RESUMEN

PURPOSE: Using brightness mode ultrasound combined with shear wave elastography, this study aims to detect structural and functional changes of the medial head of gastrocnemius (MG) in type 2 diabetes mellitus (T2DM) patients with or without diabetic peripheral neuropathy (DPN). METHODS: 149 T2DM patients (DPN group and non-DPN group) and 60 healthy volunteers (control group) were enrolled. We measured the absolute difference of fascicle length (FL), pennation angle (PA), and shear wave velocity (SWV) of both MG in neutral position and maximal ankle joint's plantar flexion and calculated ΔFL, ΔPA, and ΔSWV. These three parameters, along with muscle thickness (MT), were compared among the three groups. RESULTS: In the DPN group, the MG's MT, ΔPA, and ΔSWV were significantly lower than in the non-DPN group (p < 0.01); these parameters achieved the highest scores in the control group (p < 0.01). The area under the receiver operating characteristic curve of the combination of ΔSWV and ΔFL was the largest for predicting inpatients with or without DPN. CONCLUSIONS: Decreased muscle mass (MT) and muscle contractibility (ΔFL and ΔSWV) were detected in patients with T2DM, with or without DPN. ΔSWV and ΔFL of the MG showed high-diagnostic accuracy for DPN warning signs.

Asunto(s)

Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Humanos , Neuropatías Diabéticas/diagnóstico por imagen , Diabetes Mellitus Tipo 2/complicaciones , Curva ROC , Ultrasonografía , Músculos

RESUMEN

The nucleolus is a stress sensor associated with cell cycle progression and apoptosis. Studies have shown that nucleolar stress is positively correlated with apoptosis in breast, prostate and lung cancer cells. However, the role and function of nucleolar stress in ovarian cancer has not been reported. In this study, we found that the nucleolar stress inducer BMH-21 inhibited viability of SKOV3 ovarian cancer cells in a dose-dependent manner. Furthermore, BMH-21 induced the expression of nucleolar stress marker proteins (nucleolin, nucleophosmin and fibrillarin) and promoted the nuclear export of these proteins. BMH-21 also decreased MDM2 proto-oncogene expression and increased protein levels of the tumor suppressor p53 and p53 phosphorylated at serine 15 (p­p53­Ser15), which contributed to increased expression of the downstream apoptosis-related protein BCL2 associated X (BAX) and activation of caspase-3. Taken together, these data provide the first reported evidence that induction of p53-dependent nucleolar stress by BMH-21 induces apoptosis in ovarian cancer. Our data suggest that nucleolar stress might be a pathway suitable for targeting in ovarian cancer.

Asunto(s)

Antineoplásicos/farmacología , Nucléolo Celular/efectos de los fármacos , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Neoplasias Ováricas/tratamiento farmacológico , Estrés Fisiológico/efectos de los fármacos , Proteína p53 Supresora de Tumor/genética , Apoptosis/efectos de los fármacos , Caspasa 3/genética , Línea Celular Tumoral , Nucléolo Celular/genética , Supervivencia Celular/efectos de los fármacos , Proteínas Cromosómicas no Histona/genética , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Proteínas Nucleares/genética , Nucleofosmina , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Fosfoproteínas/genética , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteínas de Unión al ARN/genética , Proteína X Asociada a bcl-2/genética , Nucleolina