ObjectiveTo analyze the expression levels of γ-glutamyl transpeptidase (GGT) and alpha-fetoprotein (AFP) and their correlation in patients with hepatocellular carcinoma (HCC) and to evaluate their diagnostic values for HCC. MethodsA total of 160 patients consisting of 84 cases of HCC and 76 cases of liver cirrhosis, who were examined in the department of clinical laboratory, Yulin Xingyuan hospital, from December 2011 to December 2014, were selected in this study. The difference and correlation of AFP and GGT expression levels in the two groups were analyzed. The diagnostic cut-off values were determined based on sensitivity, specificity, Youden′s index, receiver operating characteristic (ROC) curve, and area under the ROC curve. Comparison between two groups was made by independent-samples t test or Mann-Whitney U test. The correlation between AFP and GGT was determined by Spearman rank correlation analysis. ResultsThe AFP and GGT expression levels in the HCC group were significantly higher than those in the cirrhosis group (Z=-8.993, P＜0.05; Z=-7.647, P＜0.05). The expression levels of AFP and GGT in both groups were positively correlated (rs=0.531, P＜0.05; rs=0.416, P＜0.05). There was also a positive correlation between the AFP and GGT expression levels for all the subjects (rs=0.701, P＜0.05). The diagnostic accuracy of AFP and GGT for HCC was moderate. The maximum Youden′s index was 0.519 for AFP when its cut-off value was 100 ng/ml and the maximum Youden′s index was up to 0.494 for GGT when its cut-off value reached 150 U/L. A combination of AFP and GGT could increase the sensitivity and decrease the specificity in the diagnosis of HCC, but no significant change in the Youden′s index for AFP was observed. ConclusionThere is a significant positive correlation between the expression levels of GGT and AFP, but the combined measurement of AFP and GGT does not improve the accuracy of HCC diagnosis.

OBJECTIVE: To explore the molecular mechanism underlying the inhibitory effects of aspirin against human breast cancer cell proliferation through bioinformatics analysis. METHODS: Drug Bank 5.1.3 was searched to identify direct protein targets (DPTs) of aspirin, and the protein-protein interaction (PPI) network of the DPTs was constructed online using STRING and the signaling pathways involved were identified. The genetic alterations of 6 DPTs associated with human breast cancer was analyzed and visualized by cBio Portal and OncoPrint, respectively. The transcriptomic data of breast cancer and normal tissues were downloaded from TCGA database, and the overexpressed genes were analyzed by DECenter. The intersection between the genes associated with the DPTs obtained by STRING analysis and the differentially over-expressed genes in TCGA was determined to confirm the candidate DPTs as a potential target of aspirin, and GO functional enrichment analysis was performed using Gene Ontology. The potential targets of aspirin against the proliferation of human breast cancer cells were verified by Western blotting. RESULTS: Eleven DPTs of aspirin were identified. KEGG pathway enrichment indicated that 6 genes (EDNRA, IKBKB, NFKB2, NFKBIA, PTGS2 and TP53) were associated with the occurrence and development of cancer. A total of 10 220 differentially expressed genes were identified from the TCGA database, and among them 4 genes (, , , ) were found to be the potential targets for aspirin. These genes were involved mostly in the regulation of cell cycle and cell division. Western blotting showed that aspirin could down-regulate the expression levels of several pivotal proteins that regulated cell cycle and cell division, including , , and . CONCLUSIONS , , and may be potential targets for aspirin to inhibit the proliferation of human breast cancer cells, by affecting the progress of cell cycle and cell division.

Objective: We aimed to examine the feasibility and toxicity of EC-T dose-dense regimen and to demonstrate the suitable dose of epirubicin in a Chinese early-stage breast cancer population with high recurrence risk. Methods: 370 patients with early-stage breast cancer at high risk of recurrence were treated with EC-T dose-dense adjuvant chemotherapy and prophylactic administration of recombinant human granulocyte stimulating factor (G-CSF). The incidence of delayed chemotherapy, drug reduction and adverse reactions were retrospectively analyzed. Results: 370 patients completed the planned eight cycles of chemotherapy, 50 patients experienced chemotherapy delay, and 90 had chemotherapy dose reductions. Overall, 61.1% of the patients experienced grade 3 or 4 hematology toxicities, 4.1% of the patients experienced grade 3 gastrointestinal toxicity, 16.3% experienced grade 3 or 4 liver malfunction, and 1.9% experienced grade 3 alopecia. In the multivariate analysis, pretreatment epirubicin levels were associated with comprehensive and hematology toxicity risk (OR=1.268, P=0.046; OR=1.244, P=0.036). With G-CSF support, the probability of grade 3-4 dose limiting toxicity, i. e. neutropenia, abnormal liver function, and gastrointestinal adverse effects did not increase as the epirubicin dose level increased(P>0.05). However, there were no statistically significant associations between epirubicin grade and treatment delay (P=0.814) or dose reduction (P=0.282). Conclusions EC-T dose-dense chemotherapy shows tolerable toxicity. High dose level is not a limiting factor for this regimen. With G-CSF support, epirubicin 85-90 mg/m² is appropriate tolerance dose for Chinese early breast cancer patients with high recurrence risk.