Bacillus Calmette-Guerin improves local and systemic response to radiotherapy in invasive bladder cancer

Autores
Prack Mc Cormick, Bárbara Patricia; Belgorosky, Denise; Langle, Yanina Verónica; Balarino, Natalia Patricia; Sandes, Eduardo Omar; Eijan, Ana Maria
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
BackgroundA key factor contributing to radio-resistance in conservative invasive bladder cancer (BCa) treatment is tumor hypoxia and a strategy to overcome it is to trigger the production of nitric oxide (NO). On the other hand, ionizing radiation (IR) applied to a primary tumor can induce immunogenic cell death which may set off a cytotoxic immune response against the primary tumor and its metastasis.PurposeTo study in vitro and in vivo, the role of BCG as a local sensitizer to overcome hypoxia-associated radio-resistance through the production of NO, and as an immune-stimulator to be used in combination with IR to generate a systemic response for invasive BCa treatment.Materials and methodsWe selected the invasive murine BCa cell line MB49-I which expresses inducible NO synthase and produces NO, cultured in vitro in 2D and 3D models, and inoculated in vivo in the subcutaneous of syngeneic mice.Resultsin vitro, multicellular murine invasive spheroids mimicked in vivo central tumor necrosis. BCG pre-treatment radio-sensitized spheroids through the induction of NO production, while no effect was shown in monolayers. In vivo, not only did BCG improve the local response to IR but it also decreased the metastatic spread and promoted the development of abscopal effect/rejection of a second tumor.ConclusionSince BCG has already and successfully been used for the treatment of non-invasive BCa and it improves the response to ionizing radiation in invasive BCa, these results are translational relevant to be analyzed in patients with this pathology.
Fil: Prack Mc Cormick, Bárbara Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina
Fil: Belgorosky, Denise. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina
Fil: Langle, Yanina Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina
Fil: Balarino, Natalia Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina
Fil: Sandes, Eduardo Omar. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina
Fil: Eijan, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina
Materia
Invasive Bladder Cancer
Bacillus Calmette-Guerin
Ionizing Radiation
Radiosensitizer
In Vivo Vaccine
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/47918
Acceder
id CONICETDig_6740c978927d85216d27d0731fea8f73
oai_identifier_str oai:ri.conicet.gov.ar:11336/47918
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Bacillus Calmette-Guerin improves local and systemic response to radiotherapy in invasive bladder cancerPrack Mc Cormick, Bárbara PatriciaBelgorosky, DeniseLangle, Yanina VerónicaBalarino, Natalia PatriciaSandes, Eduardo OmarEijan, Ana MariaInvasive Bladder CancerBacillus Calmette-GuerinIonizing RadiationRadiosensitizerIn Vivo Vaccinehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3BackgroundA key factor contributing to radio-resistance in conservative invasive bladder cancer (BCa) treatment is tumor hypoxia and a strategy to overcome it is to trigger the production of nitric oxide (NO). On the other hand, ionizing radiation (IR) applied to a primary tumor can induce immunogenic cell death which may set off a cytotoxic immune response against the primary tumor and its metastasis.PurposeTo study in vitro and in vivo, the role of BCG as a local sensitizer to overcome hypoxia-associated radio-resistance through the production of NO, and as an immune-stimulator to be used in combination with IR to generate a systemic response for invasive BCa treatment.Materials and methodsWe selected the invasive murine BCa cell line MB49-I which expresses inducible NO synthase and produces NO, cultured in vitro in 2D and 3D models, and inoculated in vivo in the subcutaneous of syngeneic mice.Resultsin vitro, multicellular murine invasive spheroids mimicked in vivo central tumor necrosis. BCG pre-treatment radio-sensitized spheroids through the induction of NO production, while no effect was shown in monolayers. In vivo, not only did BCG improve the local response to IR but it also decreased the metastatic spread and promoted the development of abscopal effect/rejection of a second tumor.ConclusionSince BCG has already and successfully been used for the treatment of non-invasive BCa and it improves the response to ionizing radiation in invasive BCa, these results are translational relevant to be analyzed in patients with this pathology.Fil: Prack Mc Cormick, Bárbara Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; ArgentinaFil: Belgorosky, Denise. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; ArgentinaFil: Langle, Yanina Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; ArgentinaFil: Balarino, Natalia Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; ArgentinaFil: Sandes, Eduardo Omar. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; ArgentinaFil: Eijan, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; ArgentinaAcademic Press Inc Elsevier Science2017-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/47918Prack Mc Cormick, Bárbara Patricia; Belgorosky, Denise; Langle, Yanina Verónica; Balarino, Natalia Patricia; Sandes, Eduardo Omar; et al.; Bacillus Calmette-Guerin improves local and systemic response to radiotherapy in invasive bladder cancer; Academic Press Inc Elsevier Science; Nitric Oxide-Biology and Chemistry; 64; 4-2017; 22-301089-8603CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.niox.2017.01.008info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1089860316301434info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:38:58Zoai:ri.conicet.gov.ar:11336/47918instacron: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 09:38:58.315CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Bacillus Calmette-Guerin improves local and systemic response to radiotherapy in invasive bladder cancer
title Bacillus Calmette-Guerin improves local and systemic response to radiotherapy in invasive bladder cancer
spellingShingle Bacillus Calmette-Guerin improves local and systemic response to radiotherapy in invasive bladder cancer
Prack Mc Cormick, Bárbara Patricia
Invasive Bladder Cancer
Bacillus Calmette-Guerin
Ionizing Radiation
Radiosensitizer
In Vivo Vaccine
title_short Bacillus Calmette-Guerin improves local and systemic response to radiotherapy in invasive bladder cancer
title_full Bacillus Calmette-Guerin improves local and systemic response to radiotherapy in invasive bladder cancer
title_fullStr Bacillus Calmette-Guerin improves local and systemic response to radiotherapy in invasive bladder cancer
title_full_unstemmed Bacillus Calmette-Guerin improves local and systemic response to radiotherapy in invasive bladder cancer
title_sort Bacillus Calmette-Guerin improves local and systemic response to radiotherapy in invasive bladder cancer
dc.creator.none.fl_str_mv Prack Mc Cormick, Bárbara Patricia
Belgorosky, Denise
Langle, Yanina Verónica
Balarino, Natalia Patricia
Sandes, Eduardo Omar
Eijan, Ana Maria
author Prack Mc Cormick, Bárbara Patricia
author_facet Prack Mc Cormick, Bárbara Patricia
Belgorosky, Denise
Langle, Yanina Verónica
Balarino, Natalia Patricia
Sandes, Eduardo Omar
Eijan, Ana Maria
author_role author
author2 Belgorosky, Denise
Langle, Yanina Verónica
Balarino, Natalia Patricia
Sandes, Eduardo Omar
Eijan, Ana Maria
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Invasive Bladder Cancer
Bacillus Calmette-Guerin
Ionizing Radiation
Radiosensitizer
In Vivo Vaccine
topic Invasive Bladder Cancer
Bacillus Calmette-Guerin
Ionizing Radiation
Radiosensitizer
In Vivo Vaccine
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv BackgroundA key factor contributing to radio-resistance in conservative invasive bladder cancer (BCa) treatment is tumor hypoxia and a strategy to overcome it is to trigger the production of nitric oxide (NO). On the other hand, ionizing radiation (IR) applied to a primary tumor can induce immunogenic cell death which may set off a cytotoxic immune response against the primary tumor and its metastasis.PurposeTo study in vitro and in vivo, the role of BCG as a local sensitizer to overcome hypoxia-associated radio-resistance through the production of NO, and as an immune-stimulator to be used in combination with IR to generate a systemic response for invasive BCa treatment.Materials and methodsWe selected the invasive murine BCa cell line MB49-I which expresses inducible NO synthase and produces NO, cultured in vitro in 2D and 3D models, and inoculated in vivo in the subcutaneous of syngeneic mice.Resultsin vitro, multicellular murine invasive spheroids mimicked in vivo central tumor necrosis. BCG pre-treatment radio-sensitized spheroids through the induction of NO production, while no effect was shown in monolayers. In vivo, not only did BCG improve the local response to IR but it also decreased the metastatic spread and promoted the development of abscopal effect/rejection of a second tumor.ConclusionSince BCG has already and successfully been used for the treatment of non-invasive BCa and it improves the response to ionizing radiation in invasive BCa, these results are translational relevant to be analyzed in patients with this pathology.
Fil: Prack Mc Cormick, Bárbara Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina
Fil: Belgorosky, Denise. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina
Fil: Langle, Yanina Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina
Fil: Balarino, Natalia Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina
Fil: Sandes, Eduardo Omar. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina
Fil: Eijan, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina
description BackgroundA key factor contributing to radio-resistance in conservative invasive bladder cancer (BCa) treatment is tumor hypoxia and a strategy to overcome it is to trigger the production of nitric oxide (NO). On the other hand, ionizing radiation (IR) applied to a primary tumor can induce immunogenic cell death which may set off a cytotoxic immune response against the primary tumor and its metastasis.PurposeTo study in vitro and in vivo, the role of BCG as a local sensitizer to overcome hypoxia-associated radio-resistance through the production of NO, and as an immune-stimulator to be used in combination with IR to generate a systemic response for invasive BCa treatment.Materials and methodsWe selected the invasive murine BCa cell line MB49-I which expresses inducible NO synthase and produces NO, cultured in vitro in 2D and 3D models, and inoculated in vivo in the subcutaneous of syngeneic mice.Resultsin vitro, multicellular murine invasive spheroids mimicked in vivo central tumor necrosis. BCG pre-treatment radio-sensitized spheroids through the induction of NO production, while no effect was shown in monolayers. In vivo, not only did BCG improve the local response to IR but it also decreased the metastatic spread and promoted the development of abscopal effect/rejection of a second tumor.ConclusionSince BCG has already and successfully been used for the treatment of non-invasive BCa and it improves the response to ionizing radiation in invasive BCa, these results are translational relevant to be analyzed in patients with this pathology.
publishDate 2017
dc.date.none.fl_str_mv 2017-04
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/11336/47918
Prack Mc Cormick, Bárbara Patricia; Belgorosky, Denise; Langle, Yanina Verónica; Balarino, Natalia Patricia; Sandes, Eduardo Omar; et al.; Bacillus Calmette-Guerin improves local and systemic response to radiotherapy in invasive bladder cancer; Academic Press Inc Elsevier Science; Nitric Oxide-Biology and Chemistry; 64; 4-2017; 22-30
1089-8603
CONICET Digital
CONICET
url http://hdl.handle.net/11336/47918
identifier_str_mv Prack Mc Cormick, Bárbara Patricia; Belgorosky, Denise; Langle, Yanina Verónica; Balarino, Natalia Patricia; Sandes, Eduardo Omar; et al.; Bacillus Calmette-Guerin improves local and systemic response to radiotherapy in invasive bladder cancer; Academic Press Inc Elsevier Science; Nitric Oxide-Biology and Chemistry; 64; 4-2017; 22-30
1089-8603
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.niox.2017.01.008
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1089860316301434
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
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 13.070432

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