EZH2 Contributes to Anoikis Resistance and Promotes Epithelial Ovarian Cancer Peritoneal Metastasis by Regulating m6A.

OBJECTIVE: Histone modification has a significant effect on gene expression. Enhancer of zeste homolog 2 (EZH2) contributes to the epigenetic silencing of target chromatin through its roles as a histone-lysine N-methyltransferase enzyme. The development of anoikis resistance in tumor cells is considered to be a critical step in the metastatic process of primary malignant tumors. The purpose of this study was to investigate the effect and mechanism of anoikis resistance in ovarian adenocarcinoma peritoneal metastasis. METHODS: In addition to examining EZH2 protein expression in ovarian cancer omental metastatic tissues, we established a model of ovarian cancer cell anoikis and a xenograft tumor model in nude mice. Anoikis resistance and ovarian cancer progression were tested after EZH2 and N6-methyladenosine (m6A) levels were modified. RESULTS: EZH2 expression was significantly higher in ovarian cancer omental metastatic tissues than in normal ovarian tissues. Reducing the level of EZH2 decreased the level of m6A and ovarian cancer cell anoikis resistance in vitro and inhibited ovarian cancer progression in vivo. M6a regulation altered the effect of EZH2 on anoikis resistance. CONCLUSION: Our results indicate that EZH2 contributes to anoikis resistance and promotes ovarian adenocarcinoma abdominal metastasis by m6A modification. Our findings imply the potential of the clinical application of m6A and EZH2 for patients with ovarian cancer.

Sex-specific gene expression patterns in head and neck squamous cell carcinomas.

Objective: The head and neck squamous cell carcinomas (HNSCCs) have higher incidence rates in men, but the reasons are still obscure. This study aimed to investigate the sex-specific gene expression patterns and predict the regulatory mechanisms. Design: Data including clinical, survival, RNA-seq, miRNA, and methylation information were derived from The Cancer Genome Atlas (TCGA). A total of 131 paired male and female cases were included based on propensity score matching. We concentrated on the prognostic values of the sex-specific pathways enriched by differentially expressed genes (DEGs) and predicted the potential regulatory mechanisms from immune cell infiltration, ceRNA regulatory network, methylation, and differential coexpression analysis. Results: Compared with females, males exhibited a lower activity of immune-related functions and higher activities of mitochondrial and ubiquitination functions. The pathway activities were associated with the prognosis of males but less relevant to females. We extracted eight pathways with sex-biased survival patterns, of which five were about down-regulated immune functions, and three were up-regulated pathways (GTP biosynthetic, DNA polymerase, and spliceosomal complex assembly). The five immune pathways were moderately or strongly correlated with the proportion of macrophages. We identified six over-expressed lncRNAs that might be involved in the regulation of the three up-regulated pathways. These lncRNAs exhibited a lower methylation density in males, which might account for their over-expression. Conclusions: For HNSCCs, males were characterized by immunosuppression. It was a sign of unfavorable prognosis and might be associated the proportion of macrophages. LncRNAs and methylation might be involved in the regulation of these pathways.

Diagnostic Value of Circulating PIGF in Combination with Flt-1 in Early Cervical Cancer.

The utility of placental growth factor (PlGF) and its receptor VEGFR-1 (Flt-1) as biomarkers for cervical cancer has not been clarified yet. To address this issue, we investigated the levels of soluble PlGF (sPlGF) and soluble Flt-1 (sFlt-1) in the serum from patients with early cervical cancer, cervical intraepithelial neoplasia (CIN) and controls in this study. sPlGF and sFlt-1 were detected in 44 preoperative patients with cervical cancer, 18 cases with CIN, and 20 controls by ELISA. It was found that both sPlGF and sFlt-1 were significantly increased in the cervical cancer group as compared with those in CIN and control groups. sPlGF presented a high diagnostic ability of cervical cancer, with a sensitivity of 61.36% and a specificity of 89.47%; and sFlt-1 with a sensitivity of 50.00% and a specificity of 92.11%. Importantly, the combined use of sPlGF and sFlt-1 could increase the diagnostic rate of cervical cancer, with a sensitivity of 70.45% and a specificity of 92.11%. These results indicated that both sPlGF and sFlt-1 in circulation can serve as possible valuable diagnostic biomarkers for cervical cancer, and the combined use of them can be more valuable to diagnose the patients with early cervical cancer.

[The role and mechanism of CXCR4 and its ligand SDF-1 in the development of cervical cancer metastasis].

BACKGROUND & OBJECTIVE: The chemokine receptor CXCR4 and its sole ligand stromal cell-derived factor-1 (SDF-1) not only actively participate in inflammation, hematopoiesis, infection of HIV, but also play a pivotal role in migration, invasion and metastasis of some malignant tumors. This study was to investigate the role of CXCR4/SDF-1 axis in mediating metastasis in cervical cancer cells through activating the mitogen-activated protein kinase (MAPK) pathway and its possible mechanism. METHODS: Intracellular calcium mobilization was observed under laser scanning confocal fluorescence microscopy. The phospharylation of extracellular signal-regulated kinase (ERK) 1/2 in HeLa cells after binding of SDF-1alpha to CXCR4 was measured by Western blot. Adhesion of CXCR4/SDF-1 to cervical cancer cells and secretion of matrix metalloproteinase (MMP) were detected by adhesion assay and gelatin zymography, respectively. RESULTS: After SDF-1alpha was bound to CXCR4, a rapid and robust mobilization of intracellular calcium in Hela cells was initiated. The difference between the average baseline fluorescence intensity (FI) and the peak FI was significant (P < 0.01). ERK-1/2 was rapidly phosphorylated in Hela cells after its exposure to SDF-1alpha, and the strongest phosphorylation occurred at 30 min. The adhesion ability of Hela cells to fibronectin (FN) and laminin (LN) was increased after SDF-1alpha treatment (P < 0.05 and P < 0.01, respectively), while pretreatment of Hela cells with an ERK-1/2 inhibitor, PD98059, decreased adhesion of Hela cells to extracellular matrix (ECM) with the presence of SDF-1alpha (P < 0.05). Increased amounts of active MMP-2 were secreted in response to increased SDF-1alpha concentrations. When the concentration of SDF-1alpha was 800ng/mL, the secretion of active MMP-2 reached the peak and started to decrease afterwards. CONCLUSION: CXCR4/SDF-1 participates in tumor invasiveness and metastasis in cervical cancer through regulating the adhesion ability by activating the MAPK signaling transduction pathway and promoting secretion of MMP-2.

Impact of menopause on quality of life in community-based women in China.

OBJECTIVE: To assess the impact of menopause, age, and other factors on quality of life (QOL). DESIGN: Generally healthy women aged 35 to 64 years were recruited from a general community in Beijing, People's Republic of China. An instrument including the Chinese version of the Menopause-Specific Quality of Life Questionnaire was used to obtain data. RESULTS: A gradual decline of QOL was seen from pre- to peri- and postmenopausal women in the same age group. Statistically impaired QOL was associated with the peri- and postmenopausal women in vasomotor and physical domains but only with the postmenopausal women in psychosocial and sexual domains. Early postmenopausal women presented the worse QOL in vasomotor, psychosocial and physical domains. The gradually declining sexual QOL was related to the advance of menopause. Age had a negative impact on QOL in vasomotor and sexual domains. Women who assessed their own health as common (fair) or weak (poor) reported worse QOL than those who decribed themselves as healthy. Women with a higher body mass index reported more vasomotor symptoms. CONCLUSIONS: Menopause might have a negative impact on QOL independent of age in community-based women in China. There seemed to be a potential model of the relationship of menopause status to change in QOL, but this needs supporting evidence from longitudinal studies. The association of QOL with age and other factors also should be considered.

[Profiles of irregular bleeding induced by low-dose hormone therapy and Chinese formulated herbs products].

OBJECTIVE: To compare profiles and related factors of irregular bleeding induced by different types of low-dose hormone therapy (HT) and a Chinese formulated herbs products. METHODS: Applied with open-labeled, randomized, and clinical trial design, 136 postmenopausal women were assigned into four groups: group A: estradiol valerate (E2 V) 1 mg/d + medroxyprogesterone acetate (MPA) 2 mg/d; group B: conjugated equine estrogen 0.45 mg/d + MPA 2 mg/d; group C: tibolone 1.25 mg/d; group D: a Chinese formulated herbs product (Kuntai) 4# tid. Each subject took element calcium 400 mg/d and vitamin D 200 IU/d concomitantly. Modified Kupperman scores were assessed on baseline and every 3 months thereafter and irregular bleeding was recorded on menopausal diary every day. The duration of this study was 1 year. Results The efficacies were similar in three HT-managed groups, but was better than in group D, although the latter was also effective in alleviating menopausal symptoms. Hazard ratio (HR) of irregular bleeding was 1.00 in group C, 2.43 in group A (95% CI: 1.08-5.46), 3.12 in group B (95% CI: 1.42-6.88), and 0.73 in group D (95% CI: 0.26-2.04). Most cases initially experienced bleeding in the first 3 months but such initiation was a bit later in group C. Endometrium, as detected by B-mode ultrasound, increased approximately 1 mm in HT groups, while it was a bit thicker in group C. Long periods in reproductive age and short time since menopause were high risk factors for irregular bleeding. CONCLUSION: Profiles of irregular bleeding in 3 commonly used types of low-dose HT are different and some factors such as long period in reproductive age and short time since menopause may contribute to bleeding initiation.

[The bond properties of Vitadur alpha on dental zirconia framework material].

PURPOSE: To evaluate the bond properties of Vitadur alpha on dental zirconia framework material. METHODS: Vitadur alpha was sintered on the surface of four groups' presintered zirconia ceramic plates which were dealt with respective procedures. SEM, energy distribution spectrum and thermal shock test were applied to evaluate the sintering properties of such interfaces. Shear bond strength of Vitadur alpha-zirconia interfaces were measured, and the results were analysed by ANOVA method. RESULTS: Satisfying result was obtained in Vitadur alpha sintered on the zirconia framework material, furthermore, chemical combination between the two laminates were confirmed by means of energy distribution spectrum. The shear bond strength of 3Y-TZP-Vitadur alpha dentin differed under different surface conditionings: highest shear bond strength appeared in the group conditioned with water sand paper (35.1662MPa), shear bond strength of the group conditioned with sandblast (27.8283MPa) was better than that of non-conditioning group (20.9677MPa), diamond condition group had the lowest shear bond strength (15.3025MPa), significant difference existed between each group (P<0.01). CONCLUSION: Further clinical research could be carried out on Vitadur alpha and zirconia ceramic framework under conditioning with sandblast.

[Reliability of an improved measurement system used in three-dimensional reconstruction of stomatognathic system by cutting and scanning layer-by-layer].

OBJECTIVE: To reconstruct 3D shape of edentulous jaw by using improved measurement system and to analyze the precision of this method. METHODS: Standard edentulous jaw models were measured with a improved measurement system by cutting and scanning layer-by-layer, and the 3D shape of the models was reconstructed by image processing with specialty software. Ten cubic plaster modes were reconstructed by the same way, data of every border before and after reconstruction were measured and analyzed. RESULTS: Data of edentulous jaw models were obtained. The errors in ten cubic before and after reconstruction were not significantly different (P > 0.05), data measured in horizontal plane were not significantly different (P > 0.05), and data measured in altitude direction were significantly different (P < 0.01), data measured after reconstruction were less than before, the error was (0.09 +/- 0.08) mm. CONCLUSION: The improved cutting and scanning measurement system can be fit for the 3D reconstruction of stomatognathic system with high precision.