Avaliação da atividade das enzimas NTPDase 1 (CD39) e Ecto-5'Nucleotidase (CD73) no plasma de pacientes idosas com câncer de mama

Detalhes bibliográficos
Autor(a) principal: Gheler, Fernanda Valente
Data de Publicação: 2019
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da PUC_RS
Texto Completo: http://tede2.pucrs.br/tede2/handle/tede/9541
Resumo: Breast cancer (BC) is the most common type of cancer and the biggest mortality cause among women in whole world, being strongly associated to ageing. This has a huge importance, once rise of population’s life expectancy is directly related to cancer (re) appearance risk. However, elderly population is frequently excluded from clinical trials and its treatments are based in data obtained from trials with younger population, not being ideal. This cancer’s etiology is multifactorial, evolving endocrine, reproductive and environmental factors and, less frequently, familiar predisposition. Tumor severity is defined by its size, node commitment, presence of metastasis, hormone receptors (estrogen and progesterone) and human epidermal growth factor receptor (HER2) expression, and the absence of all receptors, characterizing the most serious subtype. This study aimed to analyze the tumor’s molecular features on elderly patients, evaluating nucleotide hydrolysis (ATP to ADP and ADP to AMP made by CD39 and AMP to adenosine by CD73) in plasma blood as possible prognostic biomarkers and/or therapeutic targets, in order to improve these patients’ disease outcomes. Peripheral blood samples were collected from 24 BC patients with age above 60 years old at the moment of diagnosis and after 6 months of treatment, and from 15 elderly patients without cancer diagnosis. The nucleotide hydrolysis analysis of the samples from BC patients at diagnosis were related to control, prognostic factors, like Ki67, known as proliferation rate marker and the samples from the same patients after 6 months of treatment. The mean age of patients were 68 years old and about 66,6% with tumors stage I and II, and 33,3% staging III and IV, representing worse prognosis. Results showed BC patients had lower ADP and higher AMP hydrolysis when compared to control. When analyzing differences between the diagnose samples and the ones collected after 6 months, we were able to show a significant reduction on AMPase activity, making the profile of treated individuals look like the healthy individuals’, independently of which treatment was used. When comparing the hydrolysis rate with Ki67 results, where 47% of the patients presented low rate (< 20%), there was a tendency of these ones present lower AMP hydrolysis. This way, we can conclude that understanding the ectonucleotidases activity role in cancer progression can help this disease complexity understanding, looking forward to improve early detection and therapeutic approach on elderly patients.
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spelling Morrone, Fernanda Buenohttp://lattes.cnpq.br/8543061247854357Cappelari, Angélica Reginahttp://lattes.cnpq.br/3186188608071919Gheler, Fernanda Valente2021-04-13T17:17:28Z2019-02-11http://tede2.pucrs.br/tede2/handle/tede/9541Breast cancer (BC) is the most common type of cancer and the biggest mortality cause among women in whole world, being strongly associated to ageing. This has a huge importance, once rise of population’s life expectancy is directly related to cancer (re) appearance risk. However, elderly population is frequently excluded from clinical trials and its treatments are based in data obtained from trials with younger population, not being ideal. This cancer’s etiology is multifactorial, evolving endocrine, reproductive and environmental factors and, less frequently, familiar predisposition. Tumor severity is defined by its size, node commitment, presence of metastasis, hormone receptors (estrogen and progesterone) and human epidermal growth factor receptor (HER2) expression, and the absence of all receptors, characterizing the most serious subtype. This study aimed to analyze the tumor’s molecular features on elderly patients, evaluating nucleotide hydrolysis (ATP to ADP and ADP to AMP made by CD39 and AMP to adenosine by CD73) in plasma blood as possible prognostic biomarkers and/or therapeutic targets, in order to improve these patients’ disease outcomes. Peripheral blood samples were collected from 24 BC patients with age above 60 years old at the moment of diagnosis and after 6 months of treatment, and from 15 elderly patients without cancer diagnosis. The nucleotide hydrolysis analysis of the samples from BC patients at diagnosis were related to control, prognostic factors, like Ki67, known as proliferation rate marker and the samples from the same patients after 6 months of treatment. The mean age of patients were 68 years old and about 66,6% with tumors stage I and II, and 33,3% staging III and IV, representing worse prognosis. Results showed BC patients had lower ADP and higher AMP hydrolysis when compared to control. When analyzing differences between the diagnose samples and the ones collected after 6 months, we were able to show a significant reduction on AMPase activity, making the profile of treated individuals look like the healthy individuals’, independently of which treatment was used. When comparing the hydrolysis rate with Ki67 results, where 47% of the patients presented low rate (< 20%), there was a tendency of these ones present lower AMP hydrolysis. This way, we can conclude that understanding the ectonucleotidases activity role in cancer progression can help this disease complexity understanding, looking forward to improve early detection and therapeutic approach on elderly patients.O Câncer de mama é a neoplasia mais comum e a maior causa de mortalidade entre mulheres em todo o mundo, tendo forte relação com a idade. Isso é de grande importância, uma vez que o aumento da expectativa de vida da população está relacionado diretamente ao risco de (re) aparecimento da doença. Entretanto, a população idosa é frequentemente excluída de estudos clínicos e tem seus tratamentos baseados em dados obtidos da população mais jovem, o que acaba não sendo o ideal. A etiologia do câncer de mama é multifatorial, envolvendo fatores endócrinos e reprodutivos, ambientais e, em pequena proporção, predisposição familiar. A gravidade dos tumores é definida através do seu tamanho, comprometimento nodal, presença de metástases e expressão de receptores hormonais (estrogênio e progesterona), receptores de fator de crescimento epidérmico (HER2), e a ausência de todos eles, que configura o subtipo de maior gravidade. O objetivo deste trabalho é analisar as características moleculares dos tumores nas pacientes idosas, avaliando a hidrólise dos nucleotídeos ATP a ADP e ADP a AMP, realizada pela enzima CD39, e AMP a adenosina, realizada pela CD73, como possíveis biomarcadores prognósticos e/ou alvos terapêuticos, a fim de aprimorar os desfechos da doença nesse grupo de pacientes. Foram coletadas amostras de 24 pacientes idosas (> 60 anos) do Centro de Oncologia do Hospital São Lucas da PUCRS, no momento do diagnóstico e após 6 meses de tratamento, e de 15 pacientes idosas sem diagnóstico de câncer (grupo controle). Os dados de hidrólise dos nucleotídeos das pacientes no momento do diagnóstico foram relacionados ao grupo controle, a fatores prognósticos como o índice de proliferação Ki67 e às amostras posteriores ao tratamento. A média de idade das pacientes foi de 68 anos, sendo destas, 66,6% com estágios I a II, e 33,3% com estágios III e IV, representando piores prognósticos. Os resultados demonstraram alteração na hidrólise de ADP e AMP, sendo estas menor e maior que o grupo controle, respectivamente. Com relação à comparação entre as amostras do diagnóstico e após 6 meses, houve redução significativa da hidrólise de AMP após o tratamento, ficando esta semelhante à do grupo controle, independentemente do tipo de tratamento utilizado. Na comparação com o Ki67, onde 47% apresentaram baixo índice proliferativo (Ki67 <20%), houve uma tendência dos pacientes com Ki67 alto apresentarem maior atividade AMPásica, quando comparados às amostras com Ki67 baixo. Pode-se, assim, concluir que o estudo da atividade das ectonucleotidases e o entendimento do seu papel na progressão do câncer de mama podem colaborar com a compreensão da complexidade desta doença, visando aprimorar a detecção precoce e abordagem terapêutica nas pacientes idosas.Submitted by PPG Biologia Celular e Molecular (bcm@pucrs.br) on 2021-03-30T19:31:50Z No. of bitstreams: 1 FERNANDA_VALENTE_GHELER_DIS.pdf: 2634261 bytes, checksum: 9e3449e57b249ed0fa2905215a968427 (MD5)Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2021-04-13T17:12:38Z (GMT) No. of bitstreams: 1 FERNANDA_VALENTE_GHELER_DIS.pdf: 2634261 bytes, checksum: 9e3449e57b249ed0fa2905215a968427 (MD5)Made available in DSpace on 2021-04-13T17:17:28Z (GMT). No. of bitstreams: 1 FERNANDA_VALENTE_GHELER_DIS.pdf: 2634261 bytes, checksum: 9e3449e57b249ed0fa2905215a968427 (MD5) Previous issue date: 2019-02-11Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfhttp://tede2.pucrs.br:80/tede2/retrieve/180301/FERNANDA_VALENTE_GHELER_DIS.pdf.jpgporPontifícia Universidade Católica do Rio Grande do SulPrograma de Pós-Graduação em Biologia Celular e MolecularPUCRSBrasilEscola de CiênciasCâncer de MamaPacientes IdosasSistema PurinérgicoEctonucleotidaseCD39CD73Breast CancerElderly PatientsPurinergic SystemEctonucleotidasesCD39CD73CIENCIAS BIOLOGICAS::BIOLOGIA GERALAvaliação da atividade das enzimas NTPDase 1 (CD39) e Ecto-5'Nucleotidase (CD73) no plasma de pacientes idosas com câncer de mamainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisTrabalho não apresenta restrição para publicação3463594373552466096500500600-16345593859312446973590462550136975366info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da PUC_RSinstname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)instacron:PUC_RSTHUMBNAILFERNANDA_VALENTE_GHELER_DIS.pdf.jpgFERNANDA_VALENTE_GHELER_DIS.pdf.jpgimage/jpeg5976http://tede2.pucrs.br/tede2/bitstream/tede/9541/4/FERNANDA_VALENTE_GHELER_DIS.pdf.jpg9b11e805429f82f915806569ef834408MD54TEXTFERNANDA_VALENTE_GHELER_DIS.pdf.txtFERNANDA_VALENTE_GHELER_DIS.pdf.txttext/plain130344http://tede2.pucrs.br/tede2/bitstream/tede/9541/3/FERNANDA_VALENTE_GHELER_DIS.pdf.txt1f0b93ffed04bb07c7a36b29fb902bd1MD53ORIGINALFERNANDA_VALENTE_GHELER_DIS.pdfFERNANDA_VALENTE_GHELER_DIS.pdfapplication/pdf2634261http://tede2.pucrs.br/tede2/bitstream/tede/9541/2/FERNANDA_VALENTE_GHELER_DIS.pdf9e3449e57b249ed0fa2905215a968427MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-8590http://tede2.pucrs.br/tede2/bitstream/tede/9541/1/license.txt220e11f2d3ba5354f917c7035aadef24MD51tede/95412021-04-13 20:00:20.195oai:tede2.pucrs.br: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Biblioteca Digital de Teses e Dissertaçõeshttp://tede2.pucrs.br/tede2/PRIhttps://tede2.pucrs.br/oai/requestbiblioteca.central@pucrs.br||opendoar:2021-04-13T23:00:20Biblioteca Digital de Teses e Dissertações da PUC_RS - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)false
dc.title.por.fl_str_mv Avaliação da atividade das enzimas NTPDase 1 (CD39) e Ecto-5'Nucleotidase (CD73) no plasma de pacientes idosas com câncer de mama
title Avaliação da atividade das enzimas NTPDase 1 (CD39) e Ecto-5'Nucleotidase (CD73) no plasma de pacientes idosas com câncer de mama
spellingShingle Avaliação da atividade das enzimas NTPDase 1 (CD39) e Ecto-5'Nucleotidase (CD73) no plasma de pacientes idosas com câncer de mama
Gheler, Fernanda Valente
Câncer de Mama
Pacientes Idosas
Sistema Purinérgico
Ectonucleotidase
CD39
CD73
Breast Cancer
Elderly Patients
Purinergic System
Ectonucleotidases
CD39
CD73
CIENCIAS BIOLOGICAS::BIOLOGIA GERAL
title_short Avaliação da atividade das enzimas NTPDase 1 (CD39) e Ecto-5'Nucleotidase (CD73) no plasma de pacientes idosas com câncer de mama
title_full Avaliação da atividade das enzimas NTPDase 1 (CD39) e Ecto-5'Nucleotidase (CD73) no plasma de pacientes idosas com câncer de mama
title_fullStr Avaliação da atividade das enzimas NTPDase 1 (CD39) e Ecto-5'Nucleotidase (CD73) no plasma de pacientes idosas com câncer de mama
title_full_unstemmed Avaliação da atividade das enzimas NTPDase 1 (CD39) e Ecto-5'Nucleotidase (CD73) no plasma de pacientes idosas com câncer de mama
title_sort Avaliação da atividade das enzimas NTPDase 1 (CD39) e Ecto-5'Nucleotidase (CD73) no plasma de pacientes idosas com câncer de mama
author Gheler, Fernanda Valente
author_facet Gheler, Fernanda Valente
author_role author
dc.contributor.advisor1.fl_str_mv Morrone, Fernanda Bueno
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/8543061247854357
dc.contributor.advisor-co1.fl_str_mv Cappelari, Angélica Regina
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/3186188608071919
dc.contributor.author.fl_str_mv Gheler, Fernanda Valente
contributor_str_mv Morrone, Fernanda Bueno
Cappelari, Angélica Regina
dc.subject.por.fl_str_mv Câncer de Mama
Pacientes Idosas
Sistema Purinérgico
Ectonucleotidase
CD39
CD73
topic Câncer de Mama
Pacientes Idosas
Sistema Purinérgico
Ectonucleotidase
CD39
CD73
Breast Cancer
Elderly Patients
Purinergic System
Ectonucleotidases
CD39
CD73
CIENCIAS BIOLOGICAS::BIOLOGIA GERAL
dc.subject.eng.fl_str_mv Breast Cancer
Elderly Patients
Purinergic System
Ectonucleotidases
CD39
CD73
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS::BIOLOGIA GERAL
description Breast cancer (BC) is the most common type of cancer and the biggest mortality cause among women in whole world, being strongly associated to ageing. This has a huge importance, once rise of population’s life expectancy is directly related to cancer (re) appearance risk. However, elderly population is frequently excluded from clinical trials and its treatments are based in data obtained from trials with younger population, not being ideal. This cancer’s etiology is multifactorial, evolving endocrine, reproductive and environmental factors and, less frequently, familiar predisposition. Tumor severity is defined by its size, node commitment, presence of metastasis, hormone receptors (estrogen and progesterone) and human epidermal growth factor receptor (HER2) expression, and the absence of all receptors, characterizing the most serious subtype. This study aimed to analyze the tumor’s molecular features on elderly patients, evaluating nucleotide hydrolysis (ATP to ADP and ADP to AMP made by CD39 and AMP to adenosine by CD73) in plasma blood as possible prognostic biomarkers and/or therapeutic targets, in order to improve these patients’ disease outcomes. Peripheral blood samples were collected from 24 BC patients with age above 60 years old at the moment of diagnosis and after 6 months of treatment, and from 15 elderly patients without cancer diagnosis. The nucleotide hydrolysis analysis of the samples from BC patients at diagnosis were related to control, prognostic factors, like Ki67, known as proliferation rate marker and the samples from the same patients after 6 months of treatment. The mean age of patients were 68 years old and about 66,6% with tumors stage I and II, and 33,3% staging III and IV, representing worse prognosis. Results showed BC patients had lower ADP and higher AMP hydrolysis when compared to control. When analyzing differences between the diagnose samples and the ones collected after 6 months, we were able to show a significant reduction on AMPase activity, making the profile of treated individuals look like the healthy individuals’, independently of which treatment was used. When comparing the hydrolysis rate with Ki67 results, where 47% of the patients presented low rate (< 20%), there was a tendency of these ones present lower AMP hydrolysis. This way, we can conclude that understanding the ectonucleotidases activity role in cancer progression can help this disease complexity understanding, looking forward to improve early detection and therapeutic approach on elderly patients.
publishDate 2019
dc.date.issued.fl_str_mv 2019-02-11
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