RESUMO
It has been recently demonstrated that progranulin is overexpressed in ovarian cancer and that this protein is involved in the stimulation of cell proliferation, malignancy, and chemoresistance in ovarian cancer. The goal of the present study was to establish the differences in progranulin expression among normal, benign, and malignant ovarian tissues and to identify the signal transduction pathways activated by progranulin in an ovarian cancer cell line. Compared with benign tumors and normal ovarian tissue, progranulin mRNA and protein were overexpressed in malignant tumors. Survival analysis by the Kaplan-Meier method showed a correlation between high mRNA expression levels with poor survival outcome. Progranulin activated the MAPK-signaling pathway in NIH-OVCAR-3 cells. Progranulin expression may be potentially involved in the pathogenesis and malignant progression of ovarian cancer, and thus may represent a therapeutic target for this particular malignancy.
Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neoplasias Ovarianas/metabolismo , Ovário/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Sistema de Sinalização das MAP Quinases , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , ProgranulinasRESUMO
The identification of polymorphisms in genes encoding proinflammatory cytokines that affect transcription or the secretion rate has opened new ways to understand the variation in responses to infection during pregnancy. In this study, human amniochorion carrying hyper-responsive alleles of tumour necrosis factor-alpha (TNF-alpha: TNF*2 at -308) and interleukin-1beta (IL-1beta: IL-1*2 at +3953) were stimulated in vitro with bacterial lipopolysaccharide (LPS) and compared with tissues carrying the common alleles (TNF*1 and IL-1*1). Fetal membranes carrying the TNF*1 allele displayed an identical dose-response pattern to tissues carrying a TNF*2 allele, except at the highest dose of LPS tested (50 ng/ml) there was a significantly greater production of TNF-alpha in the presence of a TNF*2 allele. Membranes carrying the IL-1*2 polymorphism secreted IL-1beta in a dose-response curve that was different from IL-1* tissues when challenged with 5, 10 and 50 ng/ml LPS. These observations support the hypothesis that reproductive tissues carrying hyper-responsive proinflammatory cytokine genes may over-respond to intrauterine infection secreting higher amounts of cytokines, which in turn, may lead to adverse pregnancy outcomes.
Assuntos
Âmnio/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-1/genética , Interleucina-1/metabolismo , Polimorfismo Genético/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Âmnio/efeitos dos fármacos , Divisão Celular , Células Cultivadas , Feminino , Humanos , Lipopolissacarídeos/farmacologia , Gravidez , Fatores de TempoRESUMO
Neonato preterm birth (before 37 pregnancy weeks) account more than 80% perinatal deaths not attributable to congenital malformations. Preterm and term labor full mechanisms are unknown at present. Proinflammatory cytokinesis direct participation have been involved in the phenomena by several experimental evidence. The study's aim was to determine TNF-alpha and IL-1 beta concentration at maternal, fetal and fetal-maternal vascular compartments in women with term and preterm delivery and in women at term childbirth without labor. TNF-alpha and IL-1 beta concentration were determinated by commercial immunoassay. TNF-alpha concentration showed a tendency to be in more proportion at fetal and fetal-maternal compartments in preterm and term childbirth groups versus TNF-alpha concentration in term group without labor at same places. IL-1 beta concentration showed same tendency of increase than TNF-alpha in preterm and term childbirth groups, but alone at fetal-maternal compartment. Statistical difference were not documented at any compartment or group compared. Data allow to identify fetal-maternal compartments as target places where TNF-alpha and IL-1 beta were synthesized. Gradient concentration synthesis of cytokinesis allows to intend fetus as TNF-alpha initial producer.
Assuntos
Sangue Fetal/química , Interleucina-1/sangue , Trabalho de Parto/fisiologia , Trabalho de Parto Prematuro , Fator de Necrose Tumoral alfa/análise , Adulto , Feminino , Idade Gestacional , Humanos , Imunoensaio , GravidezRESUMO
Recurrent spontaneous abortion of unidentified cause or idiopatic is an important problem of reproduction health. In this study, the study has been started of one of the mechanisms that could act in the pathology of human pregnancy. The general hypothesis proposed, is that in the case of patients with recurrent spontaneous abortion of non identified cause (RSA) there are phenomenons in the materno/fetal/placentary means that manifest themselves in harm to the functionality and/or vitality of placentary tissue. The hypothesis was consistent with the finding of massive activation of cellular death in all the cases with RSA studied in this work.