Establishment and Comprehensive Characterization of a Novel Preclinical Platform of Metastatic Retinoblastoma for Therapeutic Developments
- Autores
- Zugbi, Santiago; Aschero, María del Rosario; Ganiewich, Daiana; Cancela, Maria Belen; Winter, Ursula Andrea; Ottaviani, Daniela; Sampor, Claudia; Dinardi, Milagros; Torbidoni, Ana Vanesa; Mena, Marcela Daniela C; Balaguer Lluna, Leire; Lamas, Gabriela; Sgroi, Mariana; Lagomarsino, Eduardo; Lubieniecki, Fabiana; Fandiño, Adriana Cristina; Radvanyi, François; Abramson, David H.; Podhajcer, Osvaldo Luis; Llera, Andrea Sabina; Cafferata, Eduardo Gustavo Alfredo; Chantada, Guillermo Luis; Montero Carcaboso, Angel; Schaiquevich, Paula Susana
- Año de publicación
- 2023
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- PURPOSE. Although there have been improvements in the management of metastatic retinoblastoma, most patients do not survive, and all patients suffer from multiple shortand long-term treatment toxicities. Reliable and informative models to assist clinicians are needed. Thus we developed and comprehensively characterized a novel preclinical platform of primary cell cultures and xenograft models of metastatic retinoblastoma to provide insights into the molecular biology underlying metastases and to perform drug screening for the identification of hit candidates with the highest potential for clinical translation. METHODS. Orbital tumor, bone marrow, cerebrospinal fluid, and lymph node tumor infiltration specimens were obtained from seven patients with metastatic retinoblastoma at diagnosis, disease progression, or relapse. Tumor specimens were engrafted in immunodeficient animals, and primary cell lines were established. Genomic, immunohistochemical/immunocytochemical, and pharmacological analysis were performed. RESULTS. We successfully established five primary cell lines: two derived from leptomeningeal, two from orbital, and one from lymph node tumor dissemination. After the intravitreal or intraventricular inoculation of these cells, we established cell-derived xenograft models. Both primary cell lines and xenografts accurately retained the histological and genomic features of the tumors from which they were derived and faithfully recapitulated the dissemination patterns and pharmacological sensitivity observed in the matched patients. CONCLUSIONS. Ours is an innovative and thoroughly characterized preclinical platform of metastatic retinoblastoma developed for the understanding of tumor biology of this highly aggressive tumor and has the potential to identify drug candidates to treat patients who currently lack effective treatment options.
Fil: Zugbi, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Aschero, María del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Ganiewich, Daiana. Fundación Instituto Leloir; Argentina
Fil: Cancela, Maria Belen. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Winter, Ursula Andrea. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ottaviani, Daniela. PSL Research University; Francia
Fil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Patología; Argentina
Fil: Dinardi, Milagros. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. 1unidad de Tratamientos Innovadores, Hospital Garrahan; Argentina
Fil: Torbidoni, Ana Vanesa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mena, Marcela Daniela C. Fundación Instituto Leloir; Argentina
Fil: Balaguer Lluna, Leire. Hospital Sant Joan de Deu Barcelona; España
Fil: Lamas, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Patología; Argentina
Fil: Sgroi, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Patología; Argentina
Fil: Lagomarsino, Eduardo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Patología; Argentina
Fil: Lubieniecki, Fabiana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Patología; Argentina
Fil: Fandiño, Adriana Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Radvanyi, François. Psl Research University; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Abramson, David H.. Memorial Sloan Kettering Cancer Center; Estados Unidos
Fil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina
Fil: Llera, Andrea Sabina. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Cafferata, Eduardo Gustavo Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Instituto Leloir; Argentina
Fil: Chantada, Guillermo Luis. Hospital Sant Joan de Deu Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Montero Carcaboso, Angel. Hospital Sant Joan de Deu Barcelona; España
Fil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina - Materia
-
RETINOBLASTOMA
DISEASE MODELS, ANIMAL
DRUG THERAPY - 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:11336/229973
Ver los metadatos del registro completo
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Establishment and Comprehensive Characterization of a Novel Preclinical Platform of Metastatic Retinoblastoma for Therapeutic DevelopmentsZugbi, SantiagoAschero, María del RosarioGaniewich, DaianaCancela, Maria BelenWinter, Ursula AndreaOttaviani, DanielaSampor, ClaudiaDinardi, MilagrosTorbidoni, Ana VanesaMena, Marcela Daniela CBalaguer Lluna, LeireLamas, GabrielaSgroi, MarianaLagomarsino, EduardoLubieniecki, FabianaFandiño, Adriana CristinaRadvanyi, FrançoisAbramson, David H.Podhajcer, Osvaldo LuisLlera, Andrea SabinaCafferata, Eduardo Gustavo AlfredoChantada, Guillermo LuisMontero Carcaboso, AngelSchaiquevich, Paula SusanaRETINOBLASTOMADISEASE MODELS, ANIMALDRUG THERAPYhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3PURPOSE. Although there have been improvements in the management of metastatic retinoblastoma, most patients do not survive, and all patients suffer from multiple shortand long-term treatment toxicities. Reliable and informative models to assist clinicians are needed. Thus we developed and comprehensively characterized a novel preclinical platform of primary cell cultures and xenograft models of metastatic retinoblastoma to provide insights into the molecular biology underlying metastases and to perform drug screening for the identification of hit candidates with the highest potential for clinical translation. METHODS. Orbital tumor, bone marrow, cerebrospinal fluid, and lymph node tumor infiltration specimens were obtained from seven patients with metastatic retinoblastoma at diagnosis, disease progression, or relapse. Tumor specimens were engrafted in immunodeficient animals, and primary cell lines were established. Genomic, immunohistochemical/immunocytochemical, and pharmacological analysis were performed. RESULTS. We successfully established five primary cell lines: two derived from leptomeningeal, two from orbital, and one from lymph node tumor dissemination. After the intravitreal or intraventricular inoculation of these cells, we established cell-derived xenograft models. Both primary cell lines and xenografts accurately retained the histological and genomic features of the tumors from which they were derived and faithfully recapitulated the dissemination patterns and pharmacological sensitivity observed in the matched patients. CONCLUSIONS. Ours is an innovative and thoroughly characterized preclinical platform of metastatic retinoblastoma developed for the understanding of tumor biology of this highly aggressive tumor and has the potential to identify drug candidates to treat patients who currently lack effective treatment options.Fil: Zugbi, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Aschero, María del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Ganiewich, Daiana. Fundación Instituto Leloir; ArgentinaFil: Cancela, Maria Belen. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Winter, Ursula Andrea. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ottaviani, Daniela. PSL Research University; FranciaFil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Patología; ArgentinaFil: Dinardi, Milagros. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. 1unidad de Tratamientos Innovadores, Hospital Garrahan; ArgentinaFil: Torbidoni, Ana Vanesa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mena, Marcela Daniela C. Fundación Instituto Leloir; ArgentinaFil: Balaguer Lluna, Leire. Hospital Sant Joan de Deu Barcelona; EspañaFil: Lamas, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Patología; ArgentinaFil: Sgroi, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Patología; ArgentinaFil: Lagomarsino, Eduardo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Patología; ArgentinaFil: Lubieniecki, Fabiana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Patología; ArgentinaFil: Fandiño, Adriana Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Radvanyi, François. Psl Research University; Francia. Centre National de la Recherche Scientifique; FranciaFil: Abramson, David H.. Memorial Sloan Kettering Cancer Center; Estados UnidosFil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: Llera, Andrea Sabina. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Cafferata, Eduardo Gustavo Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Instituto Leloir; ArgentinaFil: Chantada, Guillermo Luis. Hospital Sant Joan de Deu Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Montero Carcaboso, Angel. Hospital Sant Joan de Deu Barcelona; EspañaFil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaAssociation for Research in Vision and Ophthalmology Inc.2023-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/229973Zugbi, Santiago; Aschero, María del Rosario; Ganiewich, Daiana; Cancela, Maria Belen; Winter, Ursula Andrea; et al.; Establishment and Comprehensive Characterization of a Novel Preclinical Platform of Metastatic Retinoblastoma for Therapeutic Developments; Association for Research in Vision and Ophthalmology Inc.; Investigative Opthalmology & Visual Science; 64; 15; 12-2023; 1-111552-5783CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1167/iovs.64.15.27info:eu-repo/semantics/altIdentifier/url/https://iovs.arvojournals.org/article.aspx?articleid=2793204&resultClick=1info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:50:39Zoai:ri.conicet.gov.ar:11336/229973instacron: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 09:50:39.481CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Establishment and Comprehensive Characterization of a Novel Preclinical Platform of Metastatic Retinoblastoma for Therapeutic Developments |
| title |
Establishment and Comprehensive Characterization of a Novel Preclinical Platform of Metastatic Retinoblastoma for Therapeutic Developments |
| spellingShingle |
Establishment and Comprehensive Characterization of a Novel Preclinical Platform of Metastatic Retinoblastoma for Therapeutic Developments Zugbi, Santiago RETINOBLASTOMA DISEASE MODELS, ANIMAL DRUG THERAPY |
| title_short |
Establishment and Comprehensive Characterization of a Novel Preclinical Platform of Metastatic Retinoblastoma for Therapeutic Developments |
| title_full |
Establishment and Comprehensive Characterization of a Novel Preclinical Platform of Metastatic Retinoblastoma for Therapeutic Developments |
| title_fullStr |
Establishment and Comprehensive Characterization of a Novel Preclinical Platform of Metastatic Retinoblastoma for Therapeutic Developments |
| title_full_unstemmed |
Establishment and Comprehensive Characterization of a Novel Preclinical Platform of Metastatic Retinoblastoma for Therapeutic Developments |
| title_sort |
Establishment and Comprehensive Characterization of a Novel Preclinical Platform of Metastatic Retinoblastoma for Therapeutic Developments |
| dc.creator.none.fl_str_mv |
Zugbi, Santiago Aschero, María del Rosario Ganiewich, Daiana Cancela, Maria Belen Winter, Ursula Andrea Ottaviani, Daniela Sampor, Claudia Dinardi, Milagros Torbidoni, Ana Vanesa Mena, Marcela Daniela C Balaguer Lluna, Leire Lamas, Gabriela Sgroi, Mariana Lagomarsino, Eduardo Lubieniecki, Fabiana Fandiño, Adriana Cristina Radvanyi, François Abramson, David H. Podhajcer, Osvaldo Luis Llera, Andrea Sabina Cafferata, Eduardo Gustavo Alfredo Chantada, Guillermo Luis Montero Carcaboso, Angel Schaiquevich, Paula Susana |
| author |
Zugbi, Santiago |
| author_facet |
Zugbi, Santiago Aschero, María del Rosario Ganiewich, Daiana Cancela, Maria Belen Winter, Ursula Andrea Ottaviani, Daniela Sampor, Claudia Dinardi, Milagros Torbidoni, Ana Vanesa Mena, Marcela Daniela C Balaguer Lluna, Leire Lamas, Gabriela Sgroi, Mariana Lagomarsino, Eduardo Lubieniecki, Fabiana Fandiño, Adriana Cristina Radvanyi, François Abramson, David H. Podhajcer, Osvaldo Luis Llera, Andrea Sabina Cafferata, Eduardo Gustavo Alfredo Chantada, Guillermo Luis Montero Carcaboso, Angel Schaiquevich, Paula Susana |
| author_role |
author |
| author2 |
Aschero, María del Rosario Ganiewich, Daiana Cancela, Maria Belen Winter, Ursula Andrea Ottaviani, Daniela Sampor, Claudia Dinardi, Milagros Torbidoni, Ana Vanesa Mena, Marcela Daniela C Balaguer Lluna, Leire Lamas, Gabriela Sgroi, Mariana Lagomarsino, Eduardo Lubieniecki, Fabiana Fandiño, Adriana Cristina Radvanyi, François Abramson, David H. Podhajcer, Osvaldo Luis Llera, Andrea Sabina Cafferata, Eduardo Gustavo Alfredo Chantada, Guillermo Luis Montero Carcaboso, Angel Schaiquevich, Paula Susana |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
RETINOBLASTOMA DISEASE MODELS, ANIMAL DRUG THERAPY |
| topic |
RETINOBLASTOMA DISEASE MODELS, ANIMAL DRUG THERAPY |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
PURPOSE. Although there have been improvements in the management of metastatic retinoblastoma, most patients do not survive, and all patients suffer from multiple shortand long-term treatment toxicities. Reliable and informative models to assist clinicians are needed. Thus we developed and comprehensively characterized a novel preclinical platform of primary cell cultures and xenograft models of metastatic retinoblastoma to provide insights into the molecular biology underlying metastases and to perform drug screening for the identification of hit candidates with the highest potential for clinical translation. METHODS. Orbital tumor, bone marrow, cerebrospinal fluid, and lymph node tumor infiltration specimens were obtained from seven patients with metastatic retinoblastoma at diagnosis, disease progression, or relapse. Tumor specimens were engrafted in immunodeficient animals, and primary cell lines were established. Genomic, immunohistochemical/immunocytochemical, and pharmacological analysis were performed. RESULTS. We successfully established five primary cell lines: two derived from leptomeningeal, two from orbital, and one from lymph node tumor dissemination. After the intravitreal or intraventricular inoculation of these cells, we established cell-derived xenograft models. Both primary cell lines and xenografts accurately retained the histological and genomic features of the tumors from which they were derived and faithfully recapitulated the dissemination patterns and pharmacological sensitivity observed in the matched patients. CONCLUSIONS. Ours is an innovative and thoroughly characterized preclinical platform of metastatic retinoblastoma developed for the understanding of tumor biology of this highly aggressive tumor and has the potential to identify drug candidates to treat patients who currently lack effective treatment options. Fil: Zugbi, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Aschero, María del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Ganiewich, Daiana. Fundación Instituto Leloir; Argentina Fil: Cancela, Maria Belen. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Winter, Ursula Andrea. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Ottaviani, Daniela. PSL Research University; Francia Fil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Patología; Argentina Fil: Dinardi, Milagros. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. 1unidad de Tratamientos Innovadores, Hospital Garrahan; Argentina Fil: Torbidoni, Ana Vanesa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Mena, Marcela Daniela C. Fundación Instituto Leloir; Argentina Fil: Balaguer Lluna, Leire. Hospital Sant Joan de Deu Barcelona; España Fil: Lamas, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Patología; Argentina Fil: Sgroi, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Patología; Argentina Fil: Lagomarsino, Eduardo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Patología; Argentina Fil: Lubieniecki, Fabiana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Patología; Argentina Fil: Fandiño, Adriana Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Radvanyi, François. Psl Research University; Francia. Centre National de la Recherche Scientifique; Francia Fil: Abramson, David H.. Memorial Sloan Kettering Cancer Center; Estados Unidos Fil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina Fil: Llera, Andrea Sabina. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Cafferata, Eduardo Gustavo Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Instituto Leloir; Argentina Fil: Chantada, Guillermo Luis. Hospital Sant Joan de Deu Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Montero Carcaboso, Angel. Hospital Sant Joan de Deu Barcelona; España Fil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina |
| description |
PURPOSE. Although there have been improvements in the management of metastatic retinoblastoma, most patients do not survive, and all patients suffer from multiple shortand long-term treatment toxicities. Reliable and informative models to assist clinicians are needed. Thus we developed and comprehensively characterized a novel preclinical platform of primary cell cultures and xenograft models of metastatic retinoblastoma to provide insights into the molecular biology underlying metastases and to perform drug screening for the identification of hit candidates with the highest potential for clinical translation. METHODS. Orbital tumor, bone marrow, cerebrospinal fluid, and lymph node tumor infiltration specimens were obtained from seven patients with metastatic retinoblastoma at diagnosis, disease progression, or relapse. Tumor specimens were engrafted in immunodeficient animals, and primary cell lines were established. Genomic, immunohistochemical/immunocytochemical, and pharmacological analysis were performed. RESULTS. We successfully established five primary cell lines: two derived from leptomeningeal, two from orbital, and one from lymph node tumor dissemination. After the intravitreal or intraventricular inoculation of these cells, we established cell-derived xenograft models. Both primary cell lines and xenografts accurately retained the histological and genomic features of the tumors from which they were derived and faithfully recapitulated the dissemination patterns and pharmacological sensitivity observed in the matched patients. CONCLUSIONS. Ours is an innovative and thoroughly characterized preclinical platform of metastatic retinoblastoma developed for the understanding of tumor biology of this highly aggressive tumor and has the potential to identify drug candidates to treat patients who currently lack effective treatment options. |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023-12 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
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publishedVersion |
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http://hdl.handle.net/11336/229973 Zugbi, Santiago; Aschero, María del Rosario; Ganiewich, Daiana; Cancela, Maria Belen; Winter, Ursula Andrea; et al.; Establishment and Comprehensive Characterization of a Novel Preclinical Platform of Metastatic Retinoblastoma for Therapeutic Developments; Association for Research in Vision and Ophthalmology Inc.; Investigative Opthalmology & Visual Science; 64; 15; 12-2023; 1-11 1552-5783 CONICET Digital CONICET |
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http://hdl.handle.net/11336/229973 |
| identifier_str_mv |
Zugbi, Santiago; Aschero, María del Rosario; Ganiewich, Daiana; Cancela, Maria Belen; Winter, Ursula Andrea; et al.; Establishment and Comprehensive Characterization of a Novel Preclinical Platform of Metastatic Retinoblastoma for Therapeutic Developments; Association for Research in Vision and Ophthalmology Inc.; Investigative Opthalmology & Visual Science; 64; 15; 12-2023; 1-11 1552-5783 CONICET Digital CONICET |
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eng |
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eng |
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info:eu-repo/semantics/altIdentifier/doi/10.1167/iovs.64.15.27 info:eu-repo/semantics/altIdentifier/url/https://iovs.arvojournals.org/article.aspx?articleid=2793204&resultClick=1 |
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openAccess |
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Association for Research in Vision and Ophthalmology Inc. |
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Association for Research in Vision and Ophthalmology Inc. |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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