RESUMO
Epithelial ovarian cancer is the most lethal gynecological malignancy and the fifth leading cause of cancer deaths in women in the Western world. ETS transcription factors are known to act as positive or negative regulators of the expression of genes that are involved in various biological processes, including those that control cellular proliferation, differentiation, apoptosis, tissue remodeling, angiogenesis and transformation. ETV5 belongs to the PEA3 subfamily. PEA3 subfamily members are able to activate the transcription of proteases, matrix metalloproteinases and tissue inhibitor of metalloproteases, which is central to both tumor invasion and angiogenesis. Here, we examined the role of the ETV5 transcription factor in epithelial ovarian cancer and we found ETV5 was upregulated in ovarian tumor samples compared to ovarian tissue controls. The in vitro inhibition of ETV5 decreased cell proliferation in serum-deprived conditions, induced EMT and cell migration and decreased cell adhesion to extracellular matrix components. ETV5 inhibition also decreased cell-cell adhesion and induced apoptosis in anchorage-independent conditions. Accordingly, upregulation of ETV5 induced the expression of cell adhesion molecules and enhanced cell survival in a spheroid model. Our findings suggest that the overexpression of ETV5 detected in ovarian cancer cells may contribute to ovarian tumor progression through the ability of ETV5 to enhance proliferation of ovarian cancer cells. In addition, upregulation of ETV5 would play a role in ovarian cancer cell dissemination and metastasis into the peritoneal cavity by protecting ovarian cancer cells from apoptosis and by increasing the adhesion of ovarian cancer cells to the peritoneal wall through the regulation of cell adhesion molecules.
Assuntos
Adesão Celular/genética , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Fatores de Transcrição/genética , Apoptose/genética , Caderinas/genética , Caderinas/metabolismo , Carcinoma Epitelial do Ovário , Processos de Crescimento Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Sobrevivência Celular/genética , Proteínas de Ligação a DNA/metabolismo , Regulação para Baixo , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Feminino , Técnicas de Silenciamento de Genes/métodos , Humanos , Metástase Neoplásica , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/metabolismo , Ovário/metabolismo , Ovário/patologia , Cavidade Peritoneal/patologia , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Fatores de Transcrição/metabolismo , Regulação para Cima/genéticaRESUMO
OBJECTIVE: The aim of this study was to evaluate the safety and feasibility of extraperitoneal laparoscopic paraaortic lymphadenectomy for suspected lymph node recurrence of gynecological cancers. DESIGN: Descriptive study. SETTING: Unit of Gynecologic Oncology of an acute-care teaching hospital in Barcelona, Spain. POPULATION: Between December 2002 and October 2007, eight women underwent extraperitoneal laparoscopic paraaortic lymphadenectomy for suspected lymph node recurrence, detected by magnetic resonance image (MRI), computed tomography (CT) scan or 18F-fluorodeoxyglucose positron emission tomography (PET) scanning. The suspicious nodes were removed through an extraperitoneal laparoscopic approach. RESULTS: The median age of patients was 66.5 years (range: 54-74). The median operating time was 157.5 minutes (range: 120-240). The median blood loss was 112.5 mL (range: 50-150). The mean nodal yield was 9.4+/-4.72 (range: 1-16). There were no intraoperative or postoperative complications. The median hospital stay was two days. Histological examination revealed metastasis in seven of eight patients. CONCLUSIONS: The extraperitoneal laparoscopic paraaortic lymphadenectomy for lymph node recurrence of gynecological cancers is a safe and feasible procedure which should be considered where there is isolated involvement of retroperitoneal lymph nodes. This procedure is a minimally invasive technique that allows an excellent approach to the paraaortic lymph nodes.
Assuntos
Neoplasias dos Genitais Femininos/patologia , Laparoscopia , Excisão de Linfonodo/métodos , Idoso , Aorta Abdominal , Diagnóstico por Imagem , Estudos de Viabilidade , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgiaRESUMO
During the last years, and coinciding with the beginning of the concomitant treatment with radio-chemotherapy, a better control of local cervical cancer has been reached, although failures in the systemic control of the illness have been more frequent. One of the main causes is not treating the illness at the level of the para-aortic lymph nodes, basically because their affectation is unknown and because imaging tests have a high percentage of false negative results. At this time, it is when laparoscopic para-aortic lymphadenectomy arises, in order to be able to know the extension of the illness better before treatment. A extraperitoneal laparoscopic approach is described in order to reduce complications derived from a possible extended irradiation. Between August 2001 and October 2007, a total of 69 patients with bulky and locally advanced cervical cancer (FIGO stages IB2, IIA > 4 cm and IIB-IVA) underwent extraperitoneal laparoscopic lymphadenectomy for surgical staging. Extraperitoneal aortic lymphadenectomy by laparoscopic approach is a technique with low morbidity. Special laparoscopic material is not required and if it is performed by a team trained in technical endoscopics it is not difficult. Radio-chemotherapy treatment began immediately after laparoscopy because of its minimal aggression.
