RESUMEN
BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is an aggressive tumor type affecting cholangiocytes. CCAs frequently arise under certain cholestatic liver conditions. Intrahepatic accumulation of bile acids may facilitate cocarcinogenic effects by triggering an inflammatory response and cholangiocyte proliferation. Here, the role of bile acid receptors FXR and TGR5 in CCA progression was evaluated. METHODS: FXR and TGR5 expression was determined in human CCA tissues and cell lines. An orthotopic model of CCA was established in immunodeficient mice and tumor volume was monitored by magnetic resonance imaging under chronic administration of the specific FXR or TGR5 agonists, obeticholic acid (OCA) or INT-777 (0,03% in chow; Intercept Pharmaceuticals), respectively. Functional effects of FXR or TGR5 activation were evaluated on CCA cells in vitro. RESULTS: FXR was downregulated whereas TGR5 was upregulated in human CCA tissues compared to surrounding normal liver tissue. FXR expression correlated with tumor differentiation and TGR5 correlated with perineural invasion. TGR5 expression was higher in perihilar than in intrahepatic CCAs. In vitro, FXR was downregulated and TGR5 was upregulated in human CCA cells compared to normal human cholangiocytes. OCA halted CCA growth in vivo, whereas INT-777 showed no effect. In vitro, OCA inhibited CCA cell proliferation and migration which was associated with decreased mitochondrial energy metabolism. INT-777, by contrast, stimulated CCA cell proliferation and migration, linked to increased mitochondrial energy metabolism. CONCLUSION: Activation of FXR inhibits, whereas TGR5 activation may promote, CCA progression by regulating proliferation, migration and mitochondrial energy metabolism. Modulation of FXR or TGR5 activities may represent potential therapeutic strategies for CCA.
Asunto(s)
Neoplasias de los Conductos Biliares/patología , Colangiocarcinoma/patología , Fármacos Gastrointestinales/farmacología , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Anciano , Anciano de 80 o más Años , Animales , Ácidos y Sales Biliares/metabolismo , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Conductos Biliares/citología , Conductos Biliares/efectos de los fármacos , Conductos Biliares/metabolismo , Conductos Biliares/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ácido Quenodesoxicólico/análogos & derivados , Ácido Quenodesoxicólico/farmacología , Colangiocarcinoma/tratamiento farmacológico , Ácidos Cólicos/farmacología , Estudios de Cohortes , Progresión de la Enfermedad , Metabolismo Energético/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Femenino , Fármacos Gastrointestinales/uso terapéutico , Humanos , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Receptores Citoplasmáticos y Nucleares/agonistas , Receptores Acoplados a Proteínas G/agonistas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
In pulmonary hernia or pneumocele the lung protrudes through a defect in the chest wall. In this report of a case of spontaneous intercostal lung hernia, we describe the pathogenesis and classification of such hernias, including signs, symptoms, radiological findings and treatment methods. Our patient presented with severe chest pain at the base of the left hemithorax. A chest film and computed tomography of the region showed an left intercostal hernia. Surgical treatment was successful.
Asunto(s)
Enfermedades Pulmonares/diagnóstico , Anciano , Hernia , Humanos , Músculos Intercostales , MasculinoRESUMEN
The case of a 40 year old male that, after the etiological study performed due to rectorrhages that was the only symptom he presented, was referred to an exploratory laparotomy. A disseminated adenocarcinoma arising in Meckels diverticulum was detected and palliative segmentary resection of the small bowel was performed. The lack of previous symptoms lead to the dissemination of the disease and to the impossibility of curative surgical resection of the tumor.