The effectiveness of nano chemotherapeutic particles combined with mifepristone depends on the PR isoform ratio in preclinical models of breast cancer

Autores
Sequeira, Gonzalo Ricardo; Vanzulli, Silvia I.; Rojas, Paola Andrea; Lamb, Caroline Ana; Colombo, Lucas Luis; May, Maria; Molinolo, Alfredo; Lanari, Claudia Lee Malvina
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
There is clinical and experimental evidence suggesting that antiprogestins might be used for the treatment of selected breast cancer patients. Our aim was to evaluate the effect of albumin-bound paclitaxel (Nab-paclitaxel) and pegylated doxorubicin liposomes (PEG-LD) in combination with mifepristone (MFP) in experimental breast cancer models expressing different ratios of progesterone receptor (PR) isoforms A and B. We used two antiprogestin-responsive (PRA>PRB) and two resistant (PRAFil: Sequeira, Gonzalo Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Vanzulli, Silvia I.. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Rojas, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Lamb, Caroline Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Colombo, Lucas Luis. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologi­a "angel H. Roffo"; Argentina
Fil: May, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Molinolo, Alfredo. National Institutes of Health. National Institute of Dental and Craniofacial Research. Oral and Phayngeal Cancer Branch; Estados Unidos
Fil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Materia
BREAST CANCER
PR ISOFORMS
DOXORUBICIN
PACLITAXEL
MIFEPRISTONE
MAMMARY CARCINOMAS
NAB-PACLITAXEL
PEGYLATED DOXORUBICIN LIPOSOMES
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:11336/6289
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/6289
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The effectiveness of nano chemotherapeutic particles combined with mifepristone depends on the PR isoform ratio in preclinical models of breast cancerSequeira, Gonzalo RicardoVanzulli, Silvia I.Rojas, Paola AndreaLamb, Caroline AnaColombo, Lucas LuisMay, MariaMolinolo, AlfredoLanari, Claudia Lee MalvinaBREAST CANCERPR ISOFORMSDOXORUBICINPACLITAXELMIFEPRISTONEMAMMARY CARCINOMASNAB-PACLITAXELPEGYLATED DOXORUBICIN LIPOSOMEShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3There is clinical and experimental evidence suggesting that antiprogestins might be used for the treatment of selected breast cancer patients. Our aim was to evaluate the effect of albumin-bound paclitaxel (Nab-paclitaxel) and pegylated doxorubicin liposomes (PEG-LD) in combination with mifepristone (MFP) in experimental breast cancer models expressing different ratios of progesterone receptor (PR) isoforms A and B. We used two antiprogestin-responsive (PRA>PRB) and two resistant (PRA<PRB) murine mammary carcinomas growing in BALB/c, GFP-BALB/c or nude mice, along with human T47D-YA and T47D-YB xenografts growing in immunocompromised NSG mice. MFP improved the therapeutic effects of suboptimal doses of Nab-paclitaxel or PEG-LD in murine and human carcinomas with higher levels of PRA than PRB. MFP induced tissue remodeling in PRA-overexpressing tumors, increasing the stromal/tumor cell ratio and the number of functional vessels. Accordingly, an increase in nanoparticles and drug accumulation was observed in stromal and tumor cells in MFP-treated tumors. We conclude that MFP induces an increase in vessels during tissue remodeling, favoring the selective accumulation of nanoparticles inside the tumors. We propose that antiprogestins have the potential to enhance the efficacy of chemotherapy in breast tumors with a high PRA/PRB ratio.Fil: Sequeira, Gonzalo Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Vanzulli, Silvia I.. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Rojas, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Lamb, Caroline Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Colombo, Lucas Luis. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologi­a "angel H. Roffo"; ArgentinaFil: May, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Molinolo, Alfredo. National Institutes of Health. National Institute of Dental and Craniofacial Research. Oral and Phayngeal Cancer Branch; Estados UnidosFil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaImpact Journals2014-04-27info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/6289Sequeira, Gonzalo Ricardo; Vanzulli, Silvia I.; Rojas, Paola Andrea; Lamb, Caroline Ana; Colombo, Lucas Luis; et al.; The effectiveness of nano chemotherapeutic particles combined with mifepristone depends on the PR isoform ratio in preclinical models of breast cancer; Impact Journals; Oncotarget; 5; 10; 27-4-2014; 3246-32601949-2553enginfo:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/url/http://doi.org/10.18632/oncotarget.1922info:eu-repo/semantics/altIdentifier/pmid/PMC4102807info:eu-repo/semantics/altIdentifier/url/http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5b%5d=1922info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102807/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:40:44Zoai:ri.conicet.gov.ar:11336/6289instacron: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:34982025-09-29 09:40:44.378CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The effectiveness of nano chemotherapeutic particles combined with mifepristone depends on the PR isoform ratio in preclinical models of breast cancer
title The effectiveness of nano chemotherapeutic particles combined with mifepristone depends on the PR isoform ratio in preclinical models of breast cancer
spellingShingle The effectiveness of nano chemotherapeutic particles combined with mifepristone depends on the PR isoform ratio in preclinical models of breast cancer
Sequeira, Gonzalo Ricardo
BREAST CANCER
PR ISOFORMS
DOXORUBICIN
PACLITAXEL
MIFEPRISTONE
MAMMARY CARCINOMAS
NAB-PACLITAXEL
PEGYLATED DOXORUBICIN LIPOSOMES
title_short The effectiveness of nano chemotherapeutic particles combined with mifepristone depends on the PR isoform ratio in preclinical models of breast cancer
title_full The effectiveness of nano chemotherapeutic particles combined with mifepristone depends on the PR isoform ratio in preclinical models of breast cancer
title_fullStr The effectiveness of nano chemotherapeutic particles combined with mifepristone depends on the PR isoform ratio in preclinical models of breast cancer
title_full_unstemmed The effectiveness of nano chemotherapeutic particles combined with mifepristone depends on the PR isoform ratio in preclinical models of breast cancer
title_sort The effectiveness of nano chemotherapeutic particles combined with mifepristone depends on the PR isoform ratio in preclinical models of breast cancer
dc.creator.none.fl_str_mv Sequeira, Gonzalo Ricardo
Vanzulli, Silvia I.
Rojas, Paola Andrea
Lamb, Caroline Ana
Colombo, Lucas Luis
May, Maria
Molinolo, Alfredo
Lanari, Claudia Lee Malvina
author Sequeira, Gonzalo Ricardo
author_facet Sequeira, Gonzalo Ricardo
Vanzulli, Silvia I.
Rojas, Paola Andrea
Lamb, Caroline Ana
Colombo, Lucas Luis
May, Maria
Molinolo, Alfredo
Lanari, Claudia Lee Malvina
author_role author
author2 Vanzulli, Silvia I.
Rojas, Paola Andrea
Lamb, Caroline Ana
Colombo, Lucas Luis
May, Maria
Molinolo, Alfredo
Lanari, Claudia Lee Malvina
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BREAST CANCER
PR ISOFORMS
DOXORUBICIN
PACLITAXEL
MIFEPRISTONE
MAMMARY CARCINOMAS
NAB-PACLITAXEL
PEGYLATED DOXORUBICIN LIPOSOMES
topic BREAST CANCER
PR ISOFORMS
DOXORUBICIN
PACLITAXEL
MIFEPRISTONE
MAMMARY CARCINOMAS
NAB-PACLITAXEL
PEGYLATED DOXORUBICIN LIPOSOMES
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv There is clinical and experimental evidence suggesting that antiprogestins might be used for the treatment of selected breast cancer patients. Our aim was to evaluate the effect of albumin-bound paclitaxel (Nab-paclitaxel) and pegylated doxorubicin liposomes (PEG-LD) in combination with mifepristone (MFP) in experimental breast cancer models expressing different ratios of progesterone receptor (PR) isoforms A and B. We used two antiprogestin-responsive (PRA>PRB) and two resistant (PRA<PRB) murine mammary carcinomas growing in BALB/c, GFP-BALB/c or nude mice, along with human T47D-YA and T47D-YB xenografts growing in immunocompromised NSG mice. MFP improved the therapeutic effects of suboptimal doses of Nab-paclitaxel or PEG-LD in murine and human carcinomas with higher levels of PRA than PRB. MFP induced tissue remodeling in PRA-overexpressing tumors, increasing the stromal/tumor cell ratio and the number of functional vessels. Accordingly, an increase in nanoparticles and drug accumulation was observed in stromal and tumor cells in MFP-treated tumors. We conclude that MFP induces an increase in vessels during tissue remodeling, favoring the selective accumulation of nanoparticles inside the tumors. We propose that antiprogestins have the potential to enhance the efficacy of chemotherapy in breast tumors with a high PRA/PRB ratio.
Fil: Sequeira, Gonzalo Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Vanzulli, Silvia I.. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Rojas, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Lamb, Caroline Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Colombo, Lucas Luis. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologi­a "angel H. Roffo"; Argentina
Fil: May, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Molinolo, Alfredo. National Institutes of Health. National Institute of Dental and Craniofacial Research. Oral and Phayngeal Cancer Branch; Estados Unidos
Fil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
description There is clinical and experimental evidence suggesting that antiprogestins might be used for the treatment of selected breast cancer patients. Our aim was to evaluate the effect of albumin-bound paclitaxel (Nab-paclitaxel) and pegylated doxorubicin liposomes (PEG-LD) in combination with mifepristone (MFP) in experimental breast cancer models expressing different ratios of progesterone receptor (PR) isoforms A and B. We used two antiprogestin-responsive (PRA>PRB) and two resistant (PRA<PRB) murine mammary carcinomas growing in BALB/c, GFP-BALB/c or nude mice, along with human T47D-YA and T47D-YB xenografts growing in immunocompromised NSG mice. MFP improved the therapeutic effects of suboptimal doses of Nab-paclitaxel or PEG-LD in murine and human carcinomas with higher levels of PRA than PRB. MFP induced tissue remodeling in PRA-overexpressing tumors, increasing the stromal/tumor cell ratio and the number of functional vessels. Accordingly, an increase in nanoparticles and drug accumulation was observed in stromal and tumor cells in MFP-treated tumors. We conclude that MFP induces an increase in vessels during tissue remodeling, favoring the selective accumulation of nanoparticles inside the tumors. We propose that antiprogestins have the potential to enhance the efficacy of chemotherapy in breast tumors with a high PRA/PRB ratio.
publishDate 2014
dc.date.none.fl_str_mv 2014-04-27
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/11336/6289
Sequeira, Gonzalo Ricardo; Vanzulli, Silvia I.; Rojas, Paola Andrea; Lamb, Caroline Ana; Colombo, Lucas Luis; et al.; The effectiveness of nano chemotherapeutic particles combined with mifepristone depends on the PR isoform ratio in preclinical models of breast cancer; Impact Journals; Oncotarget; 5; 10; 27-4-2014; 3246-3260
1949-2553
url http://hdl.handle.net/11336/6289
identifier_str_mv Sequeira, Gonzalo Ricardo; Vanzulli, Silvia I.; Rojas, Paola Andrea; Lamb, Caroline Ana; Colombo, Lucas Luis; et al.; The effectiveness of nano chemotherapeutic particles combined with mifepristone depends on the PR isoform ratio in preclinical models of breast cancer; Impact Journals; Oncotarget; 5; 10; 27-4-2014; 3246-3260
1949-2553
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/
info:eu-repo/semantics/altIdentifier/url/http://doi.org/10.18632/oncotarget.1922
info:eu-repo/semantics/altIdentifier/pmid/PMC4102807
info:eu-repo/semantics/altIdentifier/url/http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5b%5d=1922
info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102807/
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
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
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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