RESUMEN
Tuberculosis (TB) is one of the most common infectious diseases worldwide. The case of a 20-year old male refugee from Somalia, who initially presented with right-sided upper abdominal pain, vomiting, weight loss and jaundice with suspected cholecystitis is reported. In the course of further diagnostics, pyloric stenosis surprisingly appeared, which, like the cholestasis, was caused by compressing peripancreatic lymph nodes. Lymph node cytology finally showed evidence of caseating necrosis with evidence of TB pathogens.
Asunto(s)
Dolor Abdominal/etiología , Tuberculosis/diagnóstico , Vómitos/etiología , Dolor Abdominal/diagnóstico , Colecistitis/diagnóstico , Humanos , Ictericia/diagnóstico , Masculino , Refugiados , Somalia , Pérdida de Peso , Adulto JovenRESUMEN
MACC1 (metastasis associated in colon cancer 1) is a prognostic biomarker for tumor progression, metastasis and survival of a variety of solid cancers including colorectal cancer (CRC). Here we aimed to identify the MACC1-induced transcriptome and key players mediating the MACC1-induced effects in CRC. We performed microarray analyses using CRC cells ectopically overexpressing MACC1. We identified more than 1300 genes at least twofold differentially expressed, including the gene SPON2 (Spondin 2) as 90-fold upregulated transcriptional target of MACC1. MACC1-dependent SPON2 expression regulation was validated on mRNA and protein levels in MACC1 high (endogenously or ectopically) and low (endogenously or by knockdown) expressing cells. Chromatin immunoprecipitation analysis demonstrated the binding of MACC1 to the gene promoter of SPON2. In cell culture, ectopic SPON2 overexpression induced cell viability, migration, invasion and colony formation in endogenously MACC1 and SPON2 low expressing cells, whereas SPON2 knockdown reduced proliferative, migratory and invasive abilities in CRC cells with high endogenous MACC1 and SPON2 expression. In intrasplenically transplanted NOD/SCID mice, metastasis induction was analyzed with control or SPON2-overexpressing CRC cells. Tumors with SPON2 overexpression induced liver metastasis (vs control animals without any metastases, P=0.0036). In CRC patients, SPON2 expression was determined in primary tumors (stages I-III), and survival time was analyzed by Kaplan-Meier method. CRC patients with high SPON2 expressing primary tumors demonstrated 8 months shorter metastasis-free survival (MFS) compared with patients with low SPON2 levels (P=0.053). Combining high levels of SPON2 and MACC1 improved the identification of high-risk patients with a 20-month shorter MFS vs patients with low biomarker expression. In summary, SPON2 is a transcriptional target of the metastasis gene MACC1. SPON2 induces cell motility in vitro and CRC metastasis in mice. In patients, SPON2 serves as prognostic indicator for CRC metastasis and survival, and might represent a promising target for therapeutic approaches.
Asunto(s)
Biomarcadores de Tumor , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Proteínas de la Matriz Extracelular/genética , Proteínas de Neoplasias/genética , Factores de Transcripción/metabolismo , Animales , Movimiento Celular/genética , Proliferación Celular , Supervivencia Celular/genética , Análisis por Conglomerados , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Biología Computacional/métodos , Modelos Animales de Enfermedad , Proteínas de la Matriz Extracelular/metabolismo , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Ontología de Genes , Xenoinjertos , Humanos , Ratones , Metástasis de la Neoplasia , Proteínas de Neoplasias/metabolismo , Estadificación de Neoplasias , Pronóstico , Unión Proteica , Curva ROC , TransactivadoresRESUMEN
The synthesis of fused aromatic carbocycles from aryl iodides and difunctional acceptors is outlined. This methodology is based on a palladium-catalyzed aromatic substitution followed by an intramolecular Heck sequence. Under the optimized conditions (Pd(OAc)(2) (10 mol %), tri-2-furylphosphine (20-30 mol %), norbornene (2 equiv), Cs(2)CO(3) (2 equiv), CH(3)CN, reflux), bromoenoates react with aryl iodides bearing numerous substituents (F, Cl, CF(3), Me, etc.). The expanded description of our initial work as well as the use of polysubstituted aryl iodides is described.
RESUMEN
OBJECTIVES: To identify risk factors for sepsis following urinary extracorporeal shock wave lithotripsy (ESWL). DESIGN: Retrospective case-control study with two control groups. SETTING: A rural, 570-bed, regional referral center. RESULTS: Six cases (four bacteremias and two fungemias) were compared with two sets of 18 controls. Cases had a higher frequency and number of urinary tract infections prior to the procedure and tended to have larger stone size. CONCLUSIONS: Patients undergoing ESWL who are at high risk for infectious complications may be identified by preprocedure evaluation. Such patients may require alternative prophylactic regimens and close postprocedure follow-up.
