Oridonin Suppresses Proliferation of Human Ovarian Cancer Cells via Blockage of mTOR Signaling.

Oridonin, an ent-kaurane diterpenoid compound isolated from the traditional Chinese herb Rabdosia rubescens, has shown various pharmacological and physiological effects such as anti-tumor, anti-bacterial, and anti-inflammatory properties. However, the effect of oridonin on human ovarian cancer cell lines has not been determined. In this study, we demonstrated that oridonin inhibited ovarian cancer cell proliferation, migration and invasion in a dose-dependent manner. Furthermore, we showed oridonin inhibited tumor growth of ovarian cancer cells (SKOV3) in vivo. We then assessed mechanisms and found that oridonin specifically abrogated the phosphorylation/activation of mTOR signaling. In summary, our results indicate that oridonin is a potential inhibitor of ovarian cancer by blocking the mTOR signaling pathway.

[Abnormal expression of miR-let-7b in primary biliary cirrhosis and its clinical significance].

OBJECTIVE: To evaluate the expression of microRNA (miR)-let-7b in peripheral blood cells of patients with primary biliary cirrhosis (PBC) and investigate its relationship to clinical disease parameters. METHODS: Peripheral blood and serum samples were obtained for study from 60 PBC patients and 60 healthy controls. Peripheral blood cells were extracted and subjected to real-time PCR to measure miR-let-7b expression. Serum levels of interleukin (IL)-18, total bilirubin (TBIL), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) were measured by standard biochemical assays. The relationship between miR-let-7b expression and disease parameters was assessed by Spearman's rank correlation test. RESULTS: PBC patients showed significantly lower expression of miR-let-7b in peripheral blood cells than healthy controls (P less than 0.001); moreover, the miR-let-7b expression level decreased in parallel to increases in disease severity (stage I > II / III > IV). In PBC patients, the miR-let-7b expression was significantly correlated with Mayo risk scores (r = -0.4930, P less than 0.001), IL-18 (r = -0.4643, P less than 0.001) and ALP (r = -4119, P less than 0.001), but not with TBIL or GGT. CONCLUSION: Decreased expression of miR-let-7b may be associated with development and progression of PBC, and this miRNA may represent a novel target of improved diagnostic and preventive strategies for PBC.

Red blood cell distribution width is a potential index to assess the disease activity of systemic lupus erythematosus.

BACKGROUND: General population-based investigations have revealed that red blood cell distribution width (RDW) is associated with inflammatory indexes such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Chronic inflammation is one of the major components of many autoimmune diseases and RDW may reflect the severity of these autoimmune diseases as well. Therefore, the objective of this study was to investigate the correlation between RDW and disease activity of systemic lupus erythematosus (SLE). METHODS: The medical records of 131 SLE patients were retrospectively analyzed. Correlations between RDW and disease activity or other inflammatory indexes were analyzed. The effect of glucocorticoid treatment for three months on RDW was estimated in 3 newly diagnosed SLE cases. RESULTS: Increased RDW was observed in SLE patients. RDW was positively correlated with serum IgM, CRP, ESR, and SLE Disease Activity Index 2000 (SLEDAI-2K). Glucocorticoid treatment decreased both SLEDAI-2K and RDW. CONCLUSION: RDW may be a useful index to estimate the disease activity of SLE.

Value of baseline platelet count for prediction of complications in primary biliary cirrhosis patients treated with ursodeoxycholic acid.

BACKGROUND: Decreased platelet count has been observed in various liver diseases, but its significance in primary biliary cirrhosis (PBC) remains unknown. The present study aimed to evaluate the predictive value of the platelet count at diagnosis for PBC-related complications in patients newly diagnosed with PBC and treated with ursodeoxycholic acid (UDCA). METHODS: Ninety-six PBC patients without complications treated with UDCA immediately after diagnosis were retrospectively reviewed. All hematologic and chemical parameters, Mayo risk score and PBC-related complications including upper gastrointestinal hemorrhage, presence of ascites, serum bilirubin concentration > 102.6 µmol/L and onset of hepatic encephalopathy were extracted. The associations between these parameters at diagnosis and complications were determined and the prognostic value of the platelet count was evaluated by receiver operating characteristics (ROC) analysis, Kaplan-Meier method and Cox proportional hazard model with the hazard ratio (HR) and 95% confidence interval (CI) calculated. RESULTS: Patients with PBC-related complications had significantly decreased platelet count and serum bilirubin concentration, prolonged prothrombin time, and increased Mayo risk score compared to those without complications. A platelet count of ≤ 132.5 × 10(9)/L was associated with the occurrence of complications, with an area under the ROC curve of 0.74 (95% CI: 0.64-0.85). The association remained even after adjustment for Mayo risk score (HR: 2.85; 95% CI: 1.46-5.54; p < 0.01), as shown in the Cox proportional hazard model. CONCLUSIONS: Decreased platelet count is a predictive factor for PBC-related complications. A cut-off value of ≤ 132.5 × 10(9)/L is recommended for the baseline platelet count to predict complications in patients newly diagnosed with PBC and treated with UDCA.

Expression and prognostic significance of cancer-testis antigens (CTA) in intrahepatic cholagiocarcinoma.

BACKGROUND: Cancer-testis antigens (CTAs) are suitable targets for cancer-specific immunotherapy. The aim of the study is to investigate the expression of CTAs in intrahepatic cholagiocarcinoma (IHCC) and evaluate their potential therapeutic values. METHODS: Eighty-nine IHCC patients were retrospectively assessed for their expression of CTAs and HLA Class I by immunohistochemistry using the following antibodies: MA454 recognizing MAGE-A1, 57B recognizing multiple MAGE-A (MAGE-A3/A4), E978 recognizing NY-ESO-1, and EMR8-5 recognizing HLA class I. The clinicopathological and prognostic significance of individual CTA markers and their combination were further evaluated. RESULTS: The expression rates of MAGE-A1, MAGE-A3/4 and NY-ESO-1 were 29.2%, 27.0% and 22.5%, respectively. The concomitant expression of CTAs and HLA class I antigen was observed in 33.7% of the IHCC tumors. We found that positive MAGE-3/4 expression correlated with larger tumor size (≥ 5 cm), tumor recurrence and poor prognosis. Moreover, we identified 52 cases (58.4%) of IHCC patients with at least one CTA marker expression, and this subgroup displayed a higher frequency of larger tumor size and a shorter survival than the other cases. Furthermore, expression of at least one CTA marker was also an independent prognostic factor in patients with IHCC. CONCLUSION: Our data suggest that specific immunotherapy targeted CTAs might be a novel treatment option for IHCC patients.