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Background The Wilms’ tumor suppressor WT1 is reported to work in a range of physiological processes at both transcriptional and posttranscriptional level. WT1-associating protein (WTAP), a nuclear protein co-localized with splicing factors, also plays a vital role in cellular function and cancer progression. However, little is known about the role of WTAP in ovarian cancer and the underlying mechanism. Materials and methods To evaluate the expression of WTAP, multiple means were applied in clinical tissues, including immunohistochemistry, quantitative reverse transcriptase PCR (qRT-PCR), and Western blot. Two representative ovarian cancer cell lines (3AO and SKOV3) were used to assess the malignant influence of WTAP on proliferation, apoptosis, and migration. To explore its function, WTAP was additionally down-regulated by lentivirus. Results High expression of WTAP in high-grade serous ovarian carcinoma (HGSOC) predicted a shorter overall survival ( P <0.01). Furthermore, WTAP expression was higher in HGSOC, compared with that in normal ovary group ( P <0.01), benign ovarian tumor group ( P <0.01), and non-HGSOC group ( P <0.05). In HGSOC, high expression of WTAP was significantly related with the lymph node metastasis ( P <0.05). In ovarian cancer cell lines, cell proliferation and migration were considerably reduced after WTAP was down-regulated, while apoptotic rate was increased. Moreover, the effect of WTAP in 3AO and SKOV3 might be relevant with MAPK and AKT signaling pathways. Conclusion WTAP is highly expressed in HGSOC, and indicates a worse survival outcome. Therefore, it is highly possible that WTAP has a prognostic implication in the patients of HGSOC. In addition, WTAP down-regulation also plays a tumor suppressor role in 3AO and SKOV3 cell lines.

Cancer is expected to rank as the leading cause of death worldwide due to increasing morbidity and mortality. Long noncoding RNAs (lncRNAs) have been found to play pivotal roles in multiple biological processes, such as transcriptional interference, posttranscriptional regulation and epigenetic modification. Small nucleolar RNA host gene 15 (SNHG15), a snoRNA host gene which produces a short half-lived lncRNA, was reported to be upregulated in tumor cells and participate in the occurrence and development of multiple cancers. And more than half of the SNHG15 research in cancers has been published within the last 2 years. In this review, we summarized the current evidence concerning the biological functions and molecular mechanisms of SNHG15 in various cancers, including gastric, hepatocellular, pancreatic, colorectal, breast, and thyroid cancer, osteosarcoma, glioma, lung cancer, renal cell carcinoma, and epithelial ovarian cancer. SNHG15 plays critical roles in regulation of cell proliferation, migration and invasion of tumors via different potential mechanisms. Moreover, the abnormal expression of SNHG15 was associated with clinical features of patients with cancers. Consequently, SNHG15 could be considered as a promising biomarker for cancer diagnosis, prognosis or treatment.

Purpose Ovarian cancer is the leading cause of death in gynecologic malignancies. Growing evidences demonstrate that a complicated relationship exists between the gut microbiota and cancer treatment. However, there are few studies explored the alterations of gut microbiota in ovarian cancer patients following anti-cancer treatments. Therefore, we aim to analyze the changes of the gut microbiota in ovarian cancer patients treated with radical surgery and chemotherapy. Patients and Methods The microbial genes were examined from a total of 75 fecal samples from 18 ovarian cancer patients, including 10 preoperative fecal samples (Group B), 4 postoperative fecal samples (Group M0), as well as 61 fecal samples after first to fifth cycles of chemotherapy, using 16S rRNA sequencing. Results Our results showed that fecal samples collected in postoperative (Group M0) exhibited significant decreases in abundance of Bacteroidetes and Firmicutes, while a significant increase in abundance of Proteobacteria compared with preoperative (Group B) fecal samples. LEfSe analysis identified that Bilophila and Faecalibacterium are the key genera in Group B, while Klebsiella and Enterococcus are the key genus in Group M0. Compared with before chemotherapy, the abundance of Bacteroidetes and Firmicutes increased, and the abundance of Proteobacteria decreased after chemotherapy. In addition, anaerobic bacteria, such as Bacteroides, Collinsella and Blautia , exhibited significant increases after chemotherapy. Moreover, we observed that certain bacterial genera were significantly correlated with clinicopathological characteristics of ovarian cancer patients. Conclusion Our study suggested that radical surgery and chemotherapy altered the composition of gut microbiota in ovarian cancer patients. Therapeutic strategies targeting the gut microbiota may be beneficial for the clinical treatment of ovarian cancer.

ObjectiveWe explored the gut microbiome and serum metabolome alterations in patients with premature ovarian insufficiency (POI) and the effects of hormone replacement therapy (HRT) with the aim to unravel the pathological mechanism underlying POI.MethodsFecal and serum samples obtained from healthy females (HC, n = 10) and patients with POI treated with (n = 10) or without (n = 10) HRT were analyzed using 16S rRNA gene sequencing and untargeted metabolomics analysis, respectively. Peripheral blood samples were collected to detect serum hormone and cytokine levels. Spearman’s rank correlation was used to evaluate correlations between sex hormones and cytokines and between the gut microbiota and serum metabolites. To further confirm the correlation between Eggerthella and ovarian fibrosis, the mice were inoculated with Eggerthella lenta (E. lenta) through oral gavage.ResultsThe abundance of genus Eggerthella significantly increased in the fecal samples of patients with POI compared to that observed in the samples of HCs. This increase was reversed in patients with POI treated with HRT. Patients with POI showed significantly altered serum metabolic signatures and increased serum TGF-β1 levels; this increase was reversed by HRT. The abundance of Eggerthella was positively correlated with altered metabolic signatures, which were, in turn, positively correlated with serum TGF-β1 levels in all subjects. Estrogen ameliorated ovarian fibrosis induced by E. lenta in mice.ConclusionsThe interactions between the gut microbiota, serum metabolites, and serum TGF-β1 in patients with POI may play a critical role in the development of POI. HRT not only closely mimicked normal ovarian hormone production in patients with POI but also attenuated gut microbiota dysbiosis and imbalance in the levels of serum metabolites and TGF-β1, which are reportedly associated with fibrosis. The findings of this study may pave the way for the development of preventive and curative therapies for patients with POI.

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Background Up to 70% of patients with advanced ovarian cancer have a relapse after primary therapy. New agents and approaches are urgently needed to avoid or slow down this recurrence.Objectives To investigate the efficacy of PARP inhibitors (PARPis) as maintenance treatment in patients with newly diagnosed advanced ovarian cancer.Search strategy PubMed, MEDLINE, EMBASE, Cochrane Library and Web of Science databases.Selection criteria All randomised clinical trials (RCTs) that compared PARPis with placebo as first-line maintenance therapy in ovarian cancer.Data collection and analysis Two reviewers extracted data. Pooled hazard ratio (HR) and risk ratio (RR) with 95% confidence interval (CI) were calculated.Main results PARPis were associated with significant improvement of progression-free survival (PFS) in advanced epithelial ovarian cancer (AeOC) (HR = 0.53, 95% CI 0.40-0.71; P < 0.0001). The benefit was not only in women with BRCA mutations (HR = 0.35, 95% CI 0.29-0.42; P < 0.00001) and homologous recombination deficiency (HRD) (HR = 0.43, 95% CI 0.32-0.60; P < 0.00001), but also in those with nonmutated BRCA (HR = 0.72, 95% CI 0.63-0.82; P < 0.00001) and even non-HRD (HR = 0.83, 95% CI 0.70-0.99; P = 0.04).Conclusions PARP inhibitors are effective as maintenance therapy among patients with newly diagnosed advanced ovarian cancer after platinum-based chemotherapy, regardless of BRCA mutation or HRD status.

The fibrinolytic characteristics and clinical pathological significance of pleural and ascitic fluid were studied in patients with malignant tumour, tuberculosis or liver cirrhosis. Urokinase plasminogen activator (uPA) and urokinase plaminogen activator receptor (uPAR) levels were measured by enzyme-linked immunoadsorbent assay and tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), plasminogen (Plg), plasmin (Pl) and alpha(2) plasmin inhibitor (alpha(2)PI) by colorimetric assay. uPA and uPAR levels were higher in malignant tumour and tuberculosis compared with liver cirrhosis, whereas tPA levels were significantly higher in liver cirrhosis and malignant tumour than in tuberculosis patients. Tuberculosis patients showed statistically higher PAI-1, Plg and Pl concentrations than malignant tumour patients, which, in turn, were higher than those in liver cirrhosis patients. alpha(2)PI levels were markedly higher in malignant tumour and liver cirrhosis than in tuberculosis. In the malignant tumour group, only uPA level was significantly different between the samples that contained cancer cells and those that did not. We found significant differences between the fibrinolytic characteristics in pleural and ascitic fluid in patients with malignant tumour, tuberculosis and liver cirrhosis. The analysis of several fibrinolytic parameters could help to determine the quality of pleural and ascitic fluid, and also to further understand the pathological processes of these diseases.