Yuanguang Meng

Arctigenin Promotes Apoptosis in Ovarian Cancer Cells via the iNOS/NO/STAT3/Survivin Signalling

Arctigenin is a biologically active lignan extracted from the seeds of Arctium lappa and shows anticancer activity against a variety of human cancers. The aim of this study was to determine the effects of arctigenin on ovarian cancer cell proliferation and survival and associated molecular mechanisms. Human ovarian cancer OVCAR3 and SKOV3 cells were treated with arctigenin, and cell proliferation and apoptosis were assessed. Western blot analysis was used to examine signal transducer and activator of transcription‐3 (STAT3) phosphorylation and survivin and inducible nitric oxide synthase (iNOS) expression. The involvement of STAT3/survivin/iNOS/NO signalling in arctigenin action was checked. Arctigenin treatment resulted in a significant and dose‐dependent inhibition of cell proliferation. Arctigenin‐treated cells showed a 4–6 times increase in the percentage of apoptosis, compared with control cells. Pre‐treatment with Ac‐DEVD‐CHO, a specific inhibitor of caspase‐3, counteracted the induction of apoptosis by arctigenin. Arctigenin treatment significantly inhibited STAT3 phosphorylation and survivin and iNOS expression. Arctigenin‐induced apoptosis was impaired by pre‐transfection with survivin‐expressing plasmid or addition of chemical nitric oxide (NO) donors. Additionally, exogenous NO prevented the suppression of STAT3 phosphorylation and survivin expression by arctigenin. Arctigenin treatment inhibits the proliferation and induces caspase‐3‐dependent apoptosis of ovarian cancer cells. Suppression of iNOS/NO/STAT3/survivin signalling is causally linked to the anticancer activity of arctigenin. Therefore, arctigenin may be applicable to anticancer therapy for ovarian cancer.

High expression of astrocyte elevated gene-1 (AEG-1) is associated with progression of cervical intraepithelial neoplasia and unfavorable prognosis in cervical cancer

BackgroundAstrocyte elevated gene-1(AEG-1) plays an important role in the development and progression of certain types of human cancers. However, the expression dynamics of AEG-1 in cervical cancer and its clinical/prognostic significance are unclear.MethodIn present study, the methods of tissue microarrays (TMA) and immunohistochemistry (IHC) were utilized to investigate AEG-1 expression in cervical intraepithelial neoplasia (CIN) and cervical cancer. Receiver operating characteristic (ROC) curve analysis, χ 2 test, Kaplan-Meier plots, and multivariate Cox regression analysis were used to analyze the data.ResultsThe expression level of AEG-1 was increased from CIN I to CIN III. High expression of AEG-1 could be observed in 61.1% (55/90) of cervical cancer. Moreover, high expression of AEG-1 correlated with tumor size and lymph node metastasis (all P <0.05). More importantly, high expression of AEG-1 was closely associated with cervical cancer patient shortened survival time as evidenced by univariate and multivariate analysis (P <0.05).ConclusionsOur data suggest for the first time that high expression of AEG-1 is associated significantly with progression of cervical cancer. AEG-1 overexpression, as examined by IHC, has the potential to be used as an immunomarker to predict prognosis of cervical cancer patients.

ARHI overexpression induces epithelial ovarian cancer cell apoptosis and excessive autophagy.

Objective ARHI is a maternally imprinted tumor suppressor gene that is responsible for initiating programmed cell death and inhibiting cancer cell growth. However, the influence of ARHI on epithelial ovarian cancer cell death and the underlying mechanisms behind how ARHI regulates cancer cells still require further studies. Methods Epithelial ovarian cancer cells TOV112D and ES-2 were used in this in vitro study. Cell proliferation, apoptosis, and autophagy activities were compared in TOV112D and ES-2 cells transfected with ARHI vectors or control vectors. Bcl-2 siRNA was transfected into TOV112D cells to investigate the roles of Bcl-2 played in regulating apoptosis and autophagy. Results ARHI expression was reduced in TOV112D and ES-2 cells compared with normal epithelial ovarian cells (NOE095 and HOSEpiC). Overexpressed ARHI inhibited cancer cell proliferation, whereas induced forced cell apoptosis and excessive formation of autophagosomes inhibited promoted cell death. Furthermore, we found that Bcl-2 expression moderately declined in response to ARHI overexpressing in ES-2 and TOV112D cells; meanwhile, more apoptotic cells and higher LC3 level presented after silence of Bcl-2 in TOV112D cells. Reduced Bcl-2–Beclin 1 complex were observed in ARHI overexpressing cells. Moreover, modulation of ARHI to Bcl-2 expression could be ascribed partially to the activation of PI3k/AKT pathway. The addition of LY294002 enabled to suppress Bcl-2 expression and cell proliferation. Conclusions The silence of ARHI expression in vitro seems to accelerate the malignant transformation of healthy ovarian cells by restraining apoptosis and autophagy. The overexpressed ARHI in TOV112D cancer cells suppresses the activation of PI3K/AKT and reduces the expression of Bcl-2, leading to enhanced cell apoptosis and autophagic cancer cell death.Objective ARHI is a maternally imprinted tumor suppressor gene that is responsible for initiating programmed cell death and inhibiting cancer cell growth. However, the influence of ARHI on epithelial ovarian cancer cell death and the underlying mechanisms behind how ARHI regulates cancer cells still require further studies. Methods Epithelial ovarian cancer cells TOV112D and ES-2 were used in this in vitro study. Cell proliferation, apoptosis, and autophagy activities were compared in TOV112D and ES-2 cells transfected with ARHI vectors or control vectors. Bcl-2 siRNA was transfected into TOV112D cells to investigate the roles of Bcl-2 played in regulating apoptosis and autophagy. Results ARHI expression was reduced in TOV112D and ES-2 cells compared with normal epithelial ovarian cells (NOE095 and HOSEpiC). Overexpressed ARHI inhibited cancer cell proliferation, whereas induced forced cell apoptosis and excessive formation of autophagosomes inhibited promoted cell death. Furthermore, we found that Bcl-2 expression moderately declined in response to ARHI overexpressing in ES-2 and TOV112D cells; meanwhile, more apoptotic cells and higher LC3 level presented after silence of Bcl-2 in TOV112D cells. Reduced Bcl-2–Beclin 1 complex were observed in ARHI overexpressing cells. Moreover, modulation of ARHI to Bcl-2 expression could be ascribed partially to the activation of PI3k/AKT pathway. The addition of LY294002 enabled to suppress Bcl-2 expression and cell proliferation. Conclusions The silence of ARHI expression in vitro seems to accelerate the malignant transformation of healthy ovarian cells by restraining apoptosis and autophagy. The overexpressed ARHI in TOV112D cancer cells suppresses the activation of PI3K/AKT and reduces the expression of Bcl-2, leading to enhanced cell apoptosis and autophagic cancer cell death.

Safety evaluation of chemically modified beta‐lactoglobulin administered intravaginally

Currently, there is no specific antiviral therapy for treatment of HPV infection. Jiang and colleagues previously reported that anhydride‐modified proteins have inhibitory activities against multiple viruses including HPV. Here, we evaluated the safety of 3‐hydroxyphthalic anhydride‐modified bovine beta‐lactoglobulin, designated JB01, vaginally applied in women infected by high‐risk HPV. After the vaginal application of JB01 in 38 women for 3 months, no serious adverse events were reported, and normalization of the vaginal micro‐environment has been observed. It can be concluded that JB01‐BD is safe for vaginal use in HPV‐infected women, suggesting its potential application for the treatment of HPV infection. J. Med. Virol. 88:1098–1101, 2016.

p16 expression in patients with cervical cancer and its prognostic significance: meta-analysis of published literature

OBJECTIVES p16, a tumour suppressor, is unable to express its suppressive effects following interaction with E7-retinoblastoma protein. Previous reports have suggested that p16 immunostaining allows precise identification of cervical intra-epithelial neoplasia and cervical cancer lesions in biopsies. The prognostic value of p16 expression in cervical cancers has been evaluated for several years, but the results remain controversial. As such, the authors undertook a systematic review and meta-analysis of studies assessing the impact of p16 expression on overall survival and disease-free survival. STUDY DESIGN Medline, Embase and China National Knowledge Infrastructures were searched to identify studies on the prognostic impact of p16 expression in patients with cervical cancer. In total, 1070 patients from 10 eligible studies were included in the analysis. Pooled risk ratios (RRs) with 95% confidence intervals (95% CI) were calculated. RESULTS A significant association was found between p16 expression and increased disease-free survival (RR 0.60; 95% CI 0.44-0.82; p=0.001). However, no significant association was found between p16 and overall survival. CONCLUSION p16 expression may be predictive of a favourable prognosis in patients with cervical cancer. However, large-scale, multicentre and well-matched cohort studies are warranted to confirm this finding.

Noninvasive prenatal test for FGFR3‐related skeletal dysplasia based on next‐generation sequencing and plasma cell‐free DNA: Test performance analysis and feasibility exploration

To explore the feasibility and accuracy of a noninvasive prenatal test for fibroblast growth factor receptor 3 (FGFR3)‐related skeletal dysplasia based on next‐generation sequencing (NGS) of plasma cell‐free DNA.

Diagnosis and surgical therapy of the retroperitoneal ectopic pregnancy: A case report

Highlights • A rare case of retroperitoneal ectopic pregnancy received surgical treatment was reported.• Discuss the mechanisms of retroperitoneal embryo migration.• Review related literatures of retroperitoneal embryo migration and discuss the surgical method.