The present study was designed to determine the significance of DNA topoisomerase IIa (TopoIIα) and Ki67 in hepatocellular carcinoma cells (HCCs). The present study included 353 patients with HCC. The association of clinicopathological data with the expression of TopoIIα and Ki67 by immunohistochemistry was analyzed by χ2 test. Cox multivariate proportional hazards regression analysis and Kaplan-Meier analysis were performed with all the variables to derive risk estimates associated with overall survival (OS)/recurrence-free survival (RFS) and to control for confounders. TopoIIα and Ki67 were detected in the nuclei of the tumor cells. With TopoIIα, 35.7% of cells exhibited high expression, which was associated with tumor-node-metastasis stage, tumor size and α-fetoprotein level. With Ki67, 37.1% of cells exhibited high expression, which was associated with tumor-node-metastasis stage, tumor size and α-fetoprotein level. Correlation was identified between the expression level of TopoIIα and Ki67 in HCCs (r=0.444). Multivariate analysis revealed that high TopoIIα expression is a prognostic indicator for RFS [hazard ratio (HR), 2.002; 95% confidence interval (CI), 1.429–2.806] and OS (HR, 2.749; 95% CI, 1.919–3.939), and high Ki67 expression is a prognostic indicator for OS (HR, 1.816; 95% CI, 1.273–2.589). The TopoIIα-low group had a significantly increased RFS rate (55.6 vs. 31.7%) and OS rate (66.5 vs. 23.8%) compared with the TopoIIα-high group. The OS rate was increased in the Ki67-low group compared with the Ki67-high group (67.0 vs. 26.5%). Expression of TopoIIα and Ki67 are independent prognostic factors for survival in HCCs. TopoIIα was positively associated with Ki67 expression.
A single-particle microbeam facility has been constructed at the Key Laboratory of Ion Beam Bioengineering (LIBB), Chinese Academy of Sciences (CAS). The system was designed to deliver a defined numbers of hydrogen ions, produced by a van de Graaff accelerator, in an energy range of 2.0-3.0 MeV, into an area smaller than that of the nucleus of an individual living cell. The beam is collimated by a borosilicate glass capillary that forms the beam-line exit. An integrated computer program recognizes the cells and locates them one by one over the microbeam exit for irradiation. We present technical details of the CAS-LIBB microbeam facility, particularly on the collimator, hardware, control program, as well as cell irradiation protocols available. Various factors contributing to the targeting and positioning precision are discussed along with accuracy measurement results.
Abstract. The present study developed a novel laboratory-based algorithm to predict long-term survival rates in patients undergoing curative resection for solitary hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). The present study included 426 patients with solitary HBV-related HCC who underwent surgery for primary tumors at a single center between 2003 and 2012. Demographic characteristics, laboratory analysis, clinical pathology and immunohistochemistry of topoisomerase II-a and Ki67 were analyzed. A simple prognostic risk calculator was developed using regression coefficients from multivariate models. A prognostic risk calculator incorporating tumor encapsulation, neutrophil-to-lymphocyte ratio, vascular invasion, α-fetoprotein level, Edmondson-Steiner classification, Topo II-α, prognostic nutritional index and Child-Pugh grade was constructed. The prognostic model demonstrated good discrimination with a C-index prior to adjustment of 0.81 (95% confidence interval: 0.78-0.84) and a bootstrap-corrected C-index of 0.81. Kaplan-Meier curves demonstrated that the probabilities of overall survival rates in the low-risk group were increased compared with those in the high-risk group. The areas under the receiver operating characteristic curve using the method were greater compared with those under the 7th Tumor-Node-Metastasis system and Cancer of the Liver Italian Program scoring system [0.83 vs. 0.62 and 0.77 (P<0.001), respectively]. The simple prognostic model of the present study accurately predicted survival rates in patients. Such a prognostic risk calculator for staging patients undergoing curative resection for solitary HBV-related HCC facilitates clinical surveillance and therapy.
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