The Complex Tumor Microenvironment in Ovarian Cancer: Therapeutic Challenges and Opportunities

Current Oncology, Journal Year: 2024, Volume and Issue: 31(7), P. 3826 - 3844

Published: July 1, 2024

The tumor microenvironment (TME) in ovarian cancer (OC) has much greater complexity than previously understood. In response to aggressive pro-angiogenic stimulus, blood vessels form rapidly and are dysfunctional, resulting poor perfusion, tissue hypoxia, leakiness, which leads increased interstitial fluid pressure (IFP). Decreased perfusion high IFP significantly inhibit the uptake of therapies into tumor. Within TME, there numerous inhibitor cells, such as myeloid-derived suppressor cells (MDSCs), association macrophages (TAMs), regulatory T (Tregs), cancer-associated fibroblasts (CAFs) that secrete numbers immunosuppressive cytokines. This environment is thought contribute lack success immunotherapies immune checkpoint (ICI) treatment. review discusses components TME OC, how these characteristics impede therapeutic efficacy, some strategies alleviate this inhibition.

Language: Английский

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Investigating the role of cathepsins in breast cancer progression: a Mendelian randomization study

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 29, 2025

Background Breast cancer, a major threat to women’s health worldwide, has mechanisms of onset that remain unclear. Within the human lysosomal system, class enzymes known as cathepsins exhibit elevated expression levels in various malignant tumors, suggesting they may play key roles cancer progression. Methods This study employed two-sample Mendelian randomization (MR) approach investigate potential causal relationship between cathepsin and risk developing breast cancer. Furthermore, we conducted MR analysis using eQTL data how gene expression, mediated by cathepsins, affects occurrence different types assessed regulatory effects cathepsins. Results revealed increased E are associated with greater tumors (IVW: p = 0.006, OR 1.103, 95% CI 1.028–1.184), F an situ 0.031, 1.190, 1.016–1.394). Additionally, Z protective effect against 0.017, 0.846, 0.737-0.971). Cathepsin can mediate APBB1IP, NT5C3B, ZNF66 on HER2-negative well DHRS9, CDK12, CD247 HER2-positive ANXA2R ZNF605 PRX, CRY2, ADCY3, PELATON Discussion These findings highlight dual factors for underscoring their diagnostic therapeutic strategies.

Language: Английский

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Unraveling the causal relationship and underlying mechanisms between cathepsins on liver cancer: findings from mendelian randomization and bioinformatics analysis

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 7, 2025

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are two major types of primary liver cancer (PLC). Earlier research has indicated a potential link between cathepsins cancer. Nonetheless, there have been limited clinical trials examining the connection PLC. Therefore, we conducted two-sample Mendelian randomization (MR) study to evaluate causal relationship Data from genome-wide association studies (GWAS) focusing on was collected. Additionally, summary data for GCST90018803 (Hepatic bile duct cancer, HBDC), GCST90018858 (related hepatic HC), were employed in discovery validation phases study, respectively. The inverse variance weighted (IVW) method served as analytical our supplemented by MR-Egger, median, simple mode, mode methods. To assess heterogeneity pleiotropy, MR-Egger intercept test, Cochran's Q well MR-Pleiotropy RESidual Sum Outlier (MR-PRESSO) analysis, along with leave-one-out analysis. After that, bioinformatic analysis based Gene Expression Omnibus (GEO) databases utilized, ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) functional enrichment utilized exploring underlying mechanisms. protein-protein docking confirm interaction related proteins. results showed that cathepsin F (CTSF), causally associated HBDC. CTSF decrease risk HBDC (OR = 0.826, 95% CI 0.711-0.959, P 0.012). may play protective roles patients No or pleiotropy observed. expression genes is lower HBDC, GO KEGG revealed mainly cell cycle, P53 pathway Docking had good binding ability MDM2, most well-established negative regulator p53. This provided new evidence suggesting plays an inhibition role progression. could be novel effective way HDBC treatment.

Language: Английский

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The relationship between cathepsins and nasopharyngeal carcinoma: a Mendelian randomization analysis

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 8, 2025

Observational studies have shown the potential for cathepsins (CTS) to an effect on nasopharyngeal carcinoma (NPC), but their conclusions are susceptible confounding factors. To investigate causal relationship between CTS and NPC, Mendelian randomization (MR) was conducted. Genetic data nine (CTS B, E, F, G, H, L2, O, S Z) obtained from a genome-wide association study. As outcome, genetic of NPC utilized FinnGen MR performed using five analytical methods including Inverse Variance-Weighted (IVW) method, MR-Egger test, Weighted Median Simple Mode test with IVW as main analysis method. Cochran's Q MR-PRESSO global "leave-one-out" sensitivity were used in analysis. Reverse whether there is reverse causality CTS. Steiger determine direction interaction NPC. Overall, authors found favorable evidence support Cathepsin F (CTSF) CTSF associated increase risk (odds ratio [OR] = 1.845, 95% confidence intervals [CI] 1.086 ~ 3.136, P 0.024) according IVW. The results proved be stable robust In unidirectional. These findings suggest that may plays important role thus providing new research ideas future basic endeavors clinical applications.

Language: Английский

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Immunocytes Mediate Oral Flora to Effect the Occurrence and Development of Coronary Atherosclerosis: A Multi-Omics and Mediation Mendelian Randomization Study

Published: Jan. 1, 2024

Language: Английский

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Association of Cathepsins with Muscle & Joint Diseases (BMJD) : a Mendelian randomisation study

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 25, 2024

Muscle & Joint Diseases (BMJD) is a group of orthopedic diseases, including osteoarthritis, osteoporosis, rheumatoid arthritis, bone tumors and myositis. It the largest disabling disease in world, but specific pathogenesis BMJD still unclear needs further research exploration.Cathepsins are proteinases mainly present lysosomes (lysosomes). Some studies have shown that cathepsins may be one causes BMJD. The relationship between them help us to deeper understanding pathogenesis, pathological process, treatment prognosis disease, guiding diagnosis, two confirming.We hope through this study, we can reveal cathepsin BMJD, so as explore potential risk factors make more accurate diagnosis decisions, form new methods prevention strategies, contribute clinical work, promote progress development medicine.

Language: Английский

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