Effectiveness and safety of prophylactic abdominal aortic balloon occlusion for patients with type III caesarean scar pregnancy: a prospective cohort study.

BACKGROUND: Caesarean scar pregnancy (CSP) is a special type of ectopic pregnancy with a high risk of massive haemorrhage. Few studies have focused on the efficacy of prophylactic abdominal aortic balloon occlusion as a minimally invasive method in caesarean section. This study aimed to evaluate the effectiveness and safety of prophylactic abdominal aortic balloon occlusion for patients with type III CSP. METHODS: This was a prospective cohort study. Patients with type III CSP in the First Affiliated Hospital of Zhengzhou University from January 2020 to June 2022 were enrolled. Eligible patients received prophylactic abdominal aortic balloon occlusion (defined as the AABO group) or uterine artery embolization (defined as the UAE group) before laparoscopic surgery. Clinical outcomes included intraoperative blood loss, body surface radiation dose, hospitalization expenses, and time to serum ß-hCG normalization, and safety were also assessed. RESULTS: A total of 68 patients met the criteria for the study, of whom 34 patients were in the AABO group and 34 patients were in the UAE group. The median intraoperative blood loss in the AABO and UAE groups was 17.5 (interquartile ranges [IQR]: 10, 45) and 10 (IQR: 6.25, 20) mL, respectively (P = 0.264). The body surface radiation dose of the AABO group was much lower than that of the UAE group (5.22 ± 0.44 vs. 1441.85 ± 11.59 mGy, P < 0.001). The AABO group also had lower hospitalization expenses than the UAE group (2.42 ± 0.51 vs. 3.42 ± 0.85 *10^5 yuan, P < 0.001). The average time to serum ß-hCG normalization in the AABO group was 28.9 ± 3.21 d, which was similar to that in the UAE group (30.3 ± 3.72 d, P = 0.099). In addition, the incidence of adverse events in the AABO group was lower than that in the UAE group (5.9% vs. 58.8%, P < 0.001). CONCLUSION: Prophylactic AABO was equally as effective as UAE in patients with type III CSP but was safer than UAE during and after the operation.

Construction of Metastasis-Specific Regulation Network in Ovarian Cancer Based on Prognostic Stemness-Related Signatures.

WE aimed to reveal the correlation between ovarian cancer (OV) metastasis and cancer stemness in OV. RNA-seq data and clinical information of 591 OV samples (551 without metastasis and 40 with metastasis) were obtained from TCGA. The edgeR method was used to determine differentially expressed genes (DEGs) and transcription factors (DETFs). Then, mRNA expression-based stemness index was calculated using one-class logistic regression (OCLR). Weighted gene co-expression network analysis (WGCNA) was used to define stemness-related genes (SRGs). Univariate and multivariate Cox proportional hazard regression were conducted to identify the prognostic SRGs (PSRGs). PSRGs, DETFs, and 50 hallmark pathways quantified by gene set variation analysis (GSVA) were integrated into Pearson co-expression analysis. Significant co-expression interactions were utilized to construct an OV metastasis-specific regulation network. Cell communication analysis was carried out based on single cell RNA sequencing data to explore the molecular regulation mechanism of OV. Eventually, assay for targeting accessible-chromatin with high throughout sequencing (ATAC), chromatin immunoprecipitation sequencing (ChIP-seq) validation, and multiple data sets were used to validate the expression levels and prognostic values of key stemness-related signatures. Moreover, connectivity map (CMap) was used to identify potential inhibitors of stemness-related signatures. Based on edgeR, WGCNA, and Cox proportional hazard regression, 22 PSRGs were defined to construct a prognostic prediction model for metastatic OV. In the metastasis-specific regulation network, key TF-PSRS interaction pair was NR4A1-EGR3 (correlation coefficient = 0.81, p < 0.05, positive), and key PSRG-hallmark pathway interaction pair was EGR3-TNFα signaling via NFκB (correlation coefficient = 0.44, p < 0.05, positive), which were validated in multi-omics databases. Thioridazine was postulated to be the most significant compound in treatment of OV metastasis. PSRGs played critical roles in OV metastasis. Specifically, EGR3 was the most significant PSRG, which was positively regulated by DETF NR4A1, inducing metastasis via TNFα signaling.

Expression of MCMs in Endometrial Cancer and its Biological Correlation Analysis.

PURPOSE: Minichromosome maintenance (MCM) has been demonstrated to be involved in tumorigenesis and pathogenesis of many cancer types. However, the role of MCMs in endometrial cancer (EC) has not been elucidated. MATERIALS AND METHODS: We first employed GEPIA, cBioPortal, and R software to perform the differential expression analysis, survival analysis, and gene alteration analysis of the MCMs family. Then, GSE17025 and GSE63678 datasets and CTPAC were used to verify the mRNA and protein expression levels of MCM4. In addition, the internal mechanism of the MCM4 was investigated by comparing MCM4 expression-correlated differentially expressed genes (DEGs) from GEPIA and MCM4-interacted genes from STRING. Last, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to identify MCM4-related biological processes. RESULTS: Compared with normal tissues, only MCM2 and MCM4 expression were significantly upregulated in EC tissues. High expression of MCM4 was related to worse clinicopathological features and poor prognosis in EC cohorts. Additionally, a certain degree of gene alterations in the MCM2-7 gene was observed. By comparing MCM4 expression-correlated DEGs and MCM4- interacted genes, six genes were obtained: SSRP1, ORC1, GINS1, CDK2, DBF4 and GINS3. Functional enrichment analysis suggested that MCM4 may be involved in regulating the biological processes of DNA replication and the p53 signaling pathway. CONCLUSION: This was the first comprehensive study to disclose the biological effects of MCMs in EC, indicating that MCM4 could be used as a new prognostic biomarker and potential therapeutic target for EC.

Retraction Notice to: Silencing of Long Non-coding RNA RP1-93H18.6 Acts as a Tumor Suppressor in Cervical Cancer through the Blockade of the PI3K/Akt Axis.

[This retracts the article DOI: 10.1016/j.omtn.2019.10.041.].

Long noncoding RNA BMPR1B-AS1 facilitates endometrial cancer cell proliferation and metastasis by sponging miR-7-2-3p to modulate the DCLK1/Akt/NF-κB pathway.

Endometrial carcinoma (EC) originates from the endometrium and is one of the most common tumors in female patients, and its incidence has continued to increase in recent decades. LncRNAs are involved in the pathogenesis and metastasis of a variety of malignant tumors, which indicates that lncRNAs can be used as tumor diagnostic markers and potential therapeutic targets. In this study, we analyzed the RNA transcripts of EC cells from The Cancer Genome Atlas (TCGA) and first reported a novel lncRNA, BMPR1B-AS1, that was more highly expressed in endometrial cancer tissues than in adjacent tissues, and BMPR1B-AS1 could promote endometrial cancer cell proliferation and metastasis. Bioinformatics prediction and experimental results both suggested that BMPR1B-AS1 could modulate the malignant behaviors of endometrial cancer cell lines by sponging miR-7-2-3p to modulate DCLK1, and a DCLK1 inhibitor blocked the activation of the PI3K/Akt/NF-κB signaling pathway. Collectively, this study suggests that the BMPR1B-AS1/miR-7-2-3p/DCLK1 axis contributes to the proliferation and metastasis of endometrial cancer cells via the PI3K/Akt/NF-κB pathway.

CircLNPEP promotes the progression of ovarian cancer through regulating miR-876-3p/ WNT5A axis.

CircRNA LNPEP has been shown to promote the development of hepatocellular carcinoma, but its function in ovarian cancer (OC) remains unclear. The Kaplan-Meier method was used to analyze the clinical significance of circLNPEP expression in OC patients. The stability of circLNPEP was detected by actinomycin D and RNase R treatment. The correlations between miR-876-3p and two genes (circLNPEP and WNT5A) were predicted by bioinformatics analysis and confirmed by dual-luciferase reporter assay. Expressions of circLNPEP, miR-876-3p, and WNT5A were determined by qRT-PCR and western blot. The effect of circLNPEP/miR-876-3p/WNT5A axis on viability, proliferation, migration, and invasion, and angiogenesis of cells was determined by cell function experiment and rescue experiment. Xenograft tumor mice were constructed for in vivo verification. Expressions of apoptosis, epithelial mesenchymal transition (EMT)-related genes, and CD34 were determined by qRT-PCR, western blot and immunohistochemistry. High level of circLNPEP was related to poor prognosis in OC. CircLNPEP was highly expressed in OC tissues and cell lines, mainly distributed in the cytoplasm, while miR-876-3p was the opposite. MiR-876-3p targeted and negatively correlated with circLNPEP and WNT5A. Sh-circLNPEP repressed cell viability, proliferation, migration, invasion, angiogenesis, and EMT but promoted apoptosis, which were related to its regulation of expression of EMT- and apoptosis-related genes, WNT5A, and CD34. The regulatory effect of sh-circLNPEP can be reversed by miR-876-3p inhibitor, and that of miR-876-3p inhibitor can be reversed by sh-WNT5A. CircLNPEP promoted cancer cell proliferation, EMT and angiogenesis, and inhibited apoptosis by regulating miR-876-3p/WNT5A axis.

Silencing of Long Non-coding RNA RP1-93H18.6 Acts as a Tumor Suppressor in Cervical Cancer through the Blockade of the PI3K/Akt Axis.

Cervical cancer (CC) remains a distinct public health stumbling block worldwide. Increasing evidence has highlighted long non-coding RNAs (lncRNAs) as tumor-associated biological molecules. In this study, by means of altering the expression of lncRNA RP1-93H18.6 in CC cells, its ability to influence the biological activities of CC cells was evaluated. Differentially expressed lncRNAs were initially screened from the GEO database. A series of RP1-93H18.6 vectors, small interfering RNA (siRNA) against RP1-93H18.6, and LY294002 (an inhibitor for the phosphatidylinositol 3-kinase [PI3K]/Akt [serine/threonine kinase] axis) were introduced in a respective manner to treat the HeLa cells in order to analyze their effects on cellular activities in vitro. Nude mice with xenograft tumors were utilized in order to assess CC tumor growth and metastasis in vivo. lncRNA RP1-93H18.6 was highly expressed in CC, which could activate the P13K/Akt axis. RP1-93H18.6 vectors exposure increased cell viability, adhesion, migration, and invasion, which resulted in more cells arrested at the S stage and reduced apoptosis, while acting to promote tumor growth and metastasis. The siRNA against RP1-93H18.6 or LY294002 exposure was observed to attenuate the effects induced by RP1-93H18.6 vectors. This study suggests that suppression of lncRNA RP1-93H18.6 exerts potent inhibitory effects on the development and progression of CC via blockade of the PI3K/Akt axis.

LncRNA LINC01305 silencing inhibits cell epithelial-mesenchymal transition in cervical cancer by inhibiting TNXB-mediated PI3K/Akt signalling pathway.

Cervical cancer (CC) remains one of the leading malignancies afflicting females worldwide, with its aetiology associated with long-term papillomavirus infection. Recent studies have shifted their focus and research attention to the relationship between long non-coding RNAs (lncRNAs) and CC therapeutic. Thus, the aim of the current study was to investigate the underlying mechanism of lncRNA LINC01305 on the cell invasion, migration and epithelial-mesenchymal transition (EMT) of CC cells via modulation of the PI3K/Akt signalling pathway by targeting tenascin-X B (TNXB). The expressions of LINC01305, TNXB, MMP2, MMP9, E-cadherin, vimentin, PI3K, Akt, p-PI3K, p-Akt and TNXB were detected in this study. After which, the cell invasion and migration abilities of the CC cells were determined respectively. Bioinformatics and the application of a dual luciferase reporter gene assay provided verification indicating that TNXB is the target gene of lncRNA LINC01305. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis methods revealed that the expressions of MMP2, MMP9, vimentin, PI3K, Akt, p-PI3K and p-Akt were decreased following the down-regulation of LncRNA LINC01305 or overexpression of TNXB. LncRNA LINC01305 silencing or TNXB overexpression was noted to decrease the migration and invasion of SiHa cells. Taken together, the key findings of the current study present evidence suggesting that lncRNA LINC01305 silencing suppresses EMT, invasion and migration via repressing the PI3K/Akt signalling pathway by means of targeting TNXB in CC cells, which ultimately provides novel insight and identification of potential therapeutic targets for CC.

IR-A/IGF-1R-mediated signals promote epithelial-mesenchymal transition of endometrial carcinoma cells by activating PI3K/AKT and ERK pathways.

BACKGROUND: Obesity is a risk factor for endometrial cancer (EC). However, it is not known how insulin receptor isoform A (IR-A) and insulin-like growth factor 1 receptor (IGF-1R), cognate receptors for insulin and IGFs, respectively, regulate malignant behaviors of EC. In this study, we examined the biological effects of IR-A/IGF-1R, explored the downstream signaling cascades, and assessed the therapeutic potential of targeting IR-A/IGF-1R in vivo. METHODS: The expression levels of IR-A and IGF-1R were examined by qRT-PCR and Western blotting. Upon down-regulating IR-A and/or IGF-1R by sh-IR-A and/or sh-IGF-1R, respectively, cell migration, invasion, apoptosis, and epithelial-mesenchymal transition (EMT) were examined by wound healing, transwell invasion, flow cytometry, and Western blotting, respectively. Furthermore, the effect of sh-IR-A and/or sh-IGF-1R on phosphatidylinositide 3-kinases (PI3K)/AKT and ERK pathways was measured by Western blotting. Lastly, we monitored xenograft growth and EMT in vivo. RESULTS: Both IR-A and IGF-1R were significantly up-regulated in EC cells. Knockdown of IR-A or IGF-1R alone was sufficient to reduce migration and invasion, enhance apoptosis, and inhibit EMT of EC cells, and the most significant alterations were observed in cells co-transfected with sh-IR-A+ sh-IGF-1R. These phenotypes were associated with inactivating PI3K/AKT and ERK signaling by sh-IR-A and/or sh-IGF-1R. Consistent with in vitro findings, sh-IR-A or sh-IGF-1R significantly inhibited xenograft growth and EMT in vivo. CONCLUSION: IR-A and IGF-1R-mediated signals, by activating PI3K/AKT and ERK pathways, can induce multiple malignant phenotypes of EC cells. Therefore, targeting IR-A or IGF-1R may provide therapeutic benefits for EC.

MicroRNA-365 targets multiple oncogenes to inhibit proliferation, invasion, and self-renewal of aggressive endometrial cancer cells.

BACKGROUND: MicroRNA-365 (miR-365) has been reported to be a tumor suppressor miRNA. However, the role of miR-365 in progression of endometrial cancer (EC) has not been explored, in this study, we have found that re-expression of miRNA-365 inhibits cell proliferation, causes apoptosis and senescence. MATERIALS AND METHODS: Overexpression of miR-365 attenuated cell migration and invasion, inhibited sphere-forming capacity, and enhanced the chemosensitivity to paclitaxel. In silico prediction tools identified the potential targets of miR-365. RESULTS: We identified EZH2 and FOS as targets of miR-365 and found that downregulating these genes imitated the tumor suppressive effect of miR-365. The outcomes of the study suggested that a reverse correlation existed between low miR-365 and overexpression of FOS and EZH2 in EC tissue specimens. CONCLUSION: The study concludes that miR-365 acts as an important tumor suppressor and contributes by suppressing cell invasiveness, proliferation, and self-renewal in cancer cell lines by regulating multiple oncogenes. We establish that miR-365-EZH2/FOS pathway is an important target for treating EC.

Effect of metformin use on the risk and prognosis of endometrial cancer: a systematic review and meta-analysis.

BACKGROUND: Previous studies have suggested that metformin may be useful for preventing and treating endometrial cancer (EC), while the results have been inconsistent. This systematic review and meta-analysis aimed to investigate the association between metformin use and risk and prognosis of patients with EC. METHODS: PubMed, Embase, and the Cochrane Library databases were searched for observational studies evaluating the effect of metformin on EC prevention or treatment. The odds ratio (OR) was used for analyzing risks, and the hazard ratio (HR) was used for analyzing survival outcomes. A random-effects model was used for data analysis. RESULTS: Seven studies reported data on EC risk. The pooled results suggested that metformin was not significantly associated with a lower risk of EC [OR = 1.05, 95% confidence interval (CI) 0.82-1.35, P = 0.70]. For patients with diabetes, metformin showed no advantage in reducing the EC risk compared with other interventions (OR = 0.99, 95% CI 0.78-1.26, P = 0.95). Further, seven studies were included for survival analysis. The pooled data showed that metformin could significantly improve the overall survival of patients with EC (HR = 0.61, 95% CI 0.48-0.77, P < 0.05) and reduce the risk of EC recurrence (OR = 0.50, 95% CI 0.28-0.92, P < 0.05) Finally, we noted metformin was associated with significantly improving the overall survival of EC patients among diabetes (HR = 0.47; 95%CI 0.33-0.67, P < 0.05). CONCLUSIONS: This meta-analysis did not prove that metformin was beneficial for preventing EC. However, metformin could prolong the overall survival of patients with EC and reduce their risk of cancer relapse.

HOTAIR: a key regulator in gynecologic cancers.

Long non-coding RNAs (lncRNAs) play critical roles in the initiation and progression of human cancers. HOX transcript antisense RNA (HOTAIR) is an lncRNA localized to the mammalian HOXC gene cluster; it can interact with polycomb repressive complex 2 and the lysine-specific histone demethylase/CoREST/REST complex, and it manipulates the expression of various genes. HOTAIR promotes tumor invasion and metastasis by silencing tumor suppressors, and activating oncogenes and signaling pathways. HOTAIR is deregulated in many human cancers; despite its critical roles in health and disease, the underlying mechanisms governing HOTAIR function are unknown. In this review, we summarize the recent findings on the roles of HOTAIR in gynecologic cancers.

Comparison of Two Techniques of Laparoscopy-Assisted Peritoneal Vaginoplasty.

Neovagina creation is essential for patients with the Mayer-Rokitansky-Kuster-Hauser syndrome. We compared a technique involved the pushing down of the peritoneum with the technique of separating the peritoneum for laparoscopy-assisted peritoneal vaginoplasty. We collected patients with congenital absence of vagina who underwent laparoscopy-assisted peritoneal vaginoplasty of the First Affiliated Hospital of Zhengzhou University between January 2011 and May 2013. The 2 surgical groups (pushing group and separating group) were compared for various parameters. The values of the following parameters were significantly lower for the pushing group compared with the separating group: mean operating time (78 ± 13 minutes vs 135 ± 28 minutes), mean duration of hospitalization (12.9 ± 2.7 days vs 18.0 ± 3.8 days), mean cost of hospitalization (14 016 ± 1640 RMB vs 18 783 ± 2143 RMB), requirement for a drainage tube (4% vs 27%; χ(2) = 8.864), requirement for analgesic drugs (20% vs 40%; χ(2) = 3.977), and postoperative rehospitalization (3.3% vs 10.0% at 2 months and 6.7% vs 26.7% at 6 months; χ(2) = 4.268 and 5.196). Mean values for blood loss (57 ± 19 mL vs 66 ± 20 mL), time to pass gas (21 ± 4 hours vs 23 ± 7 hours), and length of the reconstructed vagina (9.0 ± 0.4 cm vs 8.9 ± 0.5 cm) were not significantly different between the 2 groups. In addition, mean postoperative Female Sexual Function Index score did not differ significantly between the 2 groups or among the 2 groups and a control group (27.0 ± 4.8 vs 26.7 ± 5.2 vs 27.9 ± 4.5; p > .05). The technique involving pushing down of the peritoneum offers advantages of reduced cost, complications, hospitalization, operative time, and pain over the traditional technique. Sexuality approaches so-called "normal" sexuality.