The endogenous and reactive depression subtypes revisited: integrative animal and human studies implicate multiple distinct molecular mechanisms underlying major depressive disorder

Traditional diagnoses of major depressive disorder (MDD) suggested that the presence or absence of stress prior to onset results in either 'reactive' or 'endogenous' subtypes of the disorder, respectively. Several lines of research suggest that the biological underpinnings of 'reactive' or 'endogenous' subtypes may also differ, resulting in differential response to treatment. We investigated this hypothesis by comparing the gene-expression profiles of three animal models of 'reactive' and 'endogenous' depression. We then translated these findings to clinical samples using a human post-mortem mRNA study

Epithelial-Mesenchymal Transition in Cancer: Parallels Between Normal Development and Tumor Progression

From the earliest stages of embryonic development, cells of epithelial and mesenchymal origin contribute to the structure and function of developing organs. However, these phenotypes are not always permanent, and instead, under the appropriate conditions, epithelial and mesenchymal cells convert between these two phenotypes. These processes, termed Epithelial-Mesenchymal Transition (EMT), or the reverse Mesenchymal-Epithelial Transition (MET), are required for complex body patterning and morphogenesis. In addition, epithelial plasticity and the acquisition of invasive properties without the full commitment to a mesenchymal phenotype are critical in development, particularly during branching morphogenesis in the mammary gland. Recent work in cancer has identified an analogous plasticity of cellular phenotypes whereby epithelial cancer cells acquire mesenchymal features that permit escape from the primary tumor. Because local invasion is thought to be a necessary first step in metastatic dissemination, EMT and epithelial plasticity are hypothesized to contribute to tumor progression. Similarities between developmental and oncogenic EMT have led to the identification of common contributing pathways, suggesting that the reactivation of developmental pathways in breast and other cancers contributes to tumor progression. For example, developmental EMT regulators including Snail/Slug, Twist, Six1, and Cripto, along with developmental signaling pathways including TGF-β and Wnt/β-catenin, are misexpressed in breast cancer and correlate with poor clinical outcomes. This review focuses on the parallels between epithelial plasticity/EMT in the mammary gland and other organs during development, and on a selection of developmental EMT regulators that are misexpressed specifically during breast cancer

Tratamento de doença bílio-pancreática em pacientes portadores de divertículo duodenal periampolar

OBJETIVO: Analisar o tratamento da doença bílio-pancreática na presença do divertículo periampolar. MÉTODO: De janeiro de 1999 a julho de 2003, 13 doentes com diagnóstico de divertículo periampolar e doença bílio-pancreática associada foram tratados pelo grupo de vias biliares e pâncreas do Departamento de Cirurgia da Santa Casa de São Paulo. Foram analisados retrospectivamente quanto à idade, sexo, quadro clínico e exames laboratoriais e radiológicos, com intuito diagnóstico. O tratamento endoscópico ou cirúrgico e seus resultados foram avaliados. RESULTADOS: Quatro pacientes eram do sexo masculino (30,8%) e nove (69,2%) do sexo feminino, a maioria com idade superior a 70 anos. Os principais sintomas foram de icterícia (61,5%) e dor abdominal (53,8%). Dois doentes apresentaram-se com pancreatite aguda e um com hemorragia digestiva alta. Onze doentes tinham coledocolitíase e dois, diagnóstico de colangiocarcinoma. Dez doentes foram submetidos a colangio-pancreatografia retrógrada endoscópica com 30% de sucesso no tratamento da coledocolitíase. Os outros doentes foram operados: três coledocoduodenostomias, quatro coledocolitotomias com drenagem em T da via biliar. Três doentes foram submetidos à diverticulectomia (23,1%) e um deles (7,7%) à papiloesfincteroplastia. A mortalidade na amostra foi de 7,7%. CONCLUSÃO: A taxa de sucesso do tratamento endoscópico da coledocolitíase foi baixa na presença de divertículo periampolar e a diverticulectomia com ou sem esfincteroplastia pode elevar a morbidade e a mortalidade nestes doentes