• JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
 
  Bookmark and Share
 
 
Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2021.tde-09122021-144243
Document
Author
Full name
Mauro Rogerio de Barros Wanderley Junior
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2021
Supervisor
Committee
Ferreira, Silvia Moreira Ayub (President)
Santos, Marilia Harumi Higuchi dos
Braga, Fabiana Goulart Marcondes
Coelho Filho, Otavio Rizzi
Title in Portuguese
Avaliação do valor preditivo dos biomarcadores mieloperoxidase e galectina-3 na detecção de cardiomiopatia secundária a quimioterápicos
Keywords in Portuguese
Antagonistas adrenérgicos beta
Antraciclinas
Biomarcadores
Cardiotoxicidade
Galectina- 3,Troponina
Mieloperoxidase
Abstract in Portuguese
Introdução: Antraciclina (ANT) frequentemente, é utilizada como quimioterápico para tratamento da neoplasia de mama, porém sua aplicação clínica é limitada pela cardiotoxicidade (CTX). CECCY trial (Carvedilol for Prevention of Chemotherapy-Related Cardiotoxicity) demonstrou que o betabloqueador carvedilol (CVD) pode reduzir a injúria miocárdica secundária à ANT. Mieloperoxidase (MPO) é um biomarcador de estresse oxidativo e Galectina-3 (Gal-3) é um biomarcador de fibrose e remodelamento cardíaco. Avaliou-se a correlação entre o comportamento da MPO e Gal-3 com CTX. Métodos: Foi realizada uma análise post hoc dos pacientes que participaram do CECCY trial. 192 mulheres tiveram amostras de sangue processadas e estocadas a 80C. Após, as amostras foram analisadas em um único momento. Destas, 18 tiveram ao menos duas amostras hemolisadas e foram excluídas da pesquisa. As amostras de sangue foram obtidas na randomização e após 3 e 6 meses do início da quimioterapia (QT) com ANT. A dosagem de MPO e Gal-3 foi realizada pelo MILIPLEX MAP KIT (Merck Laboratories), com a utilização de tecnologia Luminex xMAP. Resultados: Durante o seguimento, 26 pacientes (14,9%) apresentaram queda 10% da fração de ejeção do ventrículo esquerdo (FEVE) em 6 meses após início da Qxt. Dentre estas, não houve diferença estatística no comportamento dos biomarcadores MPO e Gal-3 quando comparados com o grupo que não apresentou queda significativa de FEVE (p=0,85 para Gal-3 e MPO). Níveis séricos de MPO [basal: 13,2 (7,9; 24,8), 3 meses: 17,7 (11,1; 31,1), 6 meses: 19,2 (11,1; 37,8) ng/mL] e Gal-3 [basal: 6,3 (5,2; 9,6), 3 meses: 12,3 (9,8; 16,0), 6 meses: 10,3 (8,2; 13,1) ng/mL] aumentaram após a QT com ANT, mas as alterações longitudinais foram similares entre o grupo placebo e CVD (p para interação: 0,28 e 0,32 respectivamente). Em uma análise exploratória, os valores de MPO e Gal-3 foram divididos em grupos acima e abaixo da média. No grupo placebo, mulheres com MPO sérica basal alta demonstraram um aumento maior na elevação de TnI do que o grupo com MPO sérica abaixo da média (p=0,041). Comparado ao placebo, CVD atenuou significativamente a elevação de TnI em mulheres com MPO basal acima da média (p < 0,001) mas não atenuou a elevação de TnI em mulheres com MPO sérica basal abaixo da média (p=0,97; p para interação 0,009). Não houve diferença do comportamento da TnI em relação aos níveis séricos basais de Gal-3 (p para interação = 0,99). Conclusão: Nesta subanálise do estudo CECCY, o comportamento dos biomarcadores MPO e Gal-3 não se correlacionou com o desenvolvimento de CTX. Entretanto, níveis de MPO acima da média foram associados com maior injúria miocárdica e ajudaram a identificar mulheres mais propícias a se beneficiar de carvedilol, como prevenção primária (NCT01724450)
Title in English
Plasma biomarkers reflecting high oxidative stress predicts myocardial injury related to anthracycline chemotherapy: insights from the CECCY Trial
Keywords in English
Adrenergic beta-antagonists
Anthracyclines
Biomarkers
Cardiotoxicity
Galectin-3, Troponin
Myeloperoxidase
Abstract in English
Background: Anthracycline (ANT) is often used as a chemotherapeutic drug for breast cancer treatment, but its clinical use is limited by cardiotoxic effects. CECCY trial demonstrated that the -blocker carvedilol (CVD) could attenuate the myocardial injury secondary to ATN. Mieloperoxydase (MPO) is a biomarker of oxidative stress and galectin-3 (Gal-3) is a biomarker of fibrosis and cardiac remodeling. We evaluated the correlation between MPO and Gal-3 behavior with CTX and also the effects of CVD on MPO and Gal-3 blood levels. Methods: A post hoc analysis was performed in the patients who attended CECCY trial. 192 women had her blood samples stored during the study at - 80C until the time of assay in a single batch. Stored blood samples were obtained at baseline, 3 and 6 months after the beginning of randomization. 18 women had at least two sample hemolyzed and were excluded. MPO and Gal-3 were measured using Luminex xMAP technology through MILLIPLEX MAP KIT (Merck Laboratories). Results: 26 patients (14.9%) had a decrease of at least 10% in LVEF at 6 months after the initiation of chemotherapy. Among these, there was no significant difference in the MPO and Gal-3 when compared to the group without substantial drop in LVEF (p= 0.85 for both MPO and Gal-3). Blood levels of MPO [baseline: 13.2 (7.9; 24.8), 3 months: 17.7(11,1; 31.1), 6 months: 19.2 (11.1; 37.8) ng/mL] and Gal-3 [baseline: 6.3 (5.2; 9.6), 3 months: 12.3 (9.8; 16.0), 6 months: 10.3 (8.2; 13.1) ng/mL] increased after ANT chemotherapy, and the longitudinal changes were similar between the placebo and CVD groups (p for interaction: 0.28 and 0.32, respectively). In an exploratory analysis, as there is no normal cutoff value established for Gal-3 and MPO in the literature, the MPO and Gal-3 results were splitted in two groups: above and below average. In the placebo group, women with high (above median) baseline MPO blood levels demonstrated a greater increase in TnI blood levels than those with low baseline MPO blood levels (p=0.041). Compared with placebo, CVD significantly reduced TnI blood levels in women with high MPO blood levels (p < 0.001), but did not reduce the TnI levels in women with low baseline MPO blood levels (p=0.97; p for interaction =0.009). There was no significant interaction between CVD treatment and baseline Gal-3 blood levels (p for interaction = 0.99). Conclusion: In this subanalysis of the CECCY trial, CVD did not affect changes in galectin-3 and MPO blood levels after ANT chemotherapy in women with breast cancer. Although these biomarkers did not predict the development of CTX, high MPO blood levels was associated with worse myocardial injury and identified women who were most likely to benefit from carvedilol for primary prevention (NCT01724450)
 
WARNING - Viewing this document is conditioned on your acceptance of the following terms of use:
This document is only for private use for research and teaching activities. Reproduction for commercial use is forbidden. This rights cover the whole data about this document as well as its contents. Any uses or copies of this document in whole or in part must include the author's name.
Publishing Date
2021-12-14
 
WARNING: Learn what derived works are clicking here.
All rights of the thesis/dissertation are from the authors
CeTI-SC/STI
Digital Library of Theses and Dissertations of USP. Copyright © 2001-2022. All rights reserved.