RESUMO
The Wnt/ß-catenin signaling pathway plays a key role in development and carcinogenesis. Although some target genes of this signaling have been identified in various tissues and neoplasms, the comprehensive understanding of the target genes and their roles in the development of human cancer, including hepatoma and colorectal cancer remain to be fully elucidated. In this study, we searched for genes regulated by the Wnt signaling in liver cancer using HuH-7 hepatoma cells. A comparison of the expression profiles between cells expressing an active form of mutant ß-catenin and cells expressing enhanced green fluorescent protein (EGFP) identified seven genes upregulated by the mutant ß-catenin gene (CTNNB1). Among the seven genes, we focused in this study on ODAM, odontogenic, ameloblast associated, as a novel target gene. Interestingly, its expression was frequently upregulated in hepatocellular carcinoma, colorectal adenocarcinoma, and hepatoblastoma. We additionally identified a distant enhancer region that was associated with the ß-catenin/TCF7L2 complex. Further analyses revealed that ODAM plays an important role in the regulation of the cell cycle, DNA synthesis, and cell proliferation. These data may be useful for clarification of the main molecular mechanism(s) underlying these cancers.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Via de Sinalização Wnt/genética , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , beta Catenina/genética , Ameloblastos/metabolismo , Ameloblastos/patologia , Neoplasias Hepáticas/patologia , Proliferação de Células/genética , Regulação Neoplásica da Expressão GênicaRESUMO
OBJECTIVES: The usefulness of omega-3 lipid emulsions has been extensively studied. The objectives of the present study were to examine the effect of an omega-3 lipid emulsion in reducing oxidative stress in a rat model of intestinal ischemia-reperfusion injury and the underlying mechanism. METHODS: A total of 66 rats were divided into three dietary groups (lipid-free, soybean oil, and fish oil groups). Each animal was administered total parenteral nutrition for 3 days, followed by induction of intestinal ischemia for 100 min. Animals subjected to sham surgery served as the controls. Intestinal tissue and blood were harvested 6 and 12 h after the surgery, then, assessment of the histological damage score, plasma-related parameters, and statistical evaluation were performed. RESULTS: The histological damage score in the intestinal tissues was significantly lower in the fish oil group than in the soybean oil group (P = 0.0121). The late-phase urinary level of 8-hydroxy-2-deoxyguanosine was also significantly lower in the fish oil group as compared with that in the other groups (P = 0.0267). Furthermore, the plasma level of high-mobility group box 1 protein was also significantly lower in the fish oil group as compared with that in the lipid-free group (P = 0.0398). CONCLUSION: It appeared that intravenous administration of an omega-3 lipid emulsion prior to ischemia-reperfusion injury reduced the oxidative stress and severity of tissue damage. Modification of membrane fatty acids may serve as the mechanism underlying this reduction of tissue damage.
Assuntos
Emulsões Gordurosas Intravenosas/administração & dosagem , Ácidos Graxos Ômega-3/administração & dosagem , Intestino Delgado/irrigação sanguínea , Estresse Oxidativo/efeitos dos fármacos , Nutrição Parenteral Total , Traumatismo por Reperfusão/terapia , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismoRESUMO
The L1 cell adhesion molecule (L1CAM) protein is found primarily in the nervous system and is important in neuronal adhesion, migration, neurite outgrowth, and myelination. It is extremely rare that Hirschsprung's disease (HSCR) merges with a disorder showing abnormality of the L1CAM genes such as acrocallosal syndrome (ACS) or X-linked hydrocephalus (XLH). Herein, we report 2 cases--the first showed abnormality of the L1CAM genes and developed HSCR; and the second, with clinically suspected XLH, was successfully operated on for HSCR. When a patient with ACS or XLH presents with constipation, we must consider HSCR in the differential diagnosis, and early treatment is important. Furthermore, it is desirable to select a line treatment of HSCR to prevent infection of the ventriculoperitoneal shunt if the patient requires it.