Background: The efficacy of poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) as a maintenance therapy in patients with newly diagnosed advanced ovarian cancer remains unclear. We conducted a meta-analysis to assess the benefits and safety of PARPi maintenance therapy in patients with newly diagnosed advanced ovarian cancer. Methods: We searched the PubMed, EMBASE, and Cochrane databases for randomized controlled trials (RCTs), which assessed the efficacy of PARPi as a maintenance therapy for newly diagnosed advanced ovarian cancer. Progression-free survival (PFS) was the primary endpoint, which was assessed using hazard ratios (HRs) with 95% confidence intervals (95% CI). Progression-free survival was extracted independently, and the pooled results were used to compare the prognoses of patients who received PARPi maintenance therapy and those who received a placebo. Results: Three RCTs, SOLO1, VELIA/GOG-3005, and PRIMA, which included 1,881 patients with newly diagnosed advanced ovarian cancer, were included in the meta-analysis. The overall analysis showed that PARPi maintenance therapy significantly increased PFS (HR, 0.51; 95% CI, 0.33-0.80; P = 0.004) compared to placebo. Subgroup analyses confirmed this result. We also observed an improved PFS in patients with homologous recombination deficiency (HR, 0.50; 95% CI, 0.38-0.66; P < 0.001) and in patients with BRCA mutations (HR, 0.42; 95% CI, 0.31-0.57; P < 0.001). Moreover, there were no significant differences in health-related quality of life between the PARPi and placebo groups. Conclusions: Patients with newly diagnosed advanced ovarian cancer who received PARPi maintenance therapy had a better prognosis than did those who received a placebo. Moreover, no significant changes in health-related quality of life were seen in PARPi-treated individuals.
Endometrial carcinoma is a common gynecological malignancy. Stage IV endometrial carcinoma is associated with a high risk of early death; however, there is currently no effective prognostic tool to predict early death in stage IV endometrial cancer.Surveillance, Epidemiology, and End Results (SEER) data from patients with stage IV endometrial cancer registered between 2004 and 2015 were used in this study. Important independent prognostic factors were identified by univariate and multivariate logistic regression analyses. A nomogram of all-cause and cancer-specific early deaths was constructed using relevant risk factors such as tumor size, histological grade, histological classification, and treatment (surgery, radiotherapy, chemotherapy).A total of 2,040 patients with stage IV endometrial carcinoma were included in this study. Of these, 299 patients experienced early death (≤3 months) and 282 died from cancer-specific causes. The nomogram of all-cause and cancer-specific early deaths showed good predictive power and clinical practicality with respect to the area under the receiver operating characteristic curve and decision curve analysis. The internal validation of the nomogram revealed a good agreement between predicted early death and actual early death.We developed a clinically useful nomogram to predict early mortality from stage IV endometrial carcinoma using data from a large cohort. This tool can help clinicians screen high-risk patients and implement individualized treatment regimens.
A previous study found that a lack of SPOCK2 expression was an early event that occurs during the malignant transformation of endometriosis (EMS); however, the role played by SPOCK2 in the pathogenesis of endometriosis and its malignant transformation remains unclear.In this study, SPOCK2 expression in human endometrial epithelial cells (hEECs) was downregulated by transfection with shRNA, and the biological behavior of the transfected cells was observed.We found that downregulation of SPOCK2 promoted cell proliferation, adhesion, and invasion.Our data suggest that downregulation of SPOCK2 might participate in the pathogenesis and progression of EMS, as well as its malignant transformation, by promoting the proliferation, adhesion, and invasion of endometrial epithelial cells.
Background We aim to evaluate the global, regional, and national burden of Uterine Cancer (UC) from 1990 to 2019. Methods We gathered UC data across 204 countries and regions for the period 1990-2019, utilizing the Global Burden of Disease Database (GBD) 2019 public dataset. Joinpoint regression analysis was employed to pinpoint the year of the most significant changes in global trends. To project the UC trajectory from 2020 to 2044, we applied the Nordpred analysis, extrapolating based on the average trend observed in the data. Furthermore, the Bayesian Age-Period-Cohort (BAPC) model with integrated nested Laplace approximations was implemented to confirm the stability of the Nordpred analysis predictions. Results Globally, the age-standardized rate (ASR) of incidence for UC has increased from 1990 to 2019 with an Average Annual Percentage Change (AAPC) of 0.50%. The ASR for death has declined within the same period (AAPC: -0.8%). An increase in the ASR of incidence was observed across all Socio-demographic Index (SDI) regions, particularly in High SDI regions (AAPC: 1.12%), while the ASR for death decreased in all but the Low SDI regions. Over the past 30 years, the highest incidence rate was observed in individuals aged 55-59 (AAPC: 0.76%). Among 204 countries and regions, there was an increase in the ASR of incidence in 165 countries and an increase in the ASR of deaths in 77 countries. Our projections suggest that both the incidence and death rates for UC are likely to continue their decline from 2020 to 2044. Conclusions UC has significantly impacted global health negatively, with its influence stemming from a range of factors including geographical location, age-related and racial disparities, and SDI.
Summary Biological clock genes expressed in reproductive tissues play important roles in maintaining the normal functions of reproductive system. However, disruption of female circadian rhythm on oocyte fertilization, preimplantation embryo development and blastocyst implantation potential is still unclear. In this study, ovulation, in vivo and in vitro oocyte fertilization, embryo development, implantation and intracellular reactive oxygen species (ROS) levels in ovary and oviduct were studied in female Bmal1 +/+ and Bmal1 −/− mice. The number of naturally ovulated oocyte in Bmal1 −/− mice decreased (5.2 ± 0.8 vs 7.8 ± 0.8, P < 0.001), with an increasing abnormal oocyte ratio (20.4 ± 3.5 vs 11.7 ± 2.0%, P = 0.001) after superovulation. Significantly lower fertilization rate and obtained blastocyst number were observed in Bmal1 −/− female mice either mated with wild-type in vivo or fertilized by sperm from wild-type male mice in vitro (all P < 0.05). Interestingly, in vitro fertilization rate of oocytes derived from Bmal1 −/− increased significantly compared with in vivo study ( P < 0.01). After transferring blastocysts derived from Bmal1 +/+ and Bmal1 −/− female mice to pseudopregnant mice, the implantation sites of the latter decreased 5 days later (8.0 ± 0.8 vs 5.3 ± 1.0, P = 0.005). The intracellular ROS levels in the ovary on proestrus day and in the oviduct on metestrus day increased significantly in Bmal1 −/− mice compared with that of Bmal1 +/+ mice. Deletion of the core biological clock gene Bmal1 significantly decreases oocyte fertilization rate, early embryo development and implantation potential in female mice, and these may be possibly caused by excess ROS levels generated in ovary and oviduct.
Intergroup competition has been proven to increase ingroup cooperation, but it will divide individuals into high-status groups and low-status groups, which may lead to group-level conflict and affect cooperation behavior. In this paper, we conduct a laboratory experiment to find how group status caused by intergroup competition changes individuals’ cooperation behavior in two representative social dilemma frameworks, the public goods game and the prisoner's dilemma game. Experimental results show that both high-status group members and low-status group members will improve ingroup cooperation, and there exists the framing effect of cooperation which affects different status group members’ decisions under different situations.
Background: The comparison of survival outcomes between minimally invasive surgery and open surgery for cervical cancer patients remains controversial. We evaluated the survival outcomes of cervical cancer patients who underwent different surgical approaches. Methods: A literature search was performed in PubMed, Embase, and Cochrane databases up to February 2020, using the MESH terms "minimally invasive surgical procedures" and "Uterine Cervical Neoplasms." Included were all original comparative studies and trials both published and unpublished in English that were related to minimally invasive surgery and open surgery for cervical cancer patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage < IIB. Begg's and Egger's regressions were used to evaluate publication bias. Results: This meta-analysis included 28 studies enrolling 18,961 patients with cervical cancer. The overall analyses indicated that cervical cancer patients with FIGO 2009 stage < IIB who underwent minimally invasive surgery had a lower rate of OS (HR = 1.43, 95% CI = 1.06-1.92, P = 0.019) and DFS (HR = 1.50, 95% CI = 1.21-1.85, P < 0.001) than those who underwent open surgery. Moreover, minimally invasive surgery could lower OS (HR = 2.30, 95% CI = 1.50-3.52, P < 0.001) and DFS (HR = 1.94, 95% CI = 1.36-2.76, P < 0.001) of cervical cancer patients with FIGO 2009 stage ≤ IB1 compared to open surgery. However, there were no significant differences in OS (HR = 1.07, 95% CI = 0.65-1.76, P = 0.801) and DFS (HR = 1.20, 95% CI = 0.65-2.19, P = 0.559) in patients with tumors < 2 cm between the two groups. Conclusions: Minimally invasive radical hysterectomy was associated with poor survival outcomes compared to open surgery. Patients with FIGO 2009 stage ≤ IB1 cervical cancer who underwent minimally invasive surgery have lower OS and DFS rates than those who underwent open surgery. Therefore, open surgery should be performed for cervical cancer patients. However, patients with tumors < 2 cm might take the most advantage of minimally invasive surgery without increasing poor prognosis. There are some limitations in the meta-analysis, which needs further high-quality multicenter studies to confirm and update our findings.
A previous study found that a lack of SPOCK2 expression was an early event that occurs during the malignant transformation of endometriosis (EMS); however, the role played by SPOCK2 in the pathogenesis of endometriosis and its malignant transformation remains unclear. In this study, SPOCK2 expression in human endometrial epithelial cells (hEECs) was downregulated by transfection with shRNA, and the biological behavior of the transfected cells was observed. We found that downregulation of SPOCK2 promoted cell proliferation, adhesion, and invasion. Our data suggest that downregulation of SPOCK2 might participate in the pathogenesis and progression of EMS, as well as its malignant transformation, by promoting the proliferation, adhesion, and invasion of endometrial epithelial cells.
Abstract Uterine corpus endometrial carcinoma (UCEC) is frequently diagnosed among women worldwide. However, there are different prognostic outcomes because of heterogeneity. Thus, the aim of the current study was to identify a gene signature that can predict the prognosis of patients with UCEC. UCEC gene expression profiles were first downloaded from the The Cancer Genome Atlas (TCGA) database. After data processing and forward screening, 11 390 key genes were selected. The UCEC samples were randomly divided into training and testing sets. In total, 996 genes with prognostic value were then examined by univariate Cox survival analysis with a P ‐value <0.01 in the training set. Next, using robust likelihood‐based survival modeling, we developed a six‐gene signature ( CTSW , PCSK4 , LRRC8D , TNFRSF18 , IHH, and CDKN2A ) with a prognostic function in UCEC. A prognostic risk score system was developed by multivariate Cox proportional hazard regression based on this six‐gene signature. According to the Kaplan‐Meier curve, patients in the high‐risk group had significantly poorer overall survival (OS) outcomes than those in the low‐risk group (log‐rank test P ‐value <0.0001). This signature was further validated in the testing dataset and the entire TCGA dataset. In conclusion, we conducted an integrated study to develop a six‐gene signature for the prognostic prediction of patients with UCEC. Our findings may provide novel biomarkers for prognosis and have significant implications in the understanding of therapeutic targets for UCEC.
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