Cargando…

Paclitaxel Chemotherapy Elicits Widespread Brain Anisotropy Changes in a Comprehensive Mouse Model of Breast Cancer Survivorship: Evidence From In Vivo Diffusion Weighted Imaging

Breast cancer is one of the most common diseases in the United States with 1 in 8 women developing the disease in her lifetime. Women who develop breast cancer are often post-menopausal and undergo a complex sequence of treatments including surgery, chemotherapy, and aromatase inhibitor therapy. Bot...

Descripción completa

Detalles Bibliográficos
Autores principales: Otto, Lauren D., Russart, Kathryn L. G., Kulkarni, Praveen, McTigue, Dana M., Ferris, Craig F., Pyter, Leah M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8984118/
https://www.ncbi.nlm.nih.gov/pubmed/35402248
http://dx.doi.org/10.3389/fonc.2022.798704
_version_ 1784682112132055040
author Otto, Lauren D.
Russart, Kathryn L. G.
Kulkarni, Praveen
McTigue, Dana M.
Ferris, Craig F.
Pyter, Leah M.
author_facet Otto, Lauren D.
Russart, Kathryn L. G.
Kulkarni, Praveen
McTigue, Dana M.
Ferris, Craig F.
Pyter, Leah M.
author_sort Otto, Lauren D.
collection PubMed
description Breast cancer is one of the most common diseases in the United States with 1 in 8 women developing the disease in her lifetime. Women who develop breast cancer are often post-menopausal and undergo a complex sequence of treatments including surgery, chemotherapy, and aromatase inhibitor therapy. Both independently and through potential interactions, these factors and treatments are associated with behavioral comorbidities reported in patients (e.g., fatigue), although the underlying neurobiological mechanisms are poorly understood. Currently, brain imaging is the most feasible way to assess neurobiology in patients. Indeed, breast cancer patients display alterations in white matter connections and chemotherapy is associated with decreased white and gray matter in the corpus callosum and cortex as well as decreased hippocampal volume. However, imaging in breast cancer rodent models is lacking, impeding translation of the mechanistic neurobiological findings made possible through modeling. Furthermore, current rodent models of breast cancer often lack the complexity of typical multimodal breast cancer treatments, thereby limiting translational value. The present study aimed to develop a comprehensive model of post-menopausal breast cancer survival using immunocompetent ovariectomized mice, including an orthotopic syngeneic tumor, surgical tumor removal, chemotherapy, and aromatase inhibitor therapy. Using this model, we systematically investigated the cumulative effects of chemotherapy and hormone replacement therapy on neurostructure and behavior using diffusion weighted imaging, open field test, and spontaneous alternation test. Our previous findings, in a simplified chemotherapy-only model, indicate that this regimen of chemotherapy causes circulating and central inflammation concurrent with reduced locomotor activity. The current study, in the more comprehensive model, has recapitulated the peripheral inflammation coincident with reduced locomotor activity as well as demonstrated that chemotherapy also drives widespread changes in brain anisotropy. Validating the clinical relevance of this comprehensive rodent breast cancer model will allow for additional neurobiological investigations of the interactions among various cancer components associated with behavioral comorbidities, as well as the relationship between these mechanisms and neurostructural imaging changes that can be measured in cancer patients.
format Online
Article
Text
id pubmed-8984118
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-89841182022-04-07 Paclitaxel Chemotherapy Elicits Widespread Brain Anisotropy Changes in a Comprehensive Mouse Model of Breast Cancer Survivorship: Evidence From In Vivo Diffusion Weighted Imaging Otto, Lauren D. Russart, Kathryn L. G. Kulkarni, Praveen McTigue, Dana M. Ferris, Craig F. Pyter, Leah M. Front Oncol Oncology Breast cancer is one of the most common diseases in the United States with 1 in 8 women developing the disease in her lifetime. Women who develop breast cancer are often post-menopausal and undergo a complex sequence of treatments including surgery, chemotherapy, and aromatase inhibitor therapy. Both independently and through potential interactions, these factors and treatments are associated with behavioral comorbidities reported in patients (e.g., fatigue), although the underlying neurobiological mechanisms are poorly understood. Currently, brain imaging is the most feasible way to assess neurobiology in patients. Indeed, breast cancer patients display alterations in white matter connections and chemotherapy is associated with decreased white and gray matter in the corpus callosum and cortex as well as decreased hippocampal volume. However, imaging in breast cancer rodent models is lacking, impeding translation of the mechanistic neurobiological findings made possible through modeling. Furthermore, current rodent models of breast cancer often lack the complexity of typical multimodal breast cancer treatments, thereby limiting translational value. The present study aimed to develop a comprehensive model of post-menopausal breast cancer survival using immunocompetent ovariectomized mice, including an orthotopic syngeneic tumor, surgical tumor removal, chemotherapy, and aromatase inhibitor therapy. Using this model, we systematically investigated the cumulative effects of chemotherapy and hormone replacement therapy on neurostructure and behavior using diffusion weighted imaging, open field test, and spontaneous alternation test. Our previous findings, in a simplified chemotherapy-only model, indicate that this regimen of chemotherapy causes circulating and central inflammation concurrent with reduced locomotor activity. The current study, in the more comprehensive model, has recapitulated the peripheral inflammation coincident with reduced locomotor activity as well as demonstrated that chemotherapy also drives widespread changes in brain anisotropy. Validating the clinical relevance of this comprehensive rodent breast cancer model will allow for additional neurobiological investigations of the interactions among various cancer components associated with behavioral comorbidities, as well as the relationship between these mechanisms and neurostructural imaging changes that can be measured in cancer patients. Frontiers Media S.A. 2022-03-23 /pmc/articles/PMC8984118/ /pubmed/35402248 http://dx.doi.org/10.3389/fonc.2022.798704 Text en Copyright © 2022 Otto, Russart, Kulkarni, McTigue, Ferris and Pyter 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
Otto, Lauren D.
Russart, Kathryn L. G.
Kulkarni, Praveen
McTigue, Dana M.
Ferris, Craig F.
Pyter, Leah M.
Paclitaxel Chemotherapy Elicits Widespread Brain Anisotropy Changes in a Comprehensive Mouse Model of Breast Cancer Survivorship: Evidence From In Vivo Diffusion Weighted Imaging
title Paclitaxel Chemotherapy Elicits Widespread Brain Anisotropy Changes in a Comprehensive Mouse Model of Breast Cancer Survivorship: Evidence From In Vivo Diffusion Weighted Imaging
title_full Paclitaxel Chemotherapy Elicits Widespread Brain Anisotropy Changes in a Comprehensive Mouse Model of Breast Cancer Survivorship: Evidence From In Vivo Diffusion Weighted Imaging
title_fullStr Paclitaxel Chemotherapy Elicits Widespread Brain Anisotropy Changes in a Comprehensive Mouse Model of Breast Cancer Survivorship: Evidence From In Vivo Diffusion Weighted Imaging
title_full_unstemmed Paclitaxel Chemotherapy Elicits Widespread Brain Anisotropy Changes in a Comprehensive Mouse Model of Breast Cancer Survivorship: Evidence From In Vivo Diffusion Weighted Imaging
title_short Paclitaxel Chemotherapy Elicits Widespread Brain Anisotropy Changes in a Comprehensive Mouse Model of Breast Cancer Survivorship: Evidence From In Vivo Diffusion Weighted Imaging
title_sort paclitaxel chemotherapy elicits widespread brain anisotropy changes in a comprehensive mouse model of breast cancer survivorship: evidence from in vivo diffusion weighted imaging
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8984118/
https://www.ncbi.nlm.nih.gov/pubmed/35402248
http://dx.doi.org/10.3389/fonc.2022.798704
work_keys_str_mv AT ottolaurend paclitaxelchemotherapyelicitswidespreadbrainanisotropychangesinacomprehensivemousemodelofbreastcancersurvivorshipevidencefrominvivodiffusionweightedimaging
AT russartkathrynlg paclitaxelchemotherapyelicitswidespreadbrainanisotropychangesinacomprehensivemousemodelofbreastcancersurvivorshipevidencefrominvivodiffusionweightedimaging
AT kulkarnipraveen paclitaxelchemotherapyelicitswidespreadbrainanisotropychangesinacomprehensivemousemodelofbreastcancersurvivorshipevidencefrominvivodiffusionweightedimaging
AT mctiguedanam paclitaxelchemotherapyelicitswidespreadbrainanisotropychangesinacomprehensivemousemodelofbreastcancersurvivorshipevidencefrominvivodiffusionweightedimaging
AT ferriscraigf paclitaxelchemotherapyelicitswidespreadbrainanisotropychangesinacomprehensivemousemodelofbreastcancersurvivorshipevidencefrominvivodiffusionweightedimaging
AT pyterleahm paclitaxelchemotherapyelicitswidespreadbrainanisotropychangesinacomprehensivemousemodelofbreastcancersurvivorshipevidencefrominvivodiffusionweightedimaging