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Establishment of Pancreatobiliary Cancer Zebrafish Avatars for Chemotherapy Screening

Background: Cancers of the pancreas and biliary tree remain one of the most aggressive oncological malignancies, with most patients relying on systemic chemotherapy. However, effective biomarkers to predict the best therapy option for each patient are still lacking. In this context, an assay able to...

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Autores principales: Tavares Barroso, Mariana, Costa, Bruna, Rebelo de Almeida, Cátia, Castillo Martin, Mireia, Couto, Nuno, Carvalho, Tânia, Fior, Rita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393525/
https://www.ncbi.nlm.nih.gov/pubmed/34440847
http://dx.doi.org/10.3390/cells10082077
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author Tavares Barroso, Mariana
Costa, Bruna
Rebelo de Almeida, Cátia
Castillo Martin, Mireia
Couto, Nuno
Carvalho, Tânia
Fior, Rita
author_facet Tavares Barroso, Mariana
Costa, Bruna
Rebelo de Almeida, Cátia
Castillo Martin, Mireia
Couto, Nuno
Carvalho, Tânia
Fior, Rita
author_sort Tavares Barroso, Mariana
collection PubMed
description Background: Cancers of the pancreas and biliary tree remain one of the most aggressive oncological malignancies, with most patients relying on systemic chemotherapy. However, effective biomarkers to predict the best therapy option for each patient are still lacking. In this context, an assay able to evaluate individual responses prior to treatment would be of great value for clinical decisions. Here we aimed to develop such a model using zebrafish xenografts to directly challenge pancreatic cancer cells to the available chemotherapies. Methods: Zebrafish xenografts were generated from a Panc-1 cell line to optimize the pancreatic setting. Pancreatic surgical resected samples, without in vitro expansion, were used to establish zebrafish patient-derived xenografts (zAvatars). Upon chemotherapy exposure, zAvatars were analyzed by single-cell confocal microscopy. Results: We show that Panc-1 zebrafish xenografts are able to reveal tumor responses to both FOLFIRINOX and gemcitabine plus nanoparticle albumin-bound (nab)-paclitaxel in just 4 days. Moreover, we established pancreatic and ampullary zAvatars with patient-derived tumors representative of different histological types. Conclusion: Altogether, we provide a short report showing the feasibility of generating and analyzing with single-cell resolution zAvatars from pancreatic and ampullary cancers, with potential use for future preclinical studies and personalized treatment.
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spelling pubmed-83935252021-08-28 Establishment of Pancreatobiliary Cancer Zebrafish Avatars for Chemotherapy Screening Tavares Barroso, Mariana Costa, Bruna Rebelo de Almeida, Cátia Castillo Martin, Mireia Couto, Nuno Carvalho, Tânia Fior, Rita Cells Brief Report Background: Cancers of the pancreas and biliary tree remain one of the most aggressive oncological malignancies, with most patients relying on systemic chemotherapy. However, effective biomarkers to predict the best therapy option for each patient are still lacking. In this context, an assay able to evaluate individual responses prior to treatment would be of great value for clinical decisions. Here we aimed to develop such a model using zebrafish xenografts to directly challenge pancreatic cancer cells to the available chemotherapies. Methods: Zebrafish xenografts were generated from a Panc-1 cell line to optimize the pancreatic setting. Pancreatic surgical resected samples, without in vitro expansion, were used to establish zebrafish patient-derived xenografts (zAvatars). Upon chemotherapy exposure, zAvatars were analyzed by single-cell confocal microscopy. Results: We show that Panc-1 zebrafish xenografts are able to reveal tumor responses to both FOLFIRINOX and gemcitabine plus nanoparticle albumin-bound (nab)-paclitaxel in just 4 days. Moreover, we established pancreatic and ampullary zAvatars with patient-derived tumors representative of different histological types. Conclusion: Altogether, we provide a short report showing the feasibility of generating and analyzing with single-cell resolution zAvatars from pancreatic and ampullary cancers, with potential use for future preclinical studies and personalized treatment. MDPI 2021-08-13 /pmc/articles/PMC8393525/ /pubmed/34440847 http://dx.doi.org/10.3390/cells10082077 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Tavares Barroso, Mariana
Costa, Bruna
Rebelo de Almeida, Cátia
Castillo Martin, Mireia
Couto, Nuno
Carvalho, Tânia
Fior, Rita
Establishment of Pancreatobiliary Cancer Zebrafish Avatars for Chemotherapy Screening
title Establishment of Pancreatobiliary Cancer Zebrafish Avatars for Chemotherapy Screening
title_full Establishment of Pancreatobiliary Cancer Zebrafish Avatars for Chemotherapy Screening
title_fullStr Establishment of Pancreatobiliary Cancer Zebrafish Avatars for Chemotherapy Screening
title_full_unstemmed Establishment of Pancreatobiliary Cancer Zebrafish Avatars for Chemotherapy Screening
title_short Establishment of Pancreatobiliary Cancer Zebrafish Avatars for Chemotherapy Screening
title_sort establishment of pancreatobiliary cancer zebrafish avatars for chemotherapy screening
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393525/
https://www.ncbi.nlm.nih.gov/pubmed/34440847
http://dx.doi.org/10.3390/cells10082077
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