Skimmianine Modulates Tumor Proliferation and Immune Dynamics in Breast Cancer by Targeting PCNA and TNF-α DOI Creative Commons
Tuğcan Korak, Hayat Ayaz, Fırat Aşır

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(5), P. 756 - 756

Published: May 20, 2025

Background/Objectives: Breast cancer continues to be a major global health challenge, driving the urgent need for innovative therapeutic strategies. This study evaluates anticancer and immunomodulatory potential of skimmianine in breast through comprehensive approach, integrating biochemical, histopathological, immunohistochemical, bioinformatics analyses. Methods: Thirty-six female Wistar albino rats were divided into three groups: control, 7,12-dimethylbenz[a]anthracene (DMBA)-induced cancer, DMBA + (n = 12/group). was induced with single oral dose 50 mg/kg sesame oil. After 16 weeks, (40 mg/kg) administered intraperitoneally four weeks. Serum CA15-3 levels measured via enzyme-linked immunosorbent assay (ELISA). Histopathological assessment performed using hematoxylin eosin (H&E) staining, proliferating cell nuclear antigen (PCNA) tumor necrosis factor-alpha (TNF-α) evaluated immunohistochemically. Pathway hub gene analyses Cytoscape, functional annotation Enrichr, immune Tumor Immune System Interaction Database (TISIDB) Sangerbox. Results: The burden animals increased after induction compared control groups (0.00 ± 0.00% vs. 89.00 6.60%, respectively, p < 0.001), while treatment significantly reduced (49.00 9.40%, group, 0.191). analysis showed DMBA-induced structural disorganization malignant clustering, whereas preserved ductal structures mitigated damage. Compared administration markedly elevated serum (0.23 0.06 ng/mL 8.57 1.01 ng/mL, respectively), along PCNA (13.0 3.0% 25.0 4.0%, respectively) TNF-α (8.4 1.7% 34.0 5.3%, expression, indicating active progression. Skimmianine (3.72 0.58 ng/mL), (20.0 4.1%), (25.0 3.9%) (p 0.001). In silico indicated skimmianine’s effects on influence cycle pathways, suppression impacts toll-like receptor (TLR) signaling (adjusted 0.05). PCNA- TNF-α-related especially notable basal molecular C2 subtypes Related proteins may regulate dynamics by reducing immunosuppression tumor-promoting inflammation Conclusions: shows promise as therapy simultaneously targeting growth regulation, identified key players.

Language: Английский

Proteomic and In Silico Analyses Highlight Complement System’s Role in Bladder Cancer Immune Regulation DOI Creative Commons
Tuğcan Korak, İbrahim Halil Baloğlu, Murat Kasap

et al.

Medicina, Journal Year: 2025, Volume and Issue: 61(4), P. 735 - 735

Published: April 16, 2025

Background and Objectives: Bladder cancer (BLCA), intimately associated with the immune system, represents a substantial global health burden due to its high recurrence rates limited therapeutic effectiveness. Although immunotherapy shows promise, challenges persist lack of reliable targets. This study aims investigate potential immune-related biomarkers that could influence tumor microenvironment in BLCA, using proteomic silico approaches. Materials Methods: Tissue samples from BLCA patients (n = 27) controls were collected Şişli Hamidiye Etfal Training Research Hospital. Proteomic analysis was performed by liquid chromatography/mass spectrometry (LC-MS)/MS reveal identities differentially regulated proteins. Protein network hub protein detection Cytoscape (v.3.10.3), while functional annotation carried out EnrichR. The immunological proteins Sangerbox platform, prognostic associations evaluated through Kaplan–Meier Plotter tool. Results: LC-MS/MS identified 120 STRING analysis, an response dataset (GO:0006955), highlighted complement cascade as significantly enriched pathway (p < 0.05). Proteins, namely C4A, CFB, C4B, C8B, CFH, CFI, C5, C4BPA, C3, C2, are known play key roles system identified. Immunological these revealed phenomena infiltration checkpoint gene Four genes—CFB, C2—demonstrated significant value for Conclusions: highlights pivotal role regulation BLCA. C4B emerged target treatment, particularly immunotherapy, enhancing survival. Future research on specifically focusing may facilitate development targeted immunotherapies, ultimately improving treatment outcomes.

Language: Английский

Citations

0
Skimmianine Modulates Tumor Proliferation and Immune Dynamics in Breast Cancer by Targeting PCNA and TNF-α DOI Creative Commons
Tuğcan Korak, Hayat Ayaz, Fırat Aşır

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(5), P. 756 - 756

Published: May 20, 2025

Background/Objectives: Breast cancer continues to be a major global health challenge, driving the urgent need for innovative therapeutic strategies. This study evaluates anticancer and immunomodulatory potential of skimmianine in breast through comprehensive approach, integrating biochemical, histopathological, immunohistochemical, bioinformatics analyses. Methods: Thirty-six female Wistar albino rats were divided into three groups: control, 7,12-dimethylbenz[a]anthracene (DMBA)-induced cancer, DMBA + (n = 12/group). was induced with single oral dose 50 mg/kg sesame oil. After 16 weeks, (40 mg/kg) administered intraperitoneally four weeks. Serum CA15-3 levels measured via enzyme-linked immunosorbent assay (ELISA). Histopathological assessment performed using hematoxylin eosin (H&E) staining, proliferating cell nuclear antigen (PCNA) tumor necrosis factor-alpha (TNF-α) evaluated immunohistochemically. Pathway hub gene analyses Cytoscape, functional annotation Enrichr, immune Tumor Immune System Interaction Database (TISIDB) Sangerbox. Results: The burden animals increased after induction compared control groups (0.00 ± 0.00% vs. 89.00 6.60%, respectively, p < 0.001), while treatment significantly reduced (49.00 9.40%, group, 0.191). analysis showed DMBA-induced structural disorganization malignant clustering, whereas preserved ductal structures mitigated damage. Compared administration markedly elevated serum (0.23 0.06 ng/mL 8.57 1.01 ng/mL, respectively), along PCNA (13.0 3.0% 25.0 4.0%, respectively) TNF-α (8.4 1.7% 34.0 5.3%, expression, indicating active progression. Skimmianine (3.72 0.58 ng/mL), (20.0 4.1%), (25.0 3.9%) (p 0.001). In silico indicated skimmianine’s effects on influence cycle pathways, suppression impacts toll-like receptor (TLR) signaling (adjusted 0.05). PCNA- TNF-α-related especially notable basal molecular C2 subtypes Related proteins may regulate dynamics by reducing immunosuppression tumor-promoting inflammation Conclusions: shows promise as therapy simultaneously targeting growth regulation, identified key players.

Language: Английский

Citations

0