The immune microenvironment is crucial for epithelial ovarian cancer (EOC) progression and consists of tumorassociated macrophages (TAM) and T lymphocytes, such as regulatory T cells (Treg) and T helper 17 (Th17) cells. In this study, the Treg/Th17 ratio was significantly higher in EOC in situ and in metastatic peritoneal tissues than in benign ovarian tumors and benign peritoneum. The Treg/Th17 ratio was associated with histologic grade and was an independent prognostic factor for overall survival of EOC patients. On the basis of microarray analysis of exosomes derived from TAMs, we identified miRNAs enriched in the exosomes, including miR-29a-3p and miR-21-5p. When the two miRNA mimics were transfected into CD4 þ T cells, they directly suppressed STAT3 and regulated Treg/Th17 cells, inducing an imbalance, and they had a synergistic effect on STAT3 inhibition. Taken together, these results indicate that exosomes mediate the interaction between TAMs and T cells, generating an immune-suppressive microenvironment that facilitates EOC progression and metastasis. These findings suggest that targeting these exosomes or their associated miRNAs might pave the way for the development of novel treatments for EOC.

The aim of this study was to evaluate the effect of orlistat or metformin combined with Diane-35 on anthropometric, hormonal and metabolic parameters in overweight and obese polycystic ovary syndrome (PCOS) patients with insulin resistance (fasting insulin > 10 mIU/L). A total of 240 PCOS women were randomly allocated to orlistat plus Diane-35(OD group), metformin plus Diane-35(MD group), orlistat plus metformin plus Diane-35(OMD group) or Diane-35 (D group). Body weight, BMI, waist and hip circumference, blood pressure, endocrine profile, lipid profile and insulin resistance were assessed at baseline and after 3 months. Significant reductions in waist and hip circumference, serum LH, total testosterone and uric acid were observed in all groups compared with baseline. TG and TC significantly decreased in the OD group. Homeostasis model assessment insulin resistance (HOMA-IR) index was reduced in the OD (p = .015), MD (p = .001) and OMD (p = .004) groups. Body weight, BMI, systolic BP and HDL-C significantly changed in the OD and OMD group compared with the D group (p < .05). Side effects were less with orlistat than metformin. This study demonstrated that orlistat is more effective in reducing weight and lipid profile than metformin. Besides, orlistat has mild side-effects and is better tolerated compared with metformin.

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Background Chemotherapy resistance is a primary reason of ovarian cancer therapy failure; hence it is important to investigate the underlying mechanisms of chemotherapy resistance and develop novel potential therapeutic targets. Methods RNA sequencing of cisplatin‐resistant and ‐sensitive (chemoresistant and chemosensitive, respectively) ovarian cancer organoids was performed, followed by detection of the expression level of fibrillin‐1 (FBN1) in organoids and clinical specimens of ovarian cancer. Subsequently, glucose metabolism, angiogenesis, and chemosensitivity were analyzed in structural glycoprotein FBN1‐knockout cisplatin‐resistant ovarian cancer organoids and cell lines. To gain insights into the specific functions and mechanisms of action of FBN1 in ovarian cancer, immunoprecipitation, silver nitrate staining, mass spectrometry, immunofluorescence, Western blotting, and Fӧrster resonance energy transfer‐fluorescence lifetime imaging analyses were performed, followed by in vivo assays using vertebrate model systems of nude mice and zebrafish. Results FBN1 expression was significantly enhanced in cisplatin‐resistant ovarian cancer organoids and tissues, indicating that FBN1 might be a key factor in chemoresistance of ovarian cancer. We also discovered that FBN1 sustained the energy stress and induced angiogenesis in vitro and in vivo, which promoted the cisplatin‐resistance of ovarian cancer. Knockout of FBN1 combined with treatment of the antiangiogenic drug apatinib improved the cisplatin‐sensitivity of ovarian cancer cells. Mechanistically, FBN1 mediated the phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) at the Tyr1054 residue, which activated its downstream focal adhesion kinase (FAK)/protein kinase B (PKB or AKT) pathway, induced the phosphorylation of signal transducer and activator of transcription 2 (STAT2) at the tyrosine residue 690 (Tyr690), promoted the nuclear translocation of STAT2, and ultimately altered the expression of genes associated with STAT2‐mediated angiogenesis and glycolysis. Conclusions The FBN1/VEGFR2/STAT2 signaling axis may induce chemoresistance of ovarian cancer cells by participating in the process of glycolysis and angiogenesis. The present study suggested a novel FBN1‐targeted therapy and/or combination of FBN1 inhibition and antiangiogenic drug for treating ovarian cancer.

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ObjectiveThe aim of this study was to build a model to predict the risk of lymphovascular space invasion (LVSI) in women with endometrial cancer (EC).MethodsFrom December 2010 to June 2013, 211 patients with EC undergoing surgery at Shanghai First Maternity and Infant Hospital were enrolled in this retrospective study. Those patients were divided into a positive LVSI group and a negative LVSI group. The clinical and pathological characteristics were compared between the two groups; logistic regression was used to explore risk factors associated with LVSI occurrence. The threshold values of significant factors were calculated to build a risk model and predict LVSI.ResultsThere were 190 patients who were negative for LVSI and 21 patients were positive for LVSI out of 211 patients with EC. It was found that tumor grade, depth of myometrial invasion, number of pelvic lymph nodes, and International Federation of Gynecology and Obstetrics (FIGO) stage (p<0.05) were associated with LVSI occurrence. However, cervical involvement and age (p>0.05) were not associated with LVSI. Receiver operating characteristic (ROC) curves revealed that the threshold values of the following factors were correlated with positive LVSI: 28.1 U/mL of CA19-9, 21.2 U/mL of CA125, 2.58 mg/dL of fibrinogen (Fn), 1.84 U/mL of carcinoembryonic antigen (CEA) and (6.35×109)/L of white blood cell (WBC). Logistic regression analysis indicated that CA125 ≥21.2 (p=0.032) and Fn ≥2.58 mg/dL (p=0.014) were significantly associated with LVSI.ConclusionPositive LVSI could be predicted by CA125 ≥21.2 U/mL and Fn ≥2.58 mg/dL in women with EC. It could help gynecologists better adapt surgical staging and adjuvant therapies.

Diane-35 in combination with orlistat or metformin is more effective in reducing androgen than Diane-35 alone. Orlistat is more effective in reducing body fat percentage than metformin. In addition, orlistat has mild side-effects and is better tolerated compared with metformin.