RESUMO
The Salvador/Warts/Hippo (Hippo) signaling pathway defines a novel signaling cascade regulating cell contact inhibition, organ size control, cell growth, proliferation, apoptosis and cancer development in mammals. The upstream regulation of this pathway has been less well defined than the core kinase cassette. KIBRA has been shown to function as an upstream member of the Hippo pathway by influencing the phosphorylation of LATS and YAP, but functional consequences of these biochemical changes have not been previously addressed. We show that in MCF10A cells, loss of KIBRA expression displays epithelial-to-mesenchymal transition (EMT) features, which are concomitant with decreased LATS and YAP phosphorylation, but not MST1/2. In addition, ectopic KIBRA expression antagonizes YAP via the serine 127 phosphorylation site and we show that KIBRA, Willin and Merlin differentially regulate genes controlled by YAP. Finally, reduced KIBRA expression in primary breast cancer specimens correlates with the recently described claudin-low subtype, an aggressive sub-group with EMT features and a poor prognosis.
Assuntos
Transição Epitelial-Mesenquimal , Fator de Crescimento de Hepatócito/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Nucleares/metabolismo , Fosfoproteínas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Fatores de Transcrição/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Western Blotting , Mama/citologia , Mama/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Adesão Celular , Proteínas de Ciclo Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Claudina-1/genética , Claudina-1/metabolismo , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Feminino , Perfilação da Expressão Gênica , Fator de Crescimento de Hepatócito/antagonistas & inibidores , Fator de Crescimento de Hepatócito/genética , Humanos , Técnicas Imunoenzimáticas , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Neurofibromina 2/genética , Neurofibromina 2/metabolismo , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , Análise de Sequência com Séries de Oligonucleotídeos , Fosfoproteínas/antagonistas & inibidores , Fosfoproteínas/genética , Fosforilação , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/genética , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Serina-Treonina Quinase 3 , Transdução de Sinais , Fatores de Transcrição/antagonistas & inibidoresRESUMO
We report a case of pyometra without any related risk factor. This leads to a severe septic shock. Evolution was successful because of quick surgical management. We report literature management of such infection. Although pyometra is an uncommon disease, it should be kept in mind as delayed management may lead to fatal outcome.
Assuntos
Endometrite/diagnóstico , Piometra/diagnóstico , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Endometrite/microbiologia , Feminino , Gardnerella vaginalis , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Hipotensão , Pessoa de Meia-Idade , Peptostreptococcus , Piometra/microbiologia , Piometra/cirurgia , Choque Séptico , Taquicardia , Tomografia Computadorizada por Raios XRESUMO
The Marfan's syndrome is an autosomal dominant genetic disorder resulting in a diminished strength of connective tissue. The ocular, skeletal and cardiovascular systems are mostly at risk. Principal complications of the disease are aortic dilatation and the risk of acute dissection. Pregnancy increases this risk. Based on the experience of our obstetrics department and after reviewing medical literature, we have tried to establish guidelines for obstetric care adapted to pregnant patients affected by Marfan's syndrome. Women with aortic root > 40 mm should avoid pregnancy. In all cases B-adrenergic receptor blockers must be used as soon as possible. Because there is a 50% risk that offspring will inherit the syndrome, prenatal diagnosis should be suggested. In addition to usual pregnancy monitoring, echocardiography should be performed every 3 months as well as 2 months after delivery. No increase of obstetrical complications has been shown in these patients. Route of delivery also depends on the diameter of the aortic root: vaginal delivery is warranted if the aortic root is<40; cesarean section should be performed in the other cases. Thus, with appropriate supervision, women with Marfan's syndrome will tolerate pregnancy without any adverse effect.