RESUMEN
DHEA is known to have anti-proliferative effect. The mechanism is not completely understood. We investigated the mechanism underlying DHEA-induced growth arrest of hepatoma cells. Growth inhibition was associated with increased G6PD activity, and insensitive to reversal by mevalonate. Thus, DHEA does not act via inhibition of G6PD and HMGR. Instead, growth stagnation was accompanied by reduced expression of nucleus-encoded mitochondrial genes; morphological and functional alterations of mitochondria; and depletion of intracellular ATP. Conversely, pyruvate supplementation alleviated DHEA-induced growth inhibition. It is likely that DHEA suppresses cell growth by altering mitochondrial gene expression, morphology and functions.
Asunto(s)
Carcinoma Hepatocelular/metabolismo , Proliferación Celular , ADN Mitocondrial/metabolismo , Deshidroepiandrosterona/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/patología , Mitocondrias/metabolismo , Adenosina Trifosfato/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Metabolismo Energético , Glucosafosfato Deshidrogenasa/metabolismo , Humanos , Hidroximetilglutaril-CoA Reductasas/metabolismo , Neoplasias Hepáticas/genética , Ácido Pirúvico/metabolismo , Factores de TiempoRESUMEN
AIM: Effects of radiofrequency ablation (RFA) combining immunoadjuvant glycated chitosan (GC) on tumor control and potent cytokine responses were investigated in a syngeneic breast tumor model. MATERIALS AND METHODS: Murine 4T1 breast carcinoma cells harboring the luciferase reporter gene were used to evaluate the tumor growth rate and metastasis in vivo using bioluminescent imaging. Plasma of RFA/GC-treated tumor-bearing mice was collected for ex vivo cytotoxicity analysis and mouse chemokine array assays. RESULTS: Tumor growth and systemic metastasis were suppressed by combined RFA and GC when tumor size reached 300 mm3, not detected, however, when tumor size reached 800 mm3 The survival rate of mice bearing small tumors was also higher than that of large ones after RFA-GC treatment. Plasma extracted from RFA-GC-treated small tumor-bearing mice exhibited cytotoxicity on cultured 4T1 cells. Moreover, reduced tumor growth-related cytokines and increased antitumor-related cytokines were detected in the plasma collected. CONCLUSION: RFA combining GC could control tumor progression with induced potent antitumor cytokine responses.
Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Ablación por Catéter , Quitosano/uso terapéutico , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Neoplasias Mamarias Experimentales/cirugía , Animales , Línea Celular Tumoral , Supervivencia Celular , Quimiocinas/sangre , Terapia Combinada , Femenino , Neoplasias Mamarias Experimentales/sangre , Neoplasias Mamarias Experimentales/patología , Ratones , Ratones Endogámicos BALB C , Plasma , Carga Tumoral/efectos de los fármacosRESUMEN
Encephalitozoon cuniculi (E. cuniculi) is a microsporidian parasite commonly found in rabbits that can infect humans, causing encephalitozoonosis. Our laboratory recently confirmed the first case of encephalitozoonosis in a rabbit in Taiwan; the prevalence of encephalitozoonosis is not well documented, even when many clinics suspect pet rabbits as being infected. This study surveys the seropositivity of E. cuniculi using carbon immunoassay (CIA) and enzyme-linked immunosorbent assay (ELISA). Serological examination of 171 rabbits using CIA and ELISA showed that 63.2% (108/171) and 67.8% (116/171) were seropositive against E. cuniculi, respectively. Thirteen of the 14 rabbits (92.9%) with neurological symptoms were seropositive. Except for gender, health status and location had a significant effect on E. cuniculi seropositivity (p<0.05). Adult rabbits aged older than 4 months exhibited significantly higher seropositivity for E. cuniculi than young rabbits (p<0.05). In conclusion, this study shows that E. cuniculi is present and widespread among healthy rabbits in Taiwan. Therefore, the fields of veterinary and human medicine in Taiwan should be aware of this zoonotic issue and the resulting public health concern of encephalitozoonosis.