Fibroblast Growth Factor Receptor 1 Drives the Metastatic Progression of Prostate Cancer
- Autores
- Labanca, Estefania; Yang, Jun; Shepherd, Peter D. A.; Wan, Xinhai; Starbuck, Michael W.; Guerra, Leah D.; Anselmino, Nicolás; Bizzotto, Juan Antonio; Dong, Jiabin; Chinnaiyan, Arul M.; Ravoori, Murali K.; Kundra, Vikas; Broom, Bradley M.; Corn, Paul G.; Troncoso, Patricia; Gueron, Geraldine; Logothethis, Christopher J.; Navone, Nora
- Año de publicación
- 2021
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- BACKGROUND: No curative therapy is currently available for metastatic prostate cancer (PCa). The diverse mechanisms of progression include fibroblast growth factor (FGF) axis activation. OBJECTIVE: To investigate the molecular and clinical implications of fibroblast growth factor receptor 1 (FGFR1) and its isoforms (α/β) in the pathogenesis of PCa bone metastases. DESIGN, SETTING, AND PARTICIPANTS: In silico, in vitro, and in vivo preclinical approaches were used. RNA-sequencing and immunohistochemical (IHC) studies in human samples were conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: In mice, bone metastases (chi-square/Fisher's test) and survival (Mantel-Cox) were assessed. In human samples, FGFR1 and ladinin 1 (LAD1) analysis associated with PCa progression were evaluated (IHC studies, Fisher's test). RESULTS AND LIMITATIONS: FGFR1 isoform expression varied among PCa subtypes. Intracardiac injection of mice with FGFR1-expressing PC3 cells reduced mouse survival (α, p < 0.0001; β, p = 0.032) and increased the incidence of bone metastases (α, p < 0.0001; β, p = 0.02). Accordingly, IHC studies of human castration-resistant PCa (CRPC) bone metastases revealed significant enrichment of FGFR1 expression compared with treatment-naïve, nonmetastatic primary tumors (p = 0.0007). Expression of anchoring filament protein LAD1 increased in FGFR1-expressing PC3 cells and was enriched in human CRPC bone metastases (p = 0.005). CONCLUSIONS: FGFR1 expression induces bone metastases experimentally and is significantly enriched in human CRPC bone metastases, supporting its prometastatic effect in PCa. LAD1 expression, found in the prometastatic PCa cells expressing FGFR1, was also enriched in CRPC bone metastases. Our studies support and provide a roadmap for the development of FGFR blockade for advanced PCa. PATIENT SUMMARY: We studied the role of fibroblast growth factor receptor 1 (FGFR1) in prostate cancer (PCa) progression. We found that PCa cells with high FGFR1 expression increase metastases and that FGFR1 expression is increased in human PCa bone metastases, and identified genes that could participate in the metastases induced by FGFR1. These studies will help pinpoint PCa patients who use fibroblast growth factor to progress and will benefit by the inhibition of this pathway.
Fil: Labanca, Estefania. University of Texas; Estados Unidos
Fil: Yang, Jun. University of Texas; Estados Unidos
Fil: Shepherd, Peter D. A.. University of Texas; Estados Unidos
Fil: Wan, Xinhai. University of Texas; Estados Unidos
Fil: Starbuck, Michael W.. University of Texas; Estados Unidos
Fil: Guerra, Leah D.. University of Texas; Estados Unidos
Fil: Anselmino, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Bizzotto, Juan Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Dong, Jiabin. University of Texas; Estados Unidos
Fil: Chinnaiyan, Arul M.. University Of Michigan Medical School; Estados Unidos
Fil: Ravoori, Murali K.. University of Texas; Estados Unidos
Fil: Kundra, Vikas. University of Texas; Estados Unidos
Fil: Broom, Bradley M.. University of Texas; Estados Unidos
Fil: Corn, Paul G.. University of Texas; Estados Unidos
Fil: Troncoso, Patricia. University of Texas; Estados Unidos
Fil: Gueron, Geraldine. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Logothethis, Christopher J.. University of Texas; Estados Unidos
Fil: Navone, Nora. University of Texas; Estados Unidos - Materia
-
BONE METASTASIS
FIBROBLAST GROWTH FACTOR RECEPTOR 1
LADININ 1
PROSTATE CANCER - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/173304
Ver los metadatos del registro completo
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Fibroblast Growth Factor Receptor 1 Drives the Metastatic Progression of Prostate CancerLabanca, EstefaniaYang, JunShepherd, Peter D. A.Wan, XinhaiStarbuck, Michael W.Guerra, Leah D.Anselmino, NicolásBizzotto, Juan AntonioDong, JiabinChinnaiyan, Arul M.Ravoori, Murali K.Kundra, VikasBroom, Bradley M.Corn, Paul G.Troncoso, PatriciaGueron, GeraldineLogothethis, Christopher J.Navone, NoraBONE METASTASISFIBROBLAST GROWTH FACTOR RECEPTOR 1LADININ 1PROSTATE CANCERhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3BACKGROUND: No curative therapy is currently available for metastatic prostate cancer (PCa). The diverse mechanisms of progression include fibroblast growth factor (FGF) axis activation. OBJECTIVE: To investigate the molecular and clinical implications of fibroblast growth factor receptor 1 (FGFR1) and its isoforms (α/β) in the pathogenesis of PCa bone metastases. DESIGN, SETTING, AND PARTICIPANTS: In silico, in vitro, and in vivo preclinical approaches were used. RNA-sequencing and immunohistochemical (IHC) studies in human samples were conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: In mice, bone metastases (chi-square/Fisher's test) and survival (Mantel-Cox) were assessed. In human samples, FGFR1 and ladinin 1 (LAD1) analysis associated with PCa progression were evaluated (IHC studies, Fisher's test). RESULTS AND LIMITATIONS: FGFR1 isoform expression varied among PCa subtypes. Intracardiac injection of mice with FGFR1-expressing PC3 cells reduced mouse survival (α, p < 0.0001; β, p = 0.032) and increased the incidence of bone metastases (α, p < 0.0001; β, p = 0.02). Accordingly, IHC studies of human castration-resistant PCa (CRPC) bone metastases revealed significant enrichment of FGFR1 expression compared with treatment-naïve, nonmetastatic primary tumors (p = 0.0007). Expression of anchoring filament protein LAD1 increased in FGFR1-expressing PC3 cells and was enriched in human CRPC bone metastases (p = 0.005). CONCLUSIONS: FGFR1 expression induces bone metastases experimentally and is significantly enriched in human CRPC bone metastases, supporting its prometastatic effect in PCa. LAD1 expression, found in the prometastatic PCa cells expressing FGFR1, was also enriched in CRPC bone metastases. Our studies support and provide a roadmap for the development of FGFR blockade for advanced PCa. PATIENT SUMMARY: We studied the role of fibroblast growth factor receptor 1 (FGFR1) in prostate cancer (PCa) progression. We found that PCa cells with high FGFR1 expression increase metastases and that FGFR1 expression is increased in human PCa bone metastases, and identified genes that could participate in the metastases induced by FGFR1. These studies will help pinpoint PCa patients who use fibroblast growth factor to progress and will benefit by the inhibition of this pathway.Fil: Labanca, Estefania. University of Texas; Estados UnidosFil: Yang, Jun. University of Texas; Estados UnidosFil: Shepherd, Peter D. A.. University of Texas; Estados UnidosFil: Wan, Xinhai. University of Texas; Estados UnidosFil: Starbuck, Michael W.. University of Texas; Estados UnidosFil: Guerra, Leah D.. University of Texas; Estados UnidosFil: Anselmino, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Bizzotto, Juan Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Dong, Jiabin. University of Texas; Estados UnidosFil: Chinnaiyan, Arul M.. University Of Michigan Medical School; Estados UnidosFil: Ravoori, Murali K.. University of Texas; Estados UnidosFil: Kundra, Vikas. University of Texas; Estados UnidosFil: Broom, Bradley M.. University of Texas; Estados UnidosFil: Corn, Paul G.. University of Texas; Estados UnidosFil: Troncoso, Patricia. University of Texas; Estados UnidosFil: Gueron, Geraldine. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Logothethis, Christopher J.. University of Texas; Estados UnidosFil: Navone, Nora. University of Texas; Estados UnidosElsevier2021-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/173304Labanca, Estefania; Yang, Jun; Shepherd, Peter D. A.; Wan, Xinhai; Starbuck, Michael W.; et al.; Fibroblast Growth Factor Receptor 1 Drives the Metastatic Progression of Prostate Cancer; Elsevier; European Urology Oncology; 5; 2; 11-2021; 164-1752588-9311CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2588931121001826?via%3Dihubinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.euo.2021.10.001info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-05T09:46:35Zoai:ri.conicet.gov.ar:11336/173304instacron: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:34982025-11-05 09:46:36.208CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Fibroblast Growth Factor Receptor 1 Drives the Metastatic Progression of Prostate Cancer |
| title |
Fibroblast Growth Factor Receptor 1 Drives the Metastatic Progression of Prostate Cancer |
| spellingShingle |
Fibroblast Growth Factor Receptor 1 Drives the Metastatic Progression of Prostate Cancer Labanca, Estefania BONE METASTASIS FIBROBLAST GROWTH FACTOR RECEPTOR 1 LADININ 1 PROSTATE CANCER |
| title_short |
Fibroblast Growth Factor Receptor 1 Drives the Metastatic Progression of Prostate Cancer |
| title_full |
Fibroblast Growth Factor Receptor 1 Drives the Metastatic Progression of Prostate Cancer |
| title_fullStr |
Fibroblast Growth Factor Receptor 1 Drives the Metastatic Progression of Prostate Cancer |
| title_full_unstemmed |
Fibroblast Growth Factor Receptor 1 Drives the Metastatic Progression of Prostate Cancer |
| title_sort |
Fibroblast Growth Factor Receptor 1 Drives the Metastatic Progression of Prostate Cancer |
| dc.creator.none.fl_str_mv |
Labanca, Estefania Yang, Jun Shepherd, Peter D. A. Wan, Xinhai Starbuck, Michael W. Guerra, Leah D. Anselmino, Nicolás Bizzotto, Juan Antonio Dong, Jiabin Chinnaiyan, Arul M. Ravoori, Murali K. Kundra, Vikas Broom, Bradley M. Corn, Paul G. Troncoso, Patricia Gueron, Geraldine Logothethis, Christopher J. Navone, Nora |
| author |
Labanca, Estefania |
| author_facet |
Labanca, Estefania Yang, Jun Shepherd, Peter D. A. Wan, Xinhai Starbuck, Michael W. Guerra, Leah D. Anselmino, Nicolás Bizzotto, Juan Antonio Dong, Jiabin Chinnaiyan, Arul M. Ravoori, Murali K. Kundra, Vikas Broom, Bradley M. Corn, Paul G. Troncoso, Patricia Gueron, Geraldine Logothethis, Christopher J. Navone, Nora |
| author_role |
author |
| author2 |
Yang, Jun Shepherd, Peter D. A. Wan, Xinhai Starbuck, Michael W. Guerra, Leah D. Anselmino, Nicolás Bizzotto, Juan Antonio Dong, Jiabin Chinnaiyan, Arul M. Ravoori, Murali K. Kundra, Vikas Broom, Bradley M. Corn, Paul G. Troncoso, Patricia Gueron, Geraldine Logothethis, Christopher J. Navone, Nora |
| author2_role |
author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
BONE METASTASIS FIBROBLAST GROWTH FACTOR RECEPTOR 1 LADININ 1 PROSTATE CANCER |
| topic |
BONE METASTASIS FIBROBLAST GROWTH FACTOR RECEPTOR 1 LADININ 1 PROSTATE CANCER |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
BACKGROUND: No curative therapy is currently available for metastatic prostate cancer (PCa). The diverse mechanisms of progression include fibroblast growth factor (FGF) axis activation. OBJECTIVE: To investigate the molecular and clinical implications of fibroblast growth factor receptor 1 (FGFR1) and its isoforms (α/β) in the pathogenesis of PCa bone metastases. DESIGN, SETTING, AND PARTICIPANTS: In silico, in vitro, and in vivo preclinical approaches were used. RNA-sequencing and immunohistochemical (IHC) studies in human samples were conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: In mice, bone metastases (chi-square/Fisher's test) and survival (Mantel-Cox) were assessed. In human samples, FGFR1 and ladinin 1 (LAD1) analysis associated with PCa progression were evaluated (IHC studies, Fisher's test). RESULTS AND LIMITATIONS: FGFR1 isoform expression varied among PCa subtypes. Intracardiac injection of mice with FGFR1-expressing PC3 cells reduced mouse survival (α, p < 0.0001; β, p = 0.032) and increased the incidence of bone metastases (α, p < 0.0001; β, p = 0.02). Accordingly, IHC studies of human castration-resistant PCa (CRPC) bone metastases revealed significant enrichment of FGFR1 expression compared with treatment-naïve, nonmetastatic primary tumors (p = 0.0007). Expression of anchoring filament protein LAD1 increased in FGFR1-expressing PC3 cells and was enriched in human CRPC bone metastases (p = 0.005). CONCLUSIONS: FGFR1 expression induces bone metastases experimentally and is significantly enriched in human CRPC bone metastases, supporting its prometastatic effect in PCa. LAD1 expression, found in the prometastatic PCa cells expressing FGFR1, was also enriched in CRPC bone metastases. Our studies support and provide a roadmap for the development of FGFR blockade for advanced PCa. PATIENT SUMMARY: We studied the role of fibroblast growth factor receptor 1 (FGFR1) in prostate cancer (PCa) progression. We found that PCa cells with high FGFR1 expression increase metastases and that FGFR1 expression is increased in human PCa bone metastases, and identified genes that could participate in the metastases induced by FGFR1. These studies will help pinpoint PCa patients who use fibroblast growth factor to progress and will benefit by the inhibition of this pathway. Fil: Labanca, Estefania. University of Texas; Estados Unidos Fil: Yang, Jun. University of Texas; Estados Unidos Fil: Shepherd, Peter D. A.. University of Texas; Estados Unidos Fil: Wan, Xinhai. University of Texas; Estados Unidos Fil: Starbuck, Michael W.. University of Texas; Estados Unidos Fil: Guerra, Leah D.. University of Texas; Estados Unidos Fil: Anselmino, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Bizzotto, Juan Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Dong, Jiabin. University of Texas; Estados Unidos Fil: Chinnaiyan, Arul M.. University Of Michigan Medical School; Estados Unidos Fil: Ravoori, Murali K.. University of Texas; Estados Unidos Fil: Kundra, Vikas. University of Texas; Estados Unidos Fil: Broom, Bradley M.. University of Texas; Estados Unidos Fil: Corn, Paul G.. University of Texas; Estados Unidos Fil: Troncoso, Patricia. University of Texas; Estados Unidos Fil: Gueron, Geraldine. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Logothethis, Christopher J.. University of Texas; Estados Unidos Fil: Navone, Nora. University of Texas; Estados Unidos |
| description |
BACKGROUND: No curative therapy is currently available for metastatic prostate cancer (PCa). The diverse mechanisms of progression include fibroblast growth factor (FGF) axis activation. OBJECTIVE: To investigate the molecular and clinical implications of fibroblast growth factor receptor 1 (FGFR1) and its isoforms (α/β) in the pathogenesis of PCa bone metastases. DESIGN, SETTING, AND PARTICIPANTS: In silico, in vitro, and in vivo preclinical approaches were used. RNA-sequencing and immunohistochemical (IHC) studies in human samples were conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: In mice, bone metastases (chi-square/Fisher's test) and survival (Mantel-Cox) were assessed. In human samples, FGFR1 and ladinin 1 (LAD1) analysis associated with PCa progression were evaluated (IHC studies, Fisher's test). RESULTS AND LIMITATIONS: FGFR1 isoform expression varied among PCa subtypes. Intracardiac injection of mice with FGFR1-expressing PC3 cells reduced mouse survival (α, p < 0.0001; β, p = 0.032) and increased the incidence of bone metastases (α, p < 0.0001; β, p = 0.02). Accordingly, IHC studies of human castration-resistant PCa (CRPC) bone metastases revealed significant enrichment of FGFR1 expression compared with treatment-naïve, nonmetastatic primary tumors (p = 0.0007). Expression of anchoring filament protein LAD1 increased in FGFR1-expressing PC3 cells and was enriched in human CRPC bone metastases (p = 0.005). CONCLUSIONS: FGFR1 expression induces bone metastases experimentally and is significantly enriched in human CRPC bone metastases, supporting its prometastatic effect in PCa. LAD1 expression, found in the prometastatic PCa cells expressing FGFR1, was also enriched in CRPC bone metastases. Our studies support and provide a roadmap for the development of FGFR blockade for advanced PCa. PATIENT SUMMARY: We studied the role of fibroblast growth factor receptor 1 (FGFR1) in prostate cancer (PCa) progression. We found that PCa cells with high FGFR1 expression increase metastases and that FGFR1 expression is increased in human PCa bone metastases, and identified genes that could participate in the metastases induced by FGFR1. These studies will help pinpoint PCa patients who use fibroblast growth factor to progress and will benefit by the inhibition of this pathway. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021-11 |
| 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/11336/173304 Labanca, Estefania; Yang, Jun; Shepherd, Peter D. A.; Wan, Xinhai; Starbuck, Michael W.; et al.; Fibroblast Growth Factor Receptor 1 Drives the Metastatic Progression of Prostate Cancer; Elsevier; European Urology Oncology; 5; 2; 11-2021; 164-175 2588-9311 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/173304 |
| identifier_str_mv |
Labanca, Estefania; Yang, Jun; Shepherd, Peter D. A.; Wan, Xinhai; Starbuck, Michael W.; et al.; Fibroblast Growth Factor Receptor 1 Drives the Metastatic Progression of Prostate Cancer; Elsevier; European Urology Oncology; 5; 2; 11-2021; 164-175 2588-9311 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
| language |
eng |
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info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2588931121001826?via%3Dihub info:eu-repo/semantics/altIdentifier/doi/10.1016/j.euo.2021.10.001 |
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openAccess |
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Elsevier |
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Elsevier |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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