Oxidative Stress Parameters Can Predict the Response to Erythropoiesis-Stimulating Agents in Myelodysplastic Syndrome Patients
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/103962 https://doi.org/10.3389/fcell.2021.701328 |
Resumo: | Oxidative stress has been implicated in the development of several types of cancer, including myelodysplastic syndromes (MDS), as well as in the resistance to treatment. In this work, we assessed the potential of oxidative stress parameters to predict the response to erythropoiesis-stimulating agents (ESAs) in lower-risk MDS patients. To this end, we analyzed the systemic levels of reactive species (peroxides and NO), antioxidant defenses (uric acid, vitamin E, vitamin A, GSH, GSSG, TAS, as well as GPX and GR activities], and oxidative damage (8-OH-dG and MDA) in 66 MDS patients, from those 44 have been treated with ESA. We also calculated the peroxides/TAS and NO/TAS ratios and analyzed the gene expression of levels of the redox regulators, NFE2L2 and KEAP1. We found that patients that respond to ESA treatment showed lower levels of plasma peroxides (p < 0.001), cellular GSH (p < 0.001), and cellular GR activity (p = 0.001) when compared to patients who did not respond to ESA treatment. ESA responders also showed lower levels of peroxides/TAS ratio (p < 0.001) and higher levels of the expression of the NFE2L2 gene (p = 0.001) than those that did not respond to ESA treatment. The levels of plasmatic peroxides shown to be the most accurate biomarker of ESA response, with good sensitivity (80%) and specificity (100%) and is an independent biomarker associated with therapy response. Overall, the present study demonstrated a correlation between oxidative stress levels and the response to ESA treatment in lower-risk MDS patients, with the plasmatic peroxides levels a good predictive biomarker of drug (ESA) response. |
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Oxidative Stress Parameters Can Predict the Response to Erythropoiesis-Stimulating Agents in Myelodysplastic Syndrome Patientsmyelodysplastic syndromeerythropoiesis-stimulating agentsresponse biomarkeroxidative stressantioxidant defensesreactive oxygen speciesOxidative stress has been implicated in the development of several types of cancer, including myelodysplastic syndromes (MDS), as well as in the resistance to treatment. In this work, we assessed the potential of oxidative stress parameters to predict the response to erythropoiesis-stimulating agents (ESAs) in lower-risk MDS patients. To this end, we analyzed the systemic levels of reactive species (peroxides and NO), antioxidant defenses (uric acid, vitamin E, vitamin A, GSH, GSSG, TAS, as well as GPX and GR activities], and oxidative damage (8-OH-dG and MDA) in 66 MDS patients, from those 44 have been treated with ESA. We also calculated the peroxides/TAS and NO/TAS ratios and analyzed the gene expression of levels of the redox regulators, NFE2L2 and KEAP1. We found that patients that respond to ESA treatment showed lower levels of plasma peroxides (p < 0.001), cellular GSH (p < 0.001), and cellular GR activity (p = 0.001) when compared to patients who did not respond to ESA treatment. ESA responders also showed lower levels of peroxides/TAS ratio (p < 0.001) and higher levels of the expression of the NFE2L2 gene (p = 0.001) than those that did not respond to ESA treatment. The levels of plasmatic peroxides shown to be the most accurate biomarker of ESA response, with good sensitivity (80%) and specificity (100%) and is an independent biomarker associated with therapy response. Overall, the present study demonstrated a correlation between oxidative stress levels and the response to ESA treatment in lower-risk MDS patients, with the plasmatic peroxides levels a good predictive biomarker of drug (ESA) response.Frontiers Media S.A.2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/103962http://hdl.handle.net/10316/103962https://doi.org/10.3389/fcell.2021.701328eng2296-634XGonçalves, Ana CristinaAlves, RaquelBaldeiras, InêsJorge, JoanaMarques, BárbaraPaiva, ArturOliveiros, BárbaraCortesão, EmíliaCosta, José Manuel NascimentoSarmento-Ribeiro, Ana Belainfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-12-12T21:37:29Zoai:estudogeral.uc.pt:10316/103962Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:20:42.349489Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Oxidative Stress Parameters Can Predict the Response to Erythropoiesis-Stimulating Agents in Myelodysplastic Syndrome Patients |
title |
Oxidative Stress Parameters Can Predict the Response to Erythropoiesis-Stimulating Agents in Myelodysplastic Syndrome Patients |
spellingShingle |
Oxidative Stress Parameters Can Predict the Response to Erythropoiesis-Stimulating Agents in Myelodysplastic Syndrome Patients Gonçalves, Ana Cristina myelodysplastic syndrome erythropoiesis-stimulating agents response biomarker oxidative stress antioxidant defenses reactive oxygen species |
title_short |
Oxidative Stress Parameters Can Predict the Response to Erythropoiesis-Stimulating Agents in Myelodysplastic Syndrome Patients |
title_full |
Oxidative Stress Parameters Can Predict the Response to Erythropoiesis-Stimulating Agents in Myelodysplastic Syndrome Patients |
title_fullStr |
Oxidative Stress Parameters Can Predict the Response to Erythropoiesis-Stimulating Agents in Myelodysplastic Syndrome Patients |
title_full_unstemmed |
Oxidative Stress Parameters Can Predict the Response to Erythropoiesis-Stimulating Agents in Myelodysplastic Syndrome Patients |
title_sort |
Oxidative Stress Parameters Can Predict the Response to Erythropoiesis-Stimulating Agents in Myelodysplastic Syndrome Patients |
author |
Gonçalves, Ana Cristina |
author_facet |
Gonçalves, Ana Cristina Alves, Raquel Baldeiras, Inês Jorge, Joana Marques, Bárbara Paiva, Artur Oliveiros, Bárbara Cortesão, Emília Costa, José Manuel Nascimento Sarmento-Ribeiro, Ana Bela |
author_role |
author |
author2 |
Alves, Raquel Baldeiras, Inês Jorge, Joana Marques, Bárbara Paiva, Artur Oliveiros, Bárbara Cortesão, Emília Costa, José Manuel Nascimento Sarmento-Ribeiro, Ana Bela |
author2_role |
author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Gonçalves, Ana Cristina Alves, Raquel Baldeiras, Inês Jorge, Joana Marques, Bárbara Paiva, Artur Oliveiros, Bárbara Cortesão, Emília Costa, José Manuel Nascimento Sarmento-Ribeiro, Ana Bela |
dc.subject.por.fl_str_mv |
myelodysplastic syndrome erythropoiesis-stimulating agents response biomarker oxidative stress antioxidant defenses reactive oxygen species |
topic |
myelodysplastic syndrome erythropoiesis-stimulating agents response biomarker oxidative stress antioxidant defenses reactive oxygen species |
description |
Oxidative stress has been implicated in the development of several types of cancer, including myelodysplastic syndromes (MDS), as well as in the resistance to treatment. In this work, we assessed the potential of oxidative stress parameters to predict the response to erythropoiesis-stimulating agents (ESAs) in lower-risk MDS patients. To this end, we analyzed the systemic levels of reactive species (peroxides and NO), antioxidant defenses (uric acid, vitamin E, vitamin A, GSH, GSSG, TAS, as well as GPX and GR activities], and oxidative damage (8-OH-dG and MDA) in 66 MDS patients, from those 44 have been treated with ESA. We also calculated the peroxides/TAS and NO/TAS ratios and analyzed the gene expression of levels of the redox regulators, NFE2L2 and KEAP1. We found that patients that respond to ESA treatment showed lower levels of plasma peroxides (p < 0.001), cellular GSH (p < 0.001), and cellular GR activity (p = 0.001) when compared to patients who did not respond to ESA treatment. ESA responders also showed lower levels of peroxides/TAS ratio (p < 0.001) and higher levels of the expression of the NFE2L2 gene (p = 0.001) than those that did not respond to ESA treatment. The levels of plasmatic peroxides shown to be the most accurate biomarker of ESA response, with good sensitivity (80%) and specificity (100%) and is an independent biomarker associated with therapy response. Overall, the present study demonstrated a correlation between oxidative stress levels and the response to ESA treatment in lower-risk MDS patients, with the plasmatic peroxides levels a good predictive biomarker of drug (ESA) response. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/103962 http://hdl.handle.net/10316/103962 https://doi.org/10.3389/fcell.2021.701328 |
url |
http://hdl.handle.net/10316/103962 https://doi.org/10.3389/fcell.2021.701328 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2296-634X |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Frontiers Media S.A. |
publisher.none.fl_str_mv |
Frontiers Media S.A. |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799134099185598464 |