RESUMO
BACKGROUND: We previously identified dermicidin (DCD), which encodes a growth and survival factor, as a gene amplified and overexpressed in a subset of breast tumors. Patients with DCD-positive breast cancer have worse prognostic features. We therefore searched for specific molecular signatures in DCD-positive breast carcinomas from patients and representative cell lines. METHODS: DCD expression was evaluated by qRT-PCR, immunohistochemical and immunoblot assays in normal and neoplastic tissues and cell lines. To investigate the role of DCD in breast tumorigenesis, we analyzed the consequences of its downregulation in human breast cancer cell lines using three specific shRNA lentiviral vectors. Genes up- and down-regulated by DCD were identified using Affymetrix microarray and analyzed by MetaCore Platform. RESULTS: We identified DCD splice variant (DCD-SV) that is co-expressed with DCD in primary invasive breast carcinomas and in other tissue types and cell lines. DCD expression in breast tumors from patients with clinical follow up data correlated with high histological grade, HER2 amplification and luminal subtype. We found that loss of DCD expression led to reduced cell proliferation, resistance to apoptosis, and suppressed tumorigenesis in immunodeficient mice. Network analysis of gene expression data revealed perturbed ERBB signaling following DCD shRNA expression including changes in the expression of ERBB receptors and their ligands. CONCLUSIONS: These findings imply that DCD promotes breast tumorigenesis via modulation of ERBB signaling pathways. As ERBB signaling is also important for neural survival, HER2+ breast tumors may highjack DCD's neural survival-promoting functions to promote tumorigenesis.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Dermocidinas/genética , Dermocidinas/metabolismo , Receptor ErbB-2/metabolismo , Transdução de Sinais , Processamento Alternativo , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Biomarcadores , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Análise por Conglomerados , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Imuno-Histoquímica , Receptor ErbB-2/antagonistas & inibidores , Trastuzumab/administração & dosagem , Trastuzumab/farmacologia , Carga Tumoral/efeitos dos fármacosRESUMO
Zenker's diverticulum (ZD), also known as cricopharyngeal, pharyngoesophageal or hypopharyngeal diverticulum, is a rare condition characterized by an acquired outpouching of the mucosal and submucosal layers originating from the pharyngoesophageal junction. This false and pulsion diverticulum occurs dorsally at the pharyngoesophageal wall between the inferior pharyngeal constrictor and the cricopharyngeus muscle. The pathophysiology of ZD involves altered compliance of the cricopharyngeus muscle and raised intrabolus pressure. Decreased compliance of the upper esophageal sphincter and failure to open completely for effective bolus clearance both lead to an increase in the hypopharyngeal pressure gradient. Different open surgical techniques and transoral endoscopic approaches have been described for the management of ZD, although there is no consensus about the best option. We report the case of a 61-year-old patient with a 7-year history of dysphagia and odynophagia for solid food, which after 2 months progressed to dysphagia for liquids and after 4 months to regurgitation 2-6 h after meals. The patient experienced a 12-kg weight loss. Diagnosis was established by esophagogram, which showed a diverticulum through the posterior pharyngeal wall, suggestive of a ZD. Esophagogastroduodenoscopy showed a pouch with erythematous mucosa. Under general anesthesia, diverticulectomy and myotomy were performed. After an uneventful recovery and adequate oral intake, the patient remains free of symptoms at 4 months of follow-up.
RESUMO
It is known that adrenaline promotes hydroxyl radical generation in isolated rat hepatocytes. The aim of this work was to investigate a potential role of NADPH oxidase (Nox) isoforms for an oxidative stress signal in response to adrenaline in hepatocytes. Enriched plasma membranes from isolated rat liver cells were prepared for this purpose. These membranes showed catalytic activity of Nox isoforms, probably Nox 2 based on its complete inhibition with specific antibodies. NADPH was oxidized to convert O(2) into superoxide radical, later transformed into H(2)O(2). This enzymatic activity requires previous activation with either 3 mM Mn(2+) or guanosine 5'-0-(3-thiotriphosphate) (GTPgammaS) plus adrenaline. Experimental conditions for activation and catalytic steps were set up: ATP was not required; S(0.5) for NADPH was 44 microM; S(0.5) for FAD was 8 microM; NADH up to 1 mM was not substrate, and diphenyleneiodonium was inhibitory. Activation with GTPgammaS plus adrenaline was dose- and Ca(2+)-dependent and proceeded through alpha(1)-adrenergic receptors (AR), whereas beta-AR stimulation resulted in inhibition of Nox activity. These results lead us to propose H(2)O(2) as additional transduction signal for adrenaline response in hepatic cells.
Assuntos
Agonistas Adrenérgicos/farmacologia , Ativação Enzimática/efeitos dos fármacos , Epinefrina/farmacologia , Hepatócitos/enzimologia , Peróxido de Hidrogênio/metabolismo , Extratos Hepáticos/metabolismo , NADPH Oxidases/metabolismo , Oxidantes/metabolismo , Animais , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Receptores Adrenérgicos/química , Receptores Adrenérgicos/metabolismoRESUMO
Induction of bone tissue requires three elements: osteoprogenitor cells, osteoinductive factors, and a supporting extracellular matrix. In this study, we report on an experimental model in dogs of heterotopic bone tissue production, based on the integration of these osteo-inductive factors into abdominal implants. The implants consist of either a type I collagen sponge wrapped with periosteum and omentum or a type I collagen sponge embedded with demineralized bone powder, platelet-rich plasma, thrombin, and calcium chloride wrapped with omentum, with or without periosteum. Automated histomorphometric analysis showed an efficient production of trabecular bone, which corresponded to 50-70% of the total tissue composition 4 months after implant formation. High expression of the osteoinductive cytokines transforming growth factor-beta and bone morphogenetic proteins-2 and -4 was shown by immunohistochemistry in macrophages, endothelial cells from neoformed capillaries, osteoblasts, osteoclasts, and the mesenchymal tissue around the bone trabeculae. These approaches are novel and efficient surgical procedures to produce mature trabecular bone that could be used as a potential source of bone tissue for autotransplantation.
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Desenvolvimento Ósseo/fisiologia , Transplante Ósseo/métodos , Abdome , Animais , Proteína Morfogenética Óssea 2 , Proteínas Morfogenéticas Ósseas/metabolismo , Cães , Matriz Extracelular , Imuno-Histoquímica , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Derivado de Plaquetas/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
PURPOSE: The aim of this study was to evaluate clinical, radiologic, surgical, and histopathologic characteristics of vascular malformations of the colon (VMC) in children. METHODS: Eighteen patients with lower intestinal bleeding (LIB) and VMC were included. Clinical data, angiographic features, surgical treatments, and histopathologic findings were analyzed. RESULTS: Age of clinical onset was from 1 week to 16 years. Duration of LIB before diagnosis was from 1 month to 9 years. Admission hemoglobin level was 2 to 9 g/dL in 13 patients and in the other 5 was normal. Scintigraphy, colonoscopy, and barium enema results were normal or suggested a vascular problem. Mesenteric arteriography detected VMC in all 18 cases. Left hemicolon and rectum were affected in 83% of the cases. VMC were resected in 14 patients, 10 were anastomosed or pulled-through, and the other 4 required an intestinal stoma. Ten patients are asymptomatic, and 4 have minimal postoperative bleeding. The histopathologic study made in 15 cases (14 surgical specimens and 1 endoscopic biopsy), revealed arterial-venous VMC in 12 and arterial-venous-lymphatic VMC in 3 cases. CONCLUSIONS: The identification of VMC in children with LIB often is delayed. An early mesenteric arteriography should be added to the routine evaluation. Surgical treatment presents a challenge in rectal cases. To avoid confusion in the nomenclature a simplified morphologic classification is suggested.
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Malformações Vasculares do Sistema Nervoso Central/diagnóstico , Malformações Vasculares do Sistema Nervoso Central/terapia , Colo/irrigação sanguínea , Adolescente , Idade de Início , Angiografia , Malformações Vasculares do Sistema Nervoso Central/epidemiologia , Criança , Pré-Escolar , Colonoscopia , Comorbidade , Feminino , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Circulação Esplâncnica , Terminologia como AssuntoRESUMO
The HIV epidemic has dramatically altered the field of sexually transmitted diseases (STDs). HIV infection is unique among sexually transmitted diseases because it can modify the clinical presentation and features of other STDs. Conversely, other STDs can affect the transmission of HIV. This review is the third part of a series that has provided a general overview of STDs. In this article, genital ulcer diseases (genital herpes, syphilis, chancroid, lymphogranuloma venereum, and granuloma inguinale), human papillomavirus infection (anogenital warts and subclinical infections), molluscum contagiosum, human herpesvirus 8 infection, viral hepatitis, and ectoparasitic infestations (scabies and pediculosis pubis) are discussed as they occur in HIV-infected hosts. Additional features as they relate to HIV-infected patients, such as epidemiology and transmission, are discussed when applicable. Learning objective: At the conclusion of this learning activity, participants should improve their understanding of sexually transmitted diseases in the HIV-infected host.
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Humanos , Infecções Sexualmente Transmissíveis/etiologia , Infecções Sexualmente Transmissíveis/patologia , Infecções Sexualmente Transmissíveis/transmissão , Incidência , Infecções por HIV/complicaçõesRESUMO
El espiroadenoma ecrino es una neoplasia benigna rara que probablemente se origina en la glándula sudorípara ecrina. Por lo general, esta neoformación es subcutánea y dolorosa. Se presenta el estudio de 13 pacientes con esta neoplasia, la cual se localizó en 10 casos en cara y piel cabelluda; doce neoformaciones fueron únicas y una múltiple, 7 dolorosas y todas presentaron histología característica