Résumé
This study investigated the in vitro and in vivo antiproliferative activity of esculetin against hepatocellular carcinoma, and clarified its potential molecular mechanisms. Cell viability was determined by the MTT (tetrazolium) colorimetric assay. In vivo antitumor activity of esculetin was evaluated in a hepatocellular carcinoma mouse model. Seventy-five C57BL/6J mice were implanted with Hepa1-6 cells and randomized into five groups (n=15 each) given daily intraperitoneal injections of vehicle (physiological saline), esculetin (200, 400, or 700 mg·kg-1·day-1), or 5-Fu (200 mg·kg-1·day-1) for 15 days. Esculetin significantly decreased tumor growth in mice bearing Hepa1-6 cells. Tumor weight was decreased by 20.33, 40.37, and 55.42% with increasing doses of esculetin. Esculetin significantly inhibited proliferation of HCC cells in a concentration- and time-dependent manner and with an IC50 value of 2.24 mM. It blocked the cell cycle at S phase and induced apoptosis in SMMC-7721 cells with significant elevation of caspase-3 and caspase-9 activity, but did not affect caspase-8 activity. Moreover, esculetin treatment resulted in the collapse of mitochondrial membrane potential in vitro and in vivo accompanied by increased Bax expression and decreased Bcl-2 expression at both transcriptional and translational levels. Thus, esculetin exerted in vitro and in vivo antiproliferative activity in hepatocellular carcinoma, and its mechanisms involved initiation of a mitochondrial-mediated, caspase-dependent apoptosis pathway.
Sujets)
Adulte , Femelle , Humains , Mâle , Épuisement professionnel/génétique , Maladies chez les jumeaux/génétique , Lieu de travail , Épuisement professionnel/épidémiologie , Épuisement professionnel/étiologie , Épuisement professionnel/psychologie , Démographie , Maladies chez les jumeaux/épidémiologie , Maladies chez les jumeaux/étiologie , Maladies chez les jumeaux/psychologie , Interaction entre gènes et environnement , Enregistrements , Facteurs de risque , Enquêtes et questionnaires , Suède/épidémiologieRésumé
Antecedentes: El embarazo de gemelos monocoriales tienen un mayor riesgo de mortalidad y morbilidad perinatal, que la gestación única y el embarazo gemelar bicorial. Objetivos: Estudiar la incidencia y el manejo de las complicaciones fetales propias de las gestaciones gemelares monocoriales biamnióticas. Métodos: Se realizó un análisis retrospectivo de 94 embarazos gemelares monocoriales biamnióticos, seguidos en las Consultas de Tocología de Alto Riesgo del Hospital Universitario La Paz de Madrid, entre 2008 y 2010. Resultados: Se recogieron 94 gestaciones monocoriales biamnióticas. Aparecieron complicaciones fetales en el 23,4 por ciento de las mismas: síndrome de transfusión feto-fetal en el 9,57 por ciento de los casos, retraso del crecimiento intrauterino selectivo en el 11,7 por ciento, muerte fetal intrauterina en el 2,1 por ciento, y malformaciones fetales en el 7,4 por ciento. Conclusiones: Las gestaciones monocoriales biamnióticas son un tipo de embarazo gemelar de alto riesgo, asociado con más complicaciones fetales y muerte perinatal. Se recomienda un estrecho seguimiento ecográfico cada 2 semanas, desde la semana 16, para diagnosticar y tratar precozmente las complicaciones fetales.
Background: The monochorionic twin pregnancy has a higher risk of perinatal mortality and morbidity, than the single gestation and the dichorionic twin gestation. Objectives: To detail the incidence and management of specific fetal complications of monochorionic diamniotic twin pregnancies. Methods: We performed a retrospective analysis of monochorionic diamniotic pregnancies followed in the High Risk Obstetrics Unit of the University Hospital La Paz, Madrid, between 2008-2010. Results: We collected 94 monochorionic diamniotic pregnancies. Fetal complications occurred in 23.4 percent of them: feto-fetal transfusion syndrome in 9.57 percent of cases, selective intrauterine growth retardation in 11.7 percent, stillbirth in 2.1 percent, and fetal malformations in 7.4 percent. Conclusions: Monochorionic diamniotic twin pregnancies are a high-risk type of twin pregnancy, associated with an increased risk of death and perinatal complications. Ultrasound monitoring is recommended for uncomplicated monochorionic pregnancies every 2 weeks from week 16, to detect and treat fetal complications.
Sujets)
Humains , Femelle , Grossesse , Nouveau-né , Grossesse multiple , Maladies chez les jumeaux/épidémiologie , Maladies chez les jumeaux , Jumeaux , Amnios , Malformations/épidémiologie , Malformations/thérapie , Chorion , Âge maternel , Grossesse à haut risque , Études rétrospectives , Incidence , Mort foetale , Retard de croissance intra-utérin/épidémiologie , Retard de croissance intra-utérin/thérapie , Syndrome de transfusion foeto-foetale/épidémiologie , Syndrome de transfusion foeto-foetale/thérapie , Échographie prénataleRésumé
Breast cancer research has yielded several important results including the strong susceptibility genes,BRCA1 and BRCA2 and more recently 19 genes and genetic loci that confer a more moderate risk.The pace of discovery is accelerating as genetic technology and computational methods improve. These discoveries will change the way that breast cancer risk is understood in Mexico over the next few decades.
La investigación en cáncer de mama ha dado varios resultados importantes incluyendo los genes fuertemente susceptibles, BRCA1 y BRCA2, y más recientemente 19 genes y loci genéticos que confieren un riesgo moderado. El ritmo de los descubrimientos se acelera conforme mejora la tecnología y métodos computacionales.Estosdescubrimientoscambiarán la forma en que la investigación del cáncer es comprendida en México en las próximas décadas.
Sujets)
Femelle , Humains , Tumeurs du sein/génétique , Gènes tumoraux , Tumeurs du sein/épidémiologie , Maladies chez les jumeaux/épidémiologie , Ethnies/génétique , Santé de la famille , Prévision , Fréquence d'allèle , Gène BRCA1 , Prédisposition génétique à une maladie/génétique , Dépistage génétique , Mexique/épidémiologie , Syndromes néoplasiques héréditaires/épidémiologie , Syndromes néoplasiques héréditaires/génétiqueRésumé
Background: A higher prevalence of congenital malformations among twins than among single has been reported in the literature. Aim: To study the incidence of congenital malformations in twins in the maternity hospital of the University of Chile in the period 1983-1997. Material and methods: As part of the Latin American Collaborative Study of Congenital Malformations, every newborn in the maternity hospital was examined by a neonatologist and congenital malformations were recorded in a special file. Results: In the study period there were 48.663 deliveries of single pregnancies and 448 deliveries of twin pregnancies, giving birth to 886 twins borns alive and 17 stillbirths (1.9 percent mortality). Of these, there were 423 twins, 17 triplets, a sextuple delivery and two siamese. Seven point one percent of twins born alive and 6.5 percent of single newborns had a congenital malformation. The prevalence of malformations in twins and single stillbirths was 35.2 and 17.2 percent respectively (p <0.04). In four pairs and siamese newborns, malformations typical of monozygotic twins were present, such as an acardiac fetus with Trap sequence, a papyraceous fetus and two with hydroanencephaly. Twelve twins had malformations attributable to uterine compression. Conclusions: This study did not find a higher frequency of malformations comparing twins with single babies born alive, but in stillbirths there was a significant difference between single and twin stillbirths (7.1 percent versus 35.2 percent, respectively, p <0.05)