It was suggested that the enhancer of zeste homolog 2 (EZH2) gene is a putative candidate oncogene in several types of human cancer. The potential oncogenic role of EZH2 and its clinical/prognostic significance, however, in ovarian carcinoma are unclear. In this study, EZH2 expression was examined by immunohistochemistry (IHC) in cohorts of normal and tumorous ovarian tissues. High expression of EZH2 was examined in none of the normal ovaries, in 3% of the cystadenomas, in 23% of the borderline tumors and in 50% of the ovarian carcinomas, respectively. In the ovarian carcinomas, high expression of EZH2 was positively correlated with an ascending histological grade and/or advanced stage of the disease (P < 0.05). Moreover, high expression of EZH2 in ovarian carcinoma was determined to be a strong and an independent predictor of short overall survival (P < 0.05). In ovarian carcinoma HO-8910 and UACC-326 cell lines, EZH2 knockdown by RNA interference led to a G(1) phase cell cycle arrest, reduced cell growth/proliferation and inhibited cell migration and/or invasion in vitro. In addition, EZH2 knockdown was found to reduce transforming growth factor-beta1 (TGF-beta1) expression and increase E-cadherin expression either in the transcript or in the protein levels. Furthermore, a significant positive correlation between overexpression of EZH2 and TGF-beta1 in ovarian carcinoma tissues was observed (P < 0.001). These findings suggest a potential important role of EZH2 in the control of cell migration and/or invasion via the regulation of TGF-beta1 expression, and the high expression of EZH2, as detected by IHC, is an independent molecular marker for shortened survival time of patients with ovarian carcinoma.

Aloperine (ALO) is a quinolizidine alkaloid extracted from the leaves of Sophora alopecuroides (S. alopecuroides) and possesses anti-inflammatory, anti-allergenic, antitumor, and antiviral effects. In this study, when compared with seven other types of alkaloids extracted from S. alopecuroides, ALO treatment produced the most potent effects against HCT116 colon cancer cell types. ALO inhibited proliferation and induced apoptosis in HCT116 cells in a dose- and time-dependent manner as detected by MTT, clonogenic survival, and flow cytometric assays. Results of the western blot analysis and qPCR revealed that ALO increased the protein and mRNA of Bax and decreased Bcl-2 via the mitochondrial death pathway. In addition, ALO induced cell cycle arrest at the G2/M phase with a concomitant increase in p21 and p53 and a decrease in cyclin D1 and B1. ALO also inhibited phosphatidylinositol 3-kinase/Akt and JAK/Stat3. Generally, ALO exerted a significant anti-proliferative effect via apoptotic and cell cycle arrest induction in HCT116 cells. These results suggested that ALO should be investigated further as an agent of chemotherapeutic activity in human colon cancer.

BackgroundResearchers from several different countries have found the Social Responsiveness Scale (SRS) to have good psychometric properties. However, to our knowledge, no studies on this subject have been reported in Mainland China. In this study, we investigated the psychometric properties of the Chinese Mandarin version of the SRS when used in Mainland China.MethodsThe reliability and validity of the parent-report SRS in a sample of 749 children of 4- to 14-year-olds: 411 typically developing and 338 clinical participants (202 with autism spectrum disorder (ASD)) were examined.ResultsInternal consistency for total scale (0.871–0.922), test–retest reliability (0.81–0.94), and convergent validity with the Autism Behavior Checklist (ABC) (0.302–0.647) were satisfactory. The SRS total score discriminated between the ASD and other developmental disorders. Receiver operating characteristic (ROC) analyses revealed that the SRS was predicted to accurately classify 69.2–97.2% of youth ASD. Exploratory factor analysis (EFA) supported a single-factor solution for the ASD subsample. Confirmatory factor analysis (CFA) did not confirm the theoretical construct of five factors model with inadequate fit in the ASD subsample.ConclusionsOverall, our findings supported the reliability and validity of the parent-report SRS as one ASD screening instrument. In addition, we also suggest that the use of separate cut-offs for screening purposes (optimizing sensitivity) vs. clinical confirmation (optimizing specificity) should be considered.

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BackgroundAloperine, a natural alkaloid constituent isolated from the herb Sophora alopecuroides displays anti-inflammatory properties in vitro and in vivo. Our group previously demonstrated that aloperine significantly induced apoptosis in colon cancer SW480 and HCT116 cells. However, its specific target(s) remain to be discovered in multiple myeloma (MM) and have not been investigated.MethodsHuman myeloma cell lines (n = 8), primary myeloma cells (n = 12), drug-resistant myeloma cell lines (n = 2), and animal models were tested for their sensitivity to aloperine in terms of proliferation and apoptosis both in vitro and in vivo, respectively. We also examined the functional mechanisms underlying the apoptotic pathways triggered by aloperine.ResultsAloperine induced MM cell death in a dose- and time-dependent manner, even in the presence of the proliferative cytokines interleukin-6 and insulin-like growth factor I. Mechanistic studies revealed that aloperine not only activated caspase-8 and reduced the expression of FADD-like interleukin-1β-converting enzyme (FLICE)-like inhibitory protein long (FLIPL) and FLICE-inhibitory proteins (FLIPS) but also activated caspase-9 and decreased the expression of phosphorylated (p)-PTEN. Moreover, co-activation of the caspase-8/cellular FLICE-inhibitory protein (cFLIP)- and caspase-9/p-PTEN/p-AKT-dependent apoptotic pathways by aloperine caused irreversible inhibition of clonogenic survival. Aloperine induce more MM apoptosis with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or borterzomib. A U266 xenograft tumor model and 5T33 MM cells recapitulated the antitumor efficacy of aloperine, and the animals displayed excellent tolerance of the drug and few adverse effects.ConclusionsAloperine has multifaceted antitumor effects on MM cells. Our data support the clinical development of aloperine for MM therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-015-0120-x) contains supplementary material, which is available to authorized users.