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.

BackgroundIt has been suggested that the B-cell specific moloney leukemia virus insertion site 1 (Bmi-1) gene plays an oncogenic role in several types of human cancer, but the status of Bmi-1 amplification and expression in ovarian cancer and its clinical/prognostic significance are unclear.MethodsThe methods of immunohistochemistry and fluorescence in situ hybridization were utilized to examine protein expression and amplification of Bmi-1 in 30 normal ovaries, 30 ovarian cystadenomas, 40 borderline ovarian tumors and 179 ovarian carcinomas.ResultsIntensive expression of Bmi-1 was detected in none of the normal ovaries, 3% cystadenomas, 10% borderline tumors, and 37% ovarian carcinomas, respectively. Amplification of Bmi-1 was detected in 8% of ovarian carcinomas. In ovarian carcinomas, significant positive associations were found between intensive expression of Bmi-1 and the tumors ascending histological grade, later pT/pN/pM and FIGO stages (P < 0.05). In univariate survival analysis of the ovarian carcinoma cohorts, a significant association of intensive expression of Bmi-1 with shortened patient survival (mean 49.3 months versus 100.3 months, p < 0.001) was demonstrated. Importantly, Bmi-1 expression provided significant independent prognostic parameters in multivariate analysis (p = 0.005).ConclusionsThese findings provide evidence that intensive expression of Bmi-1 might be important in the acquisition of an invasive and/or aggressive phenotype of ovarian carcinoma, and serve as a independent biomarker for shortened survival time of patients.

BackgroundThe secretory small GTPase Rab27b was recently identified as an oncogene in breast cancer (BC) in vivo and in vitro studies. This research was designed to further explore the clinical and prognostic significance of Rab27B in BC patients.MethodsThe mRNA/protein expression level of Rab27B was examined by performing Real-time PCR, western blot, and immunohistochemistry (IHC) assays in 12 paired BC tissues and matched adjacent noncancerous tissues (NAT). Then we carried out IHC assay in a large cohort of 221 invasive BC tissues, 22 normal breast tissues, 40 fibroadenoma (FA), 30 ductual carcinoma in situ (DCIS) and 40 metastatic lymph nodes (LNs). The receiver operating characteristic curve method was applied to obtain the optimal cutoff value for high Rab27B expression. Epithelial-mesenchymal transition (EMT) marker expression levels were detected in relation to Rab27B expression.ResultsWe observed that the increased expression of Rab27B was dependent upon the magnitude of cancer progression (P < 0.001). The elevated expression of Rab27B was closely correlated with lymph node metastasis, advanced clinical stage, ascending pathology classification, and positive ER status. Furthermore, patients with high expression of Rab27B had inferior survival outcomes. Multivariate Cox regression analysis proved that Rab27B was a significantly independent risk factor for patients’ survival (P < 0.001). Furthermore, a significant positive relationship was observed between Rab27B expression and elevated mesenchymal EMT markers.ConclusionOur findings suggest that overexpression of Rab27B in BC coincides with lymph node metastasis and acquisition of a poor prognostic phenotype.

Our previous study has suggested that the cell cycle-related kinase (CCRK) is a putative candidate oncogene in glioblastoma tumorigenesis. The potential oncogenic role of CCRK and its clinical/ prognostic significance, however, in ovarian carcinoma are unclear. In this study, CCRK expression was examined by immunohistochemistry in a series of ovarian carcinoma tissues. Overexpression of CCRK was detected in 53% of the ovarian carcinomas, and it was positively correlated with an ascending histological grade and/or advanced clinical stage of the disease (p < 0.05). In addition, overexpression of CCRK in ovarian carcinoma was determined to be a strong and an independent predictor of short overall survival (p < 0.05). In ovarian carcinoma cells, CCRK knockdown by RNAi led to a G1 phase cell cycle arrest, while CCRK overexpression by stable transfection of CCRK-containing plasmid pcDNA-CCRK promoted cell proliferation in vitro and tumor growth in vivo. In addition, CCRK knockdown was found to reduce cyclin D1 expression. Consistently, CCRK overexpression increased cyclin D1 expression, and furthermore, a significant correlation between expression of CCRK and cyclin D1 in ovarian carcinomas was observed (p < 0.001). These findings suggest a potential important role of CCRK in the control of cell proliferation via regulation of cyclin D1 expression, and the overexpression of CCRK, as detected by immunohistochemistry, is an independent molecular marker for shortened survival time of patients with ovarian carcinoma. ' UICCKey words: ovarian cancer; cell cycle-related kinase; prognosis; cell cycle; cyclin D1Ovarian cancer is 1 of the 5 leading causes of cancer-related deaths in women in the United States and Europe, 1 and is the leading cause of gynecologic malignancy deaths. Recently, its incidence has been increasing in Asian countries such as China and Singapore. 2 Because of its insidious onset, about 70% of patients with ovarian cancer were diagnosed at advanced stage. 3 Although improvement of the quality of cytoreductive surgery as well as development of novel drugs and new chemotherapy regimens for ovarian cancer therapy have been made, 4 most patients relapse, very few achieve a cure and the 5-year survival rate of patients in advanced stage ranges only from 20 to 25%. [4][5][6][7] The pathogenesis of ovarian cancer is believed to be a multistep process that involves multiple genetic changes, including loss of tumor suppressor genes and activation of oncogenes. 8 Recently, we have focused our research on the genetic changes underlying the development and progression of ovarian carcinoma, and several putative candidate oncogenes, such as eIF5-A2 and SEI-1, have been identified and suggested. 9-11 Although the molecular and/or genetic alterations in this neoplasm has been widely studied, to date, the discovery of specific molecular markers that are present in ovarian carcinoma cells, which could serve as reliable clinical/prognostic factors, is still substantially limited.More recently, we have provided evidence ...