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. 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/553porABBAS, A. K.; LICHTMAN, A. H.; POBER, J. S. In: ABBAS, A. K. Imunologia celular e molecular. [Tradução de Claudia Reali e outros] 6ª ed. Rio de Janeiro: Elsevier, 2008. AGGARWAL, B.B.; SHISHODIA. S.; SANDUR, S.K. et al. Inflammation and cancer: how hot is the link? Biochem. Pharmacol., Oxford, v. 72, n. 11, p. 1605-1621, 2016. AGARWAL, R.; KAYE, S. B. Prognostic factors in ovarian cancer: how close are we to a complete picture? Ann. Oncol., Dordrecht, v. 16, n. 1, p. 4-6, 2005. AKAHIRO, J.; KONNO, R.; ITO, K. et al. Impact of serum interleukin-18 level as a prognostic indicator in patients with epithelial ovarian carcinoma. Int. J. Clin. Oncol., Tokyo, v. 9, n. 1, p. 42-46, 2004. AKAIKE, T.; MAEDA, H. Nitric oxide and virus infection. Immunology, Oxford, v. 101, n. 3, p. 300-308, 2000. ALDERTON, W.K,; COOPER, C.E.; KNOWLES, R.G. Nitric oxide synthases: structure, function and inhibition. Biochem. J., London, v. 357, n. 3, p. 593-615, 2001. ALI-FEHMI, R; SEMAAN, A; SETHI, S. et al. Molecular typing of epithelial ovarian carcinomas using inflammatory markers. Cancer, Philadelphia, v. 117, n. 2, p. 301-309. 2011 AMBS, S.; BENNETT, W.P.; MERRIAM, W.G. et al. Vascular endothelial growth factor and nitric oxide synthase expression in human lung cancer and the relation to p53. Br. J. Cancer., London, v. 78, n. 2, p. 233-239, 1998. ANDERSON, G.M.; NAKADA, M.T.; DeWITTE, M. Tumor necrosis factoralpha in the pathogenesis and treatment of cancer. Curr. Opin. Pharmacol., Oxford, v. 4, p. 3014-320, 2004. ASHER, V.; LEE, J.; INNAMAA, A. et al. Preoperative platelet lymphocyte ratio as an independent prognostic marker in ovarian cancer. Clin. Transl. Oncol., Barcelona, v. 13, n. 7, p. 499-503, 2011. ATHANASSIADOU, P.; GRAPSA, D.; ATHANASSIADES, P. et al. The prognostic significance of COX-2 and survivin expression in ovarian cancer. Pathol. Immunopathol. Res., Basel, v. 204, n. 4, p. 241-249, 2008. AUNE, G.; STUNES, A.K.; LIAN, A.M. et al. Circulating interleukin-8 and plasminogen activator inhibitor-1 are increased in women with ovarian carcinoma. Results Immunol., Oxford, v. 2, p, 190-195, 2012. BAGGIOLINI, M.; DEWALD, B.; MOSER, B. Interleukin 8 and related chemotactic cytokines – CXC and CC chemokines. Adv Immunol., New York, v. 55, p. 97-179. 1994. BALKWILL, F.; MANTOVANI, A. Inflammation and cancer: back to Virchow? Lancet, London, n. 9255, p. 539-545, 2001. BALKWILL, F. TNF-alpha in promotion and progression of cancer. Cancer Metastasis Rev., Boston, v. 25, n. 3, p. 409-416, 2006. BAMIAS, A.; TSIATAS, M. L.; KAFANTARI, E. Significant differences of lymphocytes isolated from ascites of patients with ovarian cancer compared to blood and tumor lymphocytes. Association of CD3+CD56+ cells with platinum resistance. Gynecol. Oncol., New York, v. 106, p. 75-81, 2007 BECHT, E. L. M. K.; BONAVIDA, B. Inhibitory effects of 17β-estradiol and progesterone on avarian carcinoma cell proliferation: a potencial role for inducible nitric oxide synthase. Gynecol. Oncol., New York, v. 82, n. 1, p. 127-138, 2001. BECKER, H.M.G.; GUIMARÃES, R.E.S.; NASCIMENTO, E. et al. Perfil de citocinas e tipificação de hla em pacientes com polipose nasossinusal tolerantes e intolerantes a aspirina. Rev. Bras. Otorrinolaringol., São Paulo, v. 69, n. 3, 2003. BELISLE, J.A.; GUBBELS, J.A.; RAPHAEL, C.A. et al. Peritoneal natural killer cells from epithelial ovarian cancer patients show an altered phenotype and bind to the tumour marker MUC16 (CA125). Immunology, v. 122, n. 3, p. 418-429, 2007. BELLATI, F.; VISCONTI, V.; NAPOLETANO, C. et al. Immunology of gynecologic neoplasms: analysis of the prognostic significance of the immune status. Curr. Cancer Drug Targets, Amarillo, v. 9, p. 541-565, 2009. BELLONE, S.; WATTS, K.; CANE', S. et al. High serum levels of interleukin-6 in endometrial carcinoma are associated with uterine serous papillary histology, a highly aggressive and chemotherapy-resistant variant of endometrial cancer. Gynecol. Oncol., New York, v. 98, n. 1, p. 92-98, 2005. BENJAMIM, C.F.; FERREIRA, S.H.; CUNHA, F.Q. Role of Nitric Oxide in the Failure of Neutrophil Migration in Sepsis. Jurnal Infect. Dis., Oxford, v. 182, p. 214- 223, 2000. BENJAMIN, D.; KNOBLOCK, T.J.; DAYTON, M.A. Human B cell interleukin-10 cell lines derived from patients with acquired immunodeficiency syndrome and Burkitt’s lymphoma constitutively secrete large quantities of interleukine-10. Blood, v. 80, n. 5, p. 1289-1298, 1992. BERTAZZA, L.; MOCELLIN, S. Tumor necrosis factor (TNF) biology and cell death. Front. biosci., Tampa, v. 13, p. 2736-2743, 2008. BISHARA, S.; GRIFFIN, M.; CARGILL, A. et al. Pre-treatment white blood cell subtypes as prognostic indicators in ovarian cancer. Eur. J. Obstet. Gynecol. Reprod. Biol., Amsterdam, v. 138, p. 71-75, 2008. BHOOLA, S.; HOSKINS, W. J. Diagnosis and management of epithelial ovarian cancer. Obstet. Gynecol., New York, v. 107, p. 1.399-1.410, 2006. BOGLIOLO, L., 1908-1981. Bogliolo, Patologia / [editor] Geraldo Brasileiro Filho. 8ªed. Rio de Janeiro: Guanabara Koogan, 2011. BOULTON, S.J. Cellular functions of the BRCA tumour-suppressor proteins. Biochem. Soc. Trans., London, v. 34, n. 5, p. 633-645, 2006. BRAGA, A. C. S. Pacientes oncológicos:a influência do câncer no estado emocional e a concepção de finitude. Monografia não publicada. Curso de Graduação em Psicologia, Centro Universitário de João Pessoa. João Pessoa, PB, 2005. BREWER, M. A. et. al. Prevection of varian cancer: intraepithelial neoplasia. Clin. Cancer Res., Philadelphia, v. 9, p. 20-30, 2003. BRUNETTI, G.; BOSSI, A.; BAIARDI, P. et al. Soluble interleukin 2 receptor (sIL-2R) in monitoring advanced lung cancer during chemotherapy. Lung Cancer, Limerick, v. 23, n. 1 p. 1-9, 1999. BULUT, A.S.; ERDEN, E.; SAK, S.D. et al. Significance of inducible nitric oxide synthase expression in benign and malignant breast epithelium: an immunohistochemical study of 151 cases. Virchows Arch., Berlin, v. 447, n. 1, p. 24- 30, 2005. BURKE, A.J.; SULLIVAN, F.J.; GILES, F.J. et al. The yin and yang of nitric oxide in cancer progression, Carcinogenesis, Oxford, v. 34, p. 503-512, 2013. BUTTERY, L.D.; SPRINGALL, D.R.; ANDRADE, S.P. et al. Induction of nitric oxide synthase in the neo-vasculature of experimental tumours in mice. J. Pathol., Edinburgh, v. 171, n. 4, p. 311-9, 1993. CANNISTRA, S. A. Cancer of the ovary. N. Engl. J. Med., Boston, v. 351, n. 24, p. 2519-2529, 2004. CASAGRANDE, J. T.; LOUIE, E.W.; PIKE, M.C. et al. Incessant ovulation and ovarian cancer. Lancet, London, v. 2, n. 8135, p. 170-173, 1979. CHARLES, K.A.; KULBE, H.; SOPER, R. et al. The tumor-promoting actions of TNF- α involve TNFR1 and IL-17 in ovarian cancer in mice and humans. J. Clin. Invest., New York, v. 119, n. 10, p. 3011-3023, 2009. CHENG, H.; WANG, L.; MOLLICA, M. et al. Nitric oxide in câncer metastasis, Cancer Lett. Virginia, v. 353, p. 1-7, 2014. CHERCHI, P. L.; CAPOBIANCO, G.; AMBROSINI, G. et al. Intracystic evaluation of tumor markers in benign and malignant ovarian pathology. Eur. J. Gynaecol. Oncol., Montreal, v. 23, p. 163-165, 2002. CHO, H.; HUR, H.W.; KIM, S.W. et al. Pre-treatment neutrophil to lymphocyte ratio is elevated in epithelial ovarian cancer and predicts survival after treatment. Cancer Immunol. Immunother., New York, v. 58, p. 15-23, 2009. CHOBANIAN, N.; DIETRICH, C. Ovarian Cancer. Surg. Oncol. Clin. N. Am., Philadelphia, v. 88, p. 285-299, 2008. CIANFRANI, T. A short history of obstetrics and gynecology. Springfield: CC Thomas, 1960. COBBS, C.S.; BRENMAN, J.E.; ALDAPE, K.D. et al. Expression of nitric oxide synthase in human central nervous system tumors. Cancer Res., Baltimore, v. 55, n. 4, p. 727-30, 1995. CORMIO, G.; ROSSI, C.; CAZZOLLA, A. et al. Distant metastasis in ovarian carcinoma. Int. J. Gynecol. Cancer, Cambridge, v. 13, n. 2, p. 125-129, 2003. CLUTTERBUCK, E.; SHIELDS, J.G.; GORDON, J. et al. Recombinant human interleukin 5 is an eosinophil differentiation factor but has no activity in standard human B cell growth factor assays. Eur. J. Immunol., Weinheim, v. 17, n. 12, p. 1743-1750, 1987. CURIEL, T.J.; COUKOS, G.; ZOU, L. et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat. Med., New York, v. 10, n. 9, p. 942-949, 2004. DACHS, G.U.; TOZER, G.M. Hypoxia modulated gene expression: Angiogenesis, metastasis and therapeutic exploitation. Eur. J. Cancer, Oxford, v. 36, n. 13, p. 1649- 1660, 2000. DALTOÉ, R.D.; SILVA, I.V.; PAULA, A.D. et al. O papel paradoxal do sistema imune no câncer de ovário. ACM: arquivos catarinenses de medicina, Florianópolis, v. 39, n. 2, p. 87-92, 2010. DEUTSCH, M.; BECK, D.; MANOR, D. et al. Metastatic brain tumor following negative second-look operation for ovarian carcinoma. Gynecol. Oncol., New York, v. 27, n. 1, p. 116-20, 1987. DIAZ OREA, M.A.; MUÑOZ PEREZ, V.; GÓMEZ CONDE, E. et al. Expression of Cytokines Interleukin-2, Interleukin-4, Interleukin-10 and Transforming Growth Factor β in Gastric Adenocarcinoma Biopsies Obtained from Mexican Patients. Asian Pac. J. Cancer Prev., Bangkok, v. 18, n. 2 p. 577-582, 2017. DOBRZYCKA, B.; MACKOWIAK-MATEJCZYK, B.; TERLIKOWSKA, K.M. et al. Serum levels of IL-6, IL-8 and CRP as prognostic factors in epithelial ovarian cancer. Eur. Cytokine Netw., Montrouge, v. 24, p. 106-113, 2013. DOBRZYCKA, B.; TERLIKOWSKI, S.J.; KOWALCZUK, O. et al. Circulating levels of TNF-α and its soluble receptors in the plasma of patients with epithelial ovarian cancer. Eur. Cytokine Netw., 2009, v. 20, n. 3, p. 131-134, 2009. DØRUM, A.; KRISTENSEN, G.B.; ABELER, V.M. et al. Early detection of familial ovarian cancer. Eur. J. Cancer, Oxford, v. 32, p. 1645-1651, 1996. DOTLIĆ, J.; TERZIĆ, M.; LIKIĆ, I. et al. Evaluation of adnexal masses: correlation between 39 clinical, ultrasound and histopathological findings. Vojnosanit Pregl., Belgrade, v. 68, n. 10, p. 861-866, 2011. EARLE, C.C.; SCHRAG, D.; NEVILLE, B.A. et al. Effect of surgeon specialty on processes of care and outcomes for ovarian cancer patients. J. Natl. Cancer Inst., Cary, v. 98, n. 3, p. 172-180, 2006. El-SEHEMY, A.; POSTOVIT, L.M.; FU, Y.X. Nitric oxide signaling in human ovarian cancer: a potencial therapeutic target. Nitric Oxide, Orlando, v. 54, p. 30-37. 2016. ELLYARD, J.I.; SIMSON, L.; PARISH, C.R. Th2-mediated anti-tumour immunity: friend or foe? Tissue Antigens, Copenhagen, v. 70, p 1-11, 2007. ENGELS, K.; DU BOIS, A.; HARTER, P. et al. VEGF-A and i-NOS expression are prognostic factors in serous epithelial ovarian carcinomas after complete surgical resection. J. Clin. Pathol., London, v. 62, p. 448-454, 2009. FAIRFIELD, K.M.; HANKINSON, S.E.; ROSNER, B.A. et al. Risk of ovarian carcinoma 16 and consumption of vitamins A, C and E and specific carotenoids: a prospective analysis. 17 Cancer. v.92, n.9, p.2318-2326, 2001. FATHALLA, M. F. Incessant ovulation: a factor in ovarian neoplasia? Lancet, v. 2, m. 7716, p. 163, 1971. FELDMAN, G. B.; KNAPP, R. C. Lymphatic drainage of the peritoneal cavity and its significance in ovarian cancer. Am. J. Obstet. Gynecol., St. Louis, v. 119, n. 7, p. 991- 994, Aug. 1974. FERLAY, J.; SOERJOMATARAM, I.; ERVIK, M. et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Disponível em <http://globocan.iarc.fr> Acesso em: 04/05/2017. FISHMAN, D.A.; COHEN, L.; BLANK, S.V. et al. The role of ultrasound evaluation in the detection of early-stage epithelial ovarian cancer. Am. J. Obstet. Gynecol., St. Louis, v. 192, p. 1214-1222, 2005. FLEMING, J.S.; BEAUGIÉ, C.R.; HAVIV, I. at al. Incessant ovulation, inflammation and epithelial ovarian carcinogenesis: revisiting old hypotheses. Mol. Cell Endocrinol., Limerick, v. 247, n. 1-2, p. 4-21, 2006. FLORES, M.D.; ORTEGA-CAMARILLO, C.; ROSALES-TORRES, A.M. et al. El oxido nítrico como principal efector del sistema de la interleucina-1 em la ovulacion. Gac. Mex., Cidad del Mexico, v. 137, n. 4, 2001. FREEDMAN, R.S.; DEAVERS, M.; LIU, J. et al. Peritoneal inflammation - a microenvironment for Epithelial Ovarian Cancer (EOC). J. Transl. Med., London, v. 2, p. 23, 2004. FRIDMAN, W.H.; GALON, J.; DIEU-NOSJEAN, M.C. et al. Immune infiltration in human cancer: prognostic significance and disease control. Curr. Top Microbiol. Immunol., Berlin, v. 344, p. 1-24, 2011. FUKUMURA, D.; KASHIWAGI, S.; JAIN, R.K. The role of nitric oxide in tumour progression. Nat. Rev. Cancer, London, p. 521-534, 2006. GADDUCCI, A.; COSIO, S.; TANA, R. et al. Serum and tissue biomarkers as predictive and prognostic variables in epithelial ovarian cancer. Crit. Rev. Oncol. Hematol., Boca Raton, v. 69, p. 12-27, 2009. GADDUCCI, A.; FERDEGHINI, M.; MALAGNINO, G. et al. Elevated serum levels of neopterin and soluble interleukin-2 receptor in patients with ovarian cancer. Gynecol. Oncol., New York, v. 52, n. 3, p. 386-391, 1994. GALON, J.; COSTES, A.; SANCHEZ-CABO, F. et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science, Washington, v. 313, n. 5795, p. 1960-1964, 2006. GAVALAS, N.G.; KARADIMOU, A.; DIMOPOULOS, M.A. et al. Immune Response in Ovarian Cancer: How Is the Immune System Involved in Prognosis and Therapy: Potential for Treatment Utilization. Clin. dev. immunol., Abingdon, ID 791603, 15 pages, 2010. GEBAUER, G.; RIEGER, M.; JÄGER, W. et al. Prognostic relevance of soluble interleukin-2 receptors in patients with ovarian tumors. Anticancer Res., Athens, v. 19, n. 4A, p. 2509-2511, 1999. GEOMINI, P.; KRUITWAGEN, R.; BREMER, G.L. et al. The accuracy of risk scores in predicting ovarian malignancy: a systematic review. Obstet. Gynecol., Hagerstown, v. 113, p. 384-394, 2009. GOFF, B.A.; MANDEL, L.; MUNTZ, H.G. at al. Ovarian carcinoma diagnosis. Cancer, Philadelphia, v. 89, n. 10, p. 2068-2075, 2000. GOPINATHAN, G.; MILAGRE, C.; PEARCE, O.M.T. et al. Interleukin-6 stimulates defective angiogenesis. Cancer research., Baltimore, v. 75, n. 15, p. 3098-3107, 2015. GUERRIERO, S.; AJOSSA, S.; GARAU, N. et al. Ultrasonography and Color Dopplerbased triage for adnexal masses to provide the most appropriate surgical approach. Am. J. Obstet. Gynecol., St. Louis, v. 192, p. 401-406, 2005. GREEN, L.C.; RUIZ DE LUZURIAGA, K.; WAGNER, D.A. et al. Nitrate biosynthesis in man. Proc. Natl. Acad. Sci. U. S. A., Washington, v. 78, n. 12, p. 7764-7768, 1981. GRIMM, E.A.; WILSON, D.J.; ROSENBERG, S.A. Lymphokine-activated killer cell phenomenon. II The precursor phenotype is serologically distinct from peripheral T lymphocytes, memory CTL, and NK cells. Exp. Med., Córdoba, v. 157, p. 884, 1983. HAGEMANN, T.; WILSON, J.; BURKE, F. et al. Ovarian cancer cells polarize macrophages toward a tumor-associated phenotype. J. Immunol., Baltimore, v. 176, n. 8, p. 5023-5032, 2006. HACKER, N.F.; BEREK, J.S.; LAGASSE, L.D. et al. Primary cytoreductive surgery for epithelial ovarian cancer. Obstet. Gynecol., Hagerstown, v. 61, n. 4, p. 413-420, 1983. HAGEMANN, A.R.; HAGEMANN, I.S.; CADUNGOG, M. et al. Tissue-based immune monitoring II: Multiple tumor sites reveal immunologic homogeneity in serous ovarian carcinoma. Cancer Biol. Ther., Georgetown, v. 12, n. 4, p. 367-377, 2011. HAO, X.P.; PRETLOW, T.G.; RAO, J.S. et al. Inducible nitric oxide synthase (iNOS) is expressed similarly in multiple aberrant crypt foci and colorectal tumors from the same patients. Cancer Res., Baltimore, v. 61, n. 2, p. 419-422, 2001. HAMBLIN, A. S. Cytokines and cytokine receptors. 2. ed. New York: Oxford University Press, 1993. HATAKEYAMA, M.; TSUDI, M.; MINAMOTO, S. et al. Interleukin 2 receptor beta chain gene: generation of the three receptor forms by cloned human alpha and beta chain DNAs. Science, London, v. 244, p. 551-556, 1989. HEINRICH, P.C.; CASTELL, J.V.; ANDUS, T. Interleukin-6 and the acute phase response. Biochem J., London, v. 265, n. 3, p. 621-636, 1990. HELAL, TEL-A; ALLA, A.E.; LABAN, M.A. et al. Immunophenotyping of tumor-infiltrating mononuclear cells in ovarian carcinoma. Pathol Oncol Res., Budapest, v. 10, n. 2, p. 80-4, 2004. HENNESSY, B. T.; COLEMAN, R. L.; MARKMAN, M. Ovarian cancer. Lancet, London, v. 374, p. 1374-1382, 2009. HIRASHIMA, K.; WATANABE, M.; SHIGAKI, H. et al. Prognostic significance of the modified Glasgow prognostic score in elderly patients with gastric cancer. J. Gastroenterol., Tokyo, v. 49, p. 1040-1046, 2014. HOLSCHNEIDER, C. H., BEREK, J. S. Ovarian cancer: epidemiology, biology, and prognostic factors. Semin. Surg. Oncol., New York, v. 19, p. 3-10, 2000. HONN, K.V.; TANG, D.G.; CRISSMAN, J.D. Platelets and cancer metastasis: a causal relationship? Cancer Metastasis Rev., Boston, v. 11, p. 325-51, 1992. HUANG, S.; MILLS, L.; MIAN, B. et al. Fully humanized neutralizing antibodies to interleukin-8 (ABX-IL-8) inhibit angiogenesis, tumor growth, and metastasis of human melanoma. Am. J. Pathol., New York, v. 161, n. 1, p. 125-134, 2002. IGNARRO, L. Nitric oxide biology and pathobiology. New York: Academic Press, 2000. INCA - Instituto Nacional de Câncer José Alencar Gomes da Silva. Ministério da Saúde - Rio de Janeiro, Brasil. Coordenação de Prevenção e Vigilância. Estimativa 2016 - Incidência de câncer no Brasil. INCA, 2015. Disponível em: <http://www.inca.gov.br/estimativa/2016/estimativa-2016-v11.pdf>. Acesso em: 11/04/2017. INCA - Instituto Nacional de Câncer José Alencar Gomes da Silva. Ministério da Saúde - Rio de Janeiro, Brasil. ABC do câncer: abordagens básicas para o controle do câncer. INCA, 2011. Disponível em < http://bvsms.saude.gov.br/bvs/publicacoes/abc_do_cancer.pdf>. Acesso em: 17/08/2016. INGERSOLL, S.B.; PATEL, S.; CABALLERO, L. et al. Synergistic cytotoxicity of interferonalpha-2b and interleukin-2 in combination with PBMC against ovarian cancer: development of an experimental model for cellular therapy. Gynecol. Oncol., New York, v. 112, n. 1, p. 192-198, 2009. ISCHIROPOULOS, H.; BECKMAN, J.S. Oxidative stress and nitration in neurodegeneration: Cause, effect, or association? J. Clin. Invest., New York, v. 111, n. 2, p. 163-169, 2003. KAIJSER, J.; BOURNE, T.; VALENTIN, L. et al. Improving strategies for diagnosing ovarian cancer: a summary of the International Ovarian Tumor Analysis (IOTA) studies. Ultrasound. Obstet. Gynecol., Carnforth, v. 41, p. 9-20, 2013. KAMINUMA, O.; MORI, A.; KITAMURA, N. et al. Role of GATA-3 in IL-5 gene transcription by CD4+ T cells of asthmatic patients. Int. arch. allergy immunol., Besel, v. 137, Suppl 1, p, 55-59, 2005. KASSIM, S.K.; EL-SALAHY, E.M.; FAYED, S.T. et al. Vascular endothelial growth factor and interleukin-8 are associated with poor prognosis in epithelial ovarian cancer patients. Clin. Biochem., Toronto, v. 37, n. 5, p. 363-369, 2004. KEHOE, S.; POWELL, J.; WILSON, S. et al. The influence of the operating surgeon's specialization on patients survival in ovarian carcinoma. Br. J. Cancer, London, v. 70, p. 1014-1017, 1994. KISIELEWSKI, R.; TOŁWIŃSKA, A.; MAZUREK, A. et al. Inflammation and ovarian cancer-current views. Ginekol. Pol., Warsaw, v. 84, n. 4, p. 293-297, 2013. KLEINERT, H.; SCHWARZ, P.M.; FORSTERMANN, U. Regulation of the expression of inducible nitric oxide synthase. Biol. Chem., Berlin, v. 384, n. 10-11, p. 1343-1364, 2003. KLOTZ, T.; BLOCH, W.; VOLBERG, C. et al. Selective expression of inducible nitric oxide synthase in human prostate carcinoma. Cancer, Philadelphia, v. 82, n. 10, p. 1897-1903, 1998. KÖBEL, M.; KALLOGER, S.E.; BOYD, N. et al. Ovarian carcinoma subtypes are different 5 diseases: implications for biomarker studies. PLOS Medicine, v. 5, n. 12, p. 1749-1760, 2008. KOVACS, E. The serum levels of IL-12 and IL-16 in cancer patients. Relation to the tumour stage and previous therapy. Biomed. Pharmacother., Paris, v. 55, p. 111-116, 2001. KOZŁOWSKI, L.; ZAKRZEWSKA, I.; TOKAJUK, P. et al. Concentration of interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-10 (IL-10) in blood serum of breast cancer patients. Rocz. Akad. Med. Bialymst., Bialystok, v. 48, p. 82-84, 2003. KULBE, H.; CHAKRAVARTY, P.; LEINSTER, D.A. et al. A dynamic inflammatory cytokine network in the human ovarian cancer microenvironment. Cancer Res., Baltimore, v. 72, n. 1, p. 66-75, 2012. KURIAN, A.W.; BALISE, R.R.; MCGUIRE, V. et al. Histologic types of epithelial ovarian cancer: have they different risk factors? Gynecol. Oncol., New York, v. 96, n. 2, p. 520-530, 2005. KURMAN RJ, SHIH IeM. The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am. J. Surg. Pathol., New York, v. 34, n. 3, p. 433-443, 2010. KURMAN, R.J.; SHIH IeM. Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer shifting the paradigm. Hum. Pathol., Philadelphia, v. 42, n. 7, p. 918-931, 2011. KUSUDA, T.; SHIGEMASA, K.; ARIHIRO, K. et al. Relative expression levels of Th1 and Th2 cytokine mRNA are independent prognostic factors in patients with ovarian cancer. Oncol. Rep., Atenas, v. 13, p. 1153-1158, 2005. KRISTJÁNSDÓTTIR, B.I.; PARTHEEN, K.; FUNG, E.T. et al. Early inflammatory response in epithelial ovarian tumor cyst fluids. Cancer Med., Oxford, v. 3, p. 1302- 1312, 2014. LALA, P.K.; CHAKRABORTY, C. Role of nitric oxide in carcinogenesis and tumour progression. Lancet Oncol., London, v. 2, n. 3, p. 149-156, 2001. LAMKIN, D.M.; LUTGENDORF, S.K.; MCGINN, S. et al. Positive psychosocial factors and NKT cells in ovarian cancer patients. Brain Behav. Immun., San Diego, v. 22, n. 1, p. 65-73, 2008. LEROUX, P.D., BERGER, M.S.; ELLIOTT, J.P. et al. Cerebral metastases from ovarian carcinoma. Cancer, New York, v. 67, n. 8, p. 2194-2199, Apr. 1991. LI, J.; FADARE, O.; XIANG, L. et al. Ovarian serous carcinoma: recent concepts on its origin and carcinogenesis. J. Hematol. Oncol., London, v. 5, p. 8, 2012. LIAO, W.; LIN, J.X.; LEONARD, W.J. IL-2 family cytokines: new insights into the complex roles of IL-2 as a broad regulator of T helper cell differentiation. Curr. Opin. Immunol., Philadelphia, v. 23, n. 5, p. 598-604, 2011. LILIAC, L.; AMALINEI, C.; BALAN, R. et al. Ovarian cancer: insights into genetics and pathogeny. Histol. Histopathol., Murcia, v. 27, n. 6, p. 707-719, 2012.106 LISSONI, P.; BARNI, S.; ROVELLI, F. et al. The biological significance of soluble interleukin-2 receptors in solid tumors. Eur. J. Cancer, Oxford, v. 26, n. 1, p. 33-36, 1990. LIU, C.Z.; ZHANG, L.; CHANG, X.H. et al. Overexpression and immunosuppressive functions of transforming growth factor 1, vascular endothelial growth factor and interleukin-10 in epithelial ovarian cancer. Chin. J. Cancer Res., HongKong, v. 24, n. 2, p. 130-137, 2012. LO, C.W.; CHEN, M.W.; HSIAO, M. et al. IL-6 trans-signaling in formation and progression of malignant ascites in ovarian cancer. Cancer Res., Baltimore, v. 71, n. 2, p. 424-434, 2011. LOKSHIN, A.E.; WINANS, M.; LANDSITTEL, D. et al. Circulating IL-8 and anti-IL- 8 autoantibody in patients with ovarian cancer. Gynecol. Oncol., New York, v. 102, p. 244-51, 2006. LOWE, D.B.; STORKUS, W.J. Chronic inflammation and immunologic - based constraints in malignant disease. Immunotherapy, London, v. 3, p. 1265-1274, 2011. MACKAY, F.; LOESTER, H.; STUEBER, D. et al. Tumor necrosis factor alpha (TNFalpha) induced cell adhesion to human endotelial cells is under dominant control of one TNF receptor type, TNF-R55. J. Exp. Med., New York, v. 177, p. 1277-1286, 1993. MANTOVANI, A.; ALLAVENA, P.; SICA, A. et al. Cancer - related inflammation. Nature, London, v. 454, n. 7203, p. 436-44, 2008. MANTOVANI, G.; MACCIÒ, A.; PISANO, M. et al.Tumor-associated lymphomonocytes from neoplastic effusions are immunologically defective in comparison with patient autologous PBMCs but are capable of releasing high amounts of various cytokines. Int. J. Cancer, New York, v. 71, n. 5, p. 724-731, 1997. MANTOVANI, A.; BOTTAZZI, B.; COLOTTA, F. et al. The origin and function of tumor-associated macrophages. Immunol. Today, Cambridge, v. 13, n. 7, p. 265- 270, 1992. MARSDEN, D. E.; FRIEDLANDER, M. Current Management of Epithelial Ovarian Carcinoma: A Review. Semin. Surg. Oncol., New York, v. 19, p. 11-19, 2000. MASOUMI-MOGHADDAM, S.; AMINI, A.; WEI, A.Q. et al. Intratumoral interleukin- 6 predicts ascites formation in patients with epithelial ovarian cancer: A potential tool for close monitoring. J. Ovarian Res., London, v. 8, p. 58, 2015. MASSI, D.; FRANCHI, A.; SARDI, I. et al. Inducible nitric oxide synthase expression in benign and malignant cutaneous melanocytic lesions. J. Pathol., Edinburgh, v. 194, n. 2, p. 194-200, 2001. MATTE, I.; LANE, D.; LAPLANTE, C. et al. Profiling of cytokines in human epithelial ovarian cancer ascites. Am. J. Cancer Res., Madison, v. 2, n. 5, p. 566-580, 2012. MAYER, A.R.; CHAMBERS, S.K.; GRAVES, E. et al. Ovarian cancer staging: does it require a gynecologic oncologist? Gynecol. Oncol., New York, v. 47, n. 2, p. 223-227, 1992. MAYERHOFER, K.; BODNER, K.; BODNER-ADLER, B. et al. Interleukin-8 serum level shift in patients with ovarian carcinoma undergoing paclitaxel-containing chemotherapy. Cancer, Philadelphia , v. 91, p. 388-393, 2001. MENDES, R.V.; MARTINS, A.R.; DE NUCCI, G. et al. Expression of nitric oxide synthase isoforms and nitrotyrosine immunoreactivity by B-cell non-Hodgkin's lymphomas and multiple myeloma. Histopathology, Oxford, v. 39, n. 2, p. 172-178, 2001. MICHEL, T.; FERON, O. Nitric oxide synthases: Which, where, how, and why? J. Clin. Invest., New York, v. 100, n. 9, p. 2146-2152, 1997. MICHELI, D.C. Quantificação sistêmica de mediadores inflamatórios e da expressão de receptores em neutrófilos em mulheres portadoras de tumor ovariano: efeito do tratamento nas pacientes com neoplasia maligna/Douglas Cobo Micheli. 28/07/2015. 125F. Tese (Doutorado em Ciências da Saúde) – Universidade Federal do Triângulo Mineiro, Uberaba, MG, 2015. MILBURN, M.V.; HASSELL, A.M.; LAMBERT, M.H. et al. A novel dimer configuration revealed by the crystal structure at 2.4 A resolution of human interleukin- 5. Nature, London, v. 363, n. 6425, p. 172-176, 1993. MINARETZIS, D.; TSIONOU, C.; TZIORTZIOTIS, D. et al. Ovarian tumors: prediction of the probability of malignancy by using patient’s age and tumor morphologic features with a logistic model. Gynecol. Obstet. Invest., Basel, v. 38, p. 140-144, 1994. MOCELLIN, S.; BRONTE, V.; NITTI, D. Nitric oxide, a double edged sword in cancer biology: seaching for therapeutic opportunities. Med. Res. Rev., New York, v. 27, n. 3, p. 317-352, 2007. MOCELLIN, S.; MARINCOLA, F.M.; YOUNG, H.A. Interleukin-10 and the immune response against cancer: a counterpoint. J. Leukoc. Biol., Winston-Salem, v. 78, p. 1043-1051, 2005. MONCADA, S.; PALMER, R.M.J.; HIGGS, E.A. Nitric Oxide: Physiology, pathophysiology, and pharmacology. Pharmacol. Rev., Baltimore, v. 43, p. 109-142, 1991. MURDOCH, W.J.; MARTINCHICK, J.F. Oxidative damage to DNA of ovarian surface epithelial cells affected by ovulation: carcinogenic implication and chemoprevention. Exp. Biol. Med.. Basel, v. 229, n. 6, p. 546-552, 2004. MURDOCH, W. J.; MCDONNEL, A. C. Roles of the ovarian surfasse epithelium in ovulation and carcinogenesis. Reproduction, Cambridge, v. 123, n. 6, p. 174-50, June, 2002. MURTA, E.F.C.; NOMELINI, R.S. Early diagnosis and predictors of malignancy in the evaluation of adnexal mass. Curr. Opin. Obstet. Gynecol., Philadelphia, v. 18, n. 1, p. 14-9, Feb. 2006. MURTA, E.F.C.; SILVA, C.S.; GOMES, R.A. et al. Ultrasonographic criteria and tumor marker assay are good procedures for the diagnosis of ovarian neoplasia in preselected outpatients. Eur. J. Gynaecol. Oncol., Montreal, v. 25, p. 707-712, 2004. MURTA, E. F. C.; ANDRADE, J. M.; BIGHETTI, S. Aspectos epidemiológicos do câncer de ovário. J. Bras. Ginecol., Rio de Janeiro, v. 105, p. 269-274, 1995. NAKAMURA, Y.; YASUOKA, H.; TSUJIMOTO, M. et al. Nitric oxide in breast cancer: induction of vascular endothelial growth factor-C and correlation with metastasis and poor prognosis. Clin. Cancer Res., Philadelphia, v. 12, n. 4, p. 1201- 1207, 2006. NARASIMHAN, K.; CHANGQING, Z.; CHOOLANI, M. Ovarian cancer proteomics: many technologies one goal. Clin. Proteomics, London, v. 2, n. 2, p. 195-218, Apr. 2008. NEGISHI, Y.; FURUNO, K.; SANO, Y. et al. Studies on CA 125, CA 19-9, TPA and IAP as tumor markers in patients with ovarian cancer. Gan No Rinsho, Tokyo, v. 31, Suppl 6, p. 655-63, 1985. NEGUS, R.P.; STAMP, G.W.; HADLEY, J. et al. Quantitative assessment of the leukocyte infiltrate in ovarian cancer and its relationship to the expression of C-C chemokines. Am. J. Pathol., New York, v. 150, n. 5, p. 1723-1734, 1997. NICOLINI, A.; CARPIB, A.; ROSSI, G. Cytokines in breast cancer. Cytokine Growth Factor Rev., Oxford, v. 17, p. 325-337, 2006. NIK NN, VANG R, SHIH IeM et al. Origin and pathogenesis of pelvic (ovarian, tubal, and primary peritoneal) serous carcinoma. Annu. Rev. Pathol., Bethesda, v. 9, p. 27-45, 2014. NISIDA, A. C. T. Câncer de ovário: Importância, epidemiologia e fatores de risco. In: Halbe HW. Tratado de Ginecologia. São Paulo: Roca [2000]. p.2242-2245, 2000. NOMELINI, R.S.; RIBEIRO, L.C.A, TAVARES-MURTA, B.M. et al. Production of nitric oxide and expression of inducible nitric oxide synthase in ovarian cystic tumors. Mediat. Inflamm., New York, v. 2008, n. 186584, 2008. OMURA, G.A.; BRADY, M.F.; HOMESLEY, H.D. et al: Long-term follow up and prognostic factor analysis in advanced ovarian carcinoma: the Gynecologic Oncology Group experience. J. Clin. Oncol., New York, v. 9, n. 7, p. 1138-1150, 1991. OLIVIER, R.I.; LUBSEN-BRANDSMA, M.A., VERHOEF, S. et al. Ca 125 and transvaginalultrasound monitoring in high-risk women cannot prevent the diagnosis of advanced ovarian cancer. Gynecol. Oncol., New York, v. 100, p. 20-26, 2006. OLSON, S.H.; MIGNONE, L.; NAKRASEIVE, C. et al. Symptoms of ovarian cancer. Obstet. Gynecol., Hagerstown, v. 98, n. 2, p. 212-217, 2001. ORAM, D.H.; JACOBS, I.J.; BRADY, J.L. et al. Early diagnosis of ovarian cancer. Br. J. Hosp. Med., London, v. 44, n. 5, p. 320-324, 1990. ORTH, K.; HUNG, J.; GAZDAR, A. et al. Genetic instability in human ovarian cancer cell lines. Porc. Natl. Acad. Sci. U.S.A., Washington, v. 91, n. 30, p. 9495-9499, Sept. 1994. OSE, J.; SCHOCK, H.; TJØNNELAND, A. et al. Inflammatory Markers and Risk of Epithelial Ovarian Cancer by Tumor Subtypes: The EPIC Cohort. Cancer Epidemiol. Biomark. Prev., Philadelphia, v. 24, n. 6, p. 951-961, 2015. OSMERS, R.G.; OSMERS, M.; VON MAYDELL, B. et al. Evaluation of ovarian tumors in postmenopausal women by transvaginal sonography. Eur. J. Obstet. Gynecol. Reprod. Biol., Amsterdam, v. 77, p. 81-88, 1998. OZEL, E.; PEŞTERELI, H.E.; SIMŞEK, T. et al. Expression of cyclooxygenase-2 and inducible nitric oxide synthase in ovarian surface epithelial carcinomas: is there any correlation with angiogenesis or clinic pathologic parameters? Int. J. Gynecol. Cancer., Cambridge, v. 16, n. 2, p. 549-544, 2006. PADILLA, L. A.; RADOSEVICH, D.M.; MILAD, M. P. Limitations on the pelvic examination for evaluation of the female pelvic organs. Int. J. Gynaecol. Obstet., Baltimore, v. 88, p. 84-88, 2005. PALMER, R.M.; FERRIGE, A.G.; MONCADA, S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature, London, v. 327, p. 524-526, 1987. PARKIN, D.; CRUICKSHANK, M. Pathways to the diagnosis of ovarian cancer in the UK: a cohort study in primary care. Int. J. Gynaecol. Obstet., Baltimore, v. 117, n. 1033, 2010. PARK, J.Y,; KIM, D.Y.; SUH, D.S. et al.Outcomes of fertility-sparing surgery for invasive epithelial ovarian cancer: oncologic safety and reproductive outcomes. Gynecol. Oncol., New York, v. 110, p. 345-353, 2008. PARK, S.W.; LEE, S.G.; SONG, S.H. et al. The effect of nitric oxide on cyclooxygenase-2 (COX-2) overexpression in head and neck cancer cell lines. Int. J. Cancer., New York, v. 107, n. 5, p. 729-738, 2003. PIEK, J.M.; VAN DIEST, P.J.; ZWEEMER, R.P. et al. Tubal ligation and risk of ovarian cancer. Lancet, London, v. 358, n. 9284, p. 844, 2001. PIVER, M. S.; BARLOW, J. J.; LELE, S. B. Incidence of sbclinical metastasis in stage I and II ovarian carcinoma. Obstet. Gynecol., New York, v. 52, n. 1, p. 100-104, 1978. PRIES, R.; WOLLENBERG, B. Cytokines in head and neck cancer. Cytokine Growth Factor Rev., Oxford, v. 17, p. 141-146, 2006. PYLVÄS-EEROLA M, KARIHTALA P, PUISTOLA U. Preoperative serum 8-hydroxydeoxyguanosine is associated with chemoresistance and is a powerful prognostic factor in endometrioid-type epithelial ovarian cancer. BMC Cancer., London, v. 15, p. 493, 2015. QIN, Y.; WANG, P.; HUANG, Z. et al. The value of red cell distribution width in patients with ovarian cancer. Medicine, London, v. 96, n. 17, p. 6752, 2017. RASOOL M, MALIK A, BASIT ASHRAF MA et al. Evaluation of Matrix Metalloproteinases, Cytokines and Their Potential Role in the Development of Ovarian Cancer. PLoS One, San Francisco, v. 11, n. 11, 2016. RASPOLLINI, M.R.; AMUNNI, G.; VILLANUCCI, A. et al. Expression of inducible nitric oxide synthase and cyclooxygenase-2 in ovarian cancer: correlation with clinical outcome. Gynecol. Oncol., New York, v. 92, n. 3, p. 806-812, 2004. REIS, F. J. C. Rastreamento e diagnóstico das neoplasias de ovário – papel dos marcadores tumorais. Rev. Bras. Ginecol. Obstet., Rio de Janeiro, v. 27, n. 4, p. 222- 227, 2005. RICCI, M.D.; PIATO, J.R.M.; PIATO, S. et al. Oncologia ginecológica: aspectos atuais do diagnóstico e do tratamento. Barueri: Manole, 2008. RIDNOUR, L.A.; THOMAS, D.D.; SWITZER, C. et al. Molecular mechanisms for discrete nitric oxide levels in cancer. Nitric Oxide, Orlando, v. 19, p. 73-76, 2008. RIVOIRE, W.A.; APPEL, M.; MÔNEGO, H. et al. Neoplasias de ovário e de trompa de Falópio. In: FREITAS, F. et al. Rotinas em ginecologia. 5. ed. Porto Alegre: Artmed, 2006. p. 362-384, 2006. ROETT, M. A.; EVANS, P. Ovarian cancer: an overview. Am. Fam. Physician., Kansas City, v. 80, n. 6, p. 609-616, 2009. ROMAN, V.; ZHAO, H.; FOURNEAU, J.M. et al. Expression of a functional inducible nitric oxide synthase in hairy cell leukaemia and ESKOL cell line. Leukemia, New Jersey, v. 14, n. 4, p. 696-705, 2000. RUBIN, S. C. Surgery for ovarian cancer. Hematol. Oncol. Clin. North Am., Philadelphia, v. 6, p. 851-865, 1992. SADŁECKI P, WALENTOWICZ-SADŁECKA M, SZYMAŃSKI W et al. Comparison of VEGF, IL-8 and beta-FGF concentrations in the serum and ascites of patients with ovarian cancer. Ginekol. Pol., Warsaw, p. 82, n. 7, p. 498-502, 2011. SANTIN, A.D.; BELLONE, S.; RAVAGGI, A. et al. Increased levels of interleukin-10 and transforming growth factor-beta in the plasma and ascitic fluid of patients with advanced ovarian cancer. BJOG, Oxford, v. 108, n. 8, p. 804-808, 2001. SATO, E.; OLSON, S.H.; AHN, J. et al. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc. Natl. Acad. Sci. U S A, Washington, v. 102, n. 51, p. 18538-18543, 2005. SCAMBIA, G.; TESTA, U.; BENEDETTI-PANICI P. et al. Prognostic significance of interleukin 6 serum levels in patients with ovarian cancer. Br. J. Cancer, London, v. 71, n. 2, p. 354-356, 1995. SCHMELER, K.M.; SUN, C.C.; BODURKA, D.C. et al. Prophylactic bilateral salpingo-oophorectomy compared with surveillance in women with BRCA mutations. Obstet. Gynecol., Hagerstown, v. 108, n. 3, p. 515-520, 2006. SCHOUTEN, L.J.; RIVERA, C.; HUNTER, D.J. et al. Height, body mass index, and ovarian 8 cancer: a pooled analysis of 12 cohort studies. Cancer Epidemiol. Biomark. Prev., Philadelphia, v. 17, n. 4, p. 902-912, 2008. SCULLY, R. E. Pathology of ovarian cancer precursors. J. Cell. Biochem., New York, v. 23, p. 208-218, 1995. SETHI, G.; SUNG, B.; AGGARWAL, B.B. TNF: a master switch for inflammation to cancer. Front. Biosci., Tampa, v. 13, p. 5094-5107, 2008. SINGH M, LOFTUS T, WEBB E et al. Minireview: Regulatory T Cells and Ovarian Cancer. Immunol. Invest., New York, 45, n. 8, p. 712-720, 2016. SIPAK-SZMIGIEL, O.; WŁODARSKI, P.; RONIN-WALKNOWSKA, E. et al. Serum and peritoneal fluid concentrations of soluble human leukocyte antigen, tumor necrosis factor alpha and interleukin 10 in patients with selected ovarian pathologies. J. Ovarian Res., London, v. 10, p. 25, 2017. SGO COMMITTEE OPINION. Clinical practice committee estatement on prophylactic salpingo-oophorectomy. Gynecol. Oncol., New York, v. 98, p. 179-181, 2005. SHERMAN, M.E; MINK, P.J.; CURTIS, R. et al. Survival among women with borderline ovarian tumors and ovarian carcinoma: a population-based analysis. Cancer, Philadelphia, v. 100, p. 1045-1052, 2004. SHI, F. D.; VAN, K. L. Reciprocal regulation between natural killer cells and autoreactive T cells. Nat. Rev. Immunol., London, v. 6, n. 10, p. 751-760, Oct. 2006. SHIH IeM, KURMAN RJ. Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. Am. J. Pathol., New York, v. 164, n. 5, p. 1511-1518, 2004. SIEGEL, R. L., MILLER, K. D., JEMAL, A. Cancer statistics, 2017. CA: A Cancer Journal for Clinicians, v. 67, p. 7-30, 2017. SILVA, S. S.; AQUINO, T. A. A.; SANTOS, R. M. O paciente com câncer: cognições e emoções a partir do diagnóstico. Rev. Bras. Ter. Cogn., v. 4, n. 2, p. 73-89, 2008. SILVA, V. C. E. O impacto da revelação do diagnóstico de câncer na percepção do paciente. Dissertação de Mestrado – Pós-Graduação em Enfermagem, Programa interistitucional USP/ UEL/ UNOPAR, São Paulo, 2005. SMITH, H. Clinical management of ovarian cancer [book review]. N. Engl. J. Med., Boston, v. 345, n. 2, p. 152-153, 2001. STEIN, R. C.; DALGLEISH, A. G. Immunomodulatory agents: the cytokines. Eur. J. Cancer, Oxford, v. 30, p. 400-404, 1994. STONE, R.L.; NICK, A.M.; MCNEISH, I.A. et al. Paraneoplastic thrombocytosis in ovarian cancer. N. Engl. J. Med., Boston, v. 366, p. 610-618, 2012. STURGEON, C. Practice guidelines for tumor marker use in the clinic. Clin. Chem., New York, v. 48, n. 8, p. 1151-1159, 2002. SWITZER, C.H.; CHENG, R.Y.; RIDNOUR, L.A. et al. Ets-1 is a transcriptional mediator of oncogenic nitric oxide signaling in estrogen receptor-negative breast cancer. Breast Cancer Res., London, v. 14, n. 5, p. R125, 2012. SYKES, L.; MACINTYRE, D.A.; YAP, X.J. et al. The Th1:th2 dichotomy of pregnancy and preterm labour. Mediat. Inflamm., New York, v. 2012, p. 967629, 2012. SZLOSAREK, P.W.; GRIMSHAW, M.J.; WILBANKS, G.D. et al. Aberrant regulation of argininosuccinate synthetase by TNF-alpha in human epithelial ovarian cancer. Int. J. Cancer, New York, v. 121, n. 1, p. 6-11, 2007. SZLOSAREK, P.W.; GRIMSHAW, M.J.; KULBE, H. et al. Expression and regulation of tumor necrosis factor alpha in normal and malignant ovarian epithelium. Mol. Cancer Ther., Philadelphia, v. 5, n. 2, p. 382-390, 2006. SZPUREK, D.; MOSZYNSKI, R.; ZIETKOWIAK, W. et al. An ultrasonographic morphological index for prediction of ovarian tumor malignancy. Eur. Gynaecol. Oncol., Montreal, v. 26, p. 51-54, 2005. SZUBERTA, S.; WOJTOWICZB, A.; MOSZYNSKIA, R. et al. External validation of the IOTA ADNEX model performed by two independent gynecologic centers. Gynecol. Oncol., New York, v. 142, n. 3, p. 490-495, 2016. TABIBZADEH, S.S.; POUBOURIDIS, D.; MAY, L.T. et al. Interleukin-6 immunoreactivity in human tumors. Am. J. Pathol., New York, v. 135, n. 3, p. 427-433, 1989. TAILOR, A.; JURKOVIC, D.; BOURNE, T.H. et al. Sonographic prediction of malignancy in adnexal masses using an artificial neural network. Br. J. Obstet. Gynaecol., London, v. 106, p. 21-30, 1999 TAKATSU, K.; TOMINAGA, A.; HARADA, N. et al. T cell-replacing factor (TRF)/interleukin 5 (IL-5) molecular and functional propeties. Immunol Rev., Copenhagen, v. 102, p. 107-135, 1988. TARTAGLIA, L.A.; AYRES, T.M.; WONG, G.H. et al. A novel domain within the 55 kd TNF receptor signals cell death. Cell, Cambridge, v. 74, p. 845-853, 1993. TAVARES-MURTA, B.M.; CUNHA, F.Q.; MIRANDA, R. et al. Differential tumor microenvironment in human ovarian cystic tumors. Tumori, Milano, v. 90, p. 491-197, 2004. TAVASSOLI, F.A.; DEVILEE, P. (Eds.): World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. IARC Press, Lyon, 2003 TRACEY, K.J.; CERAMI, F. A tumor necrosis factor: an update review of its biology. Crit. Care Med., New York, v. 21, p. 415-422, 1993. TSAI-TURTON, M.; SANTILLAN, A.; LU, D. et al. p53 autoantibodies, cytokine levels and ovarian carcinogenesis. Gynecol. Oncol., New York, v. 114, n. 1, p. 12-17, 2009. TEMPLETON, A.J.; MCNAMARA, M.G.; ŠERUGA, B. et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J. Natl. Cancer Inst., Cary, v. 106, n. 6, p. 124, 2014. THOMAS, D.D.; RIDNOUR, L.A.; ISENBERG, J.S. et al. The chemical biology of nitric oxide: implications in cellular signaling, Free Radic. Biol. Med., New York, v. 45, p. 18-31, 2008. THOMSEN, L.L.; LAWTON, F.G.; KNOWLES, R.G. et al. Nitric oxide synthase activity in human gynecological cancer. Cancer Res., Chicago, v. 54, n. 5, p. 1352- 1354, 1994. THOMPSON-SNIPES, L.; DHAR, V.; BOND, M.W. et al. Interleukin 10: a novel stimulatory factor mast cells and their progenitors. J. Exp. Med., New York, v. 173, p. 507-510, 1991. TIMMERMAN, D.; VAN CALSTER, B.; TESTA, A.C. et al. Ovarian cancer prediction in adnexal masses using ultrasound-based logistic regression models: a temporal and external validation study by the IOTA group. Ultrasound. Obstet. Gynecol., Carnforth, v. 36, p. 226-234, 2010. TIMMERMAN, D. The use of mathematical models to evaluate pelvic masses: can they beat an expert operator? Res. Clin. Obstet. Gynaecol., London, v. 18, p. 91-104, 2004.114 TIMMERMAN, D.; SCHWÄRZLER, P.; COLLINS, W.P. et al. Subjective assessment of adnexal masses with the use of ultrasonography: an analysis of interobserver variability and experience. Ultrasound. Obstet. Gynecol., Carnforth, v. 13, p. 11-16, 1999. TITUS-ERNSTOFF, L.; PEREZ, K.; CRAMER, D.W. et al. Menstrual and reproductive factors in relation to ovarian cancer risk. Br. J. Cancer., London, v. 84, n. 5, p. 714-721, 2001. TOGASHI, K. Ovarian cancer: the clinical role of US, CT, and MRI. Eur. Radiol., Berlin, v. 13, n. 6, p. 87-104, 2003. VAKKILA, J.; LOTZE, M.T. Inflammation and necrosis promote tumour growth. Nat. Rev. Immunol., London, v. 4, n. 8, p. 641-648, Aug., 2004. VALKO, M.; IZAKOVIC, M.; MAZUR, M. et al. Role of oxygen radicals in DNA damage and cancer incidence. Cell Biochem. Biophys., Totowa, v. 266, p. 37-56, 2004. VAN CALSTER, B.; VAN HOORDE, K.; VALENTIN, L. et al. International Ovarian Tumour Analysis IOTA Group. Evaluating the risk of ovarian cancer before surgery using the ADNEX model to differentiate between benign, borderline, early and advanced stage invasive, and secondary metastatic tumours: prospective multicenter diagnostic study. BMJ, London, v. 349, p. 5920, 2014. VAN HOLSBEKE, C.; VAN CALSTER, B.; BOURNE, T. et al. External validation of diagnostic models to estimate the risk of malignancy in adnexal masses. Clin. Cancer Res., Philadelphia, v. 18, p. 815-825, 2012. VASCONCELOS, M.; SOUSA, M.M. Conservative surgery in ovarian borderline tumours: a meta-analysis with emphasis on recurrence risk. Eur. J. Cancer, Oxford, v. 51, p. 620-631, 2015. VENKITARAMAN, A.R. Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell, Cambridge, v. 108, n. 2, p. 171-182, 2002. VERGOTE, I.; De BRABANTER, J.; FYLES, A. et al. Prognostic importance of degree of differentiation and cyst rupture in stage I invasive epithelial ovarian carcinoma. Lancet, London, v. 357, n. 9251, p. 176-182, 2001. VRABIE, C.D.; PETRESCU, A.; WALLER, M.; DINA, I. Clinical factors and biomarkers in ovarian tumors development. Rom. J. Morphol. Embryol., Bucuresti, v. 49, n. 3, p. 327-338, 2008. VURAL, P.; DEĞIRMENCIOĞLU, S.; SARAL, N.Y. et al. Tumor necrosis factor alpha (-308), interleukin-6 (-174) and interleukin-10 (-1082) gene polymorphisms in polycystic ovary syndrome. Eur. J. Obstet. Gynecol. Reprod. Biol., Amsterdam, v. 150, n. 1, p. 61-65, 2010. XIE, K. Interleukin-8 and human cancer biology. Cytokine Growth Factor. Rev., Oxford, v. 12, n. 375-391, 2001. XIE, K.; FIDLER, I.J. Therapy of cancer metastasis by activation of the inducible nitric oxide synthase. Cancer Metastasis Rev., Boston, v. 17, n. 1, p. 55-75, Mar. 1998. XU, L.; FIDLER, I.J. Interleukin 8: an autocrine growth factor for human ovarian cancer. Oncol. Res., Elmsford, v. 12, p. 97-106, 2000. XU, W.; LIU, L.Z.; LOIZIDOU, M. et al. The role of nitric oxide in cancer. Cell Res., Beijing, v. 12, n. 5-6, p. 311-320, 2002. WANG, Y.; XU, R.C.; ZHANG, X.L. et al. Interleukin-8 secretion by ovarian cancer cells increases anchorage-independent growth, proliferation, angiogenic potential, adhesion and invasion. Cytokine, San Diego, v. 59, p. 145-155, 2012. WANG, Y.; NIU, X.L.; QU, Y. et al. Autocrine production of interleukin-6 confers cisplatin and paclitaxel resistance in ovarian cancer cells. Cancer Lett., Virginia, v. 295, n. 1, p. 110-123, 2010. WATANABE, T.; SHIBATA, M.; NISHIYAMA, H. et al. Serum Levels of Rapid Turnover Proteins Are Decreased and Related to Systemic Inflammation in Patients with Ovarian Cancer. Oncology Letters, New York, v. 7, n. 2, p. 373-377, 2014. WAXMAN, J.; BALKWILL, F. Interleukin 2. Black-well Sci. Publ. Oxford. 1992. WILSON, K.T.; FU, S.; RAMANUJAM, K.S. et al. Increased expression of inducible nitric oxide synthase and cyclooxygenase-2 in Barrett's esophagus and associated adenocarcinomas. Cancer Res., Baltimore, v. 58, n. 14, p. 2929-2934, 1998. WOODRUFF, J. D. The pathogenesis of ovarian neoplasia. Johns Hopkins Med. J., Baltimore, v. 144, p. 117-120, 1979. WU, P.C.; LANG, J.H.; HUANG, R.L. et al., Lymph node metastasis and retroperitoneal lymphadenectomy in ovarian cancer. Baillieres Clin. Obstet. Gynaecol., London, v. 3, p. 143-155, 1986. WU, X., GROVES, F.D., MCLAUGHLIN, C.C. et al. Cancer incidence patterns among adolescents and young adults in the United States. Cancer Causes Control, Oxford, v. 16, n. 3, p. 309-320, 2005. YAMAGUCHI, N. H. O câncer na visão da oncologia. Em: M. M. M. J. Carvalho (Org.). Introdução à psiconcologia (pp. 22-32). São Paulo: Livro pleno, 2002. YAWN, B.P.; WOLLAN, P.; KLEE, M. et al. Ovarian carcinoma: care and survival in a community-based population. Clin. Ther., Princeton, v. 23, p. 146-159, 2001. YIGIT, R.; FIGDOR, C.G.; ZUSTERZEEL, P.L. et al. Cytokine analysis as a tool to understand tumour-host interaction in ovarian cancer. Eur. J. Cancer, Oxford, v. 47, n. 12, p. 1883- 1889, 2011. YOSHIDA, K.; MIKI, Y. Role of BRCA1 and BRCA2 as regulators of DNA repair, 22 transcription, and cell cycle in response to DNA damage. Cancer Sci., Tokyo, v. 95, n. 11, p. 866-871, 2004. ZANG, R.Y.; LI, Z.T.; ZHANG, Z.Y. et al. Surgery and salvage chemotherapy for Chinese women with recurrent advanced epithelial ovarian carcinoma: a retrospective case-control study. Int. J. Gynecol. Cancer, Cambridge, v. 13, n. 4, p. 419-127, 2003. ZANETTA, G.; ROTA, S.; CHIARI, S. The accuracy of staging: An important prognostic determinator in stage I ovarian carcinoma. A multivariate analysis. Ann. Oncol., Dordrecht, v. 9, p. 1097-1101, 1998. ZAJICEK, J. Prevention of ovarian cystomas by inhibition of ovulation: a new concept. J. Reprod. Med., Chicago, v. 20, n. 2, p. 114, 1978. ZEPPERNICK, F.; MEINHOLD-HEERLEIN, I. The new FIGO staging system for ovarian, fallopian tube, and primary peritoneal cancer. Arch Gynecol Obstet., Munchen, v. 290, n. 5, p. 839-842, 2014. ZHANG, L.; CONEJO-GARCIA, J.R.; KATSAROS, D. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N. Engl. J. Med., Boston, v. 348, p. 203-213, 2003. ZHOU, J.Y.E.; CHEN, H.; GAN, N. The expression of interleukin-10 in patients with primary ovarian epithelial carcinoma and in ovarian carcinoma cell lines. J. Int. Med. Res., Northampton, v. 35, n. 3, p. 290-300, 2007. ZWAHLEN, R.; WALZ, A.; ROT, A. In vitro and in vivo activity and pathophysiology of human interleu-kin-8 and related peptides. Int. J. Exp. Pathol., Oxford, v. 34, p. 27- 42, 1993.http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFTMinstname:Universidade Federal do Triangulo Mineiro (UFTM)instacron:UFTM2018-05-04T04:00:13Zoai:bdtd.uftm.edu.br:tede/553Biblioteca Digital de Teses e Dissertaçõeshttp://bdtd.uftm.edu.br/PUBhttp://bdtd.uftm.edu.br/oai/requestbdtd@uftm.edu.br\|\|bdtd@uftm.edu.bropendoar:2018-05-04T04:00:13Biblioteca Digital de Teses e Dissertações da UFTM - Universidade Federal do Triangulo Mineiro (UFTM)false
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
dc.relation.none.fl_str_mv	ABBAS, A. K.; LICHTMAN, A. H.; POBER, J. S. In: ABBAS, A. K. Imunologia celular e molecular. [Tradução de Claudia Reali e outros] 6ª ed. Rio de Janeiro: Elsevier, 2008. AGGARWAL, B.B.; SHISHODIA. S.; SANDUR, S.K. et al. Inflammation and cancer: how hot is the link? Biochem. Pharmacol., Oxford, v. 72, n. 11, p. 1605-1621, 2016. AGARWAL, R.; KAYE, S. B. Prognostic factors in ovarian cancer: how close are we to a complete picture? Ann. Oncol., Dordrecht, v. 16, n. 1, p. 4-6, 2005. AKAHIRO, J.; KONNO, R.; ITO, K. et al. Impact of serum interleukin-18 level as a prognostic indicator in patients with epithelial ovarian carcinoma. Int. J. Clin. Oncol., Tokyo, v. 9, n. 1, p. 42-46, 2004. AKAIKE, T.; MAEDA, H. Nitric oxide and virus infection. Immunology, Oxford, v. 101, n. 3, p. 300-308, 2000. ALDERTON, W.K,; COOPER, C.E.; KNOWLES, R.G. Nitric oxide synthases: structure, function and inhibition. Biochem. J., London, v. 357, n. 3, p. 593-615, 2001. ALI-FEHMI, R; SEMAAN, A; SETHI, S. et al. Molecular typing of epithelial ovarian carcinomas using inflammatory markers. Cancer, Philadelphia, v. 117, n. 2, p. 301-309. 2011 AMBS, S.; BENNETT, W.P.; MERRIAM, W.G. et al. Vascular endothelial growth factor and nitric oxide synthase expression in human lung cancer and the relation to p53. Br. J. Cancer., London, v. 78, n. 2, p. 233-239, 1998. ANDERSON, G.M.; NAKADA, M.T.; DeWITTE, M. Tumor necrosis factoralpha in the pathogenesis and treatment of cancer. Curr. Opin. Pharmacol., Oxford, v. 4, p. 3014-320, 2004. ASHER, V.; LEE, J.; INNAMAA, A. et al. Preoperative platelet lymphocyte ratio as an independent prognostic marker in ovarian cancer. Clin. Transl. Oncol., Barcelona, v. 13, n. 7, p. 499-503, 2011. ATHANASSIADOU, P.; GRAPSA, D.; ATHANASSIADES, P. et al. The prognostic significance of COX-2 and survivin expression in ovarian cancer. Pathol. Immunopathol. Res., Basel, v. 204, n. 4, p. 241-249, 2008. AUNE, G.; STUNES, A.K.; LIAN, A.M. et al. Circulating interleukin-8 and plasminogen activator inhibitor-1 are increased in women with ovarian carcinoma. Results Immunol., Oxford, v. 2, p, 190-195, 2012. BAGGIOLINI, M.; DEWALD, B.; MOSER, B. Interleukin 8 and related chemotactic cytokines – CXC and CC chemokines. Adv Immunol., New York, v. 55, p. 97-179. 1994. BALKWILL, F.; MANTOVANI, A. Inflammation and cancer: back to Virchow? Lancet, London, n. 9255, p. 539-545, 2001. BALKWILL, F. TNF-alpha in promotion and progression of cancer. Cancer Metastasis Rev., Boston, v. 25, n. 3, p. 409-416, 2006. BAMIAS, A.; TSIATAS, M. L.; KAFANTARI, E. Significant differences of lymphocytes isolated from ascites of patients with ovarian cancer compared to blood and tumor lymphocytes. Association of CD3+CD56+ cells with platinum resistance. Gynecol. Oncol., New York, v. 106, p. 75-81, 2007 BECHT, E. L. M. K.; BONAVIDA, B. Inhibitory effects of 17β-estradiol and progesterone on avarian carcinoma cell proliferation: a potencial role for inducible nitric oxide synthase. Gynecol. Oncol., New York, v. 82, n. 1, p. 127-138, 2001. BECKER, H.M.G.; GUIMARÃES, R.E.S.; NASCIMENTO, E. et al. Perfil de citocinas e tipificação de hla em pacientes com polipose nasossinusal tolerantes e intolerantes a aspirina. Rev. Bras. Otorrinolaringol., São Paulo, v. 69, n. 3, 2003. BELISLE, J.A.; GUBBELS, J.A.; RAPHAEL, C.A. et al. Peritoneal natural killer cells from epithelial ovarian cancer patients show an altered phenotype and bind to the tumour marker MUC16 (CA125). Immunology, v. 122, n. 3, p. 418-429, 2007. BELLATI, F.; VISCONTI, V.; NAPOLETANO, C. et al. Immunology of gynecologic neoplasms: analysis of the prognostic significance of the immune status. Curr. Cancer Drug Targets, Amarillo, v. 9, p. 541-565, 2009. BELLONE, S.; WATTS, K.; CANE', S. et al. High serum levels of interleukin-6 in endometrial carcinoma are associated with uterine serous papillary histology, a highly aggressive and chemotherapy-resistant variant of endometrial cancer. Gynecol. Oncol., New York, v. 98, n. 1, p. 92-98, 2005. BENJAMIM, C.F.; FERREIRA, S.H.; CUNHA, F.Q. Role of Nitric Oxide in the Failure of Neutrophil Migration in Sepsis. Jurnal Infect. Dis., Oxford, v. 182, p. 214- 223, 2000. BENJAMIN, D.; KNOBLOCK, T.J.; DAYTON, M.A. Human B cell interleukin-10 cell lines derived from patients with acquired immunodeficiency syndrome and Burkitt’s lymphoma constitutively secrete large quantities of interleukine-10. Blood, v. 80, n. 5, p. 1289-1298, 1992. BERTAZZA, L.; MOCELLIN, S. Tumor necrosis factor (TNF) biology and cell death. Front. biosci., Tampa, v. 13, p. 2736-2743, 2008. BISHARA, S.; GRIFFIN, M.; CARGILL, A. et al. Pre-treatment white blood cell subtypes as prognostic indicators in ovarian cancer. Eur. J. Obstet. Gynecol. Reprod. Biol., Amsterdam, v. 138, p. 71-75, 2008. BHOOLA, S.; HOSKINS, W. J. Diagnosis and management of epithelial ovarian cancer. Obstet. Gynecol., New York, v. 107, p. 1.399-1.410, 2006. BOGLIOLO, L., 1908-1981. Bogliolo, Patologia / [editor] Geraldo Brasileiro Filho. 8ªed. Rio de Janeiro: Guanabara Koogan, 2011. BOULTON, S.J. Cellular functions of the BRCA tumour-suppressor proteins. Biochem. Soc. Trans., London, v. 34, n. 5, p. 633-645, 2006. BRAGA, A. C. S. Pacientes oncológicos:a influência do câncer no estado emocional e a concepção de finitude. Monografia não publicada. Curso de Graduação em Psicologia, Centro Universitário de João Pessoa. João Pessoa, PB, 2005. BREWER, M. A. et. al. Prevection of varian cancer: intraepithelial neoplasia. Clin. Cancer Res., Philadelphia, v. 9, p. 20-30, 2003. BRUNETTI, G.; BOSSI, A.; BAIARDI, P. et al. Soluble interleukin 2 receptor (sIL-2R) in monitoring advanced lung cancer during chemotherapy. Lung Cancer, Limerick, v. 23, n. 1 p. 1-9, 1999. BULUT, A.S.; ERDEN, E.; SAK, S.D. et al. Significance of inducible nitric oxide synthase expression in benign and malignant breast epithelium: an immunohistochemical study of 151 cases. Virchows Arch., Berlin, v. 447, n. 1, p. 24- 30, 2005. BURKE, A.J.; SULLIVAN, F.J.; GILES, F.J. et al. The yin and yang of nitric oxide in cancer progression, Carcinogenesis, Oxford, v. 34, p. 503-512, 2013. BUTTERY, L.D.; SPRINGALL, D.R.; ANDRADE, S.P. et al. Induction of nitric oxide synthase in the neo-vasculature of experimental tumours in mice. J. Pathol., Edinburgh, v. 171, n. 4, p. 311-9, 1993. CANNISTRA, S. A. Cancer of the ovary. N. Engl. J. Med., Boston, v. 351, n. 24, p. 2519-2529, 2004. CASAGRANDE, J. T.; LOUIE, E.W.; PIKE, M.C. et al. Incessant ovulation and ovarian cancer. Lancet, London, v. 2, n. 8135, p. 170-173, 1979. CHARLES, K.A.; KULBE, H.; SOPER, R. et al. The tumor-promoting actions of TNF- α involve TNFR1 and IL-17 in ovarian cancer in mice and humans. J. Clin. Invest., New York, v. 119, n. 10, p. 3011-3023, 2009. CHENG, H.; WANG, L.; MOLLICA, M. et al. Nitric oxide in câncer metastasis, Cancer Lett. Virginia, v. 353, p. 1-7, 2014. CHERCHI, P. L.; CAPOBIANCO, G.; AMBROSINI, G. et al. Intracystic evaluation of tumor markers in benign and malignant ovarian pathology. Eur. J. Gynaecol. Oncol., Montreal, v. 23, p. 163-165, 2002. CHO, H.; HUR, H.W.; KIM, S.W. et al. Pre-treatment neutrophil to lymphocyte ratio is elevated in epithelial ovarian cancer and predicts survival after treatment. Cancer Immunol. Immunother., New York, v. 58, p. 15-23, 2009. CHOBANIAN, N.; DIETRICH, C. Ovarian Cancer. Surg. Oncol. Clin. N. Am., Philadelphia, v. 88, p. 285-299, 2008. CIANFRANI, T. A short history of obstetrics and gynecology. Springfield: CC Thomas, 1960. COBBS, C.S.; BRENMAN, J.E.; ALDAPE, K.D. et al. Expression of nitric oxide synthase in human central nervous system tumors. Cancer Res., Baltimore, v. 55, n. 4, p. 727-30, 1995. CORMIO, G.; ROSSI, C.; CAZZOLLA, A. et al. Distant metastasis in ovarian carcinoma. Int. J. Gynecol. Cancer, Cambridge, v. 13, n. 2, p. 125-129, 2003. CLUTTERBUCK, E.; SHIELDS, J.G.; GORDON, J. et al. Recombinant human interleukin 5 is an eosinophil differentiation factor but has no activity in standard human B cell growth factor assays. Eur. J. Immunol., Weinheim, v. 17, n. 12, p. 1743-1750, 1987. CURIEL, T.J.; COUKOS, G.; ZOU, L. et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat. Med., New York, v. 10, n. 9, p. 942-949, 2004. DACHS, G.U.; TOZER, G.M. Hypoxia modulated gene expression: Angiogenesis, metastasis and therapeutic exploitation. Eur. J. Cancer, Oxford, v. 36, n. 13, p. 1649- 1660, 2000. DALTOÉ, R.D.; SILVA, I.V.; PAULA, A.D. et al. O papel paradoxal do sistema imune no câncer de ovário. ACM: arquivos catarinenses de medicina, Florianópolis, v. 39, n. 2, p. 87-92, 2010. DEUTSCH, M.; BECK, D.; MANOR, D. et al. Metastatic brain tumor following negative second-look operation for ovarian carcinoma. Gynecol. Oncol., New York, v. 27, n. 1, p. 116-20, 1987. DIAZ OREA, M.A.; MUÑOZ PEREZ, V.; GÓMEZ CONDE, E. et al. Expression of Cytokines Interleukin-2, Interleukin-4, Interleukin-10 and Transforming Growth Factor β in Gastric Adenocarcinoma Biopsies Obtained from Mexican Patients. Asian Pac. J. Cancer Prev., Bangkok, v. 18, n. 2 p. 577-582, 2017. DOBRZYCKA, B.; MACKOWIAK-MATEJCZYK, B.; TERLIKOWSKA, K.M. et al. Serum levels of IL-6, IL-8 and CRP as prognostic factors in epithelial ovarian cancer. Eur. Cytokine Netw., Montrouge, v. 24, p. 106-113, 2013. DOBRZYCKA, B.; TERLIKOWSKI, S.J.; KOWALCZUK, O. et al. Circulating levels of TNF-α and its soluble receptors in the plasma of patients with epithelial ovarian cancer. Eur. Cytokine Netw., 2009, v. 20, n. 3, p. 131-134, 2009. DØRUM, A.; KRISTENSEN, G.B.; ABELER, V.M. et al. Early detection of familial ovarian cancer. Eur. J. Cancer, Oxford, v. 32, p. 1645-1651, 1996. DOTLIĆ, J.; TERZIĆ, M.; LIKIĆ, I. et al. Evaluation of adnexal masses: correlation between 39 clinical, ultrasound and histopathological findings. Vojnosanit Pregl., Belgrade, v. 68, n. 10, p. 861-866, 2011. EARLE, C.C.; SCHRAG, D.; NEVILLE, B.A. et al. Effect of surgeon specialty on processes of care and outcomes for ovarian cancer patients. J. Natl. Cancer Inst., Cary, v. 98, n. 3, p. 172-180, 2006. El-SEHEMY, A.; POSTOVIT, L.M.; FU, Y.X. Nitric oxide signaling in human ovarian cancer: a potencial therapeutic target. Nitric Oxide, Orlando, v. 54, p. 30-37. 2016. ELLYARD, J.I.; SIMSON, L.; PARISH, C.R. Th2-mediated anti-tumour immunity: friend or foe? Tissue Antigens, Copenhagen, v. 70, p 1-11, 2007. ENGELS, K.; DU BOIS, A.; HARTER, P. et al. VEGF-A and i-NOS expression are prognostic factors in serous epithelial ovarian carcinomas after complete surgical resection. J. Clin. Pathol., London, v. 62, p. 448-454, 2009. FAIRFIELD, K.M.; HANKINSON, S.E.; ROSNER, B.A. et al. Risk of ovarian carcinoma 16 and consumption of vitamins A, C and E and specific carotenoids: a prospective analysis. 17 Cancer. v.92, n.9, p.2318-2326, 2001. FATHALLA, M. F. Incessant ovulation: a factor in ovarian neoplasia? Lancet, v. 2, m. 7716, p. 163, 1971. FELDMAN, G. B.; KNAPP, R. C. Lymphatic drainage of the peritoneal cavity and its significance in ovarian cancer. Am. J. Obstet. Gynecol., St. Louis, v. 119, n. 7, p. 991- 994, Aug. 1974. FERLAY, J.; SOERJOMATARAM, I.; ERVIK, M. et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Disponível em <http://globocan.iarc.fr> Acesso em: 04/05/2017. FISHMAN, D.A.; COHEN, L.; BLANK, S.V. et al. The role of ultrasound evaluation in the detection of early-stage epithelial ovarian cancer. Am. J. Obstet. Gynecol., St. Louis, v. 192, p. 1214-1222, 2005. FLEMING, J.S.; BEAUGIÉ, C.R.; HAVIV, I. at al. Incessant ovulation, inflammation and epithelial ovarian carcinogenesis: revisiting old hypotheses. Mol. Cell Endocrinol., Limerick, v. 247, n. 1-2, p. 4-21, 2006. FLORES, M.D.; ORTEGA-CAMARILLO, C.; ROSALES-TORRES, A.M. et al. El oxido nítrico como principal efector del sistema de la interleucina-1 em la ovulacion. Gac. Mex., Cidad del Mexico, v. 137, n. 4, 2001. FREEDMAN, R.S.; DEAVERS, M.; LIU, J. et al. Peritoneal inflammation - a microenvironment for Epithelial Ovarian Cancer (EOC). J. Transl. Med., London, v. 2, p. 23, 2004. FRIDMAN, W.H.; GALON, J.; DIEU-NOSJEAN, M.C. et al. Immune infiltration in human cancer: prognostic significance and disease control. Curr. Top Microbiol. Immunol., Berlin, v. 344, p. 1-24, 2011. FUKUMURA, D.; KASHIWAGI, S.; JAIN, R.K. The role of nitric oxide in tumour progression. Nat. Rev. Cancer, London, p. 521-534, 2006. GADDUCCI, A.; COSIO, S.; TANA, R. et al. Serum and tissue biomarkers as predictive and prognostic variables in epithelial ovarian cancer. Crit. Rev. Oncol. Hematol., Boca Raton, v. 69, p. 12-27, 2009. GADDUCCI, A.; FERDEGHINI, M.; MALAGNINO, G. et al. Elevated serum levels of neopterin and soluble interleukin-2 receptor in patients with ovarian cancer. Gynecol. Oncol., New York, v. 52, n. 3, p. 386-391, 1994. GALON, J.; COSTES, A.; SANCHEZ-CABO, F. et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science, Washington, v. 313, n. 5795, p. 1960-1964, 2006. GAVALAS, N.G.; KARADIMOU, A.; DIMOPOULOS, M.A. et al. Immune Response in Ovarian Cancer: How Is the Immune System Involved in Prognosis and Therapy: Potential for Treatment Utilization. Clin. dev. immunol., Abingdon, ID 791603, 15 pages, 2010. GEBAUER, G.; RIEGER, M.; JÄGER, W. et al. Prognostic relevance of soluble interleukin-2 receptors in patients with ovarian tumors. Anticancer Res., Athens, v. 19, n. 4A, p. 2509-2511, 1999. GEOMINI, P.; KRUITWAGEN, R.; BREMER, G.L. et al. The accuracy of risk scores in predicting ovarian malignancy: a systematic review. Obstet. Gynecol., Hagerstown, v. 113, p. 384-394, 2009. GOFF, B.A.; MANDEL, L.; MUNTZ, H.G. at al. Ovarian carcinoma diagnosis. Cancer, Philadelphia, v. 89, n. 10, p. 2068-2075, 2000. GOPINATHAN, G.; MILAGRE, C.; PEARCE, O.M.T. et al. Interleukin-6 stimulates defective angiogenesis. Cancer research., Baltimore, v. 75, n. 15, p. 3098-3107, 2015. GUERRIERO, S.; AJOSSA, S.; GARAU, N. et al. Ultrasonography and Color Dopplerbased triage for adnexal masses to provide the most appropriate surgical approach. Am. J. Obstet. Gynecol., St. Louis, v. 192, p. 401-406, 2005. GREEN, L.C.; RUIZ DE LUZURIAGA, K.; WAGNER, D.A. et al. Nitrate biosynthesis in man. Proc. Natl. Acad. Sci. U. S. A., Washington, v. 78, n. 12, p. 7764-7768, 1981. GRIMM, E.A.; WILSON, D.J.; ROSENBERG, S.A. Lymphokine-activated killer cell phenomenon. II The precursor phenotype is serologically distinct from peripheral T lymphocytes, memory CTL, and NK cells. Exp. Med., Córdoba, v. 157, p. 884, 1983. HAGEMANN, T.; WILSON, J.; BURKE, F. et al. Ovarian cancer cells polarize macrophages toward a tumor-associated phenotype. J. Immunol., Baltimore, v. 176, n. 8, p. 5023-5032, 2006. HACKER, N.F.; BEREK, J.S.; LAGASSE, L.D. et al. Primary cytoreductive surgery for epithelial ovarian cancer. Obstet. Gynecol., Hagerstown, v. 61, n. 4, p. 413-420, 1983. HAGEMANN, A.R.; HAGEMANN, I.S.; CADUNGOG, M. et al. Tissue-based immune monitoring II: Multiple tumor sites reveal immunologic homogeneity in serous ovarian carcinoma. Cancer Biol. Ther., Georgetown, v. 12, n. 4, p. 367-377, 2011. HAO, X.P.; PRETLOW, T.G.; RAO, J.S. et al. Inducible nitric oxide synthase (iNOS) is expressed similarly in multiple aberrant crypt foci and colorectal tumors from the same patients. Cancer Res., Baltimore, v. 61, n. 2, p. 419-422, 2001. HAMBLIN, A. S. Cytokines and cytokine receptors. 2. ed. New York: Oxford University Press, 1993. HATAKEYAMA, M.; TSUDI, M.; MINAMOTO, S. et al. Interleukin 2 receptor beta chain gene: generation of the three receptor forms by cloned human alpha and beta chain DNAs. Science, London, v. 244, p. 551-556, 1989. HEINRICH, P.C.; CASTELL, J.V.; ANDUS, T. Interleukin-6 and the acute phase response. Biochem J., London, v. 265, n. 3, p. 621-636, 1990. HELAL, TEL-A; ALLA, A.E.; LABAN, M.A. et al. Immunophenotyping of tumor-infiltrating mononuclear cells in ovarian carcinoma. Pathol Oncol Res., Budapest, v. 10, n. 2, p. 80-4, 2004. HENNESSY, B. T.; COLEMAN, R. L.; MARKMAN, M. Ovarian cancer. Lancet, London, v. 374, p. 1374-1382, 2009. HIRASHIMA, K.; WATANABE, M.; SHIGAKI, H. et al. Prognostic significance of the modified Glasgow prognostic score in elderly patients with gastric cancer. J. Gastroenterol., Tokyo, v. 49, p. 1040-1046, 2014. HOLSCHNEIDER, C. H., BEREK, J. S. Ovarian cancer: epidemiology, biology, and prognostic factors. Semin. Surg. Oncol., New York, v. 19, p. 3-10, 2000. HONN, K.V.; TANG, D.G.; CRISSMAN, J.D. Platelets and cancer metastasis: a causal relationship? Cancer Metastasis Rev., Boston, v. 11, p. 325-51, 1992. HUANG, S.; MILLS, L.; MIAN, B. et al. Fully humanized neutralizing antibodies to interleukin-8 (ABX-IL-8) inhibit angiogenesis, tumor growth, and metastasis of human melanoma. Am. J. Pathol., New York, v. 161, n. 1, p. 125-134, 2002. IGNARRO, L. Nitric oxide biology and pathobiology. New York: Academic Press, 2000. INCA - Instituto Nacional de Câncer José Alencar Gomes da Silva. Ministério da Saúde - Rio de Janeiro, Brasil. Coordenação de Prevenção e Vigilância. Estimativa 2016 - Incidência de câncer no Brasil. INCA, 2015. Disponível em: <http://www.inca.gov.br/estimativa/2016/estimativa-2016-v11.pdf>. Acesso em: 11/04/2017. INCA - Instituto Nacional de Câncer José Alencar Gomes da Silva. Ministério da Saúde - Rio de Janeiro, Brasil. ABC do câncer: abordagens básicas para o controle do câncer. INCA, 2011. Disponível em < http://bvsms.saude.gov.br/bvs/publicacoes/abc_do_cancer.pdf>. Acesso em: 17/08/2016. INGERSOLL, S.B.; PATEL, S.; CABALLERO, L. et al. Synergistic cytotoxicity of interferonalpha-2b and interleukin-2 in combination with PBMC against ovarian cancer: development of an experimental model for cellular therapy. Gynecol. Oncol., New York, v. 112, n. 1, p. 192-198, 2009. ISCHIROPOULOS, H.; BECKMAN, J.S. Oxidative stress and nitration in neurodegeneration: Cause, effect, or association? J. Clin. Invest., New York, v. 111, n. 2, p. 163-169, 2003. KAIJSER, J.; BOURNE, T.; VALENTIN, L. et al. Improving strategies for diagnosing ovarian cancer: a summary of the International Ovarian Tumor Analysis (IOTA) studies. Ultrasound. Obstet. Gynecol., Carnforth, v. 41, p. 9-20, 2013. KAMINUMA, O.; MORI, A.; KITAMURA, N. et al. Role of GATA-3 in IL-5 gene transcription by CD4+ T cells of asthmatic patients. Int. arch. allergy immunol., Besel, v. 137, Suppl 1, p, 55-59, 2005. KASSIM, S.K.; EL-SALAHY, E.M.; FAYED, S.T. et al. Vascular endothelial growth factor and interleukin-8 are associated with poor prognosis in epithelial ovarian cancer patients. Clin. Biochem., Toronto, v. 37, n. 5, p. 363-369, 2004. KEHOE, S.; POWELL, J.; WILSON, S. et al. The influence of the operating surgeon's specialization on patients survival in ovarian carcinoma. Br. J. Cancer, London, v. 70, p. 1014-1017, 1994. KISIELEWSKI, R.; TOŁWIŃSKA, A.; MAZUREK, A. et al. Inflammation and ovarian cancer-current views. Ginekol. Pol., Warsaw, v. 84, n. 4, p. 293-297, 2013. KLEINERT, H.; SCHWARZ, P.M.; FORSTERMANN, U. Regulation of the expression of inducible nitric oxide synthase. Biol. Chem., Berlin, v. 384, n. 10-11, p. 1343-1364, 2003. KLOTZ, T.; BLOCH, W.; VOLBERG, C. et al. Selective expression of inducible nitric oxide synthase in human prostate carcinoma. Cancer, Philadelphia, v. 82, n. 10, p. 1897-1903, 1998. KÖBEL, M.; KALLOGER, S.E.; BOYD, N. et al. Ovarian carcinoma subtypes are different 5 diseases: implications for biomarker studies. PLOS Medicine, v. 5, n. 12, p. 1749-1760, 2008. KOVACS, E. The serum levels of IL-12 and IL-16 in cancer patients. Relation to the tumour stage and previous therapy. Biomed. Pharmacother., Paris, v. 55, p. 111-116, 2001. KOZŁOWSKI, L.; ZAKRZEWSKA, I.; TOKAJUK, P. et al. Concentration of interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-10 (IL-10) in blood serum of breast cancer patients. Rocz. Akad. Med. Bialymst., Bialystok, v. 48, p. 82-84, 2003. KULBE, H.; CHAKRAVARTY, P.; LEINSTER, D.A. et al. A dynamic inflammatory cytokine network in the human ovarian cancer microenvironment. Cancer Res., Baltimore, v. 72, n. 1, p. 66-75, 2012. KURIAN, A.W.; BALISE, R.R.; MCGUIRE, V. et al. Histologic types of epithelial ovarian cancer: have they different risk factors? Gynecol. Oncol., New York, v. 96, n. 2, p. 520-530, 2005. KURMAN RJ, SHIH IeM. The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am. J. Surg. Pathol., New York, v. 34, n. 3, p. 433-443, 2010. KURMAN, R.J.; SHIH IeM. Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer shifting the paradigm. Hum. Pathol., Philadelphia, v. 42, n. 7, p. 918-931, 2011. KUSUDA, T.; SHIGEMASA, K.; ARIHIRO, K. et al. Relative expression levels of Th1 and Th2 cytokine mRNA are independent prognostic factors in patients with ovarian cancer. Oncol. Rep., Atenas, v. 13, p. 1153-1158, 2005. KRISTJÁNSDÓTTIR, B.I.; PARTHEEN, K.; FUNG, E.T. et al. Early inflammatory response in epithelial ovarian tumor cyst fluids. Cancer Med., Oxford, v. 3, p. 1302- 1312, 2014. LALA, P.K.; CHAKRABORTY, C. Role of nitric oxide in carcinogenesis and tumour progression. Lancet Oncol., London, v. 2, n. 3, p. 149-156, 2001. LAMKIN, D.M.; LUTGENDORF, S.K.; MCGINN, S. et al. Positive psychosocial factors and NKT cells in ovarian cancer patients. Brain Behav. Immun., San Diego, v. 22, n. 1, p. 65-73, 2008. LEROUX, P.D., BERGER, M.S.; ELLIOTT, J.P. et al. Cerebral metastases from ovarian carcinoma. Cancer, New York, v. 67, n. 8, p. 2194-2199, Apr. 1991. LI, J.; FADARE, O.; XIANG, L. et al. Ovarian serous carcinoma: recent concepts on its origin and carcinogenesis. J. Hematol. Oncol., London, v. 5, p. 8, 2012. LIAO, W.; LIN, J.X.; LEONARD, W.J. IL-2 family cytokines: new insights into the complex roles of IL-2 as a broad regulator of T helper cell differentiation. Curr. Opin. Immunol., Philadelphia, v. 23, n. 5, p. 598-604, 2011. LILIAC, L.; AMALINEI, C.; BALAN, R. et al. Ovarian cancer: insights into genetics and pathogeny. Histol. Histopathol., Murcia, v. 27, n. 6, p. 707-719, 2012.106 LISSONI, P.; BARNI, S.; ROVELLI, F. et al. The biological significance of soluble interleukin-2 receptors in solid tumors. Eur. J. Cancer, Oxford, v. 26, n. 1, p. 33-36, 1990. LIU, C.Z.; ZHANG, L.; CHANG, X.H. et al. Overexpression and immunosuppressive functions of transforming growth factor 1, vascular endothelial growth factor and interleukin-10 in epithelial ovarian cancer. Chin. J. Cancer Res., HongKong, v. 24, n. 2, p. 130-137, 2012. LO, C.W.; CHEN, M.W.; HSIAO, M. et al. IL-6 trans-signaling in formation and progression of malignant ascites in ovarian cancer. Cancer Res., Baltimore, v. 71, n. 2, p. 424-434, 2011. LOKSHIN, A.E.; WINANS, M.; LANDSITTEL, D. et al. Circulating IL-8 and anti-IL- 8 autoantibody in patients with ovarian cancer. Gynecol. Oncol., New York, v. 102, p. 244-51, 2006. LOWE, D.B.; STORKUS, W.J. Chronic inflammation and immunologic - based constraints in malignant disease. Immunotherapy, London, v. 3, p. 1265-1274, 2011. MACKAY, F.; LOESTER, H.; STUEBER, D. et al. Tumor necrosis factor alpha (TNFalpha) induced cell adhesion to human endotelial cells is under dominant control of one TNF receptor type, TNF-R55. J. Exp. Med., New York, v. 177, p. 1277-1286, 1993. MANTOVANI, A.; ALLAVENA, P.; SICA, A. et al. Cancer - related inflammation. Nature, London, v. 454, n. 7203, p. 436-44, 2008. MANTOVANI, G.; MACCIÒ, A.; PISANO, M. et al.Tumor-associated lymphomonocytes from neoplastic effusions are immunologically defective in comparison with patient autologous PBMCs but are capable of releasing high amounts of various cytokines. Int. J. Cancer, New York, v. 71, n. 5, p. 724-731, 1997. MANTOVANI, A.; BOTTAZZI, B.; COLOTTA, F. et al. The origin and function of tumor-associated macrophages. Immunol. Today, Cambridge, v. 13, n. 7, p. 265- 270, 1992. MARSDEN, D. E.; FRIEDLANDER, M. Current Management of Epithelial Ovarian Carcinoma: A Review. Semin. Surg. Oncol., New York, v. 19, p. 11-19, 2000. MASOUMI-MOGHADDAM, S.; AMINI, A.; WEI, A.Q. et al. Intratumoral interleukin- 6 predicts ascites formation in patients with epithelial ovarian cancer: A potential tool for close monitoring. J. Ovarian Res., London, v. 8, p. 58, 2015. MASSI, D.; FRANCHI, A.; SARDI, I. et al. Inducible nitric oxide synthase expression in benign and malignant cutaneous melanocytic lesions. J. Pathol., Edinburgh, v. 194, n. 2, p. 194-200, 2001. MATTE, I.; LANE, D.; LAPLANTE, C. et al. Profiling of cytokines in human epithelial ovarian cancer ascites. Am. J. Cancer Res., Madison, v. 2, n. 5, p. 566-580, 2012. MAYER, A.R.; CHAMBERS, S.K.; GRAVES, E. et al. Ovarian cancer staging: does it require a gynecologic oncologist? Gynecol. Oncol., New York, v. 47, n. 2, p. 223-227, 1992. MAYERHOFER, K.; BODNER, K.; BODNER-ADLER, B. et al. Interleukin-8 serum level shift in patients with ovarian carcinoma undergoing paclitaxel-containing chemotherapy. Cancer, Philadelphia , v. 91, p. 388-393, 2001. MENDES, R.V.; MARTINS, A.R.; DE NUCCI, G. et al. Expression of nitric oxide synthase isoforms and nitrotyrosine immunoreactivity by B-cell non-Hodgkin's lymphomas and multiple myeloma. Histopathology, Oxford, v. 39, n. 2, p. 172-178, 2001. MICHEL, T.; FERON, O. Nitric oxide synthases: Which, where, how, and why? J. Clin. Invest., New York, v. 100, n. 9, p. 2146-2152, 1997. MICHELI, D.C. Quantificação sistêmica de mediadores inflamatórios e da expressão de receptores em neutrófilos em mulheres portadoras de tumor ovariano: efeito do tratamento nas pacientes com neoplasia maligna/Douglas Cobo Micheli. 28/07/2015. 125F. Tese (Doutorado em Ciências da Saúde) – Universidade Federal do Triângulo Mineiro, Uberaba, MG, 2015. MILBURN, M.V.; HASSELL, A.M.; LAMBERT, M.H. et al. A novel dimer configuration revealed by the crystal structure at 2.4 A resolution of human interleukin- 5. Nature, London, v. 363, n. 6425, p. 172-176, 1993. MINARETZIS, D.; TSIONOU, C.; TZIORTZIOTIS, D. et al. Ovarian tumors: prediction of the probability of malignancy by using patient’s age and tumor morphologic features with a logistic model. Gynecol. Obstet. Invest., Basel, v. 38, p. 140-144, 1994. MOCELLIN, S.; BRONTE, V.; NITTI, D. Nitric oxide, a double edged sword in cancer biology: seaching for therapeutic opportunities. Med. Res. Rev., New York, v. 27, n. 3, p. 317-352, 2007. MOCELLIN, S.; MARINCOLA, F.M.; YOUNG, H.A. Interleukin-10 and the immune response against cancer: a counterpoint. J. Leukoc. Biol., Winston-Salem, v. 78, p. 1043-1051, 2005. MONCADA, S.; PALMER, R.M.J.; HIGGS, E.A. Nitric Oxide: Physiology, pathophysiology, and pharmacology. Pharmacol. Rev., Baltimore, v. 43, p. 109-142, 1991. MURDOCH, W.J.; MARTINCHICK, J.F. Oxidative damage to DNA of ovarian surface epithelial cells affected by ovulation: carcinogenic implication and chemoprevention. Exp. Biol. Med.. Basel, v. 229, n. 6, p. 546-552, 2004. MURDOCH, W. J.; MCDONNEL, A. C. Roles of the ovarian surfasse epithelium in ovulation and carcinogenesis. Reproduction, Cambridge, v. 123, n. 6, p. 174-50, June, 2002. MURTA, E.F.C.; NOMELINI, R.S. Early diagnosis and predictors of malignancy in the evaluation of adnexal mass. Curr. Opin. Obstet. Gynecol., Philadelphia, v. 18, n. 1, p. 14-9, Feb. 2006. MURTA, E.F.C.; SILVA, C.S.; GOMES, R.A. et al. Ultrasonographic criteria and tumor marker assay are good procedures for the diagnosis of ovarian neoplasia in preselected outpatients. Eur. J. Gynaecol. Oncol., Montreal, v. 25, p. 707-712, 2004. MURTA, E. F. C.; ANDRADE, J. M.; BIGHETTI, S. Aspectos epidemiológicos do câncer de ovário. J. Bras. Ginecol., Rio de Janeiro, v. 105, p. 269-274, 1995. NAKAMURA, Y.; YASUOKA, H.; TSUJIMOTO, M. et al. Nitric oxide in breast cancer: induction of vascular endothelial growth factor-C and correlation with metastasis and poor prognosis. Clin. Cancer Res., Philadelphia, v. 12, n. 4, p. 1201- 1207, 2006. NARASIMHAN, K.; CHANGQING, Z.; CHOOLANI, M. Ovarian cancer proteomics: many technologies one goal. Clin. Proteomics, London, v. 2, n. 2, p. 195-218, Apr. 2008. NEGISHI, Y.; FURUNO, K.; SANO, Y. et al. Studies on CA 125, CA 19-9, TPA and IAP as tumor markers in patients with ovarian cancer. Gan No Rinsho, Tokyo, v. 31, Suppl 6, p. 655-63, 1985. NEGUS, R.P.; STAMP, G.W.; HADLEY, J. et al. Quantitative assessment of the leukocyte infiltrate in ovarian cancer and its relationship to the expression of C-C chemokines. Am. J. Pathol., New York, v. 150, n. 5, p. 1723-1734, 1997. NICOLINI, A.; CARPIB, A.; ROSSI, G. Cytokines in breast cancer. Cytokine Growth Factor Rev., Oxford, v. 17, p. 325-337, 2006. NIK NN, VANG R, SHIH IeM et al. Origin and pathogenesis of pelvic (ovarian, tubal, and primary peritoneal) serous carcinoma. Annu. Rev. Pathol., Bethesda, v. 9, p. 27-45, 2014. NISIDA, A. C. T. Câncer de ovário: Importância, epidemiologia e fatores de risco. In: Halbe HW. Tratado de Ginecologia. São Paulo: Roca [2000]. p.2242-2245, 2000. NOMELINI, R.S.; RIBEIRO, L.C.A, TAVARES-MURTA, B.M. et al. Production of nitric oxide and expression of inducible nitric oxide synthase in ovarian cystic tumors. Mediat. Inflamm., New York, v. 2008, n. 186584, 2008. OMURA, G.A.; BRADY, M.F.; HOMESLEY, H.D. et al: Long-term follow up and prognostic factor analysis in advanced ovarian carcinoma: the Gynecologic Oncology Group experience. J. Clin. Oncol., New York, v. 9, n. 7, p. 1138-1150, 1991. OLIVIER, R.I.; LUBSEN-BRANDSMA, M.A., VERHOEF, S. et al. Ca 125 and transvaginalultrasound monitoring in high-risk women cannot prevent the diagnosis of advanced ovarian cancer. Gynecol. Oncol., New York, v. 100, p. 20-26, 2006. OLSON, S.H.; MIGNONE, L.; NAKRASEIVE, C. et al. Symptoms of ovarian cancer. Obstet. Gynecol., Hagerstown, v. 98, n. 2, p. 212-217, 2001. ORAM, D.H.; JACOBS, I.J.; BRADY, J.L. et al. Early diagnosis of ovarian cancer. Br. J
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Citocinas e Óxido Nítrico Intracístico em Neoplasias Ovarianas

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