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Blood-tumor barrier opening by MRI-guided transcranial focused ultrasound in a preclinical breast cancer brain metastasis model improves efficacy of combinatorial chemotherapy
Patients with metastatic breast cancer have high and continually increasing rates of brain metastases. During the course of the disease, brain metastases can occur in up to 30% of these patients. In most cases, brain metastases are diagnosed after significant disease progression. The blood-tumor bar...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9950566/ https://www.ncbi.nlm.nih.gov/pubmed/36845739 http://dx.doi.org/10.3389/fonc.2023.1104594 |
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author | Arsiwala, Tasneem A. Blethen, Kathryn E. Wolford, Cullen P. Panchal, Dhruvi M. Sprowls, Samuel A. Fladeland, Ross A. Kielkowski, Brooke N. Pritt, Trenton A. Wang, Peng Wilson, Olivia Carpenter, Jeffrey S. Finomore, Victor Rezai, Ali Lockman, Paul R. |
author_facet | Arsiwala, Tasneem A. Blethen, Kathryn E. Wolford, Cullen P. Panchal, Dhruvi M. Sprowls, Samuel A. Fladeland, Ross A. Kielkowski, Brooke N. Pritt, Trenton A. Wang, Peng Wilson, Olivia Carpenter, Jeffrey S. Finomore, Victor Rezai, Ali Lockman, Paul R. |
author_sort | Arsiwala, Tasneem A. |
collection | PubMed |
description | Patients with metastatic breast cancer have high and continually increasing rates of brain metastases. During the course of the disease, brain metastases can occur in up to 30% of these patients. In most cases, brain metastases are diagnosed after significant disease progression. The blood-tumor barrier increases the difficulty of treating brain metastasis by preventing accumulation of chemotherapy within metastases at therapeutically effective concentrations. Traditional therapies, such as surgical resection, radiotherapy, and chemotherapy, have poor efficacy, as reflected by a low median survival rate of 5-8% after post-diagnosis. Low-intensity focused ultrasound (LiFUS) is a new treatment for enhancing drug accumulation within the brain and brain malignancies. In this study, we elucidate the effect of clinical LiFUS combined with chemotherapy on tumor survival and progression in a preclinical model of triple-negative breast cancer metastasis to the brain. LiFUS significantly increased the tumor accumulation of 14C-AIB and Texas Red compared to controls (p< 0.01). LiFUS-mediated opening of the BTB is size-dependent, which is consistent with our previous studies. Mice receiving LiFUS with combinatorial Doxil and paclitaxel showed a significant increase in median survival (60 days) compared to other groups. LiFUS plus combinatorial chemotherapy of paclitaxel and Doxil also showed the slowest progression of tumor burden compared to chemotherapy alone or individual chemotherapy and LiFUS combinations. This study shows that combining LiFUS with timed combinatorial chemotherapeutic treatment is a potential strategy for improving drug delivery to brain metastases. |
format | Online Article Text |
id | pubmed-9950566 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99505662023-02-25 Blood-tumor barrier opening by MRI-guided transcranial focused ultrasound in a preclinical breast cancer brain metastasis model improves efficacy of combinatorial chemotherapy Arsiwala, Tasneem A. Blethen, Kathryn E. Wolford, Cullen P. Panchal, Dhruvi M. Sprowls, Samuel A. Fladeland, Ross A. Kielkowski, Brooke N. Pritt, Trenton A. Wang, Peng Wilson, Olivia Carpenter, Jeffrey S. Finomore, Victor Rezai, Ali Lockman, Paul R. Front Oncol Oncology Patients with metastatic breast cancer have high and continually increasing rates of brain metastases. During the course of the disease, brain metastases can occur in up to 30% of these patients. In most cases, brain metastases are diagnosed after significant disease progression. The blood-tumor barrier increases the difficulty of treating brain metastasis by preventing accumulation of chemotherapy within metastases at therapeutically effective concentrations. Traditional therapies, such as surgical resection, radiotherapy, and chemotherapy, have poor efficacy, as reflected by a low median survival rate of 5-8% after post-diagnosis. Low-intensity focused ultrasound (LiFUS) is a new treatment for enhancing drug accumulation within the brain and brain malignancies. In this study, we elucidate the effect of clinical LiFUS combined with chemotherapy on tumor survival and progression in a preclinical model of triple-negative breast cancer metastasis to the brain. LiFUS significantly increased the tumor accumulation of 14C-AIB and Texas Red compared to controls (p< 0.01). LiFUS-mediated opening of the BTB is size-dependent, which is consistent with our previous studies. Mice receiving LiFUS with combinatorial Doxil and paclitaxel showed a significant increase in median survival (60 days) compared to other groups. LiFUS plus combinatorial chemotherapy of paclitaxel and Doxil also showed the slowest progression of tumor burden compared to chemotherapy alone or individual chemotherapy and LiFUS combinations. This study shows that combining LiFUS with timed combinatorial chemotherapeutic treatment is a potential strategy for improving drug delivery to brain metastases. Frontiers Media S.A. 2023-02-10 /pmc/articles/PMC9950566/ /pubmed/36845739 http://dx.doi.org/10.3389/fonc.2023.1104594 Text en Copyright © 2023 Arsiwala, Blethen, Wolford, Panchal, Sprowls, Fladeland, Kielkowski, Pritt, Wang, Wilson, Carpenter, Finomore, Rezai and Lockman https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Arsiwala, Tasneem A. Blethen, Kathryn E. Wolford, Cullen P. Panchal, Dhruvi M. Sprowls, Samuel A. Fladeland, Ross A. Kielkowski, Brooke N. Pritt, Trenton A. Wang, Peng Wilson, Olivia Carpenter, Jeffrey S. Finomore, Victor Rezai, Ali Lockman, Paul R. Blood-tumor barrier opening by MRI-guided transcranial focused ultrasound in a preclinical breast cancer brain metastasis model improves efficacy of combinatorial chemotherapy |
title | Blood-tumor barrier opening by MRI-guided transcranial focused ultrasound in a preclinical breast cancer brain metastasis model improves efficacy of combinatorial chemotherapy |
title_full | Blood-tumor barrier opening by MRI-guided transcranial focused ultrasound in a preclinical breast cancer brain metastasis model improves efficacy of combinatorial chemotherapy |
title_fullStr | Blood-tumor barrier opening by MRI-guided transcranial focused ultrasound in a preclinical breast cancer brain metastasis model improves efficacy of combinatorial chemotherapy |
title_full_unstemmed | Blood-tumor barrier opening by MRI-guided transcranial focused ultrasound in a preclinical breast cancer brain metastasis model improves efficacy of combinatorial chemotherapy |
title_short | Blood-tumor barrier opening by MRI-guided transcranial focused ultrasound in a preclinical breast cancer brain metastasis model improves efficacy of combinatorial chemotherapy |
title_sort | blood-tumor barrier opening by mri-guided transcranial focused ultrasound in a preclinical breast cancer brain metastasis model improves efficacy of combinatorial chemotherapy |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9950566/ https://www.ncbi.nlm.nih.gov/pubmed/36845739 http://dx.doi.org/10.3389/fonc.2023.1104594 |
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