Survival outcomes of abdominal radical hysterectomy, laparoscopic radical hysterectomy, robot-assisted radical hysterectomy and vaginal radical hysterectomy approaches for early-stage cervical cancer: a retrospective study.

BACKGROUND: This study compared the survival outcomes of abdominal radical hysterectomy (ARH) (N = 32), laparoscopic radical hysterectomy (LRH) (N = 61), robot-assisted radical hysterectomy (RRH) (N = 100) and vaginal radical hysterectomy (VRH) (N = 45) approaches for early-stage cervical cancer to identify the surgical approach that provides the best survival. METHODS: Disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method, and survival curves were compared using the log-rank test. RESULTS: The volume of intraoperative blood loss was greater in the ARH group than in the LRH group, the RRH group or the VRH group [(712.50 ± 407.59) vs. (224.43 ± 191.89), (109.80 ± 92.98) and (216.67 ± 176.78) ml, respectively; P < 0.001]. Total 5-year OS was significantly different among the four groups (ARH, 96.88%; LRH, 82.45%; RRH, 94.18%; VRH, 91.49%; P = 0.015). However, no significant difference in 5-year DFS was observed among the four groups (ARH, 96.88%; LRH, 81.99%; RRH, 91.38%; VRH, 87.27%; P = 0.061). CONCLUSION: This retrospective study demonstrated that ARH and RRH achieved higher 5-year OS rates than LRH for early-stage cervical cancer.

Carbon dot decorated Co3O4 nanozymes responsive to the NIR-II window for mild photothermal-enhanced nanocatalytic therapy.

Although NIR-II laser-mediated photothermal therapy (PTT) is considered as an emerging strategy for tumor therapy, its therapeutic effects are still seriously hampered by low photothermal conversion efficacy, limited tissue penetration depth, and inevitable damage to adjoining healthy tissues. Herein, we report a mild second-near-infrared (NIR-II) photothermal-augmented nanocatalytic therapy (NCT) nanoplatform based on CD@Co3O4 heterojunctions by depositing NIR-II-responsive carbon dots (CDs) onto the surface of Co3O4 nanozymes. The as-prepared Co3O4 nanozymes possess multi-enzyme-mimicking catalytic activity including peroxidase, catalase, and glutathione-peroxidase to realize the cascade amplification of ROS levels owing to the presence of multivalent Co2+ and Co3+. CDs with a high NIR-II photothermal conversion efficiency (PCE) (51.1%) enable the realization of mild PTT (∼43 °C), which could not only avoid damage to adjoining healthy tissues but also enhance the multi-enzyme-mimic catalytic activity of Co3O4 nanozymes. More importantly, the NIR-II photothermal properties of CDs and the multi-enzyme-mimicking catalytic activity of Co3O4 nanozymes are greatly augmented by the fabrication of heterojunctions due to the induced localized surface plasmonic resonance (LSPR) and accelerated carrier transfer. On the basis of these advantages, satisfactory mild PTT-amplified NCT is accomplished. Our work presents a promising approach for mild NIR-II photothermal-amplified NCT based on semiconductor heterojunctions.

Two cases of spontaneous rupture of the uterine artery in the perinatal period: A case report.

RATIONALE: Uterine artery spontaneous rupture is a rare but potentially life-threatening complication during pregnancy and puerperium. The lack of typical symptoms makes it difficult to diagnose, which can result in serious consequences for both the mother and fetus. PATIENT CONCERNS: Case 1 presented with fainting and lower abdominal discomfort, while Case 2 developed hypotension after delivery and remained in poor condition even after rehydration. DIAGNOSES: Both cases were diagnosed with uterine artery spontaneous rupture, with intraoperative findings revealing ruptures in different branches of the uterine artery. INTERVENTIONS: Both cases underwent surgical interventions, with laparoscopic surgery performed in Case 1 and repair of the ruptured artery in Case 2. OUTCOMES: Both cases had successful outcomes, with the ruptured arteries repaired and the patients discharged from the hospital within a week after surgery. LESSONS: Uterine artery spontaneous rupture is a rare but potentially life-threatening complication that may present with atypical symptoms. Early diagnosis and prompt surgical intervention are crucial in preventing serious complications for both the mother and fetus. Clinicians should maintain a high level of suspicion for this condition when evaluating patients presenting with unexplained symptoms or signs of peritoneal irritation during pregnancy and puerperium.

Robotic-Assisted Laparoscopic Sacrocolpopexy for Pelvic Organ Prolapse: A Single Center Experience in China.

OBJECTIVE: The aim is to investigate the efficiency and outcome of robotic-assisted sacrocolpopexy (RASC) in a cohort of patients with pelvic organ prolapse (POP) in our Gynecology Department. METHODS: We performed a retrospective study of female patients who underwent RASC in Chinese PLA General Hospital from January 2013 to December 2020. Their clinical features included age, degree of prolapse, menopause time, body mass index, pregnancy, delivery, operation time, and bleeding volume. All patients were followed up for more than 6 months. POP-Q was recorded to evaluate the position of prolapsed organs. PFDI-20, PFIQ-7, and PGI-I were used to evaluate the life quality after surgery. RESULTS: Twenty-four patients with POP received RASC in our center. The intraoperative bleeding was 86.9 ± 98.3 ml (20-300 ml). The operation time was 143.5 ± 47.3 min (60-240 minutes). The hospitalization time was 10.4 ± 2.1 days (8-16 days). And the follow-up time was 40.8 ± 22.0 months (6-72 months). In the POP-Q follow-up, postoperative Aa, Ba, Ap, Bp, and C were significantly improved than those before surgery (P < 0.05). The objective and subjective cure rate was 100%. PGI-I score was very good in 9 (9/24), very good in 10 (10/24), and good in 3 (3/24). Postoperative PFDI-20 and PFIQ-7 were 2.78 ± 3.82 and 1.57 ± 3.86, which decreased dramatically after surgery (P < 0.05). Mesh exposure occurred in 4 cases (16.7%) at 2-12 months. The exposed diameters were less than 1 cm in 3 cases (2 A/T3/S1) and 1-2 cm in 1 case (3 B/T3/S1). These mesh exposures healed after conservative observation or mesh excision. CONCLUSION: RASC for POP has the advantage of less bleeding and hospitalization time. It is a minimally invasive option for pelvic organ prolapse.

Ten years of China's new healthcare reform: a longitudinal study on changes in health resources.

BACKGROUND: China launched a new round of healthcare-system reform in 2009 and proposed the goal of equal and guaranteed essential medical and health services for all by 2020. We aimed to investigate the changes in China's health resources over the past ten years after the healthcare reform. METHODS: Data were collected from the China Statistical Yearbook and China Health Statistics Yearbook from 2009 to 2018. Four categories and ten indicators of health resources were analyzed. A descriptive analysis was used to present the overall condition. The Health Resource Density Index was applied to showcase health-resource distribution in demographic and geographic dimensions. The global and local Moran's I were used to assess the spatial autocorrelation of health resources. Concentration Index (CI) was used to quantify the equity of health-resource distribution. A Geo-Detector model and Geographic Weighted Regression (GWR) were applied to assess the association between gross domestic product (GDP) per capita and health resources. RESULTS: Health resources have increased over the past ten years. The global and local Moran's I suggested spatial aggregation in the distribution of health resources. Hospital beds were concentrated in wealthier areas, but this inequity decreased yearly (from CI=0.0587 in 2009 to CI=0.0021 in 2018). Primary medical and health institutions (PMHI) and their beds were concentrated in poorer areas (CI remained negative). Healthcare employees were concentrated in wealthier areas (CI remained positive). In 2017, the q-statistics indicated that the explanatory power of GDP per capita to beds, health personnel, and health expenditure was 40.7%, 50.3%, and 42.5%, respectively. The coefficients of GWR remained positive with statistical significance, indicating the positive association between GDP per capita and health resources. CONCLUSIONS: From 2009 to 2018, the total amount of health resources in China has increased substantially. Spatial aggregation existed in the health-resources distribution. Health resources tended to be concentrated in wealthier areas. When allocating health resources, the governments should take economic factors into account.

Characteristics of the Cervicovaginal Microenvironment in Childbearing-Age Women with Different Degrees of Cervical Lesions and HR-HPV Positivity.

Persistent infection with high-risk human papillomavirus (HR-HPV) is the most important determinate in the development of cervical cancer, and cervical microecology can modulate cervical viral infection. However, few studies have been conducted on the microecological analysis of cervical diseases using strict physiological factors. This study investigated the characteristics and dynamics of cervical microecology in childbearing-age Chinese women with different degrees of HR-HPV-positive cervical lesions. A total of 168 subjects were selected according to the selection criteria, including healthy HPV-negative individuals (n = 29), HR-HPV-infected individuals (n = 29), low-grade squamous intraepithelial lesion individuals (LSIL, n = 32), high-grade squamous intraepithelial lesion individuals (HSIL, n = 40), and cervical cancer individuals (n = 38). We sampled cervical secretions from each subject and performed comparative analysis using the 16S rRNA sequencing method. Comparison analysis showed that Lactobacillus and Ignatzschineria were the dominant genera in the healthy group, while Gardnerella and Prevotella were more enriched in the disease groups. Based on the taxa composition, we roughly divided the development of cervical cancer into two phases: phase I was from healthy status to HR-HPV infection and LSIL; phase II was from LSIL to HSIL and cervical cancer. Different interactions among different genera were observed in different groups. Prevotella inhibited the abundance of Lactobacillus in the healthy group, while Prevotella inhabited the abundance of Gardnerella in the other groups. In the HR-HPV infection group, Ignatzschineria and Enterococcus showed a positive interaction but dissociated with the increase in cervical lesions, which might eventually lead to a continuous decrease in the abundances of Lactobacillus and Ignatzschineria.

E74-like factor 3 suppresses microRNA-485-5p transcription to trigger growth and metastasis of ovarian cancer cells with the involvement of CLDN4/Wnt/ß-catenin axis.

Ovarian cancer (OC) is one of the most prevailing gynecological malignancies with high mortality rate, while E74 like ETS transcription factor 3 (ELF3) is reported to be associated with tumorigenesis. This work aims to analyze the role of ELF3 on the suppression of miR-485-5p transcription in OC. Expression of ELF3 in OC and its correlation with overall survival were predicted on a bioinformation system GEPIA. Then, the level of ELF3 in OC tissues and cells and in normal ones was evaluated. Binding relationships between ELF3 and microRNA (miR)-485-5p, and between miR-485-5p and claudin-4 (CLND4) were predicted through Bioinformatics tools. Altered expression of ELF3, miR-485-5p and CLND4 was introduced alone or jointly to probe their influences on OC cell growth. ELF3 was suggested to be highly expressed in OC, which was linked to poor prognosis in patients. Abundant expression of ELF3 was identified in OC tissues and cell lines as relative to the normal ones. ELF3 inhibition suppressed growth and metastasis of OC cells. ELF3 transcriptionally suppressed miR-485-5p expression to further enhance CLDN4 expression. Overexpression of miR-485-5p led to similar trends as ELF3 inhibition did. Importantly, upregulation of CLDN4 was found to block the roles of ELF3 inhibition in OC cells. In addition, the Wnt/signaling pathway suppressed by miR-485-5p mimic was reactivated following CLDN4 overexpression. This study evidenced that ELF3 suppresses miR-485-5p transcription to enhance CLDN4 expression, leading to Wnt/ß-catenin activation and promoting OC cell growth and metastasis. This work may provide new ideas for gene-based therapies for OC.

[Characteristics of cervical microecology in late reproductive-age women with different grades of cervical lesions].

OBJECTIVE: To analyze the characteristics of cervical microecology in late reproductive-age women with cervical lesions and explore new methods for preventing cervical lesions. METHODS: Cervical smears were obtained from a total of 147 women of late reproductive age, including 24 with high-risk HPV infection (HR-HPV), 27 with low-grade squamous intra-epithelial lesions (LSIL), 36 with high-grade squamous intra-epithelial lesions (HSIL), 35 with cervical cancer (CC) and 25 healthy women. llumina MiSeq sequencing of V3-V4 region of the 16S rRNA gene amplicons was used to characterize the vaginal microbiota of the women. OTUs analysis of the valid data was performed, and the α-diversity (Chao1, Simpson's Index and Shannon Index) and ß-diversity (T-test, weighted UniFrac ß diversity, and MetaStat analysis) were evaluated. RESULTS: Dilution curve and species accumulation boxplot validated the quality of the samples. OTUs analysis of the 5 groups demonstrated that cervical bacterial genus consisted primarily of Lactobacillus, Garrotella and Prussiella. With the aggravation of the lesions, the expression abundance of Lactobacillus was decreased, and Gardnerella and Prussiella were increased. The Chao1, Simpson and Shannon indexex showed no significant difference. T test indicated that 9 to 15 genera from 4 groups showed significant difference from the healthy control group. In all but the LSIL group, Lactobacillus (P1-2=0.025, P1-3=0.025, P1-4 < 0.001), Gardiner (P1-2=0.01, P1-3=0.001, P1-4 < 0.001), and Pruella (P1-2=0.047, P1-3=0.023, P1-4=0.048) showed the highest abundance in the cervical smears. The abundance of Gardiner (P1-3=0.021), Ignatius (P1-3=0.015) and Streptococcus (P1-3=0.041) was the highest in women with LSIL as compared with healthy women. In all the 5 groups, MetaStat analysis showed that lactobacillus (P1-4=0.025), gardnella (P1-2=0.004, P1-4=0.002, P1-5=0.001) and proctella (P3-5=0.005) had the highest abundance in the cervical flora. CONCLUSIONS: The abundance of Lactobacillus, Gardnella and Proctella is the highest in cervical bacteria at the genus level and may vary with disease progression. The α-diversity does not differ significantly, suggesting that apart from pathological factors, physiological factors also contribute to the difference in α-diversity. Women with LSIL have the most similar cervical flora to healthy women, which is consistent with the prognosis of the disease and confirms that the expression of cervical microecology is related to disease prognosis and may serve as a biological indicator for favoralble prognosis.

Identification of MicroRNAs as Potential Biomarkers in Ovarian Endometriosis.

Endometriosis, as a prevalent gynecological disease, is characterized by the presence of endometrial-like tissue outside the uterus, causing infertility and considerable pain and affecting the quality of life of women. The pathogenic mechanism has not been fully elucidated, and there are no effective biomarkers for endometriosis. In our study, microRNA (miRNA) expression profiling of 10 ectopic endometrial plasma from patients with ovarian endometriosis and 10 normal plasma from healthy controls was analyzed using a microarray. As a result, 114 differentially expressed miRNAs were identified. Among them, 14 miRNAs were significantly downregulated in patients with ovarian endometriosis, which matched the microarray results. The diagnostic value of the 14 downregulated miRNAs in ovarian endometriosis was evaluated by receiver operating characteristic (ROC) curve analysis, and hsa-let-7i-5p showed the highest area under the ROC curve (AUC) with a value of 0.900. The target genes of the 14 miRNAs were predicted by miRWalk2.0, and the genes that were targeted by at least 2 of the 14 miRNAs were analyzed by function enrichment. The target genes were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, such as microRNAs in cancer, bladder cancer, and endocrine resistance pathways, and the Gene Ontology (GO) terms such as nucleobase-containing compound metabolic process, cellular nitrogen compound biosynthetic process, and heterocycle metabolic process. The identified 14 differentially expressed miRNAs could be potential biomarkers and therapeutic targets for the diagnosis and treatment of endometriosis.

Integration analysis of microRNA and mRNA paired expression profiling identifies deregulated microRNA-transcription factor-gene regulatory networks in ovarian endometriosis.

BACKGROUND: The etiology and pathophysiology of endometriosis remain unclear. Accumulating evidence suggests that aberrant microRNA (miRNA) and transcription factor (TF) expression may be involved in the pathogenesis and development of endometriosis. This study therefore aims to survey the key miRNAs, TFs and genes and further understand the mechanism of endometriosis. METHODS: Paired expression profiling of miRNA and mRNA in ectopic endometria compared with eutopic endometria were determined by high-throughput sequencing techniques in eight patients with ovarian endometriosis. Binary interactions and circuits among the miRNAs, TFs, and corresponding genes were identified by the Pearson correlation coefficients. miRNA-TF-gene regulatory networks were constructed using bioinformatic methods. Eleven selected miRNAs and TFs were validated by quantitative reverse transcription-polymerase chain reaction in 22 patients. RESULTS: Overall, 107 differentially expressed miRNAs and 6112 differentially expressed mRNAs were identified by comparing the sequencing of the ectopic endometrium group and the eutopic endometrium group. The miRNA-TF-gene regulatory network consists of 22 miRNAs, 12 TFs and 430 corresponding genes. Specifically, some key regulators from the miR-449 and miR-34b/c cluster, miR-200 family, miR-106a-363 cluster, miR-182/183, FOX family, GATA family, and E2F family as well as CEBPA, SOX9 and HNF4A were suggested to play vital regulatory roles in the pathogenesis of endometriosis. CONCLUSION: Integration analysis of the miRNA and mRNA expression profiles presents a unique insight into the regulatory network of this enigmatic disorder and possibly provides clues regarding replacement therapy for endometriosis.

A Retrospective Analysis of the Impact of Myomectomy on Survival in Uterine Sarcoma.

Laparoscopic myomectomy is a minimally invasive, conservative surgical approach commonly used for the treatment of uterine fibroids. However, there is a lack of effective means to distinguish the nature of uterine tumors prior to surgery. The impact of fibroid morcellation during laparoscopic surgery on the dissemination of cancerous uterine fibroids and long-term survival of patients has gained increasing attention. A retrospective cohort study was conducted to analyze the impact of different surgical approaches on recurrence-free survival (RFS) and overall survival (OS) in patients with a postoperative pathological diagnosis of uterine sarcoma at a single medical center. Patients who underwent the first surgery for uterine fibroids (confined to the uterus) and had a postoperative pathological diagnosis of uterine sarcoma were selected in the Chinese PLA General Hospital from January 2005 to January 2014. Based on the use of fibroid morcellation, the subjects were divided into fibroid morcellation (FM) and total hysterectomy (TH, non-morcellation) groups. Follow-up outcomes, including RFS and OS times, were observed. In total, 59 patients were included, with 30 cases in the FM group and 29 cases in the TH group. There were no significant differences in RFS and OS time between the two groups (RFS: P = 0.16, OS: P = 0.09). Multivariate correlation analysis showed that the impact of a higher grade level on RFS and OS was nearly 2-fold the impact of a lower grade level (RFS: P = 0.04, odds ratio (OR) = 1.97; OS: P = 0.03, OR = 2.29). Intraoperative morcellation, postoperative adjuvant therapy, age, tumor size, FIGO stage, and surgical approach were not risk factors affecting RFS and OS. Fibroid morcellation during laparoscopic surgery (including laparoscopic, transvaginal and transabdominal approaches) had no significant impact on RFS and OS time in patients. However, the 5-year RFS and OS rates were both lower in the FM group than in the TH group. Grade level was a significant risk factor for the prognosis of patients with uterine sarcoma.

An special epithelial staining agents: folic acid receptor-mediated diagnosis (FRD) effectively and conveniently screen patients with cervical cancer.

High-quality screening with cytology has markedly reduced mortality from cervical cancer. However, it needs experienced pathologists to review and make the final decisions. We have developed folic acid receptor-mediated diagnosis (FRD) kits to effectively and conveniently screen patients with cervical cancer. We conduct present study aim to assess clinical significances of FRD in screening cervical cancer. A total of 169 patients were enrolled at Chinese People's liberation Army (PLA) general hospital. We compared diagnostic significances of FRD with thinprep cytology test (TCT). Meanwhile, colposcopy was also performed to confirm any lesion suspicious for cervical cancer. The sensitivity and specificity of FRD were 71.93% and 66.07% in diagnosis cervical cancer, respectively. Meanwhile, the positive predictive values (PPV), negative predictive values (NPV), Youden index were 51.90%, 82.22%, 0.38, respectively. On the other hand, the sensitivity and specificity of TCT in diagnosis cervical cancer were 73.68% and 61.61% respectively. PPV, NPV and Youden index for TCT were 49.41%, 82.14% and 0.35 respectively. Overall, FRD have high values of sensitivity, specificity and Youden index. However, this difference failed to statistical significance. FRD have comparable diagnostic significance with TCT. Therefore, FRD might serve as one effective method to screen cervical cancer. Especially for those patients living in remote regions of China, where cytology was unavailable.

Epigenome-wide association study (EWAS) of BMI, BMI change and waist circumference in African American adults identifies multiple replicated loci.

Obesity is an important component of the pathophysiology of chronic diseases. Identifying epigenetic modifications associated with elevated adiposity, including DNA methylation variation, may point to genomic pathways that are dysregulated in numerous conditions. The Illumina 450K Bead Chip array was used to assay DNA methylation in leukocyte DNA obtained from 2097 African American adults in the Atherosclerosis Risk in Communities (ARIC) study. Mixed-effects regression models were used to test the association of methylation beta value with concurrent body mass index (BMI) and waist circumference (WC), and BMI change, adjusting for batch effects and potential confounders. Replication using whole-blood DNA from 2377 White adults in the Framingham Heart Study and CD4+ T cell DNA from 991 Whites in the Genetics of Lipid Lowering Drugs and Diet Network Study was followed by testing using adipose tissue DNA from 648 women in the Multiple Tissue Human Expression Resource cohort. Seventy-six BMI-related probes, 164 WC-related probes and 8 BMI change-related probes passed the threshold for significance in ARIC (P < 1 × 10(-7); Bonferroni), including probes in the recently reported HIF3A, CPT1A and ABCG1 regions. Replication using blood DNA was achieved for 37 BMI probes and 1 additional WC probe. Sixteen of these also replicated in adipose tissue, including 15 novel methylation findings near genes involved in lipid metabolism, immune response/cytokine signaling and other diverse pathways, including LGALS3BP, KDM2B, PBX1 and BBS2, among others. Adiposity traits are associated with DNA methylation at numerous CpG sites that replicate across studies despite variation in tissue type, ethnicity and analytic approaches.

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.

Design and testing of a novel piezoelectric micro-motor actuated by asymmetrical inertial impact driving principle.

In this paper, an asymmetrical inertial impact driving principle is first proposed, and accordingly a novel piezoelectrically actuated linear micro-motor is developed. It is driven by the inertial impact force generated by piezoelectric smart cantilever (PSC) with asymmetrical clamping locations during a driving cycle. When the PSC is excited by typical harmonic voltage signals, different equivalent stiffness will be induced due to its asymmetrical clamping locations when it is vibrating back and forth, leading to a tiny displacement difference on the two opposite directions in a cycle, and then the accumulation of tiny displacement difference will allow directional movements. A prototype of the proposed motor has been developed and investigated by means of experimental tests. The motion and dynamics characteristics of the prototype are well studied. The experimental results demonstrate that the resolution of the micro-motor is 0.02 µm, the maximum velocity is 16.87 mm/s, and the maximum loading capacity can reach up to 1 kg with a voltage of 100 V and 35 Hz.

Hypoxia-induced miR-210 in epithelial ovarian cancer enhances cancer cell viability via promoting proliferation and inhibiting apoptosis.

miR-210 is upregulated in a HIF-1α-dependent way in several types of cancers. In addition, upregulated miR-210 promotes cancer proliferation, via its anti-apoptotic effects. It is blind to the regulation of miR-210 under hypoxia conditions for ovarian cancer cells and to the effect of miR-210 on ovarian cancer growth. In the present study, we determined the expression of miR-210 in epithelial ovarian cancer specimens, and in ovarian cancer cell lines under hypoxia conditions, and determined in detail the effect of miR-210 overexpression on tumor cell proliferation, and the possible mechanisms of tumor growth by miR-210 regulation. It was shown that miR-210 expression is upregulated, in response to hypoxia conditions in epithelial ovarian cancer specimens as well as epithelial ovarian cancer cell lines, with an association to HIF-1α overexpression. Furthermore, upregulated miR-210 promoted tumor growth in vitro via targeting PTPN1 and inhibiting apoptosis. Therefore, our findings shed light on the mechanism of ovarian cancer adaptation to hypoxia.

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.

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

BACKGROUND: Astrocyte 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. METHOD: In 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, χ2 test, Kaplan-Meier plots, and multivariate Cox regression analysis were used to analyze the data. RESULTS: The 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). CONCLUSIONS: Our 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.

STAT3 acetylation-induced promoter methylation is associated with downregulation of the ARHI tumor-suppressor gene in ovarian cancer.

ARHI is a Ras-related imprinted tumor-suppressor gene that inhibits cancer cell growth and motility. ARHI is downregulated in the majority of ovarian cancer cells, and promoter methylation is considered to be associated with its loss of expression. however, the underlying mechanisms are not well understood. Thus, the present study aimed to investigate the specific functions of ARHI and its methylation in ovarian cancer cell proliferation. Furthermore, we examined the possible role of acetylated STAT3 in modulating the expression of ARHI and its methylation. In accordance with the majority of previous studies, reduced ARHI expression was found in epithelial ovarian cancer tissues and cancer cell lines as indicated by immunohistochemistry and RT-PCR. In addition, CpG islands I and II within ARHI promoter regions were partially methylated or hypermethylated in cancer cell lines (SKOV-3 and HO-8910) as analyzed by pyrosequencing assays, resulting in enhanced proliferation of the cancer cells. This proliferation was reversed by the administration of 5-aza-2'-deoxycytidine. Subsequently, we demonstrated that STAT3 acetylation was increased in HO-8910 cells, and the methylation status of CpG I was altered in response to the acetylation of STAT3 using western blotting. Finally, chromatin immunoprecipitation (ChIP) and IP analysis indicated that acetylated STAT3 bound to the ARHI promoter and recruited DNA methyltransferase 1 for genetic modification. In conclusion, acetylated STAT3-induced promoter gene methylation accounts for the loss of ARHI expression and cancer cell proliferation.