Single-port laparoscopy-assisted vaginal repair of a cesarean scar defect: a single-center retrospective study.

BACKGROUND: The incidence of uterine cesarean scar defect (niche) is high, and some patients require surgery. Single-port laparoscopy can reduce post-operative pain, and provide better cosmetic effects. This study was performed to evaluate the safety and superiority of single-port laparoscopy-assisted vaginal repair of uterine cesarean scar defect (niche) in women after cesarean section. METHODS: This study included 74 patients who were diagnosed with uterine cesarean niche at the Shanghai First Maternity and Infant Hospital from January 2013 to June 2015. Thirty-seven patients underwent single-port laparoscopy-assisted vaginal surgery as the case group, and the remaining patients underwent vaginal repair surgery as the control group. We collected data from the inpatient and follow-up medical records. The clinical characteristics of these two groups were compared. The odds ratios and 95% confidential intervals were calculated for each variable by univariate and multivariate analyses. RESULTS: Patients who underwent single-port laparoscopy-assisted vaginal repair had a significantly longer operation time (2.3 [2.0-2.7] vs. 2.0 [1.6-2.3] h, P = 0.015), shorter gas passage time (1.2 [1.0-1.5] vs. 1.7 [1.0-2.0] days, P = 0.012), shorter hospital stay (3.1 [3.0-4.0] vs. 4.5 [4.0-6.0] days, P = 0.019), and fewer complications (0 vs. 4 cases). Univariate analysis showed that depth of the niche (P = 0.021) the mild adhesiolysis score (P = 0.035) and moderate adhesiolysis score (P = 0.013) were associated with the bladder injury. Multivariate analysis showed that the moderate adhesiolysis score (P = 0.029; 95% confidence interval, 1.318-3.526) was the strongest independent predictor of bladder injury. CONCLUSION: This study confirmed the safety and superiority of single-port laparoscopy-assisted vaginal repair of uterine cesarean scars.

Loss of exosomal miR-148b from cancer-associated fibroblasts promotes endometrial cancer cell invasion and cancer metastasis.

Cancer-associated fibroblasts (CAFs) play crucial roles in tumor progression, given the dependence of cancer cells on stromal support. Therefore, understanding how CAFs communicate with endometrial cancer cell in tumor environment is important for endometrial cancer therapy. Exosomes, which contain proteins and noncoding RNA, are identified as an important mediator of cell-cell communication. However, the function of exosomes in endometrial cancer metastasis remains poorly understood. In the current study we found that CAF-derived exosomes significantly promoted endometrial cancer cell invasion comparing to those from normal fibroblasts (NFs). We identified a significant decrease of miR-148b in CAFs and CAFs-derived exosomes. By exogenously transfect microRNAs, we demonstrated that miR-148b could be transferred from CAFs to endometrial cancer cell through exosomes. In vitro and in vivo studies further revealed that miR-148b functioned as a tumor suppressor by directly binding to its downstream target gene, DNMT1 to suppress endometrial cancer metastasis. In endometrial cancer DNMT1 presented a potential role in enhancing cancer cell metastasis by inducing epithelial-mesenchymal transition (EMT). Therefore, downregulated miR-148b induced EMT of endometrial cancer cell as a result of relieving the suppression of DNMT1. Taken together, these results suggest that CAFs-mediated endometrial cancer progression is partially related to the loss of miR-148b in the exosomes of CAFs and promoting the transfer of stromal cell-derived miR-148b might be a potential treatment to prevent endometrial cancer progression.

Cross-talk between p21-activated kinase 4 and ERα signaling triggers endometrial cancer cell proliferation.

Cross-talk between estrogen receptor alpha (ERα) and signal transduction pathways plays an important role in the progression of endometrial cancer (EC). Here, we show that 17ß-estradiol (E2) stimulation increases p21-activated kinase 4 (Pak4) expression and activation in ER-positive EC cells. The estrogen-induced Pak4 activation is mediated via the PI3K/AKT pathway. Estrogen increases Pak4 and phosphorylated-Pak4 (p-Pak4) nuclear accumulation, and Pak4 in turn enhances ERα trans-activation. Depletion or functional inhibition of Pak4 abrogates EC cell proliferation induced by E2, whereas overexpression of Pak4 rescues cell proliferation decreased by inhibiting the estrogen pathway. Pak4 knockdown decreases cyclin D1 expression and induces G1-S arrest. Importantly, Pak4 suppression inhibits E2 induced EC tumor growth in vivo, in a mouse xenograft model. These data demonstrate that estrogen stimulation increases Pak4 expression and activation, which in turn enhances ERα transcriptional activity and ERα-dependent gene expression, resulting in increased proliferation of EC cells. Thus inhibition of Pak4-ERα signaling may represent a novel therapeutic strategy against endometrial carcinoma.

CpG island hypermethylation-associated silencing of microRNAs promotes human endometrial cancer.

BACKGROUND: Endometrial cancer (EC) is the most common gynecologic malignancy, but the molecular events involved in the development and progression of EC remain unclear. This study aimed to explore epigenetic modification of genes and miRNAs involved in EC development. METHODS: Ishikawa and AN3CA cells were treated with 5'-Aza-2-deoxycytidine or histone deacetylase inhibitor. The expression of miRNAs and related genes were detected by PCR and Western blot. Promoter methylation was detected by bisulfite specific PCR sequencing. The proliferation, colony formation, cell cycle progression, migration and invasion of EC cells were evaluated by MTT, soft agar assay, flow cytometry, wound healing and invasion assay, respectively. RESULTS: Aberrant expression of miRNAs including miR-200b, miR-130a/b, miR-625 and miR-222 was associated with tumorigenesis and metastasis in endometrial cancer. Silencing of miR-130b induced E-cadherin expression, while ectopic expression of miR-130b and knockdown of DICER1 increased the expression of Vimentin, zeb2, N-cadherin, Twist and Snail in EC cells. Furthermore, 5'-Aza-2-deoxycytidine and Histone deacetylase (HDAC) inhibitor inhibited the proliferation, colony formation, migration and invasion of EC cells, accompanied by reduced MMP secretion. CONCLUSIONS: Our study provides the first description of epigenetic modification of epithelial mesenchymal transition associated genes and miRNAs in EC cells, which are extensively involved in the regulation of gene expression and subsequent accumulation of malignant features of EC cells.

Overexpression of p21-activated kinase 1 promotes endometrial cancer progression.

Endometrial cancer (EC) is the most common gynecologic malignancy, but the molecular events involved in the development and progression of EC remain unclear. P21-activated kinase 1 (Pak1) plays important roles in cell motility and survival. This study investigated the clinical significance of Pak1 expression and its functional roles in EC. The expression of Pak1 in clinical samples and EC cell lines was evaluated. The effects of Pak1 on EC cell functions were determined by either overexpressing it via plasmid transfection or depleting its expression using short hairpin RNA (shRNA) in human EC cell lines. Pak1 was overexpressed in clinical samples of EC compared with normal endometrium. High Pak1 expression in EC was positively correlated with lymph node metastasis, advanced disease stage and poor histological differentiation. Pak1 over-expression was also observed in multiple human EC cell lines. In EC cell lines, Pak1 overexpression promoted cell proliferation, migration, invasion and anchorage-independent growth in vitro. Conversely, shRNA-mediated stable knockdown of Pak1 reduced cell proliferation, migration, invasion and anchorage-independent growth. In addition, ectopic Pak1 overexpression protected EC cells from apoptosis, along with decreased caspase-3 activation. These results suggest that Pak1 plays important roles at multiple stages of EC progression.