Characterization of ADRB2-mediated antitumoral effects and mechanisms of action of β-blocker propranolol in osteosarcoma
- Autores
- Solernó, Luisina María; Sobol, Natasha Tatiana; Ferrero, Maximiliano Ruben; Llavona, Candela; Capobianco, Carla Sabrina; Bruzzone, Ariana; Gottardo, María Florencia; Garona, Juan
- Año de publicación
- 2022
- Idioma
- inglés
- Tipo de recurso
- documento de conferencia
- Estado
- versión publicada
- Descripción
- Osteosarcoma (OSA) is still associated with limited response to standard-of-care therapy and alarmingly elevated mortality rates. Our group recently reported for the first time that PPN, a repurposed β1/2-adrenergic receptor (ADRB1/2)antagonist, was capable of reducing tumor-associated angiogenesis and xenograft aggressiveness using different OSA preclinical models.The objective of this work was tocharacterize PPN ADRB2-mediated effects and mechanisms of action on OSA growth, migration and response to chemotherapy. After confirming ADRB2 expression by RT-qPCR in MG-63 and U-2OS OSA cells, pro-mitogenic effects of ADRB agonists epinephrine and norepinephrinewere associated with downstream activation of MAPK-associated signaling pathways, as evaluated by western blotting. ADRB2 knockdown by transfection with ADRB2-targeting siRNA reduced in vitro aggressiveness of OSA cells and impairedPPN cytostatic activity, confirming target specificity of the drug. As evaluated by flow cytometry, a significant arrest in the G0/G1 cell cycle phase of MG-63 and U-2OS cells was observed after 24 h treatment with PPN (50 µM), which was associated with a significant reduction in CCND1 gene expression, a key cell cycle regulator. OSA growth inhibition was not associated with apoptosis induction. β-blockade with PPN inhibited OSA cell chemotaxis, vasculogenicmimicry and capillary-like tube formationon Matrigel® coated substrates. Migration inhibition was linked toblockade of EGF-induced actin reorganization and stress fiber formation. After histological analysis, in vivo therapeutic benefits after addition of PPN (10 mg/kg i.p.) to cisplatin-based metronomic chemotherapy (2 mg/kg i.p.) correlated with reduced tumor mitotic index and increased necrosis. All results were significantat p<0.05 (t test or ANOVA, GraphPad Prism). We propose PPN as a potential cost-effectiveco-adjuvant therapy for OSA management. Further translational studies on metastatic disease are in progress.
Fil: Solernó, Luisina María. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Provincia de Buenos Aires. Hospital El Cruce Doctor Nestor Carlos Kirchner. Centro de Medicina Traslacional.; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Sobol, Natasha Tatiana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Provincia de Buenos Aires. Hospital El Cruce Doctor Nestor Carlos Kirchner. Centro de Medicina Traslacional.; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Ferrero, Maximiliano Ruben. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Llavona, Candela. Gobierno de la Provincia de Buenos Aires. Hospital El Cruce Doctor Nestor Carlos Kirchner. Centro de Medicina Traslacional.; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Capobianco, Carla Sabrina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Provincia de Buenos Aires. Hospital El Cruce Doctor Nestor Carlos Kirchner. Centro de Medicina Traslacional.; Argentina
Fil: Bruzzone, Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Gottardo, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Provincia de Buenos Aires. Hospital El Cruce Doctor Nestor Carlos Kirchner. Centro de Medicina Traslacional.; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Garona, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Gobierno de la Provincia de Buenos Aires. Hospital El Cruce Doctor Nestor Carlos Kirchner. Centro de Medicina Traslacional.; Argentina
Reunión Conjunta SAIC SAI & FAIC SAFIS 2022; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad Argentina de Inmunología; 3er Congreso Franco Argentino de Inmunología; Reunión Anual 2022 de la Sociedad Argentina de Fisiología
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Sociedad Argentina de Fisiología - Materia
-
OSTEOSARCOMA
BETA-BLOCKER
PROPRANOLOL
ANTITUMORAL - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/232166
Ver los metadatos del registro completo
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Characterization of ADRB2-mediated antitumoral effects and mechanisms of action of β-blocker propranolol in osteosarcomaSolernó, Luisina MaríaSobol, Natasha TatianaFerrero, Maximiliano RubenLlavona, CandelaCapobianco, Carla SabrinaBruzzone, ArianaGottardo, María FlorenciaGarona, JuanOSTEOSARCOMABETA-BLOCKERPROPRANOLOLANTITUMORALhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Osteosarcoma (OSA) is still associated with limited response to standard-of-care therapy and alarmingly elevated mortality rates. Our group recently reported for the first time that PPN, a repurposed β1/2-adrenergic receptor (ADRB1/2)antagonist, was capable of reducing tumor-associated angiogenesis and xenograft aggressiveness using different OSA preclinical models.The objective of this work was tocharacterize PPN ADRB2-mediated effects and mechanisms of action on OSA growth, migration and response to chemotherapy. After confirming ADRB2 expression by RT-qPCR in MG-63 and U-2OS OSA cells, pro-mitogenic effects of ADRB agonists epinephrine and norepinephrinewere associated with downstream activation of MAPK-associated signaling pathways, as evaluated by western blotting. ADRB2 knockdown by transfection with ADRB2-targeting siRNA reduced in vitro aggressiveness of OSA cells and impairedPPN cytostatic activity, confirming target specificity of the drug. As evaluated by flow cytometry, a significant arrest in the G0/G1 cell cycle phase of MG-63 and U-2OS cells was observed after 24 h treatment with PPN (50 µM), which was associated with a significant reduction in CCND1 gene expression, a key cell cycle regulator. OSA growth inhibition was not associated with apoptosis induction. β-blockade with PPN inhibited OSA cell chemotaxis, vasculogenicmimicry and capillary-like tube formationon Matrigel® coated substrates. Migration inhibition was linked toblockade of EGF-induced actin reorganization and stress fiber formation. After histological analysis, in vivo therapeutic benefits after addition of PPN (10 mg/kg i.p.) to cisplatin-based metronomic chemotherapy (2 mg/kg i.p.) correlated with reduced tumor mitotic index and increased necrosis. All results were significantat p<0.05 (t test or ANOVA, GraphPad Prism). We propose PPN as a potential cost-effectiveco-adjuvant therapy for OSA management. Further translational studies on metastatic disease are in progress.Fil: Solernó, Luisina María. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Provincia de Buenos Aires. Hospital El Cruce Doctor Nestor Carlos Kirchner. Centro de Medicina Traslacional.; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Sobol, Natasha Tatiana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Provincia de Buenos Aires. Hospital El Cruce Doctor Nestor Carlos Kirchner. Centro de Medicina Traslacional.; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Ferrero, Maximiliano Ruben. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Llavona, Candela. Gobierno de la Provincia de Buenos Aires. Hospital El Cruce Doctor Nestor Carlos Kirchner. Centro de Medicina Traslacional.; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Capobianco, Carla Sabrina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Provincia de Buenos Aires. Hospital El Cruce Doctor Nestor Carlos Kirchner. Centro de Medicina Traslacional.; ArgentinaFil: Bruzzone, Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Gottardo, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Provincia de Buenos Aires. Hospital El Cruce Doctor Nestor Carlos Kirchner. Centro de Medicina Traslacional.; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Garona, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Gobierno de la Provincia de Buenos Aires. Hospital El Cruce Doctor Nestor Carlos Kirchner. Centro de Medicina Traslacional.; ArgentinaReunión Conjunta SAIC SAI & FAIC SAFIS 2022; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad Argentina de Inmunología; 3er Congreso Franco Argentino de Inmunología; Reunión Anual 2022 de la Sociedad Argentina de FisiologíaMar del PlataArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaSociedad Argentina de FisiologíaFundación Revista Medicina2022info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/232166Characterization of ADRB2-mediated antitumoral effects and mechanisms of action of β-blocker propranolol in osteosarcoma; Reunión Conjunta SAIC SAI & FAIC SAFIS 2022; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad Argentina de Inmunología; 3er Congreso Franco Argentino de Inmunología; Reunión Anual 2022 de la Sociedad Argentina de Fisiología; Mar del Plata; Argentina; 2022; 269-2690025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://medicinabuenosaires.com/revistas/vol82-22/s5/1s5.pdfNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:30:38Zoai:ri.conicet.gov.ar:11336/232166instacron: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:34982025-10-22 11:30:38.306CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Characterization of ADRB2-mediated antitumoral effects and mechanisms of action of β-blocker propranolol in osteosarcoma |
| title |
Characterization of ADRB2-mediated antitumoral effects and mechanisms of action of β-blocker propranolol in osteosarcoma |
| spellingShingle |
Characterization of ADRB2-mediated antitumoral effects and mechanisms of action of β-blocker propranolol in osteosarcoma Solernó, Luisina María OSTEOSARCOMA BETA-BLOCKER PROPRANOLOL ANTITUMORAL |
| title_short |
Characterization of ADRB2-mediated antitumoral effects and mechanisms of action of β-blocker propranolol in osteosarcoma |
| title_full |
Characterization of ADRB2-mediated antitumoral effects and mechanisms of action of β-blocker propranolol in osteosarcoma |
| title_fullStr |
Characterization of ADRB2-mediated antitumoral effects and mechanisms of action of β-blocker propranolol in osteosarcoma |
| title_full_unstemmed |
Characterization of ADRB2-mediated antitumoral effects and mechanisms of action of β-blocker propranolol in osteosarcoma |
| title_sort |
Characterization of ADRB2-mediated antitumoral effects and mechanisms of action of β-blocker propranolol in osteosarcoma |
| dc.creator.none.fl_str_mv |
Solernó, Luisina María Sobol, Natasha Tatiana Ferrero, Maximiliano Ruben Llavona, Candela Capobianco, Carla Sabrina Bruzzone, Ariana Gottardo, María Florencia Garona, Juan |
| author |
Solernó, Luisina María |
| author_facet |
Solernó, Luisina María Sobol, Natasha Tatiana Ferrero, Maximiliano Ruben Llavona, Candela Capobianco, Carla Sabrina Bruzzone, Ariana Gottardo, María Florencia Garona, Juan |
| author_role |
author |
| author2 |
Sobol, Natasha Tatiana Ferrero, Maximiliano Ruben Llavona, Candela Capobianco, Carla Sabrina Bruzzone, Ariana Gottardo, María Florencia Garona, Juan |
| author2_role |
author author author author author author author |
| dc.subject.none.fl_str_mv |
OSTEOSARCOMA BETA-BLOCKER PROPRANOLOL ANTITUMORAL |
| topic |
OSTEOSARCOMA BETA-BLOCKER PROPRANOLOL ANTITUMORAL |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.3 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
Osteosarcoma (OSA) is still associated with limited response to standard-of-care therapy and alarmingly elevated mortality rates. Our group recently reported for the first time that PPN, a repurposed β1/2-adrenergic receptor (ADRB1/2)antagonist, was capable of reducing tumor-associated angiogenesis and xenograft aggressiveness using different OSA preclinical models.The objective of this work was tocharacterize PPN ADRB2-mediated effects and mechanisms of action on OSA growth, migration and response to chemotherapy. After confirming ADRB2 expression by RT-qPCR in MG-63 and U-2OS OSA cells, pro-mitogenic effects of ADRB agonists epinephrine and norepinephrinewere associated with downstream activation of MAPK-associated signaling pathways, as evaluated by western blotting. ADRB2 knockdown by transfection with ADRB2-targeting siRNA reduced in vitro aggressiveness of OSA cells and impairedPPN cytostatic activity, confirming target specificity of the drug. As evaluated by flow cytometry, a significant arrest in the G0/G1 cell cycle phase of MG-63 and U-2OS cells was observed after 24 h treatment with PPN (50 µM), which was associated with a significant reduction in CCND1 gene expression, a key cell cycle regulator. OSA growth inhibition was not associated with apoptosis induction. β-blockade with PPN inhibited OSA cell chemotaxis, vasculogenicmimicry and capillary-like tube formationon Matrigel® coated substrates. Migration inhibition was linked toblockade of EGF-induced actin reorganization and stress fiber formation. After histological analysis, in vivo therapeutic benefits after addition of PPN (10 mg/kg i.p.) to cisplatin-based metronomic chemotherapy (2 mg/kg i.p.) correlated with reduced tumor mitotic index and increased necrosis. All results were significantat p<0.05 (t test or ANOVA, GraphPad Prism). We propose PPN as a potential cost-effectiveco-adjuvant therapy for OSA management. Further translational studies on metastatic disease are in progress. Fil: Solernó, Luisina María. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Provincia de Buenos Aires. Hospital El Cruce Doctor Nestor Carlos Kirchner. Centro de Medicina Traslacional.; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina Fil: Sobol, Natasha Tatiana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Provincia de Buenos Aires. Hospital El Cruce Doctor Nestor Carlos Kirchner. Centro de Medicina Traslacional.; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina Fil: Ferrero, Maximiliano Ruben. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina Fil: Llavona, Candela. Gobierno de la Provincia de Buenos Aires. Hospital El Cruce Doctor Nestor Carlos Kirchner. Centro de Medicina Traslacional.; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina Fil: Capobianco, Carla Sabrina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Provincia de Buenos Aires. Hospital El Cruce Doctor Nestor Carlos Kirchner. Centro de Medicina Traslacional.; Argentina Fil: Bruzzone, Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina Fil: Gottardo, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Provincia de Buenos Aires. Hospital El Cruce Doctor Nestor Carlos Kirchner. Centro de Medicina Traslacional.; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina Fil: Garona, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Gobierno de la Provincia de Buenos Aires. Hospital El Cruce Doctor Nestor Carlos Kirchner. Centro de Medicina Traslacional.; Argentina Reunión Conjunta SAIC SAI & FAIC SAFIS 2022; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad Argentina de Inmunología; 3er Congreso Franco Argentino de Inmunología; Reunión Anual 2022 de la Sociedad Argentina de Fisiología Mar del Plata Argentina Sociedad Argentina de Investigación Clínica Sociedad Argentina de Inmunología Sociedad Argentina de Fisiología |
| description |
Osteosarcoma (OSA) is still associated with limited response to standard-of-care therapy and alarmingly elevated mortality rates. Our group recently reported for the first time that PPN, a repurposed β1/2-adrenergic receptor (ADRB1/2)antagonist, was capable of reducing tumor-associated angiogenesis and xenograft aggressiveness using different OSA preclinical models.The objective of this work was tocharacterize PPN ADRB2-mediated effects and mechanisms of action on OSA growth, migration and response to chemotherapy. After confirming ADRB2 expression by RT-qPCR in MG-63 and U-2OS OSA cells, pro-mitogenic effects of ADRB agonists epinephrine and norepinephrinewere associated with downstream activation of MAPK-associated signaling pathways, as evaluated by western blotting. ADRB2 knockdown by transfection with ADRB2-targeting siRNA reduced in vitro aggressiveness of OSA cells and impairedPPN cytostatic activity, confirming target specificity of the drug. As evaluated by flow cytometry, a significant arrest in the G0/G1 cell cycle phase of MG-63 and U-2OS cells was observed after 24 h treatment with PPN (50 µM), which was associated with a significant reduction in CCND1 gene expression, a key cell cycle regulator. OSA growth inhibition was not associated with apoptosis induction. β-blockade with PPN inhibited OSA cell chemotaxis, vasculogenicmimicry and capillary-like tube formationon Matrigel® coated substrates. Migration inhibition was linked toblockade of EGF-induced actin reorganization and stress fiber formation. After histological analysis, in vivo therapeutic benefits after addition of PPN (10 mg/kg i.p.) to cisplatin-based metronomic chemotherapy (2 mg/kg i.p.) correlated with reduced tumor mitotic index and increased necrosis. All results were significantat p<0.05 (t test or ANOVA, GraphPad Prism). We propose PPN as a potential cost-effectiveco-adjuvant therapy for OSA management. Further translational studies on metastatic disease are in progress. |
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2022 |
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2022 |
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http://hdl.handle.net/11336/232166 Characterization of ADRB2-mediated antitumoral effects and mechanisms of action of β-blocker propranolol in osteosarcoma; Reunión Conjunta SAIC SAI & FAIC SAFIS 2022; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad Argentina de Inmunología; 3er Congreso Franco Argentino de Inmunología; Reunión Anual 2022 de la Sociedad Argentina de Fisiología; Mar del Plata; Argentina; 2022; 269-269 0025-7680 1669-9106 CONICET Digital CONICET |
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Characterization of ADRB2-mediated antitumoral effects and mechanisms of action of β-blocker propranolol in osteosarcoma; Reunión Conjunta SAIC SAI & FAIC SAFIS 2022; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad Argentina de Inmunología; 3er Congreso Franco Argentino de Inmunología; Reunión Anual 2022 de la Sociedad Argentina de Fisiología; Mar del Plata; Argentina; 2022; 269-269 0025-7680 1669-9106 CONICET Digital CONICET |
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