Metabolism-Related Programmed Cell Death: Unveiling Prognostic Biomarkers, Immune Checkpoints, and Therapeutic Strategies in Ovarian Cancer DOI

Mengdi Fu,

Hao Wu, Peng Peng

и другие.

Cancer Investigation, Год журнала: 2025, Номер unknown, С. 1 - 22

Опубликована: Апрель 7, 2025

Ovarian cancer (OC), the gynecologic malignancy with poorest prognosis, is driven by metabolic reprogramming and dysregulated programmed cell death (PCD). However, their interplay prognostic significance remain inadequately understood. Transcriptomic data from OC patients healthy controls (TCGA GTEx) were analyzed to identify differentially expressed genes (DEGs) intersecting metabolism-related (MRGs) PCD-related (PCDRGs). Prognostic determined using univariate Cox regression, LASSO, multivariate stepwise analyses. Consensus clustering revealed enrichment differences, while a risk model nomogram developed for outcome prediction. Associations between genes, immune microenvironment, drug sensitivity also assessed. A total of 166 candidate identified, PLA2G2D, LPCAT3, ARG1, PLA2G4A, EXOSC3 emerging as significant markers. The demonstrated marked survival showed robust calibration Differential infiltration was observed groups. Additionally, Sinularin Fulvestrant exhibited variable sensitivity, validated through molecular docking models. Metabolism-related PCD identified pivotal markers in OC, providing critical insights evaluation targeted therapy development.

Язык: Английский

Original synthetic monophenolic antioxidant with combined effect inhibits tumor growth in vivo DOI Creative Commons
E. B. Menshchikova, M. V. Khrapova, П. М. Кожин

и другие.

Сибирский научный медицинский журнал, Год журнала: 2025, Номер 44(6), С. 128 - 137

Опубликована: Янв. 8, 2025

Reactive oxygen metabolites and antioxidants, as well the redox-sensitive signaling Nrf2-dependent pathway, play a dual role in formation, growth progression of malignant neoplasms. The aim study was to investigate ability original synthetic monophenolic antioxidant combined action influence tumor vivo side effects cytostatic use. Material methods . Lewis lung carcinoma (LLC) used an experimental model growth. performed on 120 female C57Bl/6 mice, which were divided into 12 groups; animals weighed weekly. Mice corresponding groups received intragastrically solution sodium 3-(3′- tert -butyl-4′-hydroxyphenyl)propylthiosulfonate (TS-13) (100 mg/kg body weight), suspension -butylhydroquinone (tBHQ) or solvent (0.9% NaCl solution) throughout experiment. 28 days after start TS-13 tBHQ administration, mice implanted intramuscularly with LLC cells at dose 2×10 5 cells/mouse; 7th 14th development, doxorubicin administered intraperitoneally twice cumulative 8 weight (4/5 LD10). On 35th day growth, removed from experiment, extracted, its linear dimensions determined; mass coefficient volume calculated, respectively. spleen also estimated. Results discussion receiving statistically significantly greater than that other carriers. Administration inhibited effectively doxorubicin, more when combination; did not exert independent inhibitory effect, enhance effect combination cytostatic. Doxorubicin reduced coefficient, while Monotherapy accompanied by hair loss dorsal surface (8 out 10), no alopecia observed administration tBHQ. Conclusions Monophenol TS-13, direct inducer Keap1/Nrf2/ARE system, is comparable terms antitumor effect. use allows reduce negative manifestations associated chemotherapy, such cachexia, splenotoxity, alopecia.

Язык: Английский

Процитировано

0

Metabolism-Related Programmed Cell Death: Unveiling Prognostic Biomarkers, Immune Checkpoints, and Therapeutic Strategies in Ovarian Cancer DOI

Mengdi Fu,

Hao Wu, Peng Peng

и другие.

Cancer Investigation, Год журнала: 2025, Номер unknown, С. 1 - 22

Опубликована: Апрель 7, 2025

Ovarian cancer (OC), the gynecologic malignancy with poorest prognosis, is driven by metabolic reprogramming and dysregulated programmed cell death (PCD). However, their interplay prognostic significance remain inadequately understood. Transcriptomic data from OC patients healthy controls (TCGA GTEx) were analyzed to identify differentially expressed genes (DEGs) intersecting metabolism-related (MRGs) PCD-related (PCDRGs). Prognostic determined using univariate Cox regression, LASSO, multivariate stepwise analyses. Consensus clustering revealed enrichment differences, while a risk model nomogram developed for outcome prediction. Associations between genes, immune microenvironment, drug sensitivity also assessed. A total of 166 candidate identified, PLA2G2D, LPCAT3, ARG1, PLA2G4A, EXOSC3 emerging as significant markers. The demonstrated marked survival showed robust calibration Differential infiltration was observed groups. Additionally, Sinularin Fulvestrant exhibited variable sensitivity, validated through molecular docking models. Metabolism-related PCD identified pivotal markers in OC, providing critical insights evaluation targeted therapy development.

Язык: Английский

Процитировано

0