Matrix stiffness affects tumor-associated macrophage functional polarization and its potential in tumor therapy

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 21, 2024

The extracellular matrix (ECM) plays critical roles in cytoskeletal support, biomechanical transduction and biochemical signal transformation. Tumor-associated macrophage (TAM) function is regulated by stiffness solid tumors often associated with poor prognosis. ECM stiffness-induced mechanical cues can activate cell membrane mechanoreceptors corresponding mechanotransducers the cytoplasm, modulating phenotype of TAMs. Currently, tuning TAM polarization through stimulation has received increasing attention, whereas its effect on fate rarely been summarized. A better understanding relationship between will contribute to development new strategies for cancer therapy. In this review, we first introduced overall stiffness, analyzed changes mediated tumor progression, finally summarized effects targeting prognosis provide insight into field.

Language: Английский

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Macrophage-mediated immunomodulation in biomaterial-assisted bone repair: Molecular insights and therapeutic prospects

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 488, P. 150631 - 150631

Published: March 26, 2024

The skeletal system is essential for preserving body structure and facilitating mobility; however, bone diseases frequently result in significant disabilities, necessitating the investigation into biomaterials restoration. Nevertheless, these may elicit immune reactions that obstruct healing process. Macrophages assume a pivotal role modulating inflammation sustaining homeostasis regeneration. A comprehensive understanding of molecular interactions between macrophages imperative development sophisticated designed to regulate environment promote remodeling. This review delves generation, polarization, interaction with principal cell types implicated osteogenesis, detailing mechanisms by which influence repair their response biomaterials. Additionally, it discusses strategies precise modulation macrophage functionality via intelligent mechanisms, outlines challenges constraints designing integrate functions. By elucidating challenges, lays groundwork creation advanced endowed smart immunomodulatory capabilities, heralding novel approaches treatment defects advancement regeneration therapies.

Language: Английский

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Targeting focal adhesion kinase boosts immune response in KRAS/LKB1 co-mutated lung adenocarcinoma via remodeling the tumor microenvironment

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: Jan. 30, 2024

KRAS mutation is one of the most common oncogenic drivers in NSCLC, however, response to immunotherapy heterogeneous owing distinct co-occurring genomic alterations. KRAS/LKB1 co-mutated lung adenocarcinoma displays poor PD-1 blockade whereas mechanism remains undetermined.

Language: Английский

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Discovery of 2,4-diaminopyrimidine derivatives as potent inhibitors of FAK capable of activating the Hippo pathway for the treatment of esophageal squamous cell carcinoma

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 287, P. 117328 - 117328

Published: Feb. 2, 2025

Language: Английский

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ADME gene-driven prognostic model for bladder cancer: a breakthrough in predicting survival and personalized treatment

Hereditas, Journal Year: 2025, Volume and Issue: 162(1)

Published: March 19, 2025

Abstract Background Genes that participate in the absorption, distribution, metabolism, excretion (ADME) processes occupy a central role pharmacokinetics. Meanwhile, variability clinical outcomes and responses to treatment is notable bladder cancer (BLCA). Methods Our study utilized expansive datasets from TCGA GEO explore prognostic factors cancer. Utilizing both univariate Cox regression lasso techniques, we identified ADME genes critical for patient outcomes. our study, model assessing risk was constructed. The evaluation of this model's predictive precision conducted using Kaplan–Meier survival curves assessments based on ROC curves. Furthermore, devised nomogram, offering straightforward visualization crucial indicators. To potential mediating differences between high low groups, performed comprehensive analyses including Gene Ontology (GO) Kyoto Encyclopedia Genomes (KEGG)-based enrichment analyses, immune infiltration variations, somatic mutation landscapes, pharmacological sensitivity response assessment etc. Immediately following this, selected core PPI network explored as well modulation, pathway activation. And differential expression verified by immunohistochemistry qRT-PCR. Finally pan-cancer biomarkers. Results efforts culminated establishment validated 17-gene ADME-centered prediction model, displaying remarkable accuracy BLCA prognosis. Through separate cox importance model’s score forecasting substantiated. novel nomogram incorporating variables alongside introduced. Comprehensive studies established strong correlation several key indicators: patterns cell infiltration, reactions immunotherapy, landscape profiles drug sensitivity. We screened gene CYP2C8, its tumor bioregulation upregulated found it can serve reliable biomarker pan-cancer. Conclusion formulated research stands formidable instrument prognosis, while also providing insights into disease's progression mechanisms guiding decision-making strategies.

Language: Английский

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Identifying squalene epoxidase as a metabolic vulnerability in high‐risk osteosarcoma using an artificial intelligence‐derived prognostic index

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(2)

Published: Feb. 1, 2024

Osteosarcoma (OSA) presents a clinical challenge and has low 5-year survival rate. Currently, the lack of advanced stratification models makes personalized therapy difficult. This study aims to identify novel biomarkers stratify high-risk OSA patients guide treatment.

Language: Английский

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Simultaneous inhibition of FAK and ROS1 synergistically repressed triple-negative breast cancer by upregulating p53 signalling

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Jan. 25, 2024

Abstract Background Triple-negative breast cancer (TNBC) is an aggressive subtype lacking effective targeted therapies, necessitating innovative treatment approaches. While targeting ROS proto-oncogene 1 (ROS1) with crizotinib has shown promise, resistance remains a limitation. Recent evidence links focal adhesion kinase (FAK) to drug resistance, prompting our study assess the combined impact of FAK inhibitor IN10018 and in TNBC elucidate underlying mechanisms. Methods We employed Timer database analyze ROS1 mRNA levels adjacent normal tissues. Furthermore, we investigated correlation between FAK, ROS1, clinical prognosis using GSE database. conducted various vitro assays, including cell viability, colony formation, flow cytometry, EdU western blotting. Additionally, xenograft human organoid models were established therapy’s efficacy. To comprehensively understand synergistic anti-tumor mechanisms, utilized multiple techniques, such as RNA sequencing, immunofluorescence, C11-BODIPY staining, MDA assay, GSH assay. Results The revealed higher tissues compared Analysis GEO databases indicated that patients high expression had poorest prognosis. Western blotting confirmed increased p-FAK crizotinib-resistant cells. In experiments showed combination therapy down-regulated cyclin B1, p-Cdc2, Bcl2 while up-regulating BAX, cleaved-Caspase-3, cleaved-Caspase-9, cleaved PARP. models, tumor volume group was 73% smaller control ( p < 0.0001). resulted 70% reduction viability sequencing analysis cells highlighted enrichment oxidative stress, glutathione metabolism, p53 pathways. displayed fivefold rise reactive oxygen species level, 69% decrease GSH/GSSG ratio, sixfold increase lipid peroxidation comparison group. demonstrated upregulation SCL7A11 GPX4 downregulation addition reversed these effects. Conclusion Our demonstrates shows antitumor effects TNBC. Mechanistically, this inhibits proliferation, enhances apoptosis, induces ferroptosis, which associated levels.

Language: Английский

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Finite Element Modeling of Cells Adhering to a Substrate: An Overview

Applied Sciences, Journal Year: 2024, Volume and Issue: 14(6), P. 2596 - 2596

Published: March 20, 2024

In tissue formation and regeneration processes, cells often move collectively, maintaining connections through intercellular adhesions. However, the specific roles of cell–substrate cell-to-cell mechanical interactions in regulation collective cell migration are not yet fully understood. Finite element modeling (FEM) may be a way to assess more deeply biological, mechanical, chemical phenomena behind adhesion. FEM is powerful tool widely used simulate described by systems partial differential equations. For example, provides information on stress/strain state adhering substrate, as well its mechanobiological behavior. This review paper, after briefly describing basic principles adhesion, surveys most important studies that have utilized investigate structural response substrate how forces acting adhesive structures affect global

Language: Английский

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Focal adhesion kinase-mediated interaction between tumor and immune cells in the tumor microenvironment: implications for cancer-associated therapies and tumor progression

Clinical & Translational Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 13, 2024

Language: Английский

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Focal Adhesion Regulation as a Strategy against Kidney Fibrosis

ACS Chemical Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Chronic kidney fibrosis poses a significant global health challenge with effective therapeutic strategies remaining elusive. While cell–extracellular matrix (ECM) interactions are known to drive progression, the specific role of focal adhesions (FAs) in is not fully understood. In this study, we investigated FAs tubular epithelial cell by employing precise nanogold patterning modulate integrin distribution. We demonstrate that increasing ligand spacing disrupts clustering, thereby inhibiting FA formation and attenuating fibrosis. Importantly, enhanced activity associated both human disease specimens murine models. Mechanistically, regulate through mechanotransduction pathways, our vivo experiments show suppressing significantly mitigates mice. These findings highlight potential targeting as strategy, offering new insights into clinical intervention

Language: Английский

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