Ning Wang

Hypoxia‐mediated high expression of TRIM15 promotes malignant progression of high‐grade serous ovarian cancer through activation of AKT signaling pathway by K63 ubiquitination

AbstractThe tripartite motif (TRIM) family member TRIM15 is an E3 ubiquitin ligase that is abnormally expressed in a variety of tumors, but its role and mechanism in high‐grade serous ovarian cancer (HGSOC) are unclear. Here, we found for the first time that TRIM15 was upregulated in HGSOC and was associated with poor overall survival. Functional experiments showed that TRIM15 drove the proliferation of HGSOC cells and inhibited the apoptosis of tumor cells in vivo and in vitro. In terms of mechanism, we found that TRIM15 contributed to the malignant proliferation of HGSOC cells by promoting the activation of AKT and that there was a direct binding between them. TRIM15 induced lysine‐63 (K63) ubiquitination of AKT through its Ring domain, which in turn activated the AKT signaling pathway. In addition, TRIM15‐mediated K63 ubiquitination occurs mainly in the pleckstrin homology (PH) domain of AKT. We further identified other proteins and their functions regulated by TRIM15 in HGSOC cells by ubiquitin proteomic analysis. Furthermore, hypoxia‐inducible factor‐1α promoted TRIM15 transcriptional activation by binding to the hypoxia response elements of the TRIM15 promoter. Our study suggests that TRIM15 induces K63 ubiquitination of the AKT PH domain through its Ring domain and activates the AKT signaling pathway, thereby promoting HGSOC progression. In addition, the abnormally high expression of TRIM15 was associated with the hypoxic microenvironment of HGSOC tissues.

Development of a 4-miRNA prognostic signature for endometrial cancer

To develop an effective uterine corpus endometrial carcinoma (UCEC) risk assessment tool to monitor treatment outcomes. Limma package was used to analyze differentially expressed microRNAs (miRNAs) between UCEC tissues and normal tissues in the TCGA database. According to univariate Cox risk regression, least absolute shrinkage, and selection operator (LASSO) Cox analysis were performed to screen prognostic miRNAs and construct a risk scoring model. The prognostic performance of signature was evaluated by Kaplan–Meier and receiver operating characteristic. Multivariate Cox regression analysis was used to determine the independent prognostic factors of UCEC. Nomogram was constructed according to age, clinical stage, and risk score. A 4-miRNA signature based on miR-31-5p, miR-34a-5p, miR-26a-1-3p and miR-4772-3p was established. Risk scores of each patient were calculated by the 4-miRNA signature. After z-score, the patients were divided into high- and low-risk groups. The overall survival of high-risk patients was significantly shorter than that of low-risk patients, pointing to the high performance and independence of the 4-miRNA signature in predicting UCEC prognosis. The nomogram showed a high accuracy in predicting overall survival of UCEC patients. We developed a 4-miRNA signature that could effectively predict the prognosis of UCEC.

Cinobufagin modulates vasculogenic mimicry and tumor-associated macrophages to inhibit ovarian cancer progression

Ovarian cancer is among the most prevalent malignant tumors affecting women. While conventional therapies like surgery do provide some measure of disease control, they are accompanied by evident side effects that may readily result in drug resistance. Cinobufagin (HCS) is a water-soluble active component extracted from the dried skin of the Bufo gargarizans. Clinical studies have demonstrated its significant anti-tumor effects. Transcriptome sequencing identified Forkhead Box S1 (FOXS1)-related targets, and Western blot analysis evaluated the expression levels of vasculogenic mimicry (VM)-related proteins and pathway proteins after cinobufagin intervention. Immunofluorescence and ELISA were used to detect the effects of cinobufagin on M1 and M2 macrophage markers. Additionally, a co-culture model of Skov3 cells and macrophages was established to study the effects of cinobufagin on tumor-associated macrophage polarization. Cinobufagin significantly inhibited the growth of Skov3 ovarian cancer cells both in vitro and in vivo. Additionally, cinobufagin decreased the expression levels of VM-related proteins, thereby affecting vasculogenesis both in vitro and in vivo. Transcriptomic analysis revealed that the regulation of the FOXS1 gene contributed to this inhibitory effect. In the co-culture system, we found that cinobufagin inhibited IL-4-induced M2 macrophage polarization. Overexpression of FOXS1 in Skov3 cells enhanced the activity of the C-C motif chemokine ligand 2/receptor 2 (CCL2/CCR2) pathway, which was suppressed by cinobufagin, thus affecting the tumor microenvironment. Cinobufagin suppressed vasculogenic mimicry by regulating the FOXS1 gene and inhibited M2 macrophage polarization through the CCL2/CCR2 pathway, thereby affecting the tumor microenvironment.

Does controlled ovarian hyperstimulation in women with a history of borderline tumor influence recurrence rate?

Abstract Purpose To determine the recurrence rate in the women with controlled ovarian hyperstimulation after a history of borderline ovarian tumors (BOT). Methods This was a retrospective analysis of 275 patients with BOT undergoing surgery for fertility preservation in our hospital between 2001 and 2017. Cases were divided into an assisted reproductive technology (ART) treatment group (n = 15) and a non-ART treatment group (n = 260). We compared the recurrence rate, survival rate and pregnancy outcomes between these two groups. Results The ART group had a higher recurrence rate (33.33% vs. 10.80%, P = 0.023). Survival analysis indicated that the recurrence time in patients undergoing ART was significantly shorter (P = 0.026). A low pregnancy rate before diagnosis, and high intraoperative blood loss, were associated with postoperative ART treatment (P < 0.05). Multivariate analysis showed that ART treatment and bilateral lesions both significantly increased the risk of recurrence (P < 0.05). The pathological type of recurrent tumors was often the same as the initial tumor. Conclusion The postoperative use of ART in patients with BOT significantly increased the recurrence rate, but does not significantly affect the overall survival rate of patients. Therefore, ART in such patients should be individualized, and close follow-up is necessary after ART.

Clinical Efficacy of Yiqi Yangyin Decoction Combined with Docetaxel on Advanced Ovarian Cancer and the Effect on the Levels of Serum Markers VEGF, HE4, and CA125

Objective. The study is designed to investigate the therapeutic effect of Yiqi Yangyin Decoction combined with docetaxel on advanced ovarian cancer (OC) patients and the effects on serum markers VEGF, HE4, and CA125. Methods. 92 patients with advanced OC were grouped into the study group and control group. The control group was given the treatment of basic chemotherapy combined with docetaxel. The study group was added the treatment of Yiqi Yangyin Decoction on the basis of the control group. The short-term efficacy, adverse reactions, tumor markers, quality of life, 3-year survival, and T cell subsets of the two groups were observed. Results. Compared to the control group, the study group’s incidence of adverse reactions was lower. VEGF, HE4, and CA125 in the study group were decreased more obviously. The levels of CD3+, CD4+, and CD4+/CD8+ were sharply higher in the study group, while CD8+ was notably reduced. After treatment, the scores of physical health, social function, and mental health in the study group were notably higher than those in the control group. Compared with the control group, the 3-year survival rate of the study group was notably higher, and the therapeutic effect of the study group was obviously better. Conclusion. The combination of Yiqi Yangyin Decoction and docetaxel can improve the body immunity and the therapeutic effect of advanced OC, decrease the incidence of adverse reactions, and prolong the survival time, with good safety and effectiveness.

Knowledge of Cervical Cancer, Human Papilloma Virus (HPV) and HPV Vaccination Among Women in Northeast China

AbstractThis study aimed to research the understanding and knowledge of cervical cancer, human papilloma virus (HPV), and HPV vaccination, and the acceptance of HPV vaccination, among a population of women in northeastern China. A cross-sectional survey was carried out by questionnaire to investigate knowledge of cervical cancer, HPV, and HPV vaccination. The 230 female participants were native residents of northeastern China, and their ages ranged between 18 and 65 years. Questionnaires were randomly acquired by the respondents from online and paper questionnaire distribution. The questionnaire included questions on three major aspects to record people’s perceptions of cervical cancer, HPV, and vaccines. Of the sample of 230 women surveyed, 80.9% had heard of cervical cancer, but understanding was only 15.7%; 38.3% knew about HPV; 20% knew about HPV vaccine; 39.6% agreed to receive HPV vaccination, and the remainder were mainly concerned about its safety and effectiveness. Data analysis showed that age, family income, and whether there was experience of screening all influenced knowledge of cervical cancer, but this was not statistically significant. The level of education had no obvious effect on the degree of knowledge about cervical cancer; however, with an improvement in education, women’s awareness of HPV vaccine improved significantly (p < 0.05). Women who have received cervical cancer screening had significantly greater knowledge about cervical cancer and HPV than those with no screening (p < 0.05). Women in northeastern China have little knowledge of cervical cancer, HPV, and HPV vaccine, lack disease knowledge, and hold a skeptical attitude about HPV vaccination. Medical institutions are the main channel providing information to these women.