From silent partners to potential therapeutic targets: macrophages in colorectal cancer

Cancer Immunology Immunotherapy, Journal Year: 2025, Volume and Issue: 74(4)

Published: Feb. 25, 2025

Cancer cells grow and survive in the tumor microenvironment, which is a complicated process. As key part of how colorectal cancer (CRC) progresses, tumor-associated macrophages (TAMs) exhibit double role. Through angiogenesis, this TAM can promote growth cancers. Although being able to modify adjust immune great advantage, these also anti-cancer properties including direct killing cells, presenting antigens, aiding T cell-mediated responses. The delicate regulatory mechanisms between system tumors are composed complex network pathways regulated by several factors hypoxia, metabolic reprogramming, cytokine/chemokine signaling, cell interactions. Decoding figuring out systems become significant building targeted treatment programs. Targeting TAMs CRC involves disrupting chemokine signaling or adhesion molecules, reprogramming them an anti-tumor phenotype using TLR agonists, CD40 modulation, selectively removing subsets that growth. Multi-drug resistance, absence accurate biomarker, drug non-specificity major problems. Combining macrophage-targeted therapies with chemotherapy immunotherapy may revolutionize treatment. Macrophage studies will advance new technology multi-omics methodologies help us understand build specific efficient treatments.

Language: Английский

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“Diagnostic and Prognostic Biomarkers of Luminal Breast Cancer: Where are We Now?”

Breast Cancer Targets and Therapy, Journal Year: 2023, Volume and Issue: Volume 15, P. 525 - 540

Published: July 1, 2023

Luminal breast cancers are hormone receptor (estrogen and/or progesterone) positive that further divided into HER2-negative luminal A and HER2-positive B subtypes. According to currently accepted convention, they represent the most common subtypes of cancer, accounting for approximately 70% cases. Biomarkers play a critical role in functional characterization, prognostication, therapeutic prediction, rendering them indispensable clinical management invasive cancer. Traditional biomarkers include clinicopathological parameters, which increasingly extended by genetic other molecular markers, enabling comprehensive characterization patients with Liquid biopsies capturing analyzing circulating tumor cells (CTCs) DNA (ctDNA) emerging technologies envision personalized through precision oncology. This article reviews key cancer ongoing developments.

Language: Английский

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Applicability of Quantum Dots in Breast Cancer Diagnostic and Therapeutic Modalities—A State-of-the-Art Review

Nanomaterials, Journal Year: 2024, Volume and Issue: 14(17), P. 1424 - 1424

Published: Aug. 31, 2024

The increasing incidence of breast cancers (BCs) in the world population and their complexity high metastatic ability are serious concerns for healthcare systems. Despite significant progress medicine made recent decades, efficient treatment invasive still remains challenging. Chemotherapy, a fundamental systemic method, is burdened with severe adverse effects, efficacy limited by resistance development risk disease recurrence. Also, current diagnostic methods have certain drawbacks, attracting attention to idea developing novel, more sensitive detection therapeutic modalities. It seems solution these issues can be provided nanotechnology. Particularly, quantum dots (QDs) been extensively evaluated as potential targeted drug delivery vehicles and, simultaneously, sensing bioimaging probes. These fluorescent nanoparticles offer unlimited possibilities surface modifications, allowing attachment biomolecules, such antibodies or proteins, molecules, among others. In this work, we discuss applicability QDs cancer diagnostics light knowledge. We begin introducing molecular histopathological features BCs, standard regimens, methods. Further, QDs, along uptake, biodistribution patterns, cytotoxicity, described. Based on reports published years, present research possible QD use improving BC chemotherapeutic photosensitizing agents, stages development. also address limitations open questions regarding topic.

Language: Английский

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LncRNA PRBC induces autophagy to promote breast cancer progression through modulating PABPC1-mediated mRNA stabilization

Oncogene, Journal Year: 2024, Volume and Issue: 43(14), P. 1019 - 1032

Published: Feb. 16, 2024

Language: Английский

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In silico evaluation of potential breast cancer receptor antagonists from GC-MS and HPLC identified compounds in Pleurotus ostreatus extracts

RSC Advances, Journal Year: 2024, Volume and Issue: 14(33), P. 23744 - 23771

Published: Jan. 1, 2024

Introduction: Pharmacotherapeutic targets for breast cancer include the estrogen receptor (ER), progesterone (PR), and human epidermal growth factor (EGFR). Inhibitors of these receptors could be interesting therapeutic candidates treatment management (BC). Aim: This study used GC-MS HPLC to identify bioactive compounds in Pleurotus ostreatus (P. ostreatus) extracts applied silico methods potent EGFR, ER, PR inhibitors from as potential drug candidates. Method: were chemicals P. aqueous (PO-A), methanol (PO-M), ethanol (PO-E), chloroform (PO-C), n-hexane (PO-H). The PR, EGFR model optimization molecular docking compounds/control binding pocket simulated using AutoDock Vina PyRx. drug-likeness, pharmacokinetic, pharmacodynamic features prospective leads all anticipated. Result: results indicated existence 29 PO-A, 36 PO-M PO-E, 42 PO-C, 22 PO-H extracts. With only o-tolylamino-acetic acid (4-nitro-benzylidene)-hydrazide (-7.5 kcal mol-1) ethanolic extract bind receptor. on other hand, identified several with higher affinities than control. Ergotaman-3',6',18-trione (-8.1 mol-1), 5,10-diethoxy-2,3,7,8-tetrahydro-1H,6H-dipyrrolo[1,2-a:1',2'-d]pyrazine (-7.8 extract; (-8.4 had better affinity compared (-7.7 mol-1). Likewise, ergotaman-3',6',18-trione (-9.7 phenol, 2,4-bis(1,1-dimethyl ethyl) (-8.2 control, gefitinib (-7.9 regards EGFR. None or outperformed control any proteins. Phenols flavonoids such quercetin, luteolin, rutin, chrysin, apigenin, ellagic acid, naringenin their Conclusion: class phenols lead molecules due ability strongly proteins' receptors. These showed promising drug-like properties; they safe new creating anticancer medicines.

Language: Английский

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Trim21-mediated CCT2 ubiquitination suppresses malignant progression and promotes CD4+T cell activation in breast cancer

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(7)

Published: July 30, 2024

Abstract Breast cancer remains a significant global health challenge, and its mechanisms of progression metastasis are still not fully understood. In this study, analysis TCGA GEO datasets revealed increase in CCT2 expression breast tissues, which was associated with poor prognosis patients. Functional that promoted growth through activation the JAK2/STAT3 signaling pathway. Additionally, E3 ubiquitin ligase Trim21 facilitated ubiquitination degradation, significantly reversing protumor effects CCT2. Most interestingly, we discovered exosomal derived from cells suppressed proinflammatory cytokine secretion CD4 + T cell. Mechanistically, constrained Ca 2+ -NFAT1 signaling, thereby reducing CD40L on These findings highlight upregulation as potential driver immune evasion. Our study provides new insights into molecular underlying progression, suggesting is promising therapeutic target prognostic predictor for cancer.

Language: Английский

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Integrating single‐cell transcriptomics and machine learning to predict breast cancer prognosis: A study based on natural killer cell‐related genes

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(15)

Published: Aug. 1, 2024

Abstract Breast cancer (BC) is the most commonly diagnosed in women globally. Natural killer (NK) cells play a vital role tumour immunosurveillance. This study aimed to establish prognostic model using NK cell‐related genes (NKRGs) by integrating single‐cell transcriptomic data with machine learning. We identified 44 significantly expressed NKRGs involved cytokine and T functions. Using 101 learning algorithms, Lasso + RSF showed highest predictive accuracy nine key NKRGs. explored cell‐to‐cell communication CellChat, assessed immune‐related pathways microenvironment gene set variation analysis ssGSEA, observed immune components HE staining. Additionally, drug activity predictions potential therapies, expression validation through immunohistochemistry RNA‐seq confirmed clinical applicability of The nomogram high concordance between predicted actual survival, linking higher purity risk scores reduced score. NKRG‐based offers novel approach for assessment personalized treatment BC, enhancing precision medicine.

Language: Английский

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BUB1, miR-495-3p, and E2F1/E2F8 axis is associated with poor prognosis of breast cancer patients and infiltration of Th2 cells in the tumor microenvironment

Cancer Biomarkers, Journal Year: 2025, Volume and Issue: 42(3)

Published: March 1, 2025

Breast cancer, the most common cancer in women, is characterized by cell cycle dysregulation and chromosome segregation errors, leading to mitotic catastrophe genomic instability. Understanding these molecular mechanisms crucial for better diagnosis treatment. We used databases like TIMER 2.0, UALCAN, Oncomine determine differential expression of Budding uninhibited benzimidazole 1 (BUB1) normal pan-cancer tissues. we also Kaplan-Meier Plotter database analyze gene associations with survival outcomes, bc-GenExMiner v5.0 BUB1 histological subtypes, ctcRbase miR-TV identify microRNAs associated breast cancer. Our data show that overexpressed tumors, metastatic tissues, circulating tumor cells, shorter overall survival, disease-free relapse-free compared low-expression patients. strongly correlated E2F1/E2F8 expression, suggesting a potential regulatory relationship between genes. The study revealed negative correlation target miRNA miR-495-3p indicating was infiltration CD4+ T helper 2 (Th2) subtypes need further research.

Language: Английский

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Label‐Free Microscale Technologies for Isolation of Heterogeneous Circulating Tumor Cells

Advanced NanoBiomed Research, Journal Year: 2025, Volume and Issue: unknown

Published: May 8, 2025

The dissemination of primary solid tumor cells to distant organs, termed metastasis, is a major cause cancer‐related deaths. Circulating (CTCs), which can exist as individual or multicellular clusters, travel through the bloodstream. Their isolation from liquid biopsy samples increasingly recognized valuable tool for diagnosis, prognosis, and treatment guidance cancer patients. Current methods typically rely on biomarkers like epithelial cell adhesion molecule (EpCAM) utilize technologies such magnetic beads microfluidic chips. However, these face limitations due heterogeneity. Furthermore, that transfer into CTCs often undergo epithelial‐to‐mesenchymal transition, gaining invasive characteristics while losing markers. As result, are difficult detect using EpCAM‐based methods. Label‐free microscale tackle biomarker‐based by leveraging distinctive physical properties CTCs, their size, electrical charge, viscoelasticity, deformability contrast them normal blood cells. This review evaluates label‐free methods, including deterministic lateral displacement, microfiltration, acoustophoresis, dielectrophoresis, whether they offer deeper insight heterogeneity dynamics progression treatment. Additionally, it highlights automated platforms high‐throughput CTC analysis.

Language: Английский

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FGFR1 overexpression promotes resistance to PI3K inhibitor alpelisib in luminal breast cancer cells through receptor tyrosine kinase signaling-mediated activation of the estrogen receptor

Cancer Drug Resistance, Journal Year: 2025, Volume and Issue: unknown

Published: May 28, 2025

Aim: Resistance to PI3K inhibitor alpelisib is an emerging challenge in breast cancer treatment. FGFR1 frequently amplified cancer. We investigated overexpression-mediated resistance and its mechanism. Methods: CCK-8, colony formation, cell cycle assays assessed overexpression-induced MCF-7 T47D cells. siRNA knockdown validated FGFR1’s role. Akt, Erk, ER signaling were analyzed by Western blot. Synergistic effects of with AZD4547 fulvestrant evaluated using the combination index. Results: overexpression conferred cells, evidenced increased viability, S-phase accumulation post Knockdown reverse overexpressing correlated sustained activation Akt Erk1/2 pathways (p-Akt, p-Erk1/2, p-S6K, p-Rb) attenuated suppression ERα phosphorylation (S118/S167), highlighting RTK-ER crosstalk. Combining synergistically inhibited growth suppressed both RTK phosphorylation. While alpelisib-fulvestrant was effective, adding further enhanced inhibition, supporting triple therapy overcome resistance. Conclusion: Our findings establish as a key mediator ER+ inhibitors alpelisib-based therapies offers viable approach for FGFR1-overexpressing tumors.

Language: Английский

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