Single CpG island methylation is not sufficient to maintain the silenced expression of CASPASE-8 apoptosis-related gene among women with epithelial ovarian cancer

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Assessment of chemokine serum levels in epithelial ovarian cancer patients

Aims and background. The study was undertaken to investigate CCL2/MCP-1, CCL3/MIP-l alpha, CCL4/MIP-1 beta, CCL5/RANTES and CXCL8/IL-8 women with epithelial ovarian cancer.Methods and study design. Sixteen patients diagnosed with epithelial ovarian cancer and 18 healthy women with no evidence of malign neoplasia (control group) aged from 23 to 89 years (mean +/- SEM, 58.7 +/- 2.3) were included. The epithelial ovarian cancer patients underwent laparotomy and debulking surgery Chemokines serum levels were measured by cytometric bead array. Statistical analysis was performed using Mann-Whitney and Kendall's tau. P <0.05 was considered statistically significant for all analyses.Results. The tumor staging (FIGO) was classified into: I in 4 cases (25%), III in 5 cases (31.3%) and stage IV in 7 cases (43.8%). Sera chemokine dosages of CCL2 /MCP-1 and CCL4/MIP-1 beta were lower in epithelial ovarian cancer patients than in the control group (P = 0.021 and P = 0.030, respectively). No significant difference between groups was observed in the levels of CCL3/MIP-l alpha, CCL5/RANTES and CXCL8/IL-8. No association between the chemokines analyzed and tumor stage was found. The serum level of CCL4/MIP-1 beta was correlated with CA-125.Conclusions. The study of serum levels of CCL2/MCP-1, CCL3/MIP-l alpha, CCL4/MIP-1 beta, CCL5/RANTES and CXCL8/IL-8 chemokines in epithelial ovarian cancer patients identified a down-regulation in CCL2/MCP-1 and CCL4/MIP-1 beta, which suggests that the two chemokines may play an important role in the pathophysiology of ovarian cancer.

AN EXTREMELY LARGE, CAULIFLOWER-TYPE, CUTANEOUS METASTASIS OF OVARIAN-CANCER ASSOCIATED WITH GOOD PROGNOSIS

We report an unusual case of a 37-year-old woman who presented in 1980 with a serous papillary cystadenocarcinoma of the ovary. The patient refused any treatment and the patient was lost to follow-up for 6 years. After this period of time she returned with an extremely large, cutaneous, cauliflower-type of metastasis located in the lower abdominal wall and measuring 20 x 20 cm. She received two courses of chemotherapy treatment consisting of intraperitoneal cisplatin (100 mg/m2) and intravenous epirubicin (50 mg/m2) every 3 weeks. After the second course of chemotherapy she received cobalt radiotherapy (5000 cGy). Subsequently, she received four more courses of chemotherapy with dramatic remission of the cutaneous metastasis. Shortly after chemotherapy, the patient underwent a laparotomy consisting of the resection of the abdominal wall including the cutaneous metastasis completed by total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. The patient is well after the surgery and without any evidence of residual disease after 6 years of follow up. This description illustrates a rare example of ovarian cancer with skin metastases and favorable outcome. (C) 1994 Academic Press, Inc.

A new proposed rodent model of chemically induced prostate carcinogenesis: Distinct time-course prostate cancer progression in the dorsolateral and ventral lobes

Background. Characterization of novel rodent models for prostate cancer studies requires evaluation of either spontaneous and carcinogen-induced tumors as well as tumor incidence in different prostatic lobes. We propose a new short-term rodent model of chemically induced prostate carcinogenesis in which prostate cancer progression occurs differentially in the dorsolateral and ventral lobes. Methods. Adult gerbils were treated with MNU alone or associated with testosterone for 3 or 6 months of treatment. Tumor incidence, latency, localization, and immunohistochemistry (AR, PCNA, smooth muscle α-actin, p63, MGMT, and E-cadherin) were studied in both lobes. Results. Comparisons between both lobes revealed that lesions developed first in the DL while the VL presented longer tumor latency. However, after 6 months, there was a dramatic increase in tumor multiplicity in the VL, mainly in MNU-treated groups. Lesions clearly progressed from a premalignant to a malignant phenotype over time and tumor latency was decreased by MNU + testosterone administration. Three-dimensional reconstruction of the prostatic complex showed that the DL developed tumors exclusively in the periurethral area and showed intense AR, PCNA, and MGMT immunostaining. Moreover, VL lesions emerged throughout the entire lobe. MNU-induced lesions presented markers indicative of an aggressive phenotype: lack of basal cells, rupture of the smooth muscle cell layer, loss of E-cadherin, and high MGMT staining. Conclusions. There are distinct pathways involved in tumor progression in gerbil prostate lobes. This animal provides a good model for prostate cancer since it allows the investigation of advanced steps of carcinogenesis with shorter latency periods in both lobes. Copyright © 2013 Wiley Periodicals, Inc.

Epigenetic and expression analysis of TRAIL-R2 and BCL2: on the TRAIL to knowledge of apoptosis in ovarian tumors

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Association among XRCC1, XRCC3, and BLHX gene polymorphisms and chromosome instability in lymphocytes from patients with endometriosis and ovarian cancer

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Melatonin attenuates the TLR4-mediated inflammatory response through MyD88-and TRIF-dependent signaling pathways in an in vivo model of ovarian cancer

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A glycolytic phenotype is associated with prostate cancer progression and aggressiveness: a role for monocarboxylate transporters as metabolic targets for therapy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação de quimiocinas séricas em mulheres com câncer epitelial de ovário

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Estudo da resposta imune humoral em mulheres com neoplasia ovariana. -

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Avaliação da resposta imune sistêmica e compartimentalizada em pacientes portadoras de cãncer de ovário: sub-titulo / (se houver)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

TRAIL-R3-related apoptosis: Epigenetic and expression analyses in women with ovarian neoplasia

Objective. To assess the expression of TRAIL-R3 and the methylation of a CpG island within the TRAIL-R3 promoter both in cystadenoma tumors and primary and metastatic epithelial ovarian carcinoma (EOC).Methods. RNA was obtained from women with normal ovarian (NO) tissues (n = 18), ovarian serous cystadenoma tumors (n = 11) and EOC (n = 16) using Trizol (R). Quantitative PCR (gRT-PCR) was performed to quantify the relative levels of TRAIL-R3. The methylation frequency of the CpG island in the TRAIL-R3 promoter was assessed using the methylation-specific PCR (MSP) assay after DNA bisulfite conversion. The differences between the groups were evaluated using the chi-square, Student's t, ANOVA, Mann-Whitney U, Wilcoxon or Kruskal-Wallis tests as indicated. The survival rates were calculated using the Kaplan-Meier method.Results. Cystadenoma and metastatic EOC tumors expressed significantly more TRAIL-R3 mRNA than primary EOC tumors. Methylation of the TRAIL-R3 promoter was absent in NO tissues, while hemimethylation of the TRAIL-R3 promoter was frequently found in the neoplasia samples with 45.4% of the cystadenoma tumors, 8.3% of the primary EOC samples and 11.1% of the metastatic EOC samples showing at least partial methylation (p = 0.018). Neither the expression of TRAIL-R3 nor alterations in the methylation profile were associated to cumulative progression-free survival or the overall survival in EOC patients.Conclusions. Primary EOC is associated to a lower TRAIL-R3 expression, which leads to a better understanding of the complex disease and highlighting potential therapeutic targets. Promoter DNA methylation was not related to this finding, suggesting the presence of other mechanisms to transcriptional control. (C) 2012 Elsevier B.V. All rights reserved.

Key participants of the tumor microenvironment of the prostate: An approach of the structural dynamic of cellular elements and extracellular matrix components during epithelial-stromal transition

Cancer is a multistep process that begins with the transformation of normal epithelial cells and continues with tumor growth, stromal invasion and metastasis. The remodeling of the peritumoral environment is decisive for the onset of tumor invasiveness. This event is dependent on epithelial–stromal interactions, degradation of extracellular matrix components and reorganization of fibrillar components. Our research group has studied in a new proposed rodent model the participation of cellular and molecular components in the prostate microenvironment that contributes to cancer progression. Our group adopted the gerbil Meriones unguiculatus as an alternative experimental model for prostate cancer study. This model has presented significant responses to hormonal treatments and to development of spontaneous and induced neoplasias. The data obtained indicate reorganization of type I collagen fibers and reticular fibers, synthesis of new components such as tenascin and proteoglycans, degradation of basement membrane components and elastic fibers and increased expression of metalloproteinases. Fibroblasts that border the region, apparently participate in the stromal reaction. The roles of each of these events, as well as some signaling molecules, participants of neoplastic progression and factors that promote genetic reprogramming during epithelial–stromal transition are also discussed.

Melatonin attenuates Her-2, p38 MAPK, p-AKT, and mTOR levels in ovarian carcinoma of ethanol-preferring rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cirurgia não ginecológica em pacientes com câncer de ovário

OBJETIVO: avaliar a freqüência da utilização de procedimentos cirúrgicos não ginecológicos no tratamento do câncer de ovário, assim como descrever as suas complicações. MÉTODOS: foram incluídas retrospectivamente 82 pacientes, atendidas no período de fevereiro de 1999 a outubro de 2003, e que haviam sido submetidas a laparotomia para tratamento cirúrgico do câncer de ovário. Foram incluídas no estudo apenas pacientes com adenocarcinoma epitelial de ovário. A média de idade foi de 54,1±15,1 anos, variando de 22 a 89 anos. O estadiamento (FIGO) mostrou 5 pacientes no estádio I (6,1%), 18 pacientes no II (21,9%), 40 pacientes no III (48,8%) e 19 pacientes no IV (23,2%). As pacientes foram divididas em 2 grupos: aquelas em que foram realizados exclusivamente procedimentos ginecológicos e aquelas com realização de procedimentos não ginecológicos. As diferenças entre as médias foram analisadas pelo teste t de Student. As comparações entre grupos independentes foram feitas pelo teste do chi2. RESULTADOS: em 35 pacientes (42,7%) foram realizados procedimentos cirúrgicos não ginecológicos, incluindo: 17 colostomias, 16 enterectomias, oito peritonectomias pélvicas, sete colectomias, cinco ressecções parciais de cúpula frênica, quatro cistectomias parciais, quatro esplenectomias, duas ileostomias e uma hepatectomia parcial. Todas as pacientes submetidas a procedimentos não ginecológicos apresentavam-se nos estádios III e IV. Esse grupo apresentou maior tempo cirúrgico (5,3±1,4 versus 3,1±0,9 horas); p<0,001). Os grupos não mostraram diferenças significativas em relação à necessidade de hemotransfusão (42,2 versus 40%; p=0,512) e tempo de internação (11,5±7,2 versus 10±9,9 dias; p=0,454). A realização de procedimentos cirúrgicos não ginecológicos associou-se a maior taxa de complicações pós-operatórias 37% versus (17,1%; p=0,042), sendo que duas pacientes desse grupo (2,4%) evoluíram para o óbito. CONCLUSÕES: os procedimentos cirúrgicos não ginecológicos são freqüentemente empregados no tratamento de pacientes com câncer de ovário. A realização dessas cirurgias está associada a maior tempo cirúrgico e maior taxa de complicações pós-operatórias.