Xi Chen

Comparison of Different Maintenance Treatment Options for Newly Diagnosed BRCA wt Advanced Ovarian Cancer: A Retrospective Cohort Analysis

Introduction Niraparib and bevacizumab are two principal maintenance therapies for newly diagnosed advanced ovarian cancer (AOC) patients with BRCA wild-type ( BRCA wt) status, regardless of homologous recombination deficiency (HRD). In China, however, a considerable proportion of BRCA wt patients have unknown or untested HRD status, complicating treatment selection. Methods To evaluate and compare the efficacy of niraparib and bevacizumab as maintenance therapy for BRCA wt AOC, we conducted a retrospective cohort study using real-world clinical data. Descriptive statistics were used to summarize clinical and demographic characteristics. Progression-free survival (PFS) was estimated using Kaplan–Meier analysis and compared using a stratified Cox proportional hazards model. A multivariable Cox regression was performed to adjust for potential confounding variables. Exploratory subgroup analyses were conducted, and propensity score matching (PSM) was applied as a sensitivity analysis. Results A total of 94 patients were included, with 51 receiving niraparib and 43 receiving bevacizumab. The median PFS was not reached in the niraparib group versus 13.77 months (95% CI, 4.12–23.41) in the bevacizumab group (HR = 0.240, 95% CI, 0.128–0.451; P  < .001). After covariate adjustment, the median PFS was 19.55 months (95% CI, 9.40–NA) with niraparib and 8.64 months (95% CI, 4.53–NA) with bevacizumab, with an adjusted HR of 0.282 (95% CI, 0.136–0.587; P  = .001). In the PSM sensitivity analysis, the median PFS was not reached (95% CI, 19.55–NR) in the niraparib group and was 18.33 months (95% CI, 8.90-25.26) in the bevacizumab group (HR = 0.360, 95% CI, 0.176–0.736; P  = .005). Conclusion This analysis suggests that niraparib may provide a progression-free survival advantage compared with bevacizumab in BRCA wt AOC patients, with both regimens appearing to be generally well tolerated in the real-world setting. These findings offer preliminary reference value for maintenance treatment selection in patients with newly diagnosed BRCA wt AOC.

Tabersonine Enhances Olaparib Sensitivity through FHL1-Mediated Epithelial–Mesenchymal Transition in an Ovarian Tumor

Ovarian cancer (OVC) is one of the most aggressive gynecological malignancies worldwide. Although olaparib treatment has shown favorable outcomes against the treatment of OVC, its effectiveness remains limited in some OVC patients. Investigating new strategies to improve the therapeutic efficacy of olaparib against OVC is imperative. Our study identified tabersonine, a natural indole alkaloid, for its potential to increase the chemosensitivity of olaparib in OVC. The combined treatment of olaparib and tabersonine synergistically inhibited cell proliferation in OVC cells and suppressed tumor growth in A2780 xenografts. The combined treatment effectively suppressed epithelial-mesenchymal transition (EMT) by altering the expression of E-cadherin, N-cadherin, and vimentin and induced DNA damage responses. Integrating quantitative proteomics, FHL1 was identified as a potential regulator to modulate EMT after tabersonine treatment. Increased expression of FHL1 was induced by tabersonine treatment, while downregulation of FHL1 reversed the inhibitory effects of tabersonine on OVC cells by mediating EMT.

A theranostic probe of indoleamine 2,3-dioxygenase 1 (IDO1) for small molecule cancer immunotherapy

Discovering novel small molecules for cancer immunotherapy represents a promising but challenging strategy in future cancer treatment. Herein, we designed the first theranostic fluorescent probes to efficiently detect and inhibit the enzymatic activity of 2,3-dioxygenase 1 (IDO1). Probe 6b is a highly active IDO1 inhibitor (IC

LncRNA linc01194 promotes the progress of endometrial carcinoma by up-regulating SOX2 through binding to IGF2BP1

Endometrial carcinoma (EC) is one of the most common gynecological malignant tumors. Our study showed that long non-coding RNA (lncRNA) linc01194 plays an important role in EC. We explored the mechanism of lncRNA linc01194 in EC. The expression of lncRNA linc01194 was detected in The Cancer Genome Atlas database and starBase database. The potential targeted protein of linc01194 was predicted through the starBase database. To determine the role of linc01194 in EC, we downregulated or upregulated the level of linc01194 in EC cell lines and analyzed the cell behaviors and the changes of its potential target proteins. The expression of linc01194 in EC tissues is higher than that in normal endometrial tissues. The knockdown of linc01194 inhibited the cell proliferation, invasion and migration and promoted the apoptosis of EC cells, while overexpression of linc01194 promoted cell proliferation, invasion and migration and inhibited the apoptosis of EC cells. The starBase database revealed that linc01194 could bind to insulin-like growth factor 2 binding protein 1 (IGF2BP1). Previous results showed that in EC, IGF2BP1 could promote the expression of sex-determining region Y-box 2 (SOX2) by promoting the stability of SOX2 mRNA. Our results showed that linc01194 regulate the expression of IGF2BP1 and SOX2. Linc01194 can promote the expression of downstream protein SOX2 through binding to IGF2BP1, thus promoting the occurrence and development of EC.