IntroductionDespite rapid advances in molecular biology, personalized molecular therapy remains a clinical challenge for endometrial cancer due to its complex and heterogeneous tumor microenvironment.Based on clinical findings, AIB1 is a marker molecule for poor prognosis in endometrial cancer and may serve as a potential therapeutic target. Moreover, it is well known that aerobic glycolysis plays an important role in tumour energy metabolism. It has been previously reported in various hormone-related tumour studies that AIB1 affects glycolysis and promotes tumour development. However, the link between AIB1 and aerobic glycolysis in estrogen-dependent endometrial cancer remains unclear.MethodsWe used two endometrial cancer cell lines to validate the high expression of target genes and the effect on the proliferative and invasive capacity of the tumours and verified the pattern of interactions and epigenetic modifications by CHIP and CO-IP techniques. Finally, the conclusions were validated on homozygous miceResultsIn this study, we investigated the transcriptional co-activation functions of AIB1, including its acetylation by PCAF, binding to the c-myc transcription factor, and recruitment of glycolysis-related gene promoters.DiscussionOur findings provide new clues that perturbation of normal homeostatic levels of AIB1 is linked with endometrial cancer. These findings suggest that targeting AIB1-mediated regulation of aerobic glycolysis may offer a novel therapeutic approach for endometrial cancer with high AIB1 expression, opening new avenues for personalized diagnostics and treatment strategies in this disease.

Carex qingyuanensis, a new species of Cyperaceae from Guangdong Province, China, is described and illustrated. The new species is morphologically similar to Carex peliosanthifolia F. T. Wang & Tang ex P. C. Li, but it can be distinguished by the racemose inflorescence branches appearing single (rarely binate or ternate) (vs. binate or ternate), one (rarely two or three) (vs. 1–3) spiked, male part of linear-cylindrical spikes much longer than the female part (vs. just male part short-cylindrical and slightly longer than female part), style base thickened (vs. not thickened) and perigynium horizontally patent with a short (vs. long and excurved) beak. Phylogenetic analysis, based on the two nuclear DNA regions (ETS 1f and ITS) and three chloroplast DNA regions (matK, ndhF and rps16), suggests that the new species belongs to sect. Siderostictaes.s. of subg. Siderosticta and shows a closer phylogenetic relationship to Carex scaposa C. B. Clarke.

We evaluated the characteristics of high-risk human papillomavirus (Hr-HPV) infection in different grades of vaginal intraepithelial neoplasia (VaIN). 7469 participants were involved in this study, of which 601 were diagnosed with VaIN, including single vaginal intraepithelial neoplasia (s-VaIN, n = 369) and VaIN+CIN (n = 232), 3414 with single cervical intraepithelial neoplasia (s-CIN), 3446 with cervicitis or vaginitis and 8 with vaginal cancer. We got those results. First, the most popular HPV genotypes in VaIN were HPV16, 52, 58, 51, and 56. Second, our study showed that higher parity and older age were risk factors for VaIN3 (p < 0.005). Third, the median Hr-HPV load of VaIN+CIN (725) was higher than that of s-CIN (258) (p = 0.027), and the median Hr-HPV load increased with the grade of VaIN. In addition, the risk of VaIN3 was higher in women with single HPV16 infections (p = 0.01), but those with multiple HPV16 infections faced a higher risk of s-VaIN (p = 0.003) or VaIN+CIN (p = 0.01). Our results suggested that women with higher gravidity and parity, higher Hr-HPV load, multiple HPV16 infections, and perimenopause or menopause status faced a higher risk for VaIN, while those with higher parity, single HPV16 infections, and menopause status are more prone to VaIN3.

In this study, we explored the risk factors for lymph node metastasis in patients with type II endometrial carcinoma (EC). Patients diagnosed with type II EC who underwent staged surgery and lymph node dissection were included. Univariate analysis was performed using a chi-square test for factors such as age, body mass index (BMI), menopausal status, histologic type, histologic grade, myometrial invasion, lymphatic vascular invasion (LVSI), tumor volume index, and para-aortic lymph node (PALN) or pelvic lymph node (PLN) metastasis. An analysis of multivariate factors was performed on the factors that were statistically significant in the univariate analysis. Pelvic lymph node metastasis was identified in 38 of the 184 patients with type II EC. Univariate analyses revealed that age >= 55 years, menopause, more than one-half myometrial invasion, and LVSI were risk factors for pelvic lymph node metastasis. Multivariate analysis indicated that myometrial invasion of more than one-half (hazard ratio (HR): 4.259) and LVSI (HR: 3.317) were independent risk factors for pelvic lymph node metastasis. Para-aortic lymph node metastasis was identified in 13 of the 184 patients with type II EC. Univariate analysis indicated that para-aortic lymph node metastasis was significantly associated with LVSI and pelvic lymph node metastases. Multivariate analysis suggested that pelvic lymph node metastasis (HR: 5.887) was an independent risk factor for para-aortic lymph node metastasis. LVSI and myometrial invasion depth >1/2 were significant predictors of pelvic lymph node metastasis in patients with type II EC. Patients with type II EC who have pelvic lymph node metastasis may be at risk of para-aortic lymph node metastasis.

The aim of the present study is to investigate whether 4SC-202, a selective class I histone deacetylase inhibitor (HDACi), plays an anti-tumor role in cervical cancer (CC) by targeting prolactin receptor (PRLR). CCK-8 and colony formation assays were used to evaluate the effects of 4SC-202 on the proliferation of CC cells in vitro. Effects of 4SC-202 on the cell cycle distribution and apoptosis in SiHa cells were determined by flow cytometry and western blotting, respectively. Immunofluorescence, western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect the activities of PRLR-related pathways and PRLR expression in CC cells. A xenograft tumor model in nude mice was established to examine effects of 4SC-202 on the tumor growth, apoptosis and PRLR-related pathways in vivo. The biochemical analyzer and H&E staining were used to detect the serum biochemical indexes and organ toxicity. 4SC-202 inhibited the proliferation of CC cells (SiHa, HeLa, and CaSki) in vitro in a time- and dose-dependent manner. SiHa cells were treated with 1 or 5 µM 4SC-202 for 72 h and then subjected to various functional assays. The assays showed that 4SC-202 significantly induced G2/M phase arrest and apoptosis, while inhibiting the activities of PRLR-related pathways and PRLR expression. In addition, 4SC-202 reduced tumor growth and induced apoptosis in vivo. 4SC-202 down-regulated the expression of PRLR and activities of PRLR-related pathways in the mouse model, displayed no effects on serum biochemical indicators and caused no toxicity to mouse organs. This finding suggests that 4SC-202 may serve as a novel therapeutic agent for CC.

This study aims to evaluate the association between passive smoking and high-grade squamous intraepithelial lesion (HSIL) at the sample of Chinese women. We conducted a case-control study to analyze the effect of passive smoking on the incidence that patients diagnosed with HSIL. The participants had undergone cervical cancer screening by cytology and human papillomavirus (HPV) co-testing within a year before the study. Multiple logistic regression was used to explore the effect and interactive effect of risk factors on HSIL. The odds ratio (OR) and 95% confidence interval (CI) were calculated. Passive smokers were 1.57 times (95% CI 1.05-2.35) higher than non-smokers to occur HSIL. The medium of the combined smoking index divided patients into low and high exposure, with the ORs of 1.64 (95%CI 1.02-2.64) and 1.71 (95%CI 1.06-2.77) relative to non-smokers, respectively. The combined smokers in the high exposure group experienced the most considerable risk of HSIL (OR= 4.67; 95%CI 1.17-18.70). The OR of HPV positive passive smoker relative to that of HPV negative non-smokers was 5.28 (95%CI 2.25-14.52;). Passive smokers who reported adolescent exposure history was 4.04 times (95%CI 1.44-11.37) more at risk of the disease than non-smokers. This study supported that passive smoking was a significant independent risk factor on the occurrence of HSIL and showed a positive correlated dose-response relationship. HPV infection interacting with passive smoking led to an even higher risk of the disease. Adolescent exposure to passive smoking persistent for more than 20 years would also increase the risk of HSIL.

Aim This study aimed to confirm whether human omental adipose-derived stem cells (O-ASC) from donors with varying body mass index (BMI, calculated in kg/m(2)) exert different effects on proliferation and migration of endometrial cancer (EC) cells. Methods Omental adipose-derived stem cells were isolated from the omental adipose tissues of eight patients who were diagnosed with EC aged from 35 to 56 years. According to the patients' BMI, the O-ASC was divided into two groups: obesity group (BMI >= 30) and normal group (18.5 < BMI <= 24.9). A broad spectrum cytokine antibody array was used to measure 62 paracrine cytokines secreted by all the O-ASC. MTS assays, direct and indirect co-culture assays were used to assess the effects of O-ASC on proliferation and migration of Hec-1A (estrogen receptor-/progesterone receptor-) and Ishikawa (estrogen receptor+/progesterone receptor+) EC cells. Results Eight samples of O-ASC were successfully isolated including four samples in obesity group and four in normal group. All the O-ASC displayed typical characteristics of mesenchymal stem cells and possessed similar secretory functions as 26 cytokines were identified in condition medium of O-ASC based on cytokine antibody array. The proliferation of Ishikawa cells was gently stimulated by O-ASC from the two groups (P < 0.05) whereas without any effects on Hec-1A cells. Both horizontal and vertical migrations of EC cells were promoted by O-ASC (P < 0.01). However, there were no statistical differences between the two groups. Conclusion Human O-ASC could influence the proliferation and migration of EC cells in vitro but the effects were not modified by donors' BMI.

Recent reports indicate that mesenchymal stem cells (MSCs) can fuse with cancer cells to promote cancer progression. Omental adipose-derived stromal cells (O-ASCs) are similar to MSCs, which could be recruited to the stroma in endometrial cancer. The aim of our study was to investigate whether O-ASCs can fuse with endometrial cancer cells to influence cancer cells biological characteristics. We isolated O-ASCs from patients with endometrial cancer. O-ASCs and endometrial cancer cells were labeled with different fluorescent tags and directly co-cultured in an Opera high-throughput spinning-disk confocal microscopy system to observe the processes involved in the fusion, division and migration of hybrid cells. Immunofluorescence and high-throughput imaging analyzes were performed to evaluate proteins related to epithelial-mesenchymal transition (EMT).We found O-ASCs could spontaneously fuse with endometrial cancer cells, including cytomembrane and nuclear fusion. After fusion, endometrial cancer cells assume an elongated and fibroblast-like appearance that exhibit mesenchymal phenotypes. The hybrid cells proliferated through bipolar and multipolar divisions and exhibited more rapid migratory speeds than were observed in the parental cells (P < 0.01), potentially because of their EMT-associated changes, including the down-regulation of E-cadherin and up-regulation of Vimentin. Our results collectively suggest that tumorigenic hybrids spontaneously formed between human O-ASCs and endometrial cancer cells, and that the resulting cells enhanced cancer mobility and heterogeneity by accelerated migration and undergoing multipolar divisions. These data provide a new avenue for investigating the roles of O-ASCs in endometrial cancer.

Background/Aims: Mitochondrial homeostasis is implicated in the development and progression of endometriosis through poorly defined mechanisms. Mst1 is the major growth suppressor related to cancer migration, apoptosis and proliferation. However, whether Mst1 is involved in endometriosis apoptosis and migration via regulating the mitochondrial function remains to be elucidated. Methods: Expression of Mst1 in endometriosis was examined via western blots. Cellular apoptosis was detected via MTT and TUNEL assay. Gain of function assay about Mst1 was conducted via adenovirus over-expression. Mitochondrial functions were evaluated via mitochondrial membrane potential JC-1 staining, ROS flow cytometry analysis, mPTP opening assessment and immunofluorescence of HtrA2/Omi. The mitophagy activity were examined via western blots and immunofluorescence. Results: First, we found that Mst1 was significantly downregulated in the ectopic endometrium of endometriosis compared to the normal endometrium. However, the recovery of Mst1 function was closely associated with the inability of endometrial stromal cells (ESCs) to migrate and survive. A functional study indicated that regaining Mst1 enhanced Drp1 post-transcriptional phosphorylation at Ser616 and repressed Parkin transcription activity via p53, leading to mitochondrial fission activation and mitophagy inhibition. Excessive Drp1-related fission forced the mitochondria to liberate HtrA2/Omi into the cytoplasm. Moreover, Mst1-induced defective mitophagy evoked cellular oxidative stress, energy metabolism and calcium overload. Through excessive mitochondrial fission and aberrant mitophagy, Mst1 launched caspase 9-related mitochondrial apoptosis and abrogated F-actin/lamellipodium-dependent cellular migration. Notably, we also defined NR4A/miR181c as the upstream signal for Mst1 dysfunction in endometriosis. Conclusion: Collectively, our results comprehensively described the important role of the NR4A-miR181c-Mst1 pathway in endometriosis, which handled mitochondrial apoptosis and F-actin/ lamellipodium-based migration via the regulation of Drp1-related mitochondrial fission and Parkin-required mitophagy, with a potential application in endometriosis therapy by limiting ESCs migration and promoting apoptosis.

We assessed the prevalence characteristics of single and multiple high-risk human papillomavirus (HR-HPV) infections. A total of 1783 women who underwent colposcopy and cervical biopsy for abnormal ThinPrep Cytology Test and/or HR-HPV subtype genotyping results were enrolled in the study. Among the participants, 770 were diagnosed with cervicitis, 395 with cervical intraepithelial neoplasia grade 1 (CIN1), 542 with CIN2-3, and 76 with squamous cell carcinoma (SCC), with HR-HPV infection rates of 75.8%, 85.8%, 95.9%, and 88.4%, respectively. The prevalence of total and multiple HR-HPV infections exhibited a bimodal age distribution with a peak at <= 25 years, a decline with age and a second peak at >= 55 years, whereas single HR-HPV infections exhibited one peak from 35 to 44 years. The four most dominant HPV genotypes were HPV 16 (29.5%), 52 (15.0%), 58 (14.2%), and 18 (10.4%). In total, 67.0%, 70.4%, and 82.1% of patients with CIN1, CIN2-3, and SCC, respectively, had a single HR-HPV infection, which increased significantly with the aggravation of the cervical lesion grade (P = 0.045). Patients with a single HPV 16 infection had higher incidences of CIN2+ (62.2%) than those with multiple HPV 16 infections (52.4%) (P = 0.021). Patients coinfected with HPV 16 had higher CIN2+ incidence than those with single HPV 52, 31, 33, 35, 39, 45, 51, 56, or 59 infections (P < 0.001). This study provided baseline data on the prevalence characteristics of single and multiple HR-HPV infections in women attending a gynecological outpatient clinic in Beijing.

Objective The exfoliation of endometrial carcinoma might intraperitoneally spread through the fallopian tube. We analyzed the influence of prior tubal ligation (TL) in endometrial carcinoma to evaluate whether it can prevent the process and improve patients’ survival. Methods A total of 562 patients with a diagnosis of endometrial carcinoma at the Peking University People’s Hospital between July 1995 and June 2012 were enrolled in this study. The patients were divided into 2 groups based on the presence or absence of prior TL. International Federation of Gynecology and Obstetrics stage distributions, recurrence rates, survival status, and histopathological findings were compared between the 2 groups. Kaplan-Meier estimates and log-rank tests were used to compare the survival status based on TL in the overall population and stratified by histopathological subtypes and International Federation of Gynecology and Obstetrics stages. Cox models analysis was used to estimate the hazard ratios and 95% confidence intervals for associations between TL and carcinoma-specific mortality. All statistical tests were 2-sided. Results Of the 562 patients, 482 (85.7%) had a diagnosis of endometrioid and 80 patients (14.2%) with nonendometrioid carcinoma. Tubal ligation was associated with negative peritoneal cytology in the total population ( P = 0.015) and in patients with endometrioid carcinomas ( P = 0.02) but not help to reduce carcinoma-specific mortality ( P = 0.095 and P = 0.277, respectively). In the nonendometrioid group, TL was not only associated with negative peritoneal cytology ( P = 0.004) but also with lower stage ( P < 0.001) and lower recurrence rate( P < 0.005), resulting in improved prognosis ( P = 0.022). In Cox models analysis adjusted for covariates, TL was inversely associated with lower endometrial carcinoma-specific mortality (hazard ratio, 0.47; 95% confidence interval, 0.14–2.6). Conclusion Tubal ligation was associated with lower positive peritoneal cytology, stages, and recurrence rate, and improved prognosis among patients with nonendometrioid carcinoma. Tubal ligation might influence metastatic spread of nonendometrioid endometrial carcinoma. It could also help to reduce positive peritoneal cytology among patients with endometrioid carcinoma, but lacked prognostic significance.