BackgroundEpithelial ovarian cancer (EOC) is the most common ovarian malignant cancer. Circular RNA is a type of endogenous noncoding RNA and is considered as a novel regulatory molecule in the development and progression of tumors. This study investigated the expression and functions of a circular RNA, circular‐phosphoglycerate mutase 1 (circ‐PGAM1), in EOC tissues and cells.MethodsThe expression of circ‐PGAM1 and miR‐542‐3p in EOC was analyzed using quantitative RT‐PCR. Immunohistochemistry and western blot were performed to confirm the localization and expression of cell division cycle 5‐like (CDC5L) and pseudopodium enriched atypical kinase 1 (PEAK1) in EOC tissues. Cell lines (CAOV3 and OVCAR3) overexpressing or silencingcirc‐PGAM1 and miR‐542‐3p were established to explore the functions of circ‐PGAM1 and miR‐542‐3p in ovarian cancer cells. Furthermore, dual‐luciferase reporter assay was performed to study the interactions between circ‐PGAM1 and miR‐542‐3p and between miR‐542‐3p and CDC5L. CCK‐8, transwell, and flow cytometry were used to study the effect of circ‐PGAM1 and miR‐542‐3p on cell biological behaviors including proliferation, migration, invasion, and apoptosis. The interaction between CDC5L and the PEAK1 gene promoter was confirmed using chromatin immunoprecipitation (ChIP).ResultsCirc‐PGAM1 was upregulated in EOC tissues, whereas linear PGAM1 was not deregulated in EOC tissues. Silencing of circ‐PAGM1 inhibited proliferation, migration, and invasion of ovarian cancer cells and promoted cell apoptosis. MiR‐542‐3p was downregulated in EOC tissues, and miR‐542‐3p overexpression inhibited malignant progression of ovarian cancer cells. Circ‐PGAM1 directly interacted with miR‐542‐3p, with mutual negative feedback between them. CDC5L was a direct target of miR‐542‐3p and played an oncogenic role in ovarian cancer cells. Furthermore, the CDC5L protein binds directly to the PEAK1 promoter to promote its transcription. PEAK1 overexpression activated ERK1/2 and JAK2 signaling pathways and promoted malignant biological behaviors of ovarian cancer cells. Circ‐PAGM1 silencing combined with miR‐542‐3p overexpression played the greatest anticancer role in vivo.ConclusionThe circ‐PGAM1/miR‐542‐3p/CDC5L/PEAK1 pathway played an important role in the progression of ovarian cancer and might be a novel therapeutic target for ovarian cancer.
ObjectiveTo compare the survival and recurrence outcomes between open and laparoscopic radically hysterectomy (RH) for stage IA2-IIA2 cervical cancer based on Federation International of Gynecology and Obstetrics (FIGO) 2018.MethodsData of 1,373 early cervical cancer patients undergoing open or laparoscopic radically hysterectomy at ShengJing Hospital of China Medical University between January 1, 2013, and December 31, 2016, were retrospectively reviewed. Propensity score-based inverse probability of treatment weighting (PS-IPTW) was used to balance the covariates between the two groups.ResultsA total of 705 cervical cancer patients of FIGO 2009 stage IA2-IIA2 were finally enrolled in this study. After IPTW adjustment, the OS (HR = 2.095, 95% CI: 1.233-3.562, P = 0.006) and PFS (HR = 1.950, 95%CI: 1.194-3.184, P = 0.008) rates were significantly higher in the open RH (ORH) group compared with the laparoscopic RH (LRH) group. Then after re-staging according to the FIGO 2018 staging system, 561 patients still belonged to stage IA2-IIA2, 144 patients were upgraded to stage IIIC1p-IIIC2p. The ORH group had a significantly superior OS (HR = 1.977, 95%CI: 1.077-3.626, P = 0.028) and PFS (HR = 1.811, 95%CI: 1.046-3.134, P = 0.034) compared with the LRH group after PS-IPTW analysis. Furthermore, in patients with no high and intermediate risks, difference of the OS (HR = 1.386, 95%CI: 0.287-6.69, P = 0.684) and PFS (HR = 1.524, 95%CI: 0.363-6.396, P = 0.565) rates between the two groups were with no statistical meaning.ConclusionsOutcomes of this retrospective cohort study were in compliance with indications for ORH recommended by the National Comprehensive Cancer Network guidelines Version 1, 2021. However, LRH showed non-inferiority for patients with no prognostic risk factors compared with ORH.
Zoledronic acid (ZA) exerts complex influence on bone by suppressing bone resorption, mostly due to the direct osteoclasts inhibition and uncertain influence on osteoblasts. Vitamin K2 (VK2, Menaquinone-4) as an anabolic agent stimulates bone formation via anti-apoptosis in osteoblasts and mild osteoclasts inhibition. Based on these knowledge, the therapeutic effect of the combined or sequential therapy of VK2 and ZA depends on the influence on the osteoblasts, since both cases exert similar inhibitory effect on osteoclasts. In a series of in vitro studies, we confirmed the protective effect of VK2 in osteoblasts culture, especially when followed by exposure to ZA, and the proliferation and mineralization inhibition induced by ZA towards osteoblasts. For mechanism study, expression of bcl-2/bax, Runx2 and Sost in cells were examined. For in vivo studies, an osteoporosis animal model was established in rats via ovariectomy (OVX) and subjected to sequential treatment, namely VK2 followed by ZA. Bone mineral density (BMD) was measured by Dual energy X-ray absorptionmetry (DEXA), morphology and mechanical parameters by micro-computed tomography (micro-CT), mechanical strength by an electro-hydraulic fatigue-testing machine. The bone calcium, hydroxyproline content, blood lipids were evaluated using microplate technique, and the bone surface turnover was evaluated using the fluorescence in corporation method. It was found that VK2 pretreatment partially prevented the inhibition of bone formation caused by ZA, which was reflected by indices like BMD, bone calcium content and bone strength. The underling mechanisms for protection of VK2 pretreatment, mainly demonstrated via in vitro studies, included inhibiting apoptosis and depressing Sost expression in osteoblasts, which in turn improved the osteoporosis therapeutic effects of ZA. These findings suggested that pretreatment with VK2 before ZA therapy might serve a new long-term therapy protocol for osteoporosis.
Aim: There is currently no universally accepted method for typing of cesarean scar pregnancy (CSP) to guide the choice of treatment approach. We introduce a new method for typing CSP and investigate its clinical significance. Method: Clinical data of 198 patients with CSP were collected and analyzed. The patients were divided into three types according to the size of their cesarean scar diverticula (CSD), measured by magnetic resonance imaging: type I (size of CSD ≤40 mm), type II (40 mm < size of CSD ≤70 mm) and type III (size of CSD >70 mm). Results: With increase in the type level, the risk of adverse events increased significantly (χ 2 = 36.345, P = 0.000). There was a significant difference in the choice of the treatment approaches in various types of the patients (χ 2 = 27.106, P = 0.000). With increase in the type level, the invasiveness level of the treatment approach increased significantly (R = 0.405, P = 0.000). Further analysis found two other factors that influenced treatment choice. Conclusion: Our study, for the first time, demonstrates the value of size of CSD in typing of CSP and, thereby supplements the CSP typing system with a novel quantitative indicator. This typing method is of significance for evaluation of risk of CSP and guiding the choice of treatment approach. This typing method, combined with the two features of cesarean scar thickness and lesions protruding outside the uterine contour, will improve the risk assessment of CSP and the rationale of treatment plan formulation for this condition.
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