Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis

Autores
Palencia Campos, Adrián; Ruiz Cañas, Laura; Abal Sanisidro, Marcelina; López Gil, Juan Carlos; Batres Ramos, Sandra; Mendes Saraiva, Sofia; Yagüe, Balbino; Navarro, Diego; Alcalá, Sonia; Rubiolo, Juan Andrés; Bidan, Nadège; Sánchez, Laura; Mura, Simona; Hermann, Patrick C.; de la Fuente, María; Sainz, Bruno
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Pancreatic ductal adenocarcinoma (PDAC) requires innovative therapeutic strategies to counteract its progression and metastatic potential. Since the majority of patients are diagnosed with advanced metastatic disease, treatment strategies targeting not only the primary tumor but also metastatic lesions are needed. Tumor-Associated Macrophages (TAMs) have emerged as central players, significantly influencing PDAC progression and metastasis. Our objective was to validate an innovative therapeutic strategy involving the reprogramming of TAMs using lipid nanosystems to prevent the formation of a pro-metastatic microenvironment in the liver.Results: In vitro results demonstrate that M2-polarized macrophages lose their M2-phenotype following treatment with lipid nanoemulsions composed of vitamin E and sphingomyelin (VitE:SM), transitioning to an M0/M1 state. Specifically, VitE:SM nanoemulsion treatment decreased the expression of macrophage M2 markers such as Arg1 and Egr2, while M1 markers such as Cd86, Il-1b and Il-12b increased. Additionally, the TGF-βR1 inhibitor Galunisertib (LY2157299) was loaded into VitE:SM nanoemulsions and delivered to C57BL/6 mice orthotopically injected with KPC PDAC tumor cells. Treated mice showed diminished primary tumor growth and reduced TAM infiltration in the liver. Moreover, we observed a decrease in liver metastasis with the nanoemulsion treatment in an intrasplenic model of PDAC liver metastasis. Finally, we validated the translatability of our VitE:SM nanosystem therapy in a human cell-based 3D co-culture model in vivo, underscoring the pivotal role of macrophages in the nanosystem´s therapeutic effect in the context of human PDAC metastasis.Conclusions: The demonstrated effectiveness and safety of our nanosystem therapy highlights a promising therapeutic approach for PDAC, showcasing its potential in reprogramming TAMs and mitigating the occurrence of liver metastasis.
Fil: Palencia Campos, Adrián. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas; España. Instituto Ramón y Cajal de Investigación Sanitaria; España
Fil: Ruiz Cañas, Laura. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas; España. Instituto Ramón y Cajal de Investigación Sanitaria; España
Fil: Abal Sanisidro, Marcelina. Universidad de Santiago de Compostela; España
Fil: López Gil, Juan Carlos. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas; España. Instituto Ramón y Cajal de Investigación Sanitaria; España. Universidad Autónoma de Madrid; España
Fil: Batres Ramos, Sandra. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas; España. Instituto Ramón y Cajal de Investigación Sanitaria; España
Fil: Mendes Saraiva, Sofia. Universidad de Santiago de Compostela; España
Fil: Yagüe, Balbino. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas; España. Instituto Ramón y Cajal de Investigación Sanitaria; España
Fil: Navarro, Diego. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas; España. Instituto Ramón y Cajal de Investigación Sanitaria; España. Universidad Autónoma de Madrid; España
Fil: Alcalá, Sonia. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas; España. Instituto Ramón y Cajal de Investigación Sanitaria; España
Fil: Rubiolo, Juan Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Cs.bioquimicas y Farmaceuticas. Laboratorio de Biotecnología Acuática.; Argentina. Universidad de Santiago de Compostela; España
Fil: Bidan, Nadège. Universite Paris-Saclay ;
Fil: Sánchez, Laura. Universidad de Santiago de Compostela; España
Fil: Mura, Simona. Universite Paris-Saclay ;
Fil: Hermann, Patrick C.. Universität Ulm; Alemania
Fil: de la Fuente, María. Universidad de Santiago de Compostela; España
Fil: Sainz, Bruno. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas; España. Instituto Ramón y Cajal de Investigación Sanitaria; España
Materia
Galunisertib
Lipid nanoemulsions
Liver metastasis
Pancreatic ductal adenocarcinoma
Reprogramming
Tumor microenvironment
Tumor-associated macrophages
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/280529
Acceder
id CONICETDig_79130dbca78181203ae3400757314dcb
oai_identifier_str oai:ri.conicet.gov.ar:11336/280529
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasisPalencia Campos, AdriánRuiz Cañas, LauraAbal Sanisidro, MarcelinaLópez Gil, Juan CarlosBatres Ramos, SandraMendes Saraiva, SofiaYagüe, BalbinoNavarro, DiegoAlcalá, SoniaRubiolo, Juan AndrésBidan, NadègeSánchez, LauraMura, SimonaHermann, Patrick C.de la Fuente, MaríaSainz, BrunoGalunisertibLipid nanoemulsionsLiver metastasisPancreatic ductal adenocarcinomaReprogrammingTumor microenvironmentTumor-associated macrophageshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/2.10https://purl.org/becyt/ford/2Background: Pancreatic ductal adenocarcinoma (PDAC) requires innovative therapeutic strategies to counteract its progression and metastatic potential. Since the majority of patients are diagnosed with advanced metastatic disease, treatment strategies targeting not only the primary tumor but also metastatic lesions are needed. Tumor-Associated Macrophages (TAMs) have emerged as central players, significantly influencing PDAC progression and metastasis. Our objective was to validate an innovative therapeutic strategy involving the reprogramming of TAMs using lipid nanosystems to prevent the formation of a pro-metastatic microenvironment in the liver.Results: In vitro results demonstrate that M2-polarized macrophages lose their M2-phenotype following treatment with lipid nanoemulsions composed of vitamin E and sphingomyelin (VitE:SM), transitioning to an M0/M1 state. Specifically, VitE:SM nanoemulsion treatment decreased the expression of macrophage M2 markers such as Arg1 and Egr2, while M1 markers such as Cd86, Il-1b and Il-12b increased. Additionally, the TGF-βR1 inhibitor Galunisertib (LY2157299) was loaded into VitE:SM nanoemulsions and delivered to C57BL/6 mice orthotopically injected with KPC PDAC tumor cells. Treated mice showed diminished primary tumor growth and reduced TAM infiltration in the liver. Moreover, we observed a decrease in liver metastasis with the nanoemulsion treatment in an intrasplenic model of PDAC liver metastasis. Finally, we validated the translatability of our VitE:SM nanosystem therapy in a human cell-based 3D co-culture model in vivo, underscoring the pivotal role of macrophages in the nanosystem´s therapeutic effect in the context of human PDAC metastasis.Conclusions: The demonstrated effectiveness and safety of our nanosystem therapy highlights a promising therapeutic approach for PDAC, showcasing its potential in reprogramming TAMs and mitigating the occurrence of liver metastasis.Fil: Palencia Campos, Adrián. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas; España. Instituto Ramón y Cajal de Investigación Sanitaria; EspañaFil: Ruiz Cañas, Laura. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas; España. Instituto Ramón y Cajal de Investigación Sanitaria; EspañaFil: Abal Sanisidro, Marcelina. Universidad de Santiago de Compostela; EspañaFil: López Gil, Juan Carlos. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas; España. Instituto Ramón y Cajal de Investigación Sanitaria; España. Universidad Autónoma de Madrid; EspañaFil: Batres Ramos, Sandra. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas; España. Instituto Ramón y Cajal de Investigación Sanitaria; EspañaFil: Mendes Saraiva, Sofia. Universidad de Santiago de Compostela; EspañaFil: Yagüe, Balbino. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas; España. Instituto Ramón y Cajal de Investigación Sanitaria; EspañaFil: Navarro, Diego. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas; España. Instituto Ramón y Cajal de Investigación Sanitaria; España. Universidad Autónoma de Madrid; EspañaFil: Alcalá, Sonia. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas; España. Instituto Ramón y Cajal de Investigación Sanitaria; EspañaFil: Rubiolo, Juan Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Cs.bioquimicas y Farmaceuticas. Laboratorio de Biotecnología Acuática.; Argentina. Universidad de Santiago de Compostela; EspañaFil: Bidan, Nadège. Universite Paris-Saclay ;Fil: Sánchez, Laura. Universidad de Santiago de Compostela; EspañaFil: Mura, Simona. Universite Paris-Saclay ;Fil: Hermann, Patrick C.. Universität Ulm; AlemaniaFil: de la Fuente, María. Universidad de Santiago de Compostela; EspañaFil: Sainz, Bruno. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas; España. Instituto Ramón y Cajal de Investigación Sanitaria; EspañaSpringer2024-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/280529Palencia Campos, Adrián; Ruiz Cañas, Laura; Abal Sanisidro, Marcelina; López Gil, Juan Carlos; Batres Ramos, Sandra; et al.; Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis; Springer; Journal of Nanobiotechnology; 22; 1; 12-2024; 1-261477-3155CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://jnanobiotechnology.biomedcentral.com/articles/10.1186/s12951-024-03010-5info:eu-repo/semantics/altIdentifier/doi/10.1186/s12951-024-03010-5info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-02-06T13:32:40Zoai:ri.conicet.gov.ar:11336/280529instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-02-06 13:32:41.118CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis
title Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis
spellingShingle Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis
Palencia Campos, Adrián
Galunisertib
Lipid nanoemulsions
Liver metastasis
Pancreatic ductal adenocarcinoma
Reprogramming
Tumor microenvironment
Tumor-associated macrophages
title_short Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis
title_full Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis
title_fullStr Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis
title_full_unstemmed Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis
title_sort Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis
dc.creator.none.fl_str_mv Palencia Campos, Adrián
Ruiz Cañas, Laura
Abal Sanisidro, Marcelina
López Gil, Juan Carlos
Batres Ramos, Sandra
Mendes Saraiva, Sofia
Yagüe, Balbino
Navarro, Diego
Alcalá, Sonia
Rubiolo, Juan Andrés
Bidan, Nadège
Sánchez, Laura
Mura, Simona
Hermann, Patrick C.
de la Fuente, María
Sainz, Bruno
author Palencia Campos, Adrián
author_facet Palencia Campos, Adrián
Ruiz Cañas, Laura
Abal Sanisidro, Marcelina
López Gil, Juan Carlos
Batres Ramos, Sandra
Mendes Saraiva, Sofia
Yagüe, Balbino
Navarro, Diego
Alcalá, Sonia
Rubiolo, Juan Andrés
Bidan, Nadège
Sánchez, Laura
Mura, Simona
Hermann, Patrick C.
de la Fuente, María
Sainz, Bruno
author_role author
author2 Ruiz Cañas, Laura
Abal Sanisidro, Marcelina
López Gil, Juan Carlos
Batres Ramos, Sandra
Mendes Saraiva, Sofia
Yagüe, Balbino
Navarro, Diego
Alcalá, Sonia
Rubiolo, Juan Andrés
Bidan, Nadège
Sánchez, Laura
Mura, Simona
Hermann, Patrick C.
de la Fuente, María
Sainz, Bruno
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Galunisertib
Lipid nanoemulsions
Liver metastasis
Pancreatic ductal adenocarcinoma
Reprogramming
Tumor microenvironment
Tumor-associated macrophages
topic Galunisertib
Lipid nanoemulsions
Liver metastasis
Pancreatic ductal adenocarcinoma
Reprogramming
Tumor microenvironment
Tumor-associated macrophages
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/2.10
https://purl.org/becyt/ford/2
dc.description.none.fl_txt_mv Background: Pancreatic ductal adenocarcinoma (PDAC) requires innovative therapeutic strategies to counteract its progression and metastatic potential. Since the majority of patients are diagnosed with advanced metastatic disease, treatment strategies targeting not only the primary tumor but also metastatic lesions are needed. Tumor-Associated Macrophages (TAMs) have emerged as central players, significantly influencing PDAC progression and metastasis. Our objective was to validate an innovative therapeutic strategy involving the reprogramming of TAMs using lipid nanosystems to prevent the formation of a pro-metastatic microenvironment in the liver.Results: In vitro results demonstrate that M2-polarized macrophages lose their M2-phenotype following treatment with lipid nanoemulsions composed of vitamin E and sphingomyelin (VitE:SM), transitioning to an M0/M1 state. Specifically, VitE:SM nanoemulsion treatment decreased the expression of macrophage M2 markers such as Arg1 and Egr2, while M1 markers such as Cd86, Il-1b and Il-12b increased. Additionally, the TGF-βR1 inhibitor Galunisertib (LY2157299) was loaded into VitE:SM nanoemulsions and delivered to C57BL/6 mice orthotopically injected with KPC PDAC tumor cells. Treated mice showed diminished primary tumor growth and reduced TAM infiltration in the liver. Moreover, we observed a decrease in liver metastasis with the nanoemulsion treatment in an intrasplenic model of PDAC liver metastasis. Finally, we validated the translatability of our VitE:SM nanosystem therapy in a human cell-based 3D co-culture model in vivo, underscoring the pivotal role of macrophages in the nanosystem´s therapeutic effect in the context of human PDAC metastasis.Conclusions: The demonstrated effectiveness and safety of our nanosystem therapy highlights a promising therapeutic approach for PDAC, showcasing its potential in reprogramming TAMs and mitigating the occurrence of liver metastasis.
Fil: Palencia Campos, Adrián. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas; España. Instituto Ramón y Cajal de Investigación Sanitaria; España
Fil: Ruiz Cañas, Laura. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas; España. Instituto Ramón y Cajal de Investigación Sanitaria; España
Fil: Abal Sanisidro, Marcelina. Universidad de Santiago de Compostela; España
Fil: López Gil, Juan Carlos. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas; España. Instituto Ramón y Cajal de Investigación Sanitaria; España. Universidad Autónoma de Madrid; España
Fil: Batres Ramos, Sandra. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas; España. Instituto Ramón y Cajal de Investigación Sanitaria; España
Fil: Mendes Saraiva, Sofia. Universidad de Santiago de Compostela; España
Fil: Yagüe, Balbino. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas; España. Instituto Ramón y Cajal de Investigación Sanitaria; España
Fil: Navarro, Diego. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas; España. Instituto Ramón y Cajal de Investigación Sanitaria; España. Universidad Autónoma de Madrid; España
Fil: Alcalá, Sonia. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas; España. Instituto Ramón y Cajal de Investigación Sanitaria; España
Fil: Rubiolo, Juan Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Cs.bioquimicas y Farmaceuticas. Laboratorio de Biotecnología Acuática.; Argentina. Universidad de Santiago de Compostela; España
Fil: Bidan, Nadège. Universite Paris-Saclay ;
Fil: Sánchez, Laura. Universidad de Santiago de Compostela; España
Fil: Mura, Simona. Universite Paris-Saclay ;
Fil: Hermann, Patrick C.. Universität Ulm; Alemania
Fil: de la Fuente, María. Universidad de Santiago de Compostela; España
Fil: Sainz, Bruno. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas; España. Instituto Ramón y Cajal de Investigación Sanitaria; España
description Background: Pancreatic ductal adenocarcinoma (PDAC) requires innovative therapeutic strategies to counteract its progression and metastatic potential. Since the majority of patients are diagnosed with advanced metastatic disease, treatment strategies targeting not only the primary tumor but also metastatic lesions are needed. Tumor-Associated Macrophages (TAMs) have emerged as central players, significantly influencing PDAC progression and metastasis. Our objective was to validate an innovative therapeutic strategy involving the reprogramming of TAMs using lipid nanosystems to prevent the formation of a pro-metastatic microenvironment in the liver.Results: In vitro results demonstrate that M2-polarized macrophages lose their M2-phenotype following treatment with lipid nanoemulsions composed of vitamin E and sphingomyelin (VitE:SM), transitioning to an M0/M1 state. Specifically, VitE:SM nanoemulsion treatment decreased the expression of macrophage M2 markers such as Arg1 and Egr2, while M1 markers such as Cd86, Il-1b and Il-12b increased. Additionally, the TGF-βR1 inhibitor Galunisertib (LY2157299) was loaded into VitE:SM nanoemulsions and delivered to C57BL/6 mice orthotopically injected with KPC PDAC tumor cells. Treated mice showed diminished primary tumor growth and reduced TAM infiltration in the liver. Moreover, we observed a decrease in liver metastasis with the nanoemulsion treatment in an intrasplenic model of PDAC liver metastasis. Finally, we validated the translatability of our VitE:SM nanosystem therapy in a human cell-based 3D co-culture model in vivo, underscoring the pivotal role of macrophages in the nanosystem´s therapeutic effect in the context of human PDAC metastasis.Conclusions: The demonstrated effectiveness and safety of our nanosystem therapy highlights a promising therapeutic approach for PDAC, showcasing its potential in reprogramming TAMs and mitigating the occurrence of liver metastasis.
publishDate 2024
dc.date.none.fl_str_mv 2024-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/280529
Palencia Campos, Adrián; Ruiz Cañas, Laura; Abal Sanisidro, Marcelina; López Gil, Juan Carlos; Batres Ramos, Sandra; et al.; Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis; Springer; Journal of Nanobiotechnology; 22; 1; 12-2024; 1-26
1477-3155
CONICET Digital
CONICET
url http://hdl.handle.net/11336/280529
identifier_str_mv Palencia Campos, Adrián; Ruiz Cañas, Laura; Abal Sanisidro, Marcelina; López Gil, Juan Carlos; Batres Ramos, Sandra; et al.; Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis; Springer; Journal of Nanobiotechnology; 22; 1; 12-2024; 1-26
1477-3155
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://jnanobiotechnology.biomedcentral.com/articles/10.1186/s12951-024-03010-5
info:eu-repo/semantics/altIdentifier/doi/10.1186/s12951-024-03010-5
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.11174

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