Barrier Integrity in Brain Metastasis over Time and after Radiation Treatment() |
title_fullStr | Evaluating Changes to Blood-Brain Barrier Integrity in Brain Metastasis over Time and after Radiation Treatment() |
title_full_unstemmed | Evaluating Changes to Blood-Brain Barrier Integrity in Brain Metastasis over Time and after Radiation Treatment() |
title_short | Evaluating Changes to Blood-Brain Barrier Integrity in Brain Metastasis over Time and after Radiation Treatment() |
title_sort | evaluating changes to blood-brain barrier integrity in brain metastasis over time and after radiation treatment() |
topic | Original article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907987/ https://www.ncbi.nlm.nih.gov/pubmed/27267840 http://dx.doi.org/10.1016/j.tranon.2016.04.006 |
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