PURPOSE: As the number of patients with localized renal cell carcinoma has increased, there are conflicting reports on the nuclear grade as a prognostic factor. The aim of this study was to evaluate the significance of the nuclear grade as a prognostic factor. MATERIALS AND METHODS: We retrospectively enrolled 172 patients with localized renal cell carcinoma and who underwent radical nephrectomy. The patients were staged according to the 1997 TNM stage and the Fuhrman grading. The survival rate was analyzed by the Kaplan-Meier method. Multivariate analysis was performed using the Cox proportional hazard model. RESULTS: The overall 1- , 5- and 10-year survival rates were 98.1, 72.5 and 68.4%, respectively. The 5-year survival rates for grades I, II, III and IV were 100, 92.6, 85.0 and 60.9%, respectively (p<0.0001). According to the Fuhrman grade in each T stage, 1) for patients with pT1b, the 5-year survival rates were 100, 85.0, 85.71 and 33.3% for patients with grade I, II, III and IV, respectively (p=0.002). 2) for patients with pT2, the 5-year survival rates were 100, 92.3, 60.0 and 25.0% for patients with grade I, II, III and IV, respectively (p<0.0001). A comparison of the survival curves by the Fuhrman grade showed a statistically significant difference. CONCLUSIONS: The Fuhrman grade is an important prognostic factor for patients with localized renal cell carcinoma. A high nuclear grade tends to have metastatic potential and a poor prognosis. This group of patients with a high nuclear grade must be followed up more closely. Determining the pathologic stage along with using the Fuhrman grade-based surveillance protocols are a logical approach to follow-up.
Carcinoma, Renal Cell* ; Cell Nucleus Shape ; Follow-Up Studies ; Humans ; Logic ; Multivariate Analysis ; Nephrectomy ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate

OBJECTIVETo determine the effect of berberine (Ber) on norepinephrine (NE)-induced apoptosis in neonatal rat cardiomyocytes.

METHODSThe cultured neonatal rat cardiomyocytes were treated with NE in the presence or absence of Ber. The activity of lactate dehydrogenase (LDH) in the culture medium was examined, and apoptosis of cardiomyocytes was assessed by Hoechst 33258, isothiocyanate (FITC)-conjugated annexin-V, and propidine iodide (PI) staining. In addition, the activities of caspases-2 and-3 were measured by a fluorescent assay kit. The level of secreted tumor necrosis factor α (TNF-α) and production of intracellular reactive oxygen species (ROS) were also determined.

RESULTSNE at a concentration of 50 μ mol/L induced an obvious increase in the activity of LDH in the culture medium (P<0.05), which was inhibited by coincubation with 0.5, 1.0, or 2.0 μ mol/L Ber (P<0.05). Ber also significantly attenuated NE-induced apoptosis in a dose-dependent manner (P<0.01). Moreover, Ber at a dose of 2 μ mol/L markedly decreased the ROS and TNF-α productions (P <0.05) and inhibited the activation of caspases-2 and -3 in cardiomyocytes exposed to NE (P<0.05)h.

CONCLUSIONThe present study suggested that Ber could reduce NE-induced apoptosis in neonatal rat cardiomyocytes through inhibiting the ROS-TNF-α-caspase signaling pathway.

Animals ; Animals, Newborn ; Annexin A5 ; metabolism ; Apoptosis ; drug effects ; Berberine ; pharmacology ; Caspase 2 ; metabolism ; Caspase 3 ; metabolism ; Caspases ; metabolism ; Cell Nucleus ; drug effects ; metabolism ; Cell Shape ; drug effects ; DNA ; metabolism ; Enzyme Activation ; drug effects ; Flow Cytometry ; Fluorescein-5-isothiocyanate ; metabolism ; Immunohistochemistry ; L-Lactate Dehydrogenase ; metabolism ; Myocytes, Cardiac ; drug effects ; enzymology ; pathology ; Norepinephrine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Signal Transduction ; Tumor Necrosis Factor-alpha ; metabolism