Biotecnologia (RENORBIO)
URI Permanente desta comunidade
Programa de Pós-Graduação em Biotecnologia Rede Nordeste de Biotecnologia (Renorbio)
Centro: CCS
Telefone: (27) 3335 7447
URL do programa: https://biotecnologia.ufes.br/pt-br/pos-graduacao/RENORBIO
Navegar
Navegando Biotecnologia (RENORBIO) por Assunto "Câncer de ovário"
Agora exibindo 1 - 4 de 4
Resultados por página
Opções de Ordenação
- ItemAnálise funcional de nove SNPs de susceptibilidade ao câncer de ovário no locus 8q21(Universidade Federal do Espírito Santo, 2018-03-19) Lyra Junior, Paulo Cilas Morais; Monteiro, Álvaro; Rangel, Letícia Batista Azevedo; Daltoé, Renata Dalmaschio; Gimba, Etel Rodrigues Pereira; Guimarães, Marco César Cunegundes; Barauna, Valério GarroneOvarian câncer (OC) is one of the most lethal cancer because of lack of early diagnosis. Genetic factors contributing to OC have recently been investigated through genome-wide association studies (GWAS), implicating in several independent OC risk loci in different chromosomal regions, among them the locus 8q21. Here, we performed an in-depth functional analysis of 9 SNPs causal candidates in the risk locus on 8q21 proximal to the CHMP4C gene. We first characterized the region for likely regulatory elements and genes associated, then we tested the 9 SNPs candidates for allele-specific activity in two different enhancer scanning assay, as well transcription factors associated.
- ItemBiomarcadores no câncer de mama e ovário : uma correlação entre alterações genéticas e aspectos histopatológicos(Universidade Federal do Espírito Santo, 2013-02-04) Wolfgramm, Eldamária de Vargas; Louro, Iúri Drumond; Paula, Flávia de; Paneto, Greiciane Gaburro; Careta, Francisco de Paula; Silva, Melissa de Fretas CordeiroBreast and ovarian cancers are hormone-related diseases and polymorphisms in cancer genetic susceptibility genes involved in the production and metabolism of steroid hormones play an important role in the carcinogenesis of these tumors. Particularly, polymorphisms in short tandem repeat regions (STR) provide information about two events: microsatellite instability (MSI) and loss of heterozygosis (LOH). To check the presence of MSI and LOH in breast and ovarian cancers, 12 STR markers (CYP11, CYP19, UGT1A1, AR, ERα, ERβ, D5S345, D17S250, D10S197, D8S135, D3S1611 and D2S119) were analyzed in this study by Polymerase Chain Reaction (PCR) in 107 breast and 24 ovarian tumors. Single nucleotide polymorphisms (SNPs) in GSTP1 (A313G) and CYP17 (T27C) genes were also analyzed to estimate the frequency of susceptibility gene polymorphisms. In addition to the molecular analysis, an epidemiological study was conducted through the analysis of two oncology reference Hospital Pathology Service records in Espirito Santo, Brazil, during years 2001 to 2004 and 2009 to 2010. The epidemiological study detected 1,758 malignant breast and 119 ovarian tumors. Mean ages for malignant breast and ovarian tumors were 53.59 and 52.98 years, respectively. Among breast tumors, infiltrating ductal carcinoma was the most frequent malignant tumor and an increased tumor frequency in age group ≤ 35 years was observed for other malignant tumors of the breast in the time period 2009-2010, as compared to time period 2001-2004. The molecular study has shown that LOH is an event more frequently observed that MSI, in both breast and ovarian cancers. In breast carcinomas, the combination of STR markers showed that AR, CYP19 and ERβ, when analyzed together, were correlated with parameters of histological grade III, ER (estrogen receptor) negative tumors and PR (progesterone receptor) negative tumors. The combination of markers did not show significant results in ovarian tumors. Combination between STR markers and GSTP1 and CYP17 genotypes were performed, showing positive correlations among GSTP1 Ile/Ile genotype, AR+CYP19 (p=0.021) and AR+ERβ+CYP19 (p=0.036) alteration in PR negatives breast cancers, while CYP17 A1/A1 genotype was associated with AR+ERβ and AR+ERβ+CYP19 alterations in ER and PR negative breast tumors (p=0.039 to all combinations). We did not find associations between gene combinations and ovarian tumors. These data support the hypothesis that genes related to steroid metabolism are important in the characterization of breast cancer and that the analysis of a single polymorphism may not be enough to molecular characterize a tumor.
- ItemO estudo da PDE7 como novo alvo terapêutico em potencial no câncer de ovário(Universidade Federal do Espírito Santo, 2017-07-20) Tessarollo, Nayara Gusmão; Rangel, Leticia Batista Azevedo; Zeidler, Sandra Ventorin Von; Silva, Ian Victor; Pires, Rita Gomes Wanderley; Gonçalves, Juliana Barbosa CoitinhoOvarian cancer (OC) is the leading cause of death among gynecological tumors. Despite significant advances in this kind of tumor research, the treatment still faces significant challenges, including chemoresistance. Among the potential targets in the treatment of CAOV, highlight the phosphodiesterase 7-A (PDE7-A). This enzyme degrades the cyclic adenosine monophosphate (cAMP) to adenosine monophosphate. In this context, this project aims to investigate the role of PDE7 and its mechanism of action in ovarian carcinoma. Previous data from RNA-seq showed higher expression of PDE7-A enzyme in ovarian serous carcinoma compared to the fallopian tube. Considering what has been said, metabolic cell viability assays (MCV) were conducted in two CAOV cell lines, A2780 and OVCAR3, using the selective PDE7 isoform inhibitor, designate BRL50481, in monotherapy and in combination with cisplatin (CISP) and paclitaxel (PTX). Our results showed that the use of the BRL50481 inhibitor in monotherapy reduced the A2780 cells MCV by about 60% in a dose-dependent manner in the 48 hour treatment. Although the treatment with BRL50481 in monotherapy in OVCAR3 cell line did not change the MCV, its association with CISP in 48 hour-treated cell, promoted a reduction of MCV. On the other hand, the association of BRL50481 and PTX promoted inhibition of MCV in both cell lines analyzed. An increase in the potency of PTX was also observed, an aspect verified with the reduction of the IC50 of PTX in relation to monotherapy. The treatment chronology in cell survival was also verified. Thus, pretreatment of A2780 with 200 μM BRL50481 followed by the associated treatment of BRL50481 and PTX promoted a reduction in MCV of around 70% compared to the treatment with PTX alone. For OVCAR3, 400 μM pretreatment of BRL 50481 provided a VCM reduction of about 20%. Therefore, our data showed beneficial effect between the PDE7 inhibitor and PTX, which allowed a reduction of the PTX concentration used in A2780 and OVCAR3 by about 82.7x108 and 80.4x103 times, respectively. Moreover, the possible mechanisms of action involved in the inhibition of PDE7 have been investigated. It has been observed that the PDE7 inhibition does not affect cell cycle progression. Furthermore, the combination of BRL50481 and PTX promoted increased cell necrosis in OVCAR3. In addition, pretreatment of the OVCAR3 with BRL50481 modulated the gene expression of the cytokines IL-6, IL-1α and IL-1β, as well as increased IL-6 secretion. The combination of BRL50481 and PTX further modulated negatively the PI3K / AKT / mTOR cell signaling pathway in both cell lines studied. In addition, the A2780 pre-treated cells showed an increase in the expression of the pro-apoptotic Bax protein. Still, cell death may be related to the induction of autophagy in the two study models. It has also been observed that CLDN-16 expression is modulated by the PKC, PI3K/AKT and PKA pathways and, by inhibiting PDE7, a greater expression of CLDN-16 was verified. Immunohistochemical analyzes revealed that 80% of the analyzed cases overexpress this protein. Interestingly, this is an anomalous expression, since in all the cases that showed expression of CLDN-16, it was restricted to the cytoplasm of the cells. These studies contributed to a better understanding of the mechanisms involved in the cellular proliferation of CAOV, allowing the exploration of new therapeutic strategies.
- ItemO PAPEL DE CXCR2 EM CÉLULAS PANQUIMIORRESISTENTES DE CÂNCER DE OVÁRIO SEROSO DE ALTO GRAU(Universidade Federal do Espírito Santo, 2020-07-02) Henriques, Taciane Barbosa; Rangel, Leticia Batista Azevedo; https://orcid.org/0000000261504064; http://lattes.cnpq.br/6706127386696883; https://orcid.org/0000000249205117; http://lattes.cnpq.br/; Guimaraes, Marco Cesar Cunegundes; https://orcid.org/0000000321460180; http://lattes.cnpq.br/0261991057482057; Goncalves, Juliana Barbosa Coitinho; https://orcid.org/000000025892050X; http://lattes.cnpq.br/3448669742301744; Gimba, Etel Rodrigues Pereira; https://orcid.org/; http://lattes.cnpq.br/; Junior, Paulo Cilas Morais LyraOvarian cancer (CAOV) represents the eighth most common cancer among women, being the fifth leading cause of cancer death in the female universe. Despite the initial satisfactory response to platinum/taxane based therapy, chemoresistance still represents