The ovarian surface epithelium, a very small portion of the total mass of the ovary, is generally thought to be the site of origin of over 85% of ovarian cancers. Such cancers are classified with the "Common Epithelial Tumours" of the ovary. In most industrialized countries, malignancies of the ovary rank fourth in cancer deaths in women; over 70% of these neoplasms have spread beyond the ovary when first diagnosed. Experimental approaches to the study of carcinogenesis in this tissue have been limited by the lack of pure populations of ovarian surface epithelial cells. Studies done on rodents in vivo suggest that both chemicals and C-type RNA viruses can induce ovarian cancers similar to those which are said to arise from the surface epithelium. However, the cell of origin cannot be proven in such studies. The purpose of this project was to develop a model for ovarian cancers of surface epithelial origin based on-carcinogenesis in vitro. To this end a method was devised to culture the rat ovarian surface epithelium in pure form. These cultured cells, whose identity has been confirmed by morphological, histochemical and ultrastructural means, are polygonal with clear cytoplasm, have well-defined borders, and grow in confluent monolayers. Their morphology is quite distinct from those of other ovarian cells in vitro. Cultured rat ovarian surface epithelial cells are histochemically positive for 17β-hydroxysteroid dehydrogenase, and negative for Δ5-3β-hydroxysteroid dehydrogenase, the same as in frozen sections of whole rat ovary. Ultrastructurally, cultured surface epithelial cells have basal laminae, microvilli, apical intercellular junctions, large nuclei, abundant rough endoplasmic reticulum, Golgi complexes, perinuclear bundles of microfilaments, and numerous vesicles. Although the ovarian suface epithelium is suspected of being an estrogen target tissue, there is no previous report of estrogen receptors in these cells. In this study cultured rat ovarian surface epithelial cells have been shown by autoradiographic means to exhibit estrogen receptor-like activity. Translocation of tritiated estradiol from cytoplasm to nucleus, and estrogen-specific binding have been demonstrated. Estradiol was shown to be mitogenic for cultured ovarian surface epithelial cells. From these results, the surface epithelial .cells of the ovary should be considered an estrogen target tissue. Kirsten murine sarcoma virus was used to produce three transformed cell lines from pure, first passage cultures of these cells. These three lines retained 170-hydroxysteroid dehydrogenase activity and showed slight Δ5-3β-hydroxysteroid dehydrogenase activity. Tumours resulting when these cells were injected into immunosuppressed female rats were highly malignant and resembled histologically human endometrioid stromal sarcomas of the ovary. This neoplasm is classed with the "Common Epithelial Tumours" of the ovary, but is generally not considered a derivative of the surface epithelium. In light of this study, perhaps this tumour should: be considered, to be of surface epithelial origin. A continuous cell line arising from pure cultures of rat ovarian surface epithelial cells produced structures in vitro resembling those found in ovarian serous papillary cystadenomas of borderline malignancy. This tumour is classed as a common epithelial ovarian tumour. Hence, in this study the rat ovarian surface epithelium has been cultured in pure form, has been characterized for a number of properties by several investigative techniques, and has been shown to be susceptible to transformation by an oncogenic virus; This work supports the theory that the "Common Epithelial Tumours" of the ovary are, in fact, derived from the surface epithelium. The availability of cultured ovarian surface epithelial cells should allow investigation into factors which make this tissue so susceptible to malignant transformation. From such cultures could come markers suitable for use in tests to detect ovarian cancers at an early stage. The culture of pure rat ovarian surface epithelium, as described herein, could readily be used to study chemical, physical and viral carcinogenesis in this tissue to produce experimental models of cancers arising in the ovarian surface epithelium. / Science, Faculty of / Zoology, Department of / Graduate

Heterozygous mutations in BRCA1 or BRCA2 predispose carriers to an increased risk for breast or ovarian cancer. Both BRCA1 and BRCA2 (BRCA1/2) play an integral role in promoting genomic stability through their respective actions during homologous recombination (HR) mediated repair and stalled replication fork protection from nucleolytic degradation. SMARCAD1 (SD1) is a SWI/SNF chromatin remodeler that has been implicated in promoting long-range end resection and contributes to HR. Using human cell lines, we show that SMARCAD1 promotes nucleolytic degradation in BRCA1/2-deficient cells dependent on its chromatin remodeling activity. Moreover, SMARCAD1 prevents DNA break formation and promotes fork restart at stalled replication forks. These studies identify a new role for SMARCAD1 at the replication fork. In addition to the work presented here, I discuss a method for introducing stop codons (nonsense mutations) into genes using CRISPR-mediated base editing, called iSTOP, and provide an online resource for accessing the sequence of iSTOP sgRNASs (sgSTOPs) for five base editor variants (VQR-BE3, EQR-BE3, VRER-BE3, SaBE3, and SaKKH-BE3) in humans and over 3 million targetable gene coordinates for eight eukaryotic species. Ultimately, with improvements to CRISPR base editors this method can help model and study nonsense mutations in human disease.

Electronic biosensors utilizing micron-scale interdigitate electrodes (IDEs) in an SD card format have been developed with the objective of fast, sensitive detection of ovarian cancer biomarkers CA-125, CEA, and He4. The signal generated by the biosensors is a result of electrochemical impedance spectroscopy (EIS), a technique which probes changes that occur in the biosensor's electrical properties when the biosensor has detected one of the target biomarkers. A label-free biosensor has been developed to detect CA-125 in spiked buffer at concentrations between 10 and 80units/mL. A similar label-free biosensor was developed to detect CEA at concentrations between 10ug/mL and 10mg/mL. A biosensor employing a protein-enzyme conjugated label was developed to detect He4 at concentrations ranging from 1.56 to 100ng/mL in spiked buffer. All concentration ranges of CA-125, CEA, and He4 detected by the biosensors include the serum concentration currently used for clinical diagnosis of ovarian cancer. Efforts to improve the signals generated by the biosensors included altering the dimensions and composition of the IDEs used in the initial biosensors through software-created models. Modeled alterations included the size of the electrodes, the shape of the electrodes, and the incorporation of nanomaterials into the IDEs. An ideal geometry for the IDEs was developed through the models and IDEs with those dimensions were fabricated and tested against the IDEs used in the biosensors initially with the model-developed geometry improving the signal generated by the biosensor. Another attempt to improve the biosensor's signal was to generate a single strand of DNA (ssDNA) that would bind to CA-125, called an aptamer, that could be easily incorporated into the sensing layer on the IDEs. Through a multistep selection process nine different aptamers that exhibited binding to CA-125 were identified.

published_or_final_version / abstract / Pathology / Master / Master of Philosophy

This dissertation examines the production and management of genetic risk for breast and ovarian cancer in the United States in the new era of multi-gene panel testing. Drawing on three years of ethnographic fieldwork and in-depth interviews with genetics health professionals and women with mutations, this project is the first social science study to examine how breast and ovarian cancer genetic risk is constructed and managed among women with variants of uncertain significance or moderate-risk mutations. Moving beyond an individual-level focus on women’s risk management decisions, this project instead explores how the structures, practices, and organization of genetic medicine constrain and enable those decisions. There are four key findings from this study. First, the adoption of panel testing has shifted the boundaries of risk, disease, and patienthood and contributed to a spectrum of medicalization of breast and ovarian cancer risk. Women with high-risk breast and ovarian cancer mutations are now typically viewed and treated like full patients with a "disease," while women with moderate-risk mutations occupy a liminal space of qualified patienthood. Second, the structures and organization of genetic medicine in the United States point women with breast and ovarian cancer mutations toward risk-reducing mastectomy and breast reconstruction and encourage choosing those surgical responses over breast surveillance or staying flat. Mastectomy has become the standard “treatment” for the “disease” of genetic risk for breast cancer, regardless of whether women have high- or moderate-risk mutations and despite more conservative recommendations in clinical guidelines. Third, the structures of genetic medicine and the contemporary gender order in the United States are mutually constituted and co-produced. Breast reconstruction and gynecologic surgery practices both emerge from and reinforce gendered social and cultural norms that prioritize women's appearance and their reproductive capacity over their embodied experiences and daily quality of life. Finally, the discourses and practices of genetic medicine leave many women un- or under-prepared for the duration and severity of the side effects and consequences associated with breast reconstruction and risk-reducing salpingo-oophorectomy. By closely examining the social and structural dimensions of how cancer genetic risk is produced and managed in the United States, this project illuminates how clinical practices that magnify and focus on reducing certain risks simultaneously obscure and generate exposure to others.

In the studies about ovarian cancer cells, basal iNOS expression in the chemosensitive OV2008 cells was significantly higher than in the chemoresistant C13* cells. Cisplatin further increased iNOS expression in OV2008 cells, but had no effect in C13* cells. Furthermore, cisplatin dramatically reduced the expression levels of eNOS and nNOS, but again only in OV2008 cells. The data suggest that failure of cisplatin to upregulate iNOS and downregulate eNOS and nNOS in C13* cells could be an etiological factor in chemoresistance. Addition of exogenous NO at high levels, using SNAP, significantly increased p53 protein levels and caused apoptosis in both cell types. Specific iNOS inhibitor (1400W) partially blocked the pro-apoptotic effects of cisplatin in OV2008 cells, suggesting involvement of iNOS in cisplatin-induced apoptosis. However, blocking of all three isoforms of NOS with NG-amino-L-arginine in C13* cells dramatically changed these cells from chemoresistant to chemosensitive, greatly potentiating the pro-apoptotic effects of cisplatin. / Inhibition of Src-kinase activity reduces DNA synthesis in ovarian cancer cells. In an in vitro experiment, Src phosphorylated PKG on a tyrosine residue and PKG, presumable via serine-phosphorylation of Src, enhanced Src auto(tyrosine)phosphorylation. In ovarian cancer cells, inhibition of basal PKG activity with DT-2 decreased both basal and EGF-stimulated Src kinase activation and DNA synthesis. The data suggest that PKG at basal activity, is necessary for both basal and growth factor-stimulated Src kinase activation and enhanced DNA synthesis in human ovarian cancer cells. / The novel role of sGC/cGMP/PKG pathway on stimulating cell proliferation, potentially via interaction with the Src kinase pathway in human ovarian cancer cells, was demonstrated. ODQ dramatically reduced DNA synthesis rates, suggesting that basal sGC activity and basal cGMP levels are needed for ovarian cancer cell proliferation. DT-2 also reduced cell proliferation, suggesting the direct involvement of PKG. ANP and BNP had no effect on cell proliferation, suggesting that further activation of cGMP/PKG pathway above basal levels does not further enhance cell proliferation. / The present study also demonstrated that elevating cGMP slightly above the basal levels further protects pancreatic islet cells against spontaneous onset of apoptosis. The results showed that natriuretic peptides (both ANP and BNP) and low-level NO (i.e. physiological levels) as supply by NO donor, S-nitroso-N-acetylpenicilamine (SNAP) further prevented spontaneous apoptosis in pancreatic islets after isolation, whereas NO at high concentrations (i.e. pathological levels) promoted apoptosis in pancreatic islet cells. The commonly-used PKG inhibitor KT5823 and the newly-developed specific PKG inhibitor DT-2 completely prevented anti-apoptosic effect of ANP, suggesting the direct involvement of PKG in protection against spontaneous apoptosis. / The present study demonstrated that basal activity of sGC/cGMP/PKG signaling pathway is essential for partially limiting spontaneous apoptosis in pancreatic islet cells. The sGC inhibitor ODQ caused induction of apoptosis, which was completely blocked by co-treatment with ANP or BNP, agents that elevate cGMP via pGC, bypassing the ODQ block. Co-treatment with 8-Br-cGMP, a direct activator of PKG also completely prevented ODQ-induced apoptosis in islets. / Leung Lai-han. / "July 2006." / Adviser: Ronald Ray Fiscus. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1483. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 175-191). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

In this dissertation, we developed cell stiffness as a biomarker in ovarian cancer for the purpose of grading metastatic potential. By measuring single cell stiffness with atomic force microscopy and quantifying in vitro invasiveness of healthy and cancerous ovarian cells, we demonstrated that cancerous ovarian cells have reduced stiffness compared to the healthy ones and invasive ovarian cancer cells are more deformable than noninvasive ovarian cancer cells. The difference in cell stiffness between two genetically similar cell lines was attributed to actin-mediated cytoskeletal remodeling as revealed by comparative gene expression profile analysis, and was further confirmed by fluorescent visualization of actin cytoskeletal structures. The actin cytoskeletons were innovatively quantified and correlates with cell stiffness distributions, further implicating actin-mediated cytoskeletal remodeling in stiffness alteration from the perspective of structure-property relationship. The correlation between stiffness and metastatic potential was also demonstrated in pancreatic cancer cell line AsPC-1, which shows reduced invasivess and increased stiffness upon treatment with N-acetyl-L-cysteine (NAC), a well known antioxidant, reactive oxygen species (ROS), scavenger and glutathione precursor. The correlation between cell stiffness and metastatic potential as demonstrated in ovarian and pancreatic cancer cells indicated that mechanical stiffness may be a useful biomarker to evaluate the relative metastatic potential of ovarian and perhaps other types of cancer cells, and might be useful clinically with the development of rapid biomechanical assaying techniques. We have also investigated the stiffness evolution through progression of the cell cycle for the healthy ovarian phenotype and the invasive cancer ovarian phenotype, and found that the healthy phenotype at G1 phase are significantly stiffer than other single cells except the invasive phenotype at late mitosis; other groups are not significantly different from each other. We have also investigated intracellular heterogeneity and mechanical nonlinearity in single cells. To this end, we developed a methodology to analyze the deformation-dependent mechanical nonlinearity using a pointwise Hertzian method, and tested the method on ultrathin polydimethylsiloxane (PDMS) films which underwent extremely large strains (greater than 50%). Mechanical stiffening due to large strain and geometrical confinement were observed. The onset of nonlinearity or mechanical stiffening occurs at 45% of the film thickness, the geometry induced stiffening causes an increase in stiffness which shows a strong power law dependence on film thickness. By applying the pointwise Hertzian method on stiffness measurements with AFM that were collected on living cells, we also investigated the nonlinear and heterogeneous mechanics of single cells, since attachment of cells to stiff substrate during indentation may impact their mechanical responses. Even under natural biological conditions, cells confined in narrow spaces may experience heightened mechanical stiffness. Through indentation-dependent force mapping, analysis of the local cell stiffness demonstrated spatial variation. The results indicated that the mechanical properties of single cells are highly nonlinear and are dependent upon the subcellular features under the applied force as well as the dimensions of the cellular material. We identified single cell stiffness as a potential biomarker of the metastatic potential in ovarian cancer, and quantified the effect of geometrical confinement on cell mechanics. The results presented in this dissertation not only made contributions to the development of accurate, non-invasive clinical methods to estimate metastatic potential of ovarian and perhaps other types of cancer, but also shed light on the intracellular mechanical information by developing new techniques to quantify the effect of geometry on cell mechanics.

Purpose: Control of micrometastatic ovarian cancer in the peritoneal cavity remains a major objective in post-surgical treatment. The purpose of this project was to investigate the efficacy and toxicity of targeted alpha therapy (TAT) for ovarian cancer in vitro and in vivo in animal models and to select the optimal targeting vector for an ovarian cancer clinical trial. Animal models of ovarian, breast and prostate cancer were developed and for further TAT; a phase I melanoma clinical trial was supported, paving the way for an ovarian cancer clinical trial. Methods: The expression of the turnor-associated antigens (Her2, MUC1, uPAfuPAR) on cancer cell line, animal model xenografts and human ovarian cancer tissue was tested by immunostaining. MTS and TUNEL assays were used to evaluate cell killing of alpha conjugates in monolayer and spheroids. Toxicity and maximum tolerance doses for different vectors were tested and determined in vivo. Pharmacokinetics was studied for different time points and different parameters. The antiproliferative effect of 213Bi-C595 and 213Bi-PAI2 was tested at 9 days post-peritoneal cell inoculation of the ovarian cancer cell line OVCAR3. The treatment efficacy of 213Bi-Herceptin was tested at a 2 days post-subcutaneous breast cancer cell BT474 inoculation. Mice were injected (i.p) with various concentrations of alpha conjugates (AC). Changes in cancer progression were assessed by girth size and tumor size. Results: uPA/uPAR and MUCI are expressed on ovarian cancer cell lines and more than 45% ovarian cancer tissue, while HER2 was only positive in one cell line and was positive in less than 15% of ovarian cancer tissues. The ACs can target and kill cancer cells in vitro in a dose dependent fashion. TUNEL positive cells were found after incubation with the different ACs. PAI2 and C595 vectors were selected for in vivo ascites model study of OVCARJ cell with high expression. Delayed and acute toxicity in animal models showed that radiation nephropathy was the cause of body weight loss. Biodistribution studies showed that kidney was the major uptake organ. L-lysine can reduce kidney uptake for 213Bi-PAI2, but no significant differences were found. A single ip injection of 213Bi-C595 or 213Bi-PAI2 can inhibit ascites growth, whereas, 213Bi-Herceptin can inhibit breast cancer growth in a nude mice model. Conclusion: 213Bi labelled targeting vectors can specifically target ovarian cancer cells in vitro and inhibit tumor growth in vivo. These ACs may be useful agents for the treatment of ovarian cancer at the minimum residual disease stage.

Made available in DSpace on 2015-03-03T11:52:48Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-02-24Bitstream added on 2015-03-03T12:07:01Z : No. of bitstreams: 1 000807311.pdf: 1576554 bytes, checksum: 8c98005febc992a7fec3f6de5d99dd6a (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo á Pesquisa do Estado de Minas Gerais (FAPEMIG) / Fundação Oswaldo Cruz (FIOCRUZ) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / O câncer epitelial de ovário representa um desafio para Oncologia Ginecológica, devido à sua natureza insidiosa e alta mortalidade. Há também uma compreensão limitada da etiologia da doença ao nível molecular, o que continua a dificultar o desenvolvimento de alvos terapêuticos. Estudos recentes de morfologia, imuno-histoquímica e de genética molecular têm levado ao desenvolvimento de um novo paradigma para a patogênese e a origem do câncer epitelial de ovário, baseado em um modelo dualista de carcinogênese que divide o câncer epitelial de ovário (CEO) em duas grandes categorias chamadas de tipos I e II. O objetivo deste estudo foi avaliar o padrão das citocinas e quimiocinas encontradas no tecido ovariano de mulheres saudáveis e mulheres com CEO tipo I e tipo II. Além disso, descrever a associação desses biomarcadores com os dados clínico-patológicos. Foram analisadas amostras de tecido ovariano e ascite obtidas de mulheres com CEO (n=26) e amostras de tecido ovariano e lavado peritoneal de mulheres sem evidências de malignidade (n=16 - grupo de controle). Nas amostras de tecido, a expressão gênica foi avaliada utilizando a metodologia de PCR quantitativo em tempo real (qPCR) para os genes IFNG, IL-10, TGFB1, CCL2, CCL3, CCL5, CXCL8, CXCL9 e CXCL10. A detecção dos níveis de citoquinas/quimioquinas nos fluidos peritoneais foi realizada através do método Cytometric Bead Array (CBA) os marcadores IL-12p70, TNF, IL-10, IL-6, IL-1--8, IL-17A, IFN-IL-4, IL-2, CCL2, CCL5, CXCL-9 e CXCL-10. No grupo das pacientes com CEO, 10 (38,5%) apresentavam estágios I/II e 16 (61,5%) estágios III/IV. Com relação ao tipo de tumor, de acordo com a nova classificação, 8 (30,8%) eram do tipo I e 18 (69,2 %) do tipo II. A citorredução ótima foi obtida em 15 (57,7%) das mulheres com CEO. Mulheres com CEO tipo II apresentaram maiores níveis séricos do marcador CA-125 quando comparado às do tipo I. Não houve óbito no grupo ... / The epithelial ovarian cancer represents a challenge to Gynecologic Oncology due to its insidious nature and high mortality. There is also a limited understanding of disease etiology at the molecular level, which continues to hamper targeted therapeutic development. Recent morphological, immunohistochemical, and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer based on a dualistic model of carcinogenesis that divides epithelial ovarian cancer into 2 broad categories designated types I and II. The aim of this study was to evaluate the cytokines and chemokines pattern in ovarian tissue from healthy women and women with EOC type I and type II. Also, we described the association of these biomarkers with the clinicopathological data. Samples of ovarian tissue and ascite obtained from women with EOC (n=26), samples of ovarian tissue and peritoneal wash from women with no evidence of malignancy were analyzed (n=16 – control group). In the tissue samples, gene expression were evaluated by quantitative real time PCR (qPCR) IFNG, IL-10, TGFB1, CCL2, CCL3, CCL5, CXCL8, CXCL9 and CXCL10. The detection of cytokine/chemokine levels in peritoneal fluids was measured by cytometric bead array immunoassay (CBA), IL-12p70, TNF, IL-10, IL-6, IL-1--8, IL-17A, IFN--4, IL-2, CCL2, CCL5, CXCL-9 and CXCL-10. In the group of women with EOC, 10 (38.5 %) had stage I/II and 16 (61.5 %) were stage III/IV . Concerning tumor type , according to the new classification, 8 (30.8 %) were type I and type II were 18 ( 69.2 % ) . Optimal cytoreduction was achieved in 15 (57.7 %) women with EOC. The CA-125 showed higher serum levels in patients with EOC type II compared to type I. There were no deaths in women with type I tumor while 6 (33.3 %) of patients with type II tumor died . Increased expression of IL-10, CXCL8 and CXCL9 genes in the group of women

Orientador: Agnaldo Lopes da Silva Filho / Coorientador: Andréa Teixeira de Carvalho / Resumo: O câncer epitelial de ovário representa um desafio para Oncologia Ginecológica, devido à sua natureza insidiosa e alta mortalidade. Há também uma compreensão limitada da etiologia da doença ao nível molecular, o que continua a dificultar o desenvolvimento de alvos terapêuticos. Estudos recentes de morfologia, imuno-histoquímica e de genética molecular têm levado ao desenvolvimento de um novo paradigma para a patogênese e a origem do câncer epitelial de ovário, baseado em um modelo dualista de carcinogênese que divide o câncer epitelial de ovário (CEO) em duas grandes categorias chamadas de tipos I e II. O objetivo deste estudo foi avaliar o padrão das citocinas e quimiocinas encontradas no tecido ovariano de mulheres saudáveis e mulheres com CEO tipo I e tipo II. Além disso, descrever a associação desses biomarcadores com os dados clínico-patológicos. Foram analisadas amostras de tecido ovariano e ascite obtidas de mulheres com CEO (n=26) e amostras de tecido ovariano e lavado peritoneal de mulheres sem evidências de malignidade (n=16 - grupo de controle). Nas amostras de tecido, a expressão gênica foi avaliada utilizando a metodologia de PCR quantitativo em tempo real (qPCR) para os genes IFNG, IL-10, TGFB1, CCL2, CCL3, CCL5, CXCL8, CXCL9 e CXCL10. A detecção dos níveis de citoquinas/quimioquinas nos fluidos peritoneais foi realizada através do método Cytometric Bead Array (CBA) os marcadores IL-12p70, TNF, IL-10, IL-6, IL-1--8, IL-17A, IFN-IL-4, IL-2, CCL2, CCL5, CXCL-9 e CXCL-10. No grupo das pacientes com CEO, 10 (38,5%) apresentavam estágios I/II e 16 (61,5%) estágios III/IV. Com relação ao tipo de tumor, de acordo com a nova classificação, 8 (30,8%) eram do tipo I e 18 (69,2 %) do tipo II. A citorredução ótima foi obtida em 15 (57,7%) das mulheres com CEO. Mulheres com CEO tipo II apresentaram maiores níveis séricos do marcador CA-125 quando comparado às do tipo I. Não houve óbito no grupo... / Abstract: The epithelial ovarian cancer represents a challenge to Gynecologic Oncology due to its insidious nature and high mortality. There is also a limited understanding of disease etiology at the molecular level, which continues to hamper targeted therapeutic development. Recent morphological, immunohistochemical, and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer based on a dualistic model of carcinogenesis that divides epithelial ovarian cancer into 2 broad categories designated types I and II. The aim of this study was to evaluate the cytokines and chemokines pattern in ovarian tissue from healthy women and women with EOC type I and type II. Also, we described the association of these biomarkers with the clinicopathological data. Samples of ovarian tissue and ascite obtained from women with EOC (n=26), samples of ovarian tissue and peritoneal wash from women with no evidence of malignancy were analyzed (n=16 - control group). In the tissue samples, gene expression were evaluated by quantitative real time PCR (qPCR) IFNG, IL-10, TGFB1, CCL2, CCL3, CCL5, CXCL8, CXCL9 and CXCL10. The detection of cytokine/chemokine levels in peritoneal fluids was measured by cytometric bead array immunoassay (CBA), IL-12p70, TNF, IL-10, IL-6, IL-1--8, IL-17A, IFN--4, IL-2, CCL2, CCL5, CXCL-9 and CXCL-10. In the group of women with EOC, 10 (38.5 %) had stage I/II and 16 (61.5 %) were stage III/IV . Concerning tumor type, according to the new classification, 8 (30.8 %) were type I and type II were 18 ( 69.2 % ) . Optimal cytoreduction was achieved in 15 (57.7 %) women with EOC. The CA-125 showed higher serum levels in patients with EOC type II compared to type I. There were no deaths in women with type I tumor while 6 (33.3 %) of patients with type II tumor died . Increased expression of IL-10, CXCL8 and CXCL9 genes in the group of women / Doutor