Combined use of immunoreactivities of Efp and ZCCHC3 for predicting prognosis of patients with triple‐negative breast cancer

Pathology International, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Abstract We previously reported that strong immunoreactivity (IR) of estrogen‐responsive finger protein (Efp), also known as tripartite motif‐containing 25 (TRIM25), predicts poor prognosis in patients with estrogen receptor‐positive and ‐negative invasive breast cancers. In the present study, we investigated clinicopathological role Efp ZCCHC3, latter which is an interactor, a triple‐negative cancer (TNBC) cohort was composed 118 Japanese female underwent surgical treatment. ZCCHC3 IRs were analyzed using specific antibodies for these proteins. demonstrated positive IR significantly associated shorter distant disease‐free survival ( p = 0.0108) 0.0153). Notably, positively 0.003). When two proteins combined, double positivity 0.0007) independent factor prognosis. These results suggest has clinical significance prognostic TNBC. Thus, propose combined use both can be used marker

Language: Английский

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zDHHC-Mediated S-Palmitoylation in Skin Health and Its Targeting as a Treatment Perspective

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1673 - 1673

Published: Feb. 15, 2025

S-acylation, which includes S-palmitoylation, is the only known reversible lipid-based post-translational protein modification. S-palmitoylation mediated by palmitoyl acyltransferases (PATs), a family of 23 enzymes commonly referred to as zDHHCs, catalyze addition palmitate cysteine residues on specific target proteins. Aberrant events have been linked pathogenesis multiple human diseases. While there advances in elucidating molecular mechanisms underlying various skin conditions, remain gaps knowledge, specifically with respect contribution maintenance barrier function. Towards this goal, we performed PubMed literature searches relevant define current knowledge and areas that may benefit from further research studies. Furthermore, identify alterations gene products are S-palmitoylated, utilized bioinformatic tools such SwissPalm analyzed data publicly available databases cBioportal. Since targeting S-palmitoylated targets offer an innovative treatment perspective, surveyed small molecules inhibiting including 2-bromopalmitate (2-BP) associated off-target effects, other strategies. Collectively, our work aims advance both basic clinical function focus zDHHCs contribute conditions atopic dermatitis, psoriasis, cancers melanoma.

Language: Английский

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DECIPHERING THE IMMUNE LANDSCAPE OF OVARIAN CANCER: AN IN-DEPTH ANALYSIS OF IGCH CD4+, CD8+, AND PD-L1 IN TUMOR MICROENVIRONMENT AND THEIR THERAPEUTIC IMPLICATIONS

Medical science of Uzbekistan, Journal Year: 2025, Volume and Issue: 1, P. 22 - 26

Published: Feb. 25, 2025

Relevance. Ovarian cancer is one of the most lethal gynecological malignancies worldwide, with high mortality primarily due to late-stage diagnosis and lack effective early screening. The tumor microenvironment (TME) plays a crucial role in progression, immune evasion, resistance therapy. Immune cells, particularly CD4+ CD8+ T along checkpoint proteins like PD-L1, significantly influence behavior therapeutic response. Understanding their roles ovarian may provide insights into novel immunotherapeutic strategies. Materials methods study. A total 135 patients from Republican Specialized Scientific Practical Medical Center Oncology Radiology, Samarkand Branch, were included this Tumor samples obtained through biopsy or surgical resection, profiling was performed using multiplex immunohistochemistry flow cytometry. expression levels CD4+, CD8+, PD-L1 quantified, spatial distribution within TME analyzed. Correlations between profiles clinical outcomes, including survival rates response immunotherapy, assessed. Research results. helper cells exhibited functional diversity, Th1 promoting anti-tumor immunity, whereas Th2 regulatory (Tregs) contributed suppression advanced tumors. High T-cell infiltration correlated improved survival; however, elevated associated exhaustion (PD-1, TIM-3, LAG-3) evasion. Increased linked poor prognosis, reinforcing its as key regulator. Conclusion. This study highlights prognostic significance cancer. aid personalized treatment strategies, optimizing immunotherapy efficacy. Future research should focus on integrating multi-omics approaches enhance patient stratification improve outcomes.

Language: Английский

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Programmed Cell Death Ligand as a Biomarker for Response to Immunotherapy: Contribution of Mass Spectrometry-Based Analysis

Cancers, Journal Year: 2025, Volume and Issue: 17(6), P. 1001 - 1001

Published: March 17, 2025

Immune checkpoint inhibition is a major component in today’s cancer immunotherapy. In recent years, the FDA has approved number of immune inhibitors (ICIs) for treatment melanoma, non-small-cell lung, breast and gastrointestinal cancers. These inhibitors, which target cytotoxic T-lymphocyte antigen-4, programmed cell death (PD-1), ligand (PD-L1) checkpoints have assumed leading role The same exert significant antitumor effects by overcoming tumor evasion reversing T-cell exhaustion. initial impact this therapy was justly described as revolutionary, however, clinical well research data followed demonstrated that these innovative drugs are costly, associated with potentially severe adverse effects, only benefit small subset patients. limitations encouraged enhanced efforts to identify predictive biomarkers stratify patients who most likely from form therapy. discovery characterization class pivotal guiding individualized against various forms cancer. Currently, there three FDA-approved biomarkers, none on its own can deliver reliable precise response Present literature identifies absence poor understanding mechanisms behind resistance main obstacles facing ICIs present text, we discuss dual PD-L1 biomarker immunotherapy an checkpoint. contribution mass spectrometry-based analysis, particularly protein post-translational modifications performance underlined.

Language: Английский

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Exploiting E3 Ligases for Lung Cancer Therapy: The Promise of DCAF-PROTACs

Pathology - Research and Practice, Journal Year: 2025, Volume and Issue: 270, P. 156001 - 156001

Published: May 10, 2025

Language: Английский

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Cracking the Codes behind Cancer Cells’ Immune Evasion

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8899 - 8899

Published: Aug. 15, 2024

Immune evasion is a key phenomenon in understanding tumor recurrence, metastasis, and other critical steps progression. The microenvironment (TME) constant flux due to the tumor's ability release signals that affect it, while immune cells within it can impact cancer cell behavior. Cancer undergo several changes, which change enrichment of different modulate activity existing microenvironment. evade surveillance by downregulating antigen presentation or expressing checkpoint molecules. High levels tumor-infiltrating lymphocytes (TILs) correlate with better outcomes, robust responses control growth. On contrary, increased Tregs, myeloid-derived suppressor cells, M2-like anti-inflammatory macrophages hinder effective predict poor prognosis. Overall, these mechanisms guides therapeutic strategies. Researchers aim TME enhance improve patient outcomes. In this review article, we strive summarize composition microenvironment, factors affecting (TIME), modalities targeting cells. This first-hand reference understand basics evasion.

Language: Английский

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Role and therapeutic potential of E3s in the tumor microenvironment of hepatocellular carcinoma

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 31, 2024

Hepatocellular carcinoma (HCC) is a high-incidence, poor-prognosis malignancy worldwide, requiring new strategies for treatment. Ubiquitination, especially ubiquitination through E3 ubiquitin ligases, plays an indispensable role in the development and progression of HCC. ligases are crucial enzymes ubiquitination, controlling degradation specific substrate proteins influencing various cellular functions, such as tumor cell proliferation, apoptosis, migration, immune evasion. In this review, we systematically summarize mechanisms HCC, with focus on significance RING, HECT, RBR types HCC progression. The review also looks at potential targeting to modulate microenvironment (TME) increase immunotherapy efficacy. Future studies will optimize treatment by formulating inhibitors or approaches that be based gene therapy order overcome resistance issues present treatments create optimism journey patients.

Language: Английский

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