Citocinas e Óxido Nítrico Intracístico em Neoplasias Ovarianas

MARTINS FILHO, Agrimaldo

Citocinas e Óxido Nítrico Intracístico em Neoplasias Ovarianas

Detalhes bibliográficos
Autor(a) principal:	MARTINS FILHO, Agrimaldo
Data de Publicação:	2017
Tipo de documento:	Tese
Idioma:	por
Título da fonte:	Biblioteca Digital de Teses e Dissertações da UFTM
Texto Completo:	http://bdtd.uftm.edu.br/handle/tede/553
Resumo:	INTRODUÇÃO: O câncer ovariano ainda representa um grande desafio para a oncologia ginecológica e a maioria das pacientes são diagnosticadas em um estágio avançado. É uma doença heterogênea e muitos estudos indicam que a inflamação crônica é um dos mecanismos centrais na sua patogênese. Há uma necessidade no desenvolvimento de novos biomarcadores de diagnóstico e prognóstico do câncer ovariano, que podem também, idealmente, servir como alvos de novas modalidades terapêuticas. Para isso, nossos objetivos foram comparar a dosagem de citocinas (IL-2, IL-5, IL-6, IL-8, IL-10 e TNF-α) e metabólitos de óxido nítrico (NO) no líquido intracístico de tumores não neoplásicos, neoplasias benignas e malignas primárias de ovário; e relacionar a dosagem de citocinas e metabólitos de NO intracístico com parâmetros clínicos, laboratoriais e patológicos de pacientes com neoplasia maligna primária de ovário. PACIENTES E MÉTODOS: Foram avaliadas 110 pacientes com diagnóstico de massa anexial. O critério de inclusão foi diagnóstico pós-operatório de tumor não neoplásico ovariano ou neoplasia ovariana pelo anatomopatológico em parafina. A avaliação anatomopatológica e o estadiamento dos casos foram realizados de acordo com os critérios da International Federation of Gynaecology and Obstetrics – FIGO. Todos os tumores ovarianos foram submetidos à punção logo após a exérese da massa anexial. As concentrações de IL-2, IL-5, IL-6, IL-8, IL-10 e TNF-α foram quantificadas por meio de ensaio imunoenzimático (ELISA) e a quantificação do nitrato foi determinada por meio da redução enzimática do nitrito com a nitrato redutase. Os Resultados foram analisados pelo teste de Kruskal-Wallis, com pós-teste de Dunn. A avaliação dos fatores prognósticos foi realizada pelo teste de Mann Whitney. Um valor de p< 0,05 foi considerado estatisticamente significativo. RESULTADOS: Houve aumento dos níveis de IL-6, e IL-8 e NO no grupo de neoplasias malignas de ovário quando comparadas com o grupo de neoplasias benignas (p = 0,0006; p = 0,0110 e p = 0,0178, respectivamente). Houve níveis mais elevados de IL-2 nos tumores com grau histológico 1 quando comparados com grau histológico 2 e 3 (p = 0,0232). Níveis de IL- 8 foram mais altos em pacientes com Relação Neutrófilo/Linfócito (RNL) maior que 2.6 (p = 0,0433) e em pacientes com sobrevida livre da doença menor que 36 meses (p = 0,0288). Os níveis de IL-10 foram mais altos em pacientes com dosagens de CA19.9 normais (p = 0,0019). Os níveis de TNF-α foram mais altos em tumores com modelo de carcinogênese do tipo 2 (p = 0,0364) e em pacientes com Relação Plaquetas/Linfócitos (RPL) menor que 300 (p10 = 0,0420). Os níveis de NO foram mais elevados em pacientes com RNL menor que 2.6 (p = 0,0443), assim como em pacientes com CA19.9 maior que 35U/mL (p = 0,0112). CONCLUSÃO: O aumento dos valores intracísticos de algumas citocinas podem estar associados com o pior prognóstico no câncer ovariano, especialmente IL-6 e IL-8. Novos estudos com maior amostra de pacientes são necessários para confirmar o papel das citocinas como um fator de diagnóstico e prognóstico no câncer ovariano.

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spelling	Citocinas e Óxido Nítrico Intracístico em Neoplasias OvarianasCitocinas.Oxido nítrico.Fatores prognósticos.Neoplasias ovarianas.Cytokines.Nitric oxide.Prognostic factors.Ovarian neoplasms.Ciências da SaúdeINTRODUÇÃO: O câncer ovariano ainda representa um grande desafio para a oncologia ginecológica e a maioria das pacientes são diagnosticadas em um estágio avançado. É uma doença heterogênea e muitos estudos indicam que a inflamação crônica é um dos mecanismos centrais na sua patogênese. Há uma necessidade no desenvolvimento de novos biomarcadores de diagnóstico e prognóstico do câncer ovariano, que podem também, idealmente, servir como alvos de novas modalidades terapêuticas. Para isso, nossos objetivos foram comparar a dosagem de citocinas (IL-2, IL-5, IL-6, IL-8, IL-10 e TNF-α) e metabólitos de óxido nítrico (NO) no líquido intracístico de tumores não neoplásicos, neoplasias benignas e malignas primárias de ovário; e relacionar a dosagem de citocinas e metabólitos de NO intracístico com parâmetros clínicos, laboratoriais e patológicos de pacientes com neoplasia maligna primária de ovário. PACIENTES E MÉTODOS: Foram avaliadas 110 pacientes com diagnóstico de massa anexial. O critério de inclusão foi diagnóstico pós-operatório de tumor não neoplásico ovariano ou neoplasia ovariana pelo anatomopatológico em parafina. A avaliação anatomopatológica e o estadiamento dos casos foram realizados de acordo com os critérios da International Federation of Gynaecology and Obstetrics – FIGO. Todos os tumores ovarianos foram submetidos à punção logo após a exérese da massa anexial. As concentrações de IL-2, IL-5, IL-6, IL-8, IL-10 e TNF-α foram quantificadas por meio de ensaio imunoenzimático (ELISA) e a quantificação do nitrato foi determinada por meio da redução enzimática do nitrito com a nitrato redutase. Os Resultados foram analisados pelo teste de Kruskal-Wallis, com pós-teste de Dunn. A avaliação dos fatores prognósticos foi realizada pelo teste de Mann Whitney. Um valor de p< 0,05 foi considerado estatisticamente significativo. RESULTADOS: Houve aumento dos níveis de IL-6, e IL-8 e NO no grupo de neoplasias malignas de ovário quando comparadas com o grupo de neoplasias benignas (p = 0,0006; p = 0,0110 e p = 0,0178, respectivamente). Houve níveis mais elevados de IL-2 nos tumores com grau histológico 1 quando comparados com grau histológico 2 e 3 (p = 0,0232). Níveis de IL- 8 foram mais altos em pacientes com Relação Neutrófilo/Linfócito (RNL) maior que 2.6 (p = 0,0433) e em pacientes com sobrevida livre da doença menor que 36 meses (p = 0,0288). Os níveis de IL-10 foram mais altos em pacientes com dosagens de CA19.9 normais (p = 0,0019). Os níveis de TNF-α foram mais altos em tumores com modelo de carcinogênese do tipo 2 (p = 0,0364) e em pacientes com Relação Plaquetas/Linfócitos (RPL) menor que 300 (p10 = 0,0420). Os níveis de NO foram mais elevados em pacientes com RNL menor que 2.6 (p = 0,0443), assim como em pacientes com CA19.9 maior que 35U/mL (p = 0,0112). CONCLUSÃO: O aumento dos valores intracísticos de algumas citocinas podem estar associados com o pior prognóstico no câncer ovariano, especialmente IL-6 e IL-8. Novos estudos com maior amostra de pacientes são necessários para confirmar o papel das citocinas como um fator de diagnóstico e prognóstico no câncer ovariano.INTRODUCTION: Ovarian cancer still represents a major challenge for oncology gynecology and most patients are diagnosed at an advanced stage. It is a heterogeneous disease and many studies indicate that chronic inflammation is one of the main mechanisms in its pathogenesis. There is a need for the development of new biomarkers for the diagnosis and prognosis of ovarian cancer, which may ideally serve as targets for new therapeutic modalities. For this, our objectives were to compare the dosage of cytokines (IL-2, IL-5, IL-6, IL-8, IL-10 and TNF-α) and nitric oxide (NO) metabolites in non-neoplastic tumors, benign neoplasms and malignant primary ovarian neoplasms; and to relate the dosage of cytokines and intracellular NO metabolites with clinical, laboratory and pathological parameters of patients with primary ovarian malignancy. PATIENTS AND METHODS: We assessed 110 patients with an adnexal mass diagnosis. The inclusion criterion was a postoperative diagnosis of a non-neoplastic ovarian tumor or ovarian neoplasm by anatomopathological paraffin. The anatomopathological evaluation of tumors and the staging of the malignant tumors were performed according to the criteria of the International Federation of Gynaecology and Obstetrics - FIGO. All ovarian tumors underwent puncture soon after excision of the cyst. The concentrations of IL-2, IL-5, IL-6, IL- 8, IL-10 and TNF-α were quantified by enzyme-linked immunosorbent assay (ELISA) and nitrate quantification determined by enzymatic reduction of nitrite by nitrate reductase. The results were analyzed by Kruskal-Wallis test, with Dunn's post-test. The evaluation of the prognostic factors was performed by Mann Whitney test. A p-value < 0.05 was considered statistically significant. RESULTS: There was higher IL-6, IL-8 and NO levels in the ovarian malignancy group when compared to the benign neoplasm group (p = 0.0006; p = 0.0110 and p = 0.0178, respectively). There was higher IL-2 levels in tumors with histological grade 1 when compared to histological grades 2 and 3 (p = 0.0112). IL-6 levels were higher in patients with anemia (p = 0.0232). IL-8 levels were higher in patients with the Neutrophil/Lymphocyte Ratio (NLR) greater than 2.6 (p = 0.0443), and in patients with disease-free survival less than 36 months (p = 0.0288). IL-10 levels were higher in patients with normal CA 19.9 (p = 0.0019). TNF-α levels were higher in tumors with Type 2 carcinogenesis model (p = 0.0364), and in patients with Platelet/Lymphocyte Ratio (PLR) less than 300 (p = 0.0420). NO levels were higher in patients with NLR less than 2.6 (p = 0.0443), as well as in patients with CA 19.9 greater than 35 U/mL (p = 0.0112).12 CONCLUSION: Higher intracystic values of some cytokines are associated with worse prognostic factors in ovarian cancer, especially IL-6 and IL-8. Further studies with a larger sample of patients are needed to confirm the role of cytokines as diagnostic and prognostic factors.Conselho Nacional de Desenvolvimento Científico e TecnológicoFundação de Amparo à Pesquisa do Estado de Minas GeraisFundação de Ensino e Pesquisa de UberabaUniversidade Federal do Triângulo MineiroInstituto de Ciências da Saúde - ICS::Curso de MedicinaBrasilUFTMPrograma de Pós-Graduação em Ciências da SaúdeNOMELINI, Rosekeila Simões03651235602http://lattes.cnpq.br/0564643325267326MURTA, Eddie Fernando Cândido47668632649http://lattes.cnpq.br/5724192420139830MARTINS FILHO, Agrimaldo2018-05-03T17:44:31Z2017-08-22info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfapplication/pdfMARTINS FILHO, Agrimaldo. Citocinas e Óxido Nítrico Intracístico em Neoplasias Ovarianas. 2017. 129f. 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dc.title.none.fl_str_mv	Citocinas e Óxido Nítrico Intracístico em Neoplasias Ovarianas
title	Citocinas e Óxido Nítrico Intracístico em Neoplasias Ovarianas
spellingShingle	Citocinas e Óxido Nítrico Intracístico em Neoplasias Ovarianas MARTINS FILHO, Agrimaldo Citocinas. Oxido nítrico. Fatores prognósticos. Neoplasias ovarianas. Cytokines. Nitric oxide. Prognostic factors. Ovarian neoplasms. Ciências da Saúde
title_short	Citocinas e Óxido Nítrico Intracístico em Neoplasias Ovarianas
title_full	Citocinas e Óxido Nítrico Intracístico em Neoplasias Ovarianas
title_fullStr	Citocinas e Óxido Nítrico Intracístico em Neoplasias Ovarianas
title_full_unstemmed	Citocinas e Óxido Nítrico Intracístico em Neoplasias Ovarianas
title_sort	Citocinas e Óxido Nítrico Intracístico em Neoplasias Ovarianas
author	MARTINS FILHO, Agrimaldo
author_facet	MARTINS FILHO, Agrimaldo
author_role	author
dc.contributor.none.fl_str_mv	NOMELINI, Rosekeila Simões 03651235602 http://lattes.cnpq.br/0564643325267326 MURTA, Eddie Fernando Cândido 47668632649 http://lattes.cnpq.br/5724192420139830
dc.contributor.author.fl_str_mv	MARTINS FILHO, Agrimaldo
dc.subject.por.fl_str_mv	Citocinas. Oxido nítrico. Fatores prognósticos. Neoplasias ovarianas. Cytokines. Nitric oxide. Prognostic factors. Ovarian neoplasms. Ciências da Saúde
topic	Citocinas. Oxido nítrico. Fatores prognósticos. Neoplasias ovarianas. Cytokines. Nitric oxide. Prognostic factors. Ovarian neoplasms. Ciências da Saúde
description	INTRODUÇÃO: O câncer ovariano ainda representa um grande desafio para a oncologia ginecológica e a maioria das pacientes são diagnosticadas em um estágio avançado. É uma doença heterogênea e muitos estudos indicam que a inflamação crônica é um dos mecanismos centrais na sua patogênese. Há uma necessidade no desenvolvimento de novos biomarcadores de diagnóstico e prognóstico do câncer ovariano, que podem também, idealmente, servir como alvos de novas modalidades terapêuticas. Para isso, nossos objetivos foram comparar a dosagem de citocinas (IL-2, IL-5, IL-6, IL-8, IL-10 e TNF-α) e metabólitos de óxido nítrico (NO) no líquido intracístico de tumores não neoplásicos, neoplasias benignas e malignas primárias de ovário; e relacionar a dosagem de citocinas e metabólitos de NO intracístico com parâmetros clínicos, laboratoriais e patológicos de pacientes com neoplasia maligna primária de ovário. PACIENTES E MÉTODOS: Foram avaliadas 110 pacientes com diagnóstico de massa anexial. O critério de inclusão foi diagnóstico pós-operatório de tumor não neoplásico ovariano ou neoplasia ovariana pelo anatomopatológico em parafina. A avaliação anatomopatológica e o estadiamento dos casos foram realizados de acordo com os critérios da International Federation of Gynaecology and Obstetrics – FIGO. Todos os tumores ovarianos foram submetidos à punção logo após a exérese da massa anexial. As concentrações de IL-2, IL-5, IL-6, IL-8, IL-10 e TNF-α foram quantificadas por meio de ensaio imunoenzimático (ELISA) e a quantificação do nitrato foi determinada por meio da redução enzimática do nitrito com a nitrato redutase. Os Resultados foram analisados pelo teste de Kruskal-Wallis, com pós-teste de Dunn. A avaliação dos fatores prognósticos foi realizada pelo teste de Mann Whitney. Um valor de p< 0,05 foi considerado estatisticamente significativo. RESULTADOS: Houve aumento dos níveis de IL-6, e IL-8 e NO no grupo de neoplasias malignas de ovário quando comparadas com o grupo de neoplasias benignas (p = 0,0006; p = 0,0110 e p = 0,0178, respectivamente). Houve níveis mais elevados de IL-2 nos tumores com grau histológico 1 quando comparados com grau histológico 2 e 3 (p = 0,0232). Níveis de IL- 8 foram mais altos em pacientes com Relação Neutrófilo/Linfócito (RNL) maior que 2.6 (p = 0,0433) e em pacientes com sobrevida livre da doença menor que 36 meses (p = 0,0288). Os níveis de IL-10 foram mais altos em pacientes com dosagens de CA19.9 normais (p = 0,0019). Os níveis de TNF-α foram mais altos em tumores com modelo de carcinogênese do tipo 2 (p = 0,0364) e em pacientes com Relação Plaquetas/Linfócitos (RPL) menor que 300 (p10 = 0,0420). Os níveis de NO foram mais elevados em pacientes com RNL menor que 2.6 (p = 0,0443), assim como em pacientes com CA19.9 maior que 35U/mL (p = 0,0112). CONCLUSÃO: O aumento dos valores intracísticos de algumas citocinas podem estar associados com o pior prognóstico no câncer ovariano, especialmente IL-6 e IL-8. Novos estudos com maior amostra de pacientes são necessários para confirmar o papel das citocinas como um fator de diagnóstico e prognóstico no câncer ovariano.
publishDate	2017
dc.date.none.fl_str_mv	2017-08-22 2018-05-03T17:44:31Z
dc.type.status.fl_str_mv	info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv	info:eu-repo/semantics/doctoralThesis
format	doctoralThesis
status_str	publishedVersion
dc.identifier.uri.fl_str_mv	MARTINS FILHO, Agrimaldo. Citocinas e Óxido Nítrico Intracístico em Neoplasias Ovarianas. 2017. 129f. Tese (Mestrado em Ciências da Saúde) - Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal do Triângulo Mineiro, Uberaba, 2017. http://bdtd.uftm.edu.br/handle/tede/553
identifier_str_mv	MARTINS FILHO, Agrimaldo. Citocinas e Óxido Nítrico Intracístico em Neoplasias Ovarianas. 2017. 129f. Tese (Mestrado em Ciências da Saúde) - Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal do Triângulo Mineiro, Uberaba, 2017.
url	http://bdtd.uftm.edu.br/handle/tede/553
dc.language.iso.fl_str_mv	por
language	por
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Citocinas e Óxido Nítrico Intracístico em Neoplasias Ovarianas

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