ATP6V1B1 regulates ovarian cancer progression and cisplatin sensitivity through the mTOR/autophagy pathway.

Early detection and effective chemotherapy for ovarian cancer, a serious gynecological malignancy, require further progress. This study aimed to investigate the molecular mechanism of ATPase H+-Transporting V1 Subunit B1 (ATP6V1B1) in ovarian cancer development and chemoresistance. Our data show that ATP6V1B1 is upregulated in ovarian cancer and correlated with decreased progression-free survival. Gain- and loss-of-function experiments demonstrated that ATP6V1B1 promotes the proliferation, migration, and invasion of ovarian cancer cells in vitro, while ATP6V1B1 knockout inhibits tumor growth in vivo. In addition, knocking down ATP6V1B1 increases the sensitivity of ovarian cancer cells to cisplatin. Mechanistic studies showed that ATP6V1B1 regulates the activation of the mTOR/autophagy pathway. Overall, our study confirmed the oncogenic role of ATP6V1B1 in ovarian cancer and revealed that ATP6V1B1 promotes ovarian cancer progression via the mTOR/autophagy axis.

The overexpression of actin related protein 2/3 complex subunit 1B(ARPC1B) promotes the ovarian cancer progression via activation of the Wnt/ß-catenin signaling pathway.

Introduction: Ovarian cancer is one of the most fatal malignancies of the female reproductive system. The purpose of this study is to explore the mechanism of Actin Related Protein 2/3 Complex Subunit 1B(ARPC1B) in the progression of ovarian cancer. Methods: The expressions and prognostic value of ARPC1B in ovarian cancer were identified using the GEPIA database and the Kaplan-Meier Plotter database. The expression of ARPC1B was manipulated to evaluate its impact on the malignant phenotypes of ovarian cancer. The cell proliferation ability was analyzed through CCK-8 assay and clone formation assay. The cell migration and invasion capacity was evaluated through wound healing assay and trans well assay. Mice xenografts were conducted to measure the effects of ARPC1B on tumor development in vivo. Results: Our data suggested that ARPC1B was overexpressed in ovarian cancer, which was correlated with a poorer survival compared to low mRNA expression of ARPC1B in ovarian cancer patients. The overexpression of ARPC1B promoted cell proliferation, migration, and invasion of ovarian cancer cells. Conversely, the knockdown of ARPC1B resulted in the opposite effect. Additionally, ARPC1B expression could activate Wnt/ß-catenin signaling pathway. The administration of the ß-catenin inhibitor XAV-939 abolished the promotion of cell proliferation, migration, and invasion activities induced by ARPC1B overexpression in vitro. Conclusions: ARPC1B was overexpressed in ovarian cancer and was correlated with poor prognosis. ARPC1B promoted ovarian cancer progression through activation of Wnt/ß-catenin Signaling Pathway.

Lymphatic tuberculosis after lymphadenectomy for ovarian cancer: a case report.

Background: We present the case of one patient with early ovarian cancer complicated with lymphatic tuberculosis (TB) and discuss the significance of lymph node resection for ovarian cancer. We also reflect on the limitations of the preoperative imaging evaluation of lymph node metastasis and suggest possible solutions. The clinical data of a patient with early ovarian cancer complicated with lymphatic TB were analyzed retrospectively. Case Description: A 37-year-old woman was diagnosed with a left ovarian malignant tumor and multiple pelvic and abdominal lymph node metastases using full abdominal computed tomography (CT) and 18-fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG-PET/CT) before surgery. Intraoperative frozen pathology findings suggested an adult-type granulosa cell tumor (AGCT). Transabdominal debulking surgery and lymph node dissection were performed. Routine pathological results suggested that the tumor was confined to the left ovary and the lesion in the pelvis and abdomen was lymph node TB. The Federation International of Gynecology and Obstetrics (FIGO) pathological stage was IA1, so lymph node dissection was unnecessary. After discharge, the patient received anti-TB drugs. She recovered without bleeding, lymphatic cyst, lymphedema, or other surgery-related complications. Conclusions: Clinicians should, therefore, avoid relying exclusively on imaging results. Instead, it is necessary to make comprehensive decisions based on a combination of the patients' medical history, intraoperative condition, and histopathological type. If necessary, clinicians should sample suspicious and/or increased lymph nodes and send them for intraoperative frozen pathological examination. Excessive surgical treatment and early misdiagnosis in ovarian cancer should be avoided.

Comprehensive analysis of the transcriptional expressions and prognostic value of S100A family in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a treatment-refractory malignancy with poor prognosis. It is urgent to identify novel and valid biomarkers to predict the progress and prognosis of PDAC. The S100A family have been identified as being involved in cell proliferation, migration and differentiation progression of various cancer types. However, the expression patterns and prognostic values of S100As in PDAC remain to be analyzed. METHODS: We investigated the transcriptional expressions, methylation level and prognostic value of S100As in PDAC patients from the Oncomine, GEPIA2, Linkedomics and cBioPortal databases. Real-time PCR was used to detect the expressions of S100A2/4/6/10/14/16 in four pancreatic cancer cell lines and pancreatic cancer tissues from PDAC patients undergoing surgery. To verify the results further, immunohistochemistry was used to measure the expression of S100A2/4/6/10/14/16 in 43 PDAC patients' tissue samples. The drug relations of S100As were analyzed by using the Drugbank database. RESULTS: The results suggested that, the expression levels of S100A2/4/6/10/14/16 were elevated to PDAC tissues than in normal pancreatic tissues, and the promoter methylation levels of S100A S100A2/4/6/10/14/16 in PDAC (n = 10) were lower compared with normal tissue (n = 184) (P < 0.05). In addition, their expressions were negatively correlated with PDAC patient survival. CONCLUSIONS: Taken together, these results suggest that S100A2/4/6/10/14/16 might be served as prognostic biomarkers for survivals of PDAC patients.

Inhibition of microRNA let-7b expression by KDM2B promotes cancer progression by targeting EZH2 in ovarian cancer.

MicroRNA let-7b is a potent tumor suppressor and targets crucial oncogenes. Previous studies have shown that let-7b expression is suppressed in ovarian cancer; however, the regulatory mechanisms of let-7b in ovarian cancer are still not well defined. The cellular role and targets of let-7b in ovarian cancer remain elusive. In the present study, we showed that histone demethylase, KDM2B, directly suppressed let-7b expression by H3K36me2 demethylation. Moreover, let-7b inhibited EZH2 expression in ovarian cancer cells. Based on these results we know that let-7b antagonizes the enhancement of EZH2 expression caused by KDM2B overexpression, and its expression is negatively correlated with KDM2B and EZH2 expression. More importantly, proliferation, migration, and wound healing assays showed that let-7b inhibited ovarian cancer cell proliferation and migration in vitro. Additionally, let-7b overexpression neutralized KDM2B-promoted cell proliferation and migration. Furthermore, downregulation of let-7b increased the xenografted tumor volumes in nude mice that were transplanted with KDM2B-silenced cells. EZH2 silencing reversed the tumor growth enhancement mediated by inhibition of let-7b. Last, we show that let-7b expression is suppressed in ovarian carcinomas and its expression is negatively associated with the clinicopathological features of ovarian cancer, including histological type, histological grade, International Federation of Gynecology and Obstetrics (FIGO) stage, and lymph node metastatic status. In conclusion, in ovarian cancer, let-7b expression is epigenetically suppressed by high expression of KDM2B. The loss of let-7b upregulates the expression of EZH2, which promotes ovarian cancer growth in vitro and in vivo.

Enhanced hydrogen production from food waste dark fermentation by potassium ferrate pretreatment.

Hydrogen generation from food waste anaerobic dark fermentation is identified as a promising strategy for resource recovery. In this work, an innovative strategy of using potassium ferrate (PF), a strong oxidant, to promote anaerobic dark fermentation of food waste to produce hydrogen has been reported. The experimental results revealed that PF enhanced the hydrogen production from food waste, the maximal hydrogen yield was 173.5 mL/g, and the optimal PF dosage was 0.4 g/g total suspended solids. PF shortened the lag phase for hydrogen generation from 120 to 96 h. Mechanisms investigation revealed that PF accelerated the disintegration of organic compounds and increased the soluble organic matter in the liquid phase. The strong oxidation of PF inhibited the processes of hydrolysis, acidification, acetogenesis, homoacetogenesis, and methanogenesis by using synthetic wastewater in the fermentation process. The inhibition of PF on these processes was further verified by the enzyme activity analysis. Economic analysis indicated that 0.1 g/g PF was the optimal dosage. PF treatment is a promising strategy to enhance the production of hydrogen from food waste dark fermentation.

Catheter-Based Renal Denervation Attenuates Kidney Interstitial Fibrosis in a Canine Model of High-Fat Diet-Induced Hypertension.

BACKGROUND/AIMS: Catheter-based renal denervation (RDN) has emerged as an innovative interventional approach for reducing blood pressure (BP), suppressing ventricular substrate remodeling, and attenuating heart failure, which suggests that it might reduce kidney fibrosis in a canine model of high-fat diet-induced hypertension. This study thus sought to assess whether RDN could reduce kidney fibrosis and halt the progression of renal impairment in a canine model of high-fat diet-induced hypertension. METHODS: Thirty-two beagles were randomized into either the normal control group (normal diet, n = 10) or the hypertension group (high-fat diet, n = 22). After successful establishment of the model, the hypertension model group was randomized to either the RDN group (n = 9) or the sham-surgery group (n = 8). Renal artery angiography, BP, heart rate (HR), and blood and urine biochemistry results were assessed at 1, 3, and 6 months after surgery. Canines were sacrificed at 6 months after surgery. The extent of kidney interstitial fibrosis, transforming growth factor-beta 1, alpha-smooth muscle actin, connective tissue growth factor, and E-cadherin protein were measured. RESULTS: The group fed a high-fat diet had significantly (p ˂ 0.05) increased body weight, BP, and HR and higher levels of urine albumin, serum noradrenaline (NE), and angiotensin II (AngII) than the control group. The sham-surgery group and RDN group also had higher levels than the control group (p ˂ 0.05). Compared with the sham-surgery group, the RDN group had lower BP, urine albumin, serum NE, and AngII and less fibrotic tissue (all p ˂ 0.05). CONCLUSION: RDN reduced BP, slowed progression of albuminuria, and suppressed renal remodeling in a canine model of high-fat diet-induced hypertension.

Enhancement of the efficiency of oocyte vitrification through regulation of histone deacetylase 6 expression.

OBJECTIVE: Successful oocyte vitrification (OV) is critical for cryopreservation of the oocytes from female patients with infertility, polycystic ovaries, and gynecologic cancers. Recent evidence suggests that relatively low levels of histone acetylation are critical for maintenance of the maturation capacity of cryopreserved oocytes. However, previous studies have only demonstrated a key role of histone deacetylases (HDAC) 1 and 2 in the cryopreservation of oocytes. METHODS: In this study, we investigated the role of HDAC6 in these settings. We found that mouse oocytes with low HDAC6 levels decreased survival rate, cleavage rate, and blastocyst rate after OV. Bioinformatics analyses were used to predict HDAC6-targeting microRNAs (miRNAs), while the functional binding of miRNAs to HDAC6 mRNA was evaluated by a dual luciferase reporter assay. RESULTS: Among all HDAC6-targeting miRNAs, we detected expression of miR-558, miR-527, and miR-762 in mouse oocytes. Specifically, we found that only miR-762 significantly inhibited protein translation of HDAC6 via binding to the 3'-UTR of the HDAC6 mRNA. Transfection of oocytes with HDAC6 or antisense of miR-762 significantly increased the survival rate, the cleavage rate, and blastocyst rate after OV. CONCLUSION: As a result, our data suggest that induction of HDAC6 levels by miR-762 suppression may improve the current protocol for OV.

Association between induced abortion history and later in vitro fertilization outcomes.

OBJECTIVE: To establish an effective and safe clinical fertility strategy by investigating the relationship between abortion history and pregnancy outcomes of in vitro fertilization (IVF) treatment. METHODS: In the present retrospective cohort study, data from IVF treatment cycles performed at a reproductive center in China between October 1, 2014, and October 31, 2015, were assessed. Outcomes were compared between women with a history of induced abortion and those without. RESULTS: There were 1532 IVF treatment cycles included; 454 patients had a history of induced abortion and 1078 did not. The spontaneous abortion rate was significantly higher (30/170 [17.6%] vs 41/420 [9.8%]; P=0.002) and the endometrium was significantly thinner (8.8 ± 1.8 vs 9.7 ± 1.8 cm; P=0.001) among patients with a history of induced abortion compared with those without. In a subgroup analysis of patients with a history of induced abortion, women who had undergone surgical abortions had a lower live delivery rate compared with medical abortions (29/76 [38%] vs 101/378 [27%]; P=0.039). Further, women who had a history of more than two surgical abortions had lower live delivery and clinical pregnancy rates (both P<0.05). CONCLUSION: A history of induced abortion was associated with worse IVF outcomes, especially a history of more than two surgical abortions.

Inhibition of enhancer of zeste homolog 2 increases the expression of p16 and suppresses the proliferation and migration of ovarian carcinoma cells in vitro and in vivo.

Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase, which targets histone H3 lysine 27. Studies have reported that EZH2 is involved in the development of several types of tumor, including ovarian cancer. p16, a well-known cell cycle regulator, has been demonstrated to be a tumor suppressor gene in a variety of malignant cells. However, the regulatory association between EZH2 and p16 in ovarian cancer remains to be fully elucidated. The present study aimed to determine whether EZH2 is involved in the development of ovarian cancer by regulating the expression of p16. An EZH2 short hairpin RNA (shRNA) lentiviral vector was constructed and used for transducing A2780 and SKOV3 ovarian cancer cell lines. The expression levels of EZH2 and p16 in the ovarian cancer cells were detected using a reverse transcription-quantitative polymerase chain reaction and western blot analyses, respectively. The function of the inhibition of EZH2 in cell proliferation and migration were determined using a CCK-8 assay and Transwell assay. In addition, a nude mouse xenograft model was used to determine the function of EZH2 and p16 in the formation of ovarian cancer in vivo. The results revealed that the inhibition of EZH2 increased the expression of p16, and suppressed the proliferation and migration capabilities of ovarian cancer in vitro. The downregulated expression of EZH2 suppressed ovarian tumor formation in vivo. The results of the study revealed that p16 was negatively regulated by EZH2 in ovarian cancer, and that p16 and EZH2 are important in the tumorigenesis of ovarian cancer. EZH2 and p16 represent potential biomarkers for the diagnosis of ovarian cancer and as targets for ovarian cancer gene therapy.

Overexpression of CREPT confers colorectal cancer sensitivity to fluorouracil.

AIM: To investigate expression of cell cycle-related and expression-elevated protein in tumor (CREPT) in colorectal cancer (CRC) and determine its prognostic value in response to 5-fluorouracil (5-FU). METHODS: The relative expression of CREPT in CRC tumor samples was determined using immunohistochemistry. The protein content in cell lines was analyzed by immunoblotting. Cell viability was measured with the CCK-8 assay. Cell cycle and apoptosis analyses were performed with flow cytometry. RESULTS: CREPT was overexpressed in CRC tissues and correlated with histological grade. Clinicopathological analysis indicated that CREPT was positively related to tumor progression. Exogenous expression of CREPT stimulated cell proliferation and accelerated the cell cycle. More importantly, high expression of CREPT sensitized CRC cells to 5-FU treatment. Furthermore, we demonstrated that 5-FU elicited significant apoptosis in CREPT-positive cells. CONCLUSION: Aberrant overexpression of CREPT contributes to tumorigenesis of CRC by promoting cell proliferation and accelerating the cell cycle, and confers sensitivity to 5-FU. CREPT is a potential prognostic biomarker for 5-FU in CRC.

Knockdown of Gab1 Inhibits Cellular Proliferation, Migration, and Invasion in Human Oral Squamous Carcinoma Cells.

Grb2-associated binder 1 (Gab1) is often aberrant in cancerous cells and tissues, whose alteration is responsible for aggressive phenotypes. In this study, we examined the Gab1 expression in human oral squamous cell carcinoma (OSCC) tissues and investigated the cellular and molecular effect of Gab1 on migration, invasion, and cell growth of the OSCC cell lines SCC15 and SCC25. We found that Gab1 was overexpressed in OSCC tissues and cells, which is related to the protein levels of various molecules associated with cellular proliferation, migration, and invasion. Functional assays identified that Gab1 overexpression promoted cell proliferation and invasion of OSCC cells and inhibited cell apoptosis in the SCC15 and SCC25 cell lines. On the other hand, Gab1 silencing affected the proliferation and invasion of OSCC cells and induced cell apoptosis. Western blot assay identified that Gab1 overexpression suppressed the expression of Cdc20 homolog 1 (Cdh1) and then promoted cell invasion in OSCC cells. Furthermore, Gab1-mediated Cdh1 downregulation was significantly reversed when the cells were subjected to an inhibitor of p-Akt. In conclusion, these results suggested that Gab1 induced malignant progression of OSCC cells probably via activation of the Akt/Cdh1 signaling pathway. Thus, Gab1 may be a potential therapeutic target in the treatment of OSCC patients.

Histone demethylase KDM2B upregulates histone methyltransferase EZH2 expression and contributes to the progression of ovarian cancer in vitro and in vivo.

Aberrant histone methylation contributes to the progression and development of many tumors. Histone methylation is a dynamic process regulated by both histone demethylase and histone methyltransferase, which ultimately alters the levels of gene transcription. However, the relationship between histone demethylase and histone methyltransferase, as well as their regulatory mechanisms in ovarian cancer development, is still unclear. Lysine-specific demethylase 2B (KDM2B) is a key demethylase of H3K36me3 and H3K4me3 that regulates gene expression and plays a role in tumorigenesis via epigenetic mechanisms. To determine the expression pattern of KDM2B in ovarian neoplasms, we analyzed the mRNA and protein levels of KDM2B and the histone methyltransferase enhancer of zester homolog 2 (EZH2) in normal, benign, borderline, and malignant ovarian tissue samples. We found that KDM2B expression was gradually increased in ovarian tumors, with the highest expression found in the malignant ovarian tissues, and the differences in KDM2B expression among the different International Federation of Gynecology and Obstetrics stages and pathological grades/types were statistically significant. Moreover, KDM2B expression was positively correlated with EZH2 expression in ovarian tissues. To determine the role of KDM2B in tumorigenesis in vitro and in vivo, we silenced KDM2B expression in ovarian cancer cells using the KDM2B short hairpin RNA expression lentivirus and established a nude mouse xenograft model. Downregulation of endogenous KDM2B decreased the expression of EZH2 and reduced the proliferation and migration of ovarian cancer cells. Loss of KDM2B suppressed ovarian tumor formation in vivo. Our results suggest that KDM2B plays an important role in the tumorigenesis of ovarian cancer, with a possible mechanism of increasing the expression of the oncogene EZH2; this indicates that certain histone methyltransferase may be positively regulated by certain histone demethylase in the epigenetic regulation of ovarian tumors. KDM2B may be a novel therapeutic target for the clinical treatment of ovarian cancer.

Antiangiogenic drugs used with chemotherapy for patients with recurrent ovarian cancer: a meta-analysis.

OBJECTIVE: The value of antiangiogenic inhibitors for patients with recurrent ovarian cancer has not been completely affirmed. Therefore, we aimed to assess the effectiveness and toxicities of various antiangiogenic drugs for the treatment of recurrent ovarian cancer. METHODS: In this meta-analysis, we searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials databases for complete randomized controlled trials. The searches were extended to May 15, 2016. The risk of bias of the included studies was evaluated via a Cochrane systematic evaluation, and the statistical analyses were performed using RevMan 5.2 software. RESULTS: In total, we included 8 randomized controlled trials involving 3,211 patients and divided them into 3 groups, vascular endothelial growth factor receptor inhibitors (VEGFRIs), vascular endothelial growth factor (VEGF) inhibitors (bevacizumab), and angiopoietin inhibitors (trebananib). The progression-free survival improved significantly in all the groups being given antiangiogenic drugs (hazard ratio [HR]: 0.55, 95% confidence interval [CI]: 0.45-0.67, I2=0%, P<0.00001 for the VEGFRI group; HR: 0.53, 95% CI: 0.45-0.63, I2=51%, P<0.00001 for the VEGF inhibitor group; HR: 0.67, 95% CI: 0.58-0.77, I2=0%, P<0.00001 for the trebananib group). Overall survival was obviously prolonged in the VEGFRI (HR: 0.76, 95% CI: 0.59-0.97, I2=0%, P=0.03), the VEGF inhibitor (HR: 0.87, 95% CI: 0.77-0.99, I2=0%, P=0.03), and trebananib groups (HR: 0.81, 95% CI: 0.67-0.99, I2=0%, P=0.04). The incidence of grade 3/4 side effects was different among the 3 groups, for example, proteinuria, hypertension, gastrointestinal perforation, and arterial thromboembolism were presented in the VEGF inhibitor group. Increased incidences of fatigue, diarrhea, and hypertension were seen in the VEGFRI group, and the trebananib group had a higher incidence of hypokalemia. CONCLUSION: This meta-analysis showed that antiangiogenic drugs improved the progression-free survival. The VEGFRI, bevacizumab, and trebananib groups showed increased overall survival. Adding antiangiogenic drugs to chemotherapy treatment resulted in a higher incidence of grade 3/4 side effects, but these were manageable.

miR-944 acts as a prognostic marker and promotes the tumor progression in endometrial cancer.

microRNA-944 (miR-944) has been reported to be deregulation and play either tumor suppressive or oncogenic function in human malignancies. Previous studies have reported that miR-944 is overexpressed in gynecological malignancies including cervical cancer and breast cancer. While, the clinical significance of miR-944 and its function in human endometrial carcinoma (EC) keep unknown. The levels of miR-944 were analyzed in 68 EC tissues and 20 normal endometrial tissues. Results showed that miR-944 was significantly overexpressed in EC tissues compared to normal endometrial tissues. In addition, increased levels of miR-944 also observed in EC cell lines. Clinicopathological analysis verified that miR-944 expression was associated with international federation of gynecology and obstetrics (FIGO) stages and pathology classification of EC. Moreover, Kaplan-Meier analysis found that miR-944 highly expressing EC patients showed a notable shorter survival. Further experiments revealed that miR-944 knockdown significantly inhibited growth and cell cycle progression while facilitated apoptosis in Ishikawa cells. In turn, miR-944 overexpression prominently promoted proliferation and cell cycle progression, and suppressed apoptosis in KLE cells. In vivo experiments further confirmed that miR-944 silencing notably restrained the tumor growth of EC in nude mice. Mechanically, cell adhesion molecule 2 (CADM2) was recognized as a direct downstream target of miR-944 in EC cells. An inverse correlation between miR-944 and CADM2 expression was observed in EC tissues. Interestingly, CADM2 overexpression showed similar effects to miR-944 knockdown in Ishikawa cells with decreased growth, cell cycle arrest at G1 phase and increased apoptosis. Taken together, this work support the first evidence that miR-944 can be potentially used as a promising biomarker and novel therapeutic target for human EC.

Neoadjuvant chemotherapy for Patients with advanced epithelial ovarian cancer: A Meta-Analysis.

The value of neoadjuvant chemotherapy (NAC) has not yet been fully defined. We aimed to systematically evaluate the influence of neoadjuvant chemotherapy (NAC) on survival and complete cytoreduction after debulking surgery in advanced epithelial ovarian cancer (AEOC) patients. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for the randomized controlled trials (RCTs) comparing NAC and primary debulking surgery (PDS) in AEOC patients. The last search date is February 25, 2016. Cochrane systematic evaluation was used to evaluate bias risk of included studies. RevMan 5.3 software was used for statistical analysis. A total of 4 RCTs involving 1922 patients were included. Compared with PDS, NAC may contribute to the completeness of debulking removal [no residual disease (RR: 2.37; 95%CI: 1.94-2.91; P<0.00001), residual disease ≤1 cm (RR: 1.28; 95%CI: 1.04-1.57; P = 0.02), optimal cytoreduction rate (RR: 1.76; 95%CI: 1.57-1.98; P<0.00001)], but there were no significant differences in both groups with regard to overall survival (HR: 0.94; 95%Cl: 0.81-1.08; P = 0.38) and progression-free survival (HR: 0.89; 95%Cl: 0.77-1.03; P = 0.12). This meta-analysis indicates that the higher rate of optimal debulking made NAC more favorable as a treatment option for AEOC patients with non-inferior survival compared with PDS.

Elevated progesterone on the trigger day does not impair the outcome of Human Menotrophins Gonadotrophin and Medroxyprogesterone acetate treatment cycles.

To demonstrate the incidence and effects of elevated progesterone (P) on the trigger day on the outcome of in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles using Medroxyprogesterone acetate (MPA) co-treated with Human Menotrophins Gonadotrophin (hMG + MPA), we performed a retrospective analysis including 4106 IVF/ICSI cycles. The cycles were grouped according to the P level on the trigger day: <1 ng/mL, between 1-1.5 ng/ml (including 1), between 1.5-2 ng/mL (including 1.5), and ≥2 ng/mL. The primary outcome measure was live birth rate. The prevalence of P level categories was 12.93% (531/4106), 2.92% (120/4106), and 1.92% (79/4106) in women with P between 1-1.5 ng/mL, between 1.5-2 ng/mL, and ≥2 ng/mL, respectively. The mean stimulation duration, total hMG dose, serum follicle stimulating hormone (FSH), estrogen(E2) on the trigger day and the number of oocytes in patients with elevated P were significantly higher than patients with P < 1 ng/mL (P < 0.05). However, there were no significant differences in the oocyte retrieval rates, fertilization rates, implantation rates, clinical pregnancy rates and live birth rates between the groups based on frozen embryo transfer (FET). We concluded that elevated P on the trigger day had no negative effect on the final outcome of the hMG + MPA treatment cycles based on FET.

Screening of potential biomarkers for chemoresistant ovarian carcinoma with miRNA expression profiling data by bioinformatics approach.

The aim of the present study was to screen out the biomarkers associated with chemoresistance in ovarian carcinomas and to investigate the molecular mechanisms. microRNA (miRNA) expression data was obtained from published microarray data of the GSE43867 dataset from Gene Expression Omnibus (GEO), including the data of 86 chemotherapy-treated patients with serous epithelial ovarian carcinomas (response group, 36 complete response cases and 12 partial response cases; non-response group, 10 stable cases and 28 progressive disease cases), and identification of differentially-expressed miRNAs were conducted with a GEO2R online tool based on R language. TargetScan 6.2 was used to predict the targets of differentially-expressed miRNAs. Protein-protein interaction network analysis was conducted by STRING 9.1, while functional enrichment [Gene Ontology (GO) biological process terms] and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted by GeneCodis3 for the target genes. A total of 6 differentially-expressed miRNAs were screened out, with 317 target genes obtained. It was found that 67 interactions existed among 76 genes/proteins through the PPI network analysis, and that 6 of these were potential key genes (PIK3R5, MAPK3, PTEN, S1PR3, BDKRB2 and NCBP2). The main biological processes involved in chemoresistant ovarian carcinoma were apoptosis, programmed cell death, cell migration, cell death and cell motility. The miRNA target genes were found to be associated with the ErbB signaling pathway, the gonadotropin-releasing hormone signaling pathway and other pathways in cancer. IK3R5, MAPK3 and PIK3R5 are involved in the majority of GO terms and KEGG pathways associated with chemoresistance in ovarian carcinoma.

Systematic enrichment analysis of microRNA expression profiling studies in endometriosis.

OBJECTIVES: The purpose of this study was to conduct a meta-analysis on human microRNAs (miRNAs) expression data of endometriosis tissue profiles versus those of normal controls and to identify novel putative diagnostic markers. MATERIALS AND METHODS: PubMed, Embase, Web of Science, Ovid Medline were used to search for endometriosis miRNA expression profiling studies of endometriosis. The miRNAs expression data were extracted, and study quality of each article was assessed. The frequently reported miRNAs with consistent regulation were screened out by a meta-profiling algorithm. The putative targets of consistently expressed miRNAs were predicted by using four target prediction tools (TargetScan, PicTar, miRanda, miRDB), and gene ontology pathway enrichment analysis (KEGG and Panther pathways) of the miRNA targets were carried out with GeneCodis web tool. RESULTS: A total of 194 related literatures were retrieved in four databases. One hundred and thirty four differentially expressed miRNAs were found in the 12 microRNA expression profiling studies that compared endometriosis tissues with normal tissues, with 28 miRNAs reported in at least two studies, and 9882 candidate genes retrieved for 13 consistently expressed miRNAs. Kyoto encyclopedia of genes and genomes (KEGG) and Panther pathways enrichment analysis showed that endometriosis related differently expressed miRNA targets were mainly enriched in cancer, endocytosis, Wnt signalling pathway, and angiogenesis. It showed that these differently expressed miRNAs and gene are potential biomarkers of endometriosis. CONCLUSION: miRNAs appear to be potent regulators of gene expression in endometriosis and its associated reproductive disorders, raising the prospect of using miRNAs as biomarkers and therapeutic agent in endometriosis.

Clinical observations of sequential therapy with Chinese medicine and hysteroscopic mechanical stimulation of the endometrium in infertile patients with repeated implantation failure undergoing frozen-thawed embryo transfer.

OBJECTIVES: To investigate the clinical effect of sequential therapeutic intervention Yupei Qisun [compensating for weakness by invigorating Kidney (Shen) and Spleen (Pi) in advance] in Chinese medicine (CM) and hysteroscopic endometrial mechanical stimulation on the treatment of infertile patients with repeated implantation failure (RIF); and to study the differences in patients' endometrial thickness and type on the day of embryo transfer, serum hormone levels on embryo transfer day and clinical pregnancy outcomes. METHODS: In the clinical study, 168 frozen-thawed embryo transfer (FET) cycles for couples with RIF conforming to the research protocol were randomly divided into three groups: a CM group with 56 cycles (CM combined with FET), a hysteroscopy group with 55 cycles (hysteroscopic endometrial mechanical stimulation), and a control group with 57 cycles (conventional FET). Differences in endometrial thickness on the embryo transfer day, levels of serum estradiol (E2) and progesterone (P) on the embryo transfer day, the E2/P ratio on the embryo transfer day, biochemical and clinical pregnancy rates, implantation rate, abnormal pregnancy rate and other indices were compared among the three groups. RESULTS: Endometrial thickness, E2 and P levels, and the E2/P ratio on embryo transfer day and other factors had no significant differences among groups. The biochemical pregnancy, clinical pregnancy, and implantation rates of the CM and hysteroscopy groups were significantly higher than the control group (P<0.05), and there were no significant differences between these two groups. The abnormal pregnancy rate had no significant difference among the three groups. CONCLUSIONS: Sequential therapy of Yupei Qisun could significantly improve the clinical outcomes of rif-fet cycles, being equivalent to hysteroscopic endometrial mechanical stimulation, and provided a reliable method to treat such infertile couples.