Peptidome analysis of human intrauterine adhesion tissues and the identification of antifibrotic peptide.

Intrauterine adhesion (IUA) is a common clinical endometrial disease, which can severely damage the fertility and quality of life in women. This study aims to find the differentially expressed endogenous peptides and their possible roles in IUA. Liquid chromatography-mass spectrometry was used to identify the peptidomic profiling of IUA tissues, and the differentially expressed peptides were screened out. Using real-time quantitative PCR, Western blotting, and immunocytochemistry staining, the function of six endogenous peptides was verified in vitro. It was found that peptide 6 (T6) (peptide sequence: TFGGAPGFPLGSPLSSVFPR) could inhibit the expression of TGF-ß1-induced cell fibrosis in human endometrial stromal cell line and primary human endometrial stromal cell at a concentration of 50 µmol/L. This study provides new targets for further clarifying the formation and prevention of IUA.

The efficacy and safety of triptorelin-therapy following conservative surgery for deep infiltrating endometriosis: A multicenter, prospective, non-interventional study in China.

ABSTRACT: Triptorelin is one of the most commonly used gonadotropin-releasing hormone agonists and has been used in the treatment of deep infiltrating endometriosis (DIE). This study aimed to evaluate the efficacy and safety of up to 24 weeks of triptorelin treatment after conservative surgery for DIE.This prospective, non-interventional study was performed in 18 tertiary hospitals in China. Premenopausal women aged ≥18 years treated with triptorelin 3.75 mg once every 28 days for up to 24 weeks after conservative surgery for DIE were included. Endometriosis symptoms were assessed, using a visual analogue scale (0-10 cm) or numerical range (0-10), at baseline (pre-surgery) and routine visits 3, 6, 9, 12, 18, and 24 months after surgery. Changes in symptom intensity over time were primary outcome measures.A total of 384 women (mean [standard deviation] age, 33.4 [6.2] years) were analyzed. Scores for all symptoms (pelvic pain, dysmenorrhea, ovulation pain, dyspareunia, menorrhagia, metrorrhagia, and gastrointestinal and urinary symptoms) assessed decreased from baseline over 24 months. Cumulative improvement rates in pelvic pain, dysmenorrhoa, ovulation pain, and dyspareunia were 74.4%, 83.6%, 55.1%, and 66.9%, respectively. The 24-month cumulative recurrence rate (≥1 symptom) was 22.2%. The risk of symptom recurrence was higher in patients with ≥2 versus 1 lesion (odds ratio [OR] 2.539; 95% CI: 1.458-4.423; P = .001) and patients with moderate (OR 5.733; 95% CI: 1.623-20.248; P = .007) or severe (OR 8.259; 95% CI: 2.449-27.851; P = .001) pain versus none/mild pain. Triptorelin was well tolerated without serious adverse events.Triptorelin after conservative surgery for DIE improved symptoms over 24 months of follow up. The recurrence rate of symptoms was low and triptorelin was generally well tolerated.Trial registration number: ClinicalTrials.gov, NCT01942369.

Exosomal miR-21-5p contributes to ovarian cancer progression by regulating CDK6.

Ovarian cancer is a predominant gynecologic malignancy and correlated with high mortality and severe morbidity. Exosomal microRNAs (miRNAs) play crucial roles in various processes during the progression of ovarian cancer, such as cell proliferation, apoptosis, and invasion. However, the function of exosomal miR-21-5p in ovarian cancer is still unknown. Here, we found that miR-21-5p was upregulated in ovarian cancer tissues, plasma exosomes of ovarian cancer patients, and exosomes from ovarian cancer cells. MiR-21-5p was incorporated in the exosomes from the ovarian cancer cells. In addition, 5-ethynyl-2'-deoxyuridine (Edu), a marker of cancer cell proliferation, was enhanced by miR-21-5p mimic while reduced by miR-21-5p inhibitor in ovarian cancer cells. MiR-21-5p mimic could increase, but miR-21-5p inhibitor could decrease the migration and invasion of cancer cells. Ovarian cancer cell apoptosis was induced by miR-21-5p inhibitor. Moreover, miR-21-5p inhibitor could up-regulate the expression of pro-apoptotic cleaved caspase3 and Bax while downregulate the expression of anti-apoptotic Bcl2 in the cells. Exosomal miR-21-5p inhibited the expression of cyclin-dependent kinase 6 (CDK6) by targeting its 3'-untranslated region (3'-UTR) at both the mRNA and protein levels. Tumorigenicity analysis in nude mice revealed that exosomal miR-21-5p could increase tumor volume, size, and weight of ovarian cancer in vivo. Besides, miR-21-5p targeted CDK6 in tumor tissues of nude mice. In conclusion, exosomal miR-21-5p contributes to the progression of ovarian cancer by regulating CDK6. Our findings will provide novel insights into the mechanism of exosomal miR-21-5p in the development of ovarian cancer. Exosomal miR-21-5p may serve as a potential target for the therapy of ovarian cancer.

A novel human monoclonal Trop2-IgG antibody inhibits ovarian cancer growth in vitro and in vivo.

Trop2 is a tumor-related antigen closely related to the development of a variety of tumors and has been identified as a promising target for cancer immunotherapy. In this study, a Trop2-IgG antibody was constructed by a eukaryotic expression system based on our previously constructed Trop2-Fab antibody. SDS-PAGE, cell ELISA, affinity assays, fluorescence staining and FACS analyses were performed to characterize Trop2-IgG. Then, CCK-8, wound healing, Transwell and annexin V-PI assays were employed to evaluate the tumor inhibitory effects of Trop2-IgG on OC in vitro, while tumor-bearing mice were constructed to examine the tumor inhibitory effects of Trop2-IgG on OC in vivo. Trop2-IgG was successfully constructed by a eukaryotic expression system and maintained recognition characteristics to Trop2 antigen. In vitro, Trop2-IgG could inhibited tumor cell growth, migration, and invasion compared to those of control cells and induced tumor cell apoptosis. In vivo, Trop2-IgG exerted critical tumor inhibitory effects in OC xenografts. Our data suggest that the use of Trop2-IgG provides a potential therapeutic strategy for the immunotherapy of Trop2-expressing OC.

ROR1 expression correlated with poor clinical outcome in human ovarian cancer.

The receptor-tyrosine-kinase-like orphan receptor 1 (ROR1) is a transmembrane protein belongs to receptor tyrosine kinase (RTK) family. This study aimed to examine the expression of ROR1 in human ovarian cancer and investigate the relationship between its expression and the prognosis of ovarian cancer patients. In this present study, one-step quantitative reverse transcription-polymerase chain reaction (15 ovarian cancer samples of high FIGO stage, 15 ovarian cancer samples of low FIGO stage and nine normal ovary tissue samples) and immunohistochemistry by tissue microarrays (100 ovarian cancer samples and 50 normal ovary samples) were performed to characterize expression of the ROR1 gene in ovarian cancer. Kaplan-Meier survival and Cox regression analyses were executed to evaluate the prognosis of ovarian cancer. The results of qPCR and IHC analysis showed that the expression of ROR1 in ovarian cancer was significantly higher than that in normal ovary tissues (all p < 0.05). Survival analysis showed that ROR1 protein expression was one of the independent prognostic factors for disease-free survival and overall survival (both p < 0.05). The data suggest that ROR1 expression is correlated with malignant attributes of ovarian cancer and it may serve as a novel prognostic marker in ovarian cancer.

Hysteroscopic transcervical resection of uterine septum.

OBJECTIVE: To explore the method of diagnosis for uterine septum and the clinical effect of hysteroscopic transcervical resection of the septum. METHODS: One-hundred ninety cases of patients with uterine septum who were diagnosed and treated at our hospital during 2007-2011 were selected, and their general information, perioperative status, postoperative recovery treatment, and postoperative pregnancy rates were statistically analyzed. RESULTS: All 190 patients were cured with one surgery, with an average hysteroscopic operating time of 22.60 ± 10.67 minutes and intraoperative blood loss of 15.74 ± 9.64 mL. There were no complications such as uterine perforation, water intoxication, infection, or heavy bleeding. Among the 115 patients that we followed up, 86 became pregnant and delivered infants, 81 of which were born at term and 5 that were born premature. CONCLUSION: The combination of hysteroscopy and laparoscopy is still the most reliable method for the diagnosis of uterine septum. With a shorter operative time, less blood loss, a significantly increased postoperative pregnancy rate and live birth rate, and a significantly lower spontaneous abortion rate, transcervical resection of the septum was the preferred method for the treatment of uterine septum, and surgical instruments and skills were critical to the prognosis of uterine septum.