Yu Wang

Research Progress of Traditional Chinese Medicine Monomer Inhibiting Metastatic Colonization of Ovarian Cancer Cells Based on Cell Biology

Ovarian cancer, a frequently occurring gynecological malignancy with a poor prognosis and a 5-year survival rate below 45%, often progresses due to metastatic colonization. This review highlights the potential of traditional Chinese medicine (TCM) monomers as anticancer agents that inhibit the metastatic colonization of ovarian cancer cells. TCM monomers exhibit various mechanisms of action, including (1) inhibiting epithelial-to-mesenchymal transformation by modulating cell adhesion molecules; (2) reducing extracellular matrix damage through inhibition of degrading enzymes; (3) affecting cytoskeletal dynamics to alter cell movement; and (4) preventing angiogenesis by downregulating angiogenic factors. Additionally, TCM monomers can reshape the tumor microenvironment, enhance immune responses, and induce oxidative stress, resulting in reduced proliferation and survival of cancer cells. The comprehensive action of TCM monomers makes them promising candidates for individualized, multi-target therapies in drug-resistant cases. This paper reviews the current research on the mechanisms through which TCM monomers combat metastatic colonization, aiming to provide insights for future studies and clinical applications in ovarian cancer treatment, ultimately offering hope to affected patients.

RETRACTED: LINC00461 Promoted Endometrial Carcinoma Growth and Migration by Targeting MicroRNA-219-5p/Cyclooxygenase-2 Signaling Axis

Endometrial carcinoma (EC) ranks as the most common female genital cancer in developed countries. Lately, more and more long noncoding RNAs (lncRNAs) have been identified as vital regulators in numerous physiological and pathological processes, including EC. However, the expression pattern and precise functions of different lncRNAs in EC remain unclear. In this study, we reported LINC00461 was upregulated in EC patient tissues and cell lines. In addition, LINC00461 knockdown could remarkably suppress cell proliferation, cell cycle progression, cell migration, and promote cell apoptosis in EC cells. We discovered LINC00461 could sponge microRNA-219-5p (miR-219-5p) and suppress its expression, thereby upregulating expression level of miR-219-5p's target, cyclooxygenase-2 (COX-2).

Genetic Variations in CYP19A1 and SLCO1B1 Genes and Their Association with Endometrial Cancer Risk in the Taiwanese Population: A Case–Control Study

Endometrial cancer is the most common gynecologic malignancy in developed countries, and its incidence is rising globally. Genetic predisposition plays a significant role in modulating risk, particularly in Asian populations. In Taiwan, the burden of endometrial cancer has increased, highlighting the need to gain a better understanding of the genetic loci associated with this disease. This retrospective case–control study included 373 endometrial cancer patients and 3730 controls from the Taiwan Precision Medicine Initiative. Genotype data were obtained using the TWB 2.0 SNP chip. Statistical analyses were conducted using PLINK and SPSS, with logistic regression models assessing the associations between genetic variants and endometrial cancer risk. In this study, we identified two SNPs, rs17601876 in CYP19A1 and rs2900478 in SLCO1B1, that were associated with endometrial cancer. The AG/GG genotypes of rs17601876 showed a protective effect (OR = 0.743, p = 0.006), while the TA/AA genotypes of rs2900478 exhibited a nonsignificant trend toward an increased risk. Higher BMI, LDL, triglyceride, total cholesterol, and HbA1c, as well as lower HDL, were strongly associated with greater risk. Our findings demonstrated a protective role of rs17601876 in CYP19A1 and further showed its potential impact on estrogen biosynthesis. Genetic factors involved in endometrial cancer risk are an important issue. Further functional studies are needed to validate the present findings.

Successful delivery in a case of in vitro fertilization and embryo transplantation after conservative treatment for endometrial cancer

A Neutrophil Extracellular Traps–Related Signature Predicts Clinical Outcomes and Identifies Immune Landscape in Ovarian Cancer

ABSTRACTOvarian cancer (OvCa) is the most lethal gynaecology malignancies worldwide. Neutrophil extracellular traps (NETs), net‐like protein structures produced by activated neutrophils and DNA‐histone complexes, have a central role in tumours, though haven't been fully explored in OvCa. We obtained transcriptome data from TCGA‐OvCa database (n = 376) as training, ICGC‐OvCa database (n = 111) as validation and GTEx database (n = 180) as controls. Through LASSO‐COX Regression analysis, we identified an eight‐gene signature among 87 NETs‐related genes, which was significantly related to poor prognosis in both TCGA‐OvCa and ICGC‐OvCa cohorts (Log‐rank p‐value = 0.0003 and 0.0014). Next, we constructed and validated a prognostic nomogram, consist of NETs‐related signature and clinical features (C‐index = 0.82). We evaluated 22 typical immune cell infiltration through CIBERSORT analysis, which implied upregulation of memory CD4 + T cells, follicular helper T cells and neutrophils in high‐risk group. Additionally, we predicted therapy sensitivity through TIDE algorithm, indicating that high NETs‐riskscore exhibited more sensitivity towards Sorafenib and less sensitivity towards immunotherapy. We initially reported that RAC2 upregulation was associated with NETs formation and poor prognosis (p‐value < 0.05) through IHC analysis of tissue microarrays (n = 125). Conclusively, NETs‐related signature was reliable for OvCa prognosis prediction and therapy assessment. Especially, RAC2 was predominantly related to NETs formation, thus providing hints towards anti‐tumour mechanism of NETs in OvCa.

Targeting CDK 9 With Harmine Induces Homologous Recombination Deficiency and Synergizes With PARP Inhibitors in Ovarian Cancer

ABSTRACT Ovarian cancer patients with homologous recombination (HR) proficiency are more likely to develop resistance to poly (ADP‐ribose) polymerase (PARP) inhibitors, resulting in poor prognosis. Harmine, a natural compound with verified clinical safety, is a potential inhibitor of HR activity. However, its effect on HR has not been tested in ovarian cancer. More importantly, its specific target involving the HR pathway is still unknown. A fluorescent reporter cell system was employed to assess the HR efficiency of cells treated by harmine. The target of harmine in the HR pathway was identified via a molecular docking screening in silico and confirmed using a cellular thermal shift assay. Evaluation of harmine treatment combined with the PARP inhibitor olaparib in BRCA1/2 wild‐type ovarian cancer was performed. Treatment with harmine inhibited HR activity in a dose‐dependent manner in ovarian cancer cells and selectively suppressed HR‐proficient cells with high replication stress, marked with CCNE1 amplification. HR‐related protein cyclin‐dependent kinase 9 (CDK9) was identified as the target of harmine. Specifically, harmine diminished the interaction of CDK9 with cyclin T, resulting in impaired formation of the p‐TEFb complex and subsequent transcription elongation. Hence, harmine downregulated the transcription of key HR‐related genes. Moreover, harmine synergized with PARP inhibitor olaparib in BRCA1/2 wild‐type ovarian cancer. Harmine inhibits HR repair by interfering with CDK9‐mediated transcription elongation for HR‐related genes, thus enhancing the potency of olaparib, providing a promising therapeutic strategy to improve the prognosis of HR‐proficient ovarian cancer patients.

Readout-segmented echo-planar imaging and conventional single-shot echo-planar imaging for determining cervical cancer image quality, lymphovascular space invasion, and lymph node metastasis status: a comparative study

Diffusion-weighted imaging (DWI) using single-shot echo-planar imaging (ss-EPI) is prone to artifacts, geometric distortion, and T2* blurring. Readout-segmented echo-planar imaging (rs-EPI) may improve image quality in the DWI of cervical cancer (CC). This study aimed to compare the image quality between rs-EPI and ss-EPI DWI in CC and to evaluate whether the apparent diffusion coefficient (ADC) values of ss-EPI (ssADC) and rs-EPI (rsADC) can differentiate the status of lymphovascular space invasion (LVSI) and lymph node metastasis (LNM). This prospective study included 69 patients with CC who underwent ss-EPI and rs-EPI DWI before surgery. Qualitative reader scores, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and ADC values derived from ss-EPI and rs-EPI were compared. The differences in ADC values were analyzed in patients who were (a) LNM-positive (LNM+, n = 17) and LNM-negative (LNM-, n = 52); (b) LVSI-positive (LVSI+, n = 33) and LVSI-negative (LVSI-, n = 36). The rs-EPIs of CC had higher subjective image quality scores and a lower SNR than ss-EPI (all Over a similar scan time, rs-EPI improves the qualitative image quality of DWI significantly more than ss-EPI and has good diagnostic accuracy for LNM status in CC. However, neither could predict the LVSI status. Readout-segmented EPI improves the qualitative image quality of DWI and has good diagnostic accuracy for LNM status in CC, compared with conventional ss-EPI. It is more inclined to qualitative analysis of CC foci and provides a better scheme when choosing the DWI sequence scanning strategy for CC.

Achieving flexible fairness metrics in federated medical imaging

The rapid adoption of Artificial Intelligence (AI) in medical imaging raises fairness and privacy concerns across demographic groups, especially in diagnosis and treatment decisions. While federated learning (FL) offers decentralized privacy preservation, current frameworks often prioritize collaboration fairness over group fairness, risking healthcare disparities. Here we present FlexFair, an innovative FL framework designed to address both fairness and privacy challenges. FlexFair incorporates a flexible regularization term to facilitate the integration of multiple fairness criteria, including equal accuracy, demographic parity, and equal opportunity. Evaluated across four clinical applications (polyp segmentation, fundus vascular segmentation, cervical cancer segmentation, and skin disease diagnosis), FlexFair outperforms state-of-the-art methods in both fairness and accuracy. Moreover, we curate a multi-center dataset for cervical cancer segmentation that includes 678 patients from four hospitals. This diverse dataset allows for a more comprehensive analysis of model performance across different population groups, ensuring the findings are applicable to a broader range of patients.

Correlation Analysis of Prognostic Gene Expression, Tumor Microenvironment, and Tumor-Infiltrating Immune Cells in Ovarian Cancer

Objective. Tumor microenvironment (TME) research can provide a crucial direction for the innovation and continuous improvement of novel biologic therapies for cancer. This study examined the relationship between the TME, expression profiles of the tumor-infiltrating immune cell, and prognostic gene expression in ovarian cancer (OC). Materials and Methods. Screening of CD3E, CD3G, CD2, CD3D, CCL19, and IL2RG was performed using the bioinformatics methods. Results. All six genes were found to participate in immune-related molecular mechanisms and could regulate the expression of tumor-infiltrating cells. A Kaplan–Meier survival analysis results demonstrated a strong association between overall survival and all gene expressions in patients with OC. CIBERSORT analysis results showed that the expression level of all genes was positively correlated with γδ T cell proportions. Conclusion. Therefore, in the OC microenvironment, CD3E, CD3G, CD2, CD3D, CCL19, and IL2RG can be potential immunotherapy targets and prognostic markers.

Anlotinib induces apoptosis and second growth/mitosis phase block in cisplatin-resistant ovarian cancer cells via the aurora kinase A/p53 pathway

Background Cisplatin (DDP) resistance in ovarian cancer (OC) patients usually leads to treatment failure and increased mortality. Anlotinib has been shown to improve progression-free survival and overall survival in patients with platinum-resistant ovarian cancer, but the mechanism is unclear. This study aims to explore the mechanism by which anlotinib ameliorates platinum resistance in OC cells. Methods Cell viability was detected by the 3-4,5-dimethylthiazol-2,5-diphenyltetrazolium bromide (MTT) method, and the apoptosis rate and changes in the cell cycle distribution were evaluated by flow cytometry. Bioinformatics analysis was used to predict the potential gene target of anlotinib in DDP-resistance SKOV3 cells, and its expression was verifies it by RT-qPCR, western blotting and immunofluorescence staining. Finally, ovarian cancer cells overexpressing AURKA were constructed, and the predicted results were verified by animal experiments. Results Anlotinib effectively induced apoptosis and G2/M arrest in OC cells and decreased the proportion of EdU-positive cells. AURKA was identified as a possible key target of anlotinib for inhibiting tumorigenic behaviors in SKOV3/DDP cells. Through combined immunofluorescence and western blot analyses, it was demonstrated that anlotinib could effectively inhibit the protein expression of AURKA and upregulate the expression of p53/p21, CDK1, and Bax protein. After overexpression of AURKA in OC cells, the induction of apoptosis and G2/M arrest by anlotinib were significantly inhibited. Anlotinib also effectively inhibited the growth of tumors in nude mice injected with OC cells. Conclusions This study demonstrated that anlotinib can induce apoptosis and G2/M arrest in cisplatin-resistant ovarian cancer cells through the AURKA/p53 pathway.

Circular RNA hsa_circ_0078607 suppresses ovarian cancer progression by regulating miR-518a-5p/Fas signaling pathway

Abstract Background Increasing researches have demonstrated the critical functions of circular RNAs (circRNAs) in the progression of malignant tumors, including ovarian cancer. In this study, we aim to investigate abnormally expression of hsa_circ_0078607 and the role of hsa_circ_0078607 during ovarian cancer pathogenesis. Methods RT-PCR were used to detect the expression of circ_0078607 in ovarian cancer tissues. To determine the functional roles of circ_0078607 in ovarian cancer, cell proliferation and cell invasion assays were performed. Bioinformatics and luciferase reporter analysis were used to predict the target of circ_0078607. Results In the present study, we first found that circ_0078607 was downregulated in ovarian cancer. Forced circ_0078607 expression significantly suppressed proliferation and promoted apoptosis of ovarian cancer cells. Mechanically, bioinformatics and luciferase reporter analysis identified miR-518a-5p as a direct target of circ_0078607, while Fas as a direct target of miR-518a-5p. MiR-518a-5p negatively regulated Fas in ovarian cancer cells, while overexpression of circ_0078607 could increase the expression of Fas inhibited by miR-518a-5p. Furthermore, overexpression of circ_0078607 could inhibit the proliferation and invasion of ovarian cancer cells caused by miR-518a-5p mimic. Conclusion The results of the present study revealed that circ_0078607 suppressed ovarian cancer progression by sponging oncogenic miR-518a-5p to induce Fas expression, which may provide new therapeutic approach for ovarian cancer.

Clinical significance for combined coagulation indexes in epithelial ovarian cancer prognosis

AbstractBackgroundIncreasing evidence supported an association between cancer and coagulation system. We aimed to identify prognostic values of coagulation biomarkers in epithelial ovarian cancer (EOC).MethodsA retrospective study was conducted on patients who underwent optimal tumor debulking followed by platinum-based chemotherapy at our institution. The predictive value of coagulation variables was evaluated by receiver operating characteristic (ROC) curves. Through Cox hazards regression models, prognostic factors were determined for recurrence-free survival (RFS) and overall survival (OS). Survival curves were visualized by Kaplan–Meier method and compared through Log-rank analysis.ResultsWe involved 482 EOC patients and followed up for 64 (range, 36–87) months. According to ROC curves, D-dimer and International normalized ratio (INR) had superior predictive value than other coagulation indexes, with area under curve (AUC) of 0.758 and 0.742. Patients were then stratified into three combined D-dimer and INR (DD-INR) groups based on the cut-off value of 0.97 mg/L and 0.86, respectively. Through regression analysis, we demonstrated that age (HR 1.273; 95%CI 1.048–2.047;p = 0.045), pathological grade (HR 1.419; 95% CI 1.102–2.491;p = 0.032), clinical stage (HR 2.038; 95%CI 1.284–3.768;p = 0.008), CA-125 (HR 1.426; 95%CI 1.103–1.894;p = 0.038) and DD-INR (HR 2.412; 95%CI 1.683–3.241;p = 0.009) were independent prognostic factors. Survival analysis showed that patients with higher DD-INR experienced poor survival (p = 0.0013 for RFS andp = 0.0068 for OS). Further subgroup analysis revealed that evaluated DD-INR was significantly associated with poor survival among patients with advanced stage (p = 0.0028 for RFS andp = 0.0180 for OS).ConclusionOur findings suggested that coagulation indexes, especially the combined DD-INR were promising biomarkers for prognosis stratification in EOC patients, especially those with advanced clinical stages.

Extracellular vesicles derived from M2-polarized tumor-associated macrophages promote immune escape in ovarian cancer through NEAT1/miR-101-3p/ZEB1/PD-L1 axis

Evidence has been presented demonstrating that CD8

Comparison of the safety between cervical conization and hysterectomy for patients with cervical adenocarcinoma in situ

To compare the safety between cervical conization (CC) alone and hysterectomy for patients with adenocarcinoma in situ (AIS) of the cervix. Patients diagnosed with AIS after CC during 2007-2021 were identified by computerized databases at Women's Hospital of Zhejiang University School of Medicine. A total of 453 AIS patients were divided into 2 groups according to uterus preservation: hysterectomy group (n=300) and CC(s) alone group (n=153). The prevalence of residual disease and disease recurrence was compared between patients treated by CC(s) alone and hysterectomy. The prevalence of residual disease in specimens from women who had a hysterectomy and repeat CC were compared between positive and negative margins of CC. The factors influencing residual disease and disease recurrence were assessed. Among 310 specimens from women who had a hysterectomy or repeat CC, the prevalence of residual disease was 50.6% (45/89) for a positive margin and 2.3% (5/221) for a negative margin (p=0.000). Four patients had recurrence of vaginal intraepithelial neoplasia in those treated by hysterectomy and one had recurrence of cervical squamous intraepithelial neoplasia in those treated by CC(s) alone. The prevalence of recurrence was 0.7% (1/153) for CC(s) alone and 1.3% (4/300) for hysterectomy (p=0.431). Hysterectomy did not influence residual disease or disease recurrence. CC is an efficacious and safe option for patients with AIS of the cervix provided the margin is negative.

Molecular Imaging of Ovarian Follicles and Tumors With Near‐Infrared II Bioconjugates

AbstractFollicular tracking is typically conducted using ultrasound technology, but its effectiveness is constrained by limited resolution. High‐resolution imaging of deep tissues can be accomplished using luminescence imaging in the near‐infrared II window (NIR‐II, 1000–1700 nm); however, the contrast agents that are used lack specificity. Here, it is reported that the FDA‐approved indocyanine green (ICG)‐conjugated recombinant human chorionic gonadotropin (hCG) protein can target early follicles with long‐term effectiveness. A novel high‐resolution NIR‐II imaging approach is developed for monitoring follicular development as well as ovulation using multi‐color imaging of ovarian vessels with a combination of non‐overlapping downconversion nanoparticles (DCNPs). The results showed that the ability to monitor early follicles of around 50 µm in diameter exceeded the spatial and temporal resolution of ultrasound or MRI without the reproductive damage associated with computed tomography radiation, and this enabled the clinical identification of the follicular reserve in patients with infertility diseases such as polycystic ovary syndrome (PCOS). In addition, NIR‐II imaging clearly targeted ovarian tumors and showed micro‐metastatic lesions, thus providing a new tool for monitoring tumors in vivo and guiding surgical resection.

Whole-tumor histogram analysis of multiple non-Gaussian diffusion models at high b values for assessing cervical cancer

To assess the diagnostic potential of whole-tumor histogram analysis of multiple non-Gaussian diffusion models for differentiating cervical cancer (CC) aggressive status regarding of pathological types, differentiation degree, stage, and p16 expression. Patients were enrolled in this prospective single-center study from March 2022 to July 2023. Diffusion-weighted images (DWI) were obtained including 15 b-values (0 ~ 4000 s/mm 89 women (mean age, 55 ± 11 years) with CC were enrolled in our study. The combined model, which incorporated the CTRW, DKI, FROC, and IVIM diffusion models, offered a significantly higher AUC than that from any individual models (0.836 vs. 0.664, 0.642, 0.651, 0.649, respectively; p < 0.05) in distinguishing cervical squamous cell cancer from cervical adenocarcinoma. To distinguish tumor differentiation degree, except the combined model showed a better predictive performance compared to the DKI model (AUC, 0.839 vs. 0.697, respectively; p < 0.05), no significant differences in AUCs were found among other individual models and combined model. To predict the International Federation of Gynecology and Obstetrics (FIGO) stage, only DKI and FROC model were established and there was no significant difference in predictive performance among different models. In terms of predicting p16 expression, the predictive ability of DKI model is significantly lower than that of FROC and combined model (AUC, 0.693 vs. 0.850, 0.859, respectively; p < 0.05). Multiple non-Gaussian diffusion models with whole-tumor histogram analysis show great promise to assess the aggressive status of CC.