Olaparib reverses prostate cancer resistance to Rapamycin by promoting macrophage polarization towards the M1 phenotype

Molecular and Cellular Biochemistry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 21, 2025

Язык: Английский

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Tumor Microenvironment On‐A‐Chip and Single‐Cell Analysis Reveal Synergistic Stromal–Immune Crosstalk on Breast Cancer Progression

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Март 8, 2025

Solid tumors develop within a complex environment called the tumor microenvironment (TME), which is sculpted by presence of other cells, such as cancer-associated fibroblasts (CAFs) and immune cells like macrophages (Mφs). Despite orchestrate tumor-supportive through intricate interaction with components TME. However, specific mechanism this intercellular dialogue regulated not fully understood. To that end, development an organotypic 3D breast TME-on-a-chip (TMEC) model, integrated single-cell RNA sequencing analysis, reported to mechanistically evaluate progression triple-negative cancer (TNBC) in patient-derived CAFs Mφs. Extensive functional assays, including invasion morphometric characterization, reveal synergistic influence Mφs on cells. Furthermore, gene expression pathway enrichment analyses identify involvement KYNU gene, suggesting potential evasion kynurenine pathway. Lastly, pharmacological targeting identified investigated.

Язык: Английский

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GLUT1 inhibitor BAY-876 induces apoptosis and enhances anti-cancer effects of bitter receptor agonists in head and neck squamous carcinoma cells

Cell Death Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Июль 25, 2024

Abstract Head and neck squamous cell carcinomas (HNSCCs) are cancers that arise in the mucosa of upper aerodigestive tract. The five-year patient survival rate is ~50%. Treatment includes surgery, radiation, and/or chemotherapy associated with lasting effects even when successful irradicating disease. New molecular targets therapies must be identified to improve outcomes for HNSCC patients. We recently bitter taste receptors (taste family 2 receptors, or T2Rs) as a novel candidate activate apoptosis cells through mitochondrial Ca 2+ overload depolarization. hypothesized targeting another component tumor metabolism, namely glycolysis, may increase efficacy T2R-directed therapies. GLUT1 ( SLC2A1 ) facilitated-diffusion glucose transporter expressed by many cancer fuel their increased rates glycolysis. already being investigated possible target, but studies HNSCCs limited. Examination immortalized cells, samples, Cancer Genome Atlas revealed high expression upregulation some samples. tissue express on plasma membrane within cytoplasm (perinuclear, likely co-localized Golgi apparatus). developed small molecule inhibitor GLUT1, BAY-876. This compound decreased uptake, viability, metabolism induced apoptosis. Moreover, BAY-876 had enhanced combined at low concentrations T2R receptor agonists. Notably, also TNFα-induced IL-8 production, indicating an additional mechanism tumor-suppressive effects. Our study demonstrates via kill particularly combination agonists, potential treatment strategy worth exploring further future translational studies.

Язык: Английский

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Integrins as Key Mediators of Metastasis

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 904 - 904

Опубликована: Янв. 22, 2025

Metastasis is currently becoming a major clinical concern, due to its potential cause therapeutic resistance. Its development involves series of phases that describe the metastatic cascade: preparation pre-metastatic niche, epithelial–mesenchymal transition, dissemination, latency and colonization new tissue. In last few years, targets, such as integrins, are arising face this disease. Integrins transmembrane proteins found in every cell have key role cascade. They intervene adhesion intracellular signaling dependent on extracellular matrix cytokines microenvironment. case, integrins can initiate guide formation niche increase tumor migration survival. also take part vascularization process necessary sustain metastasis. This fact emphasizes importance inhibitory therapies capable interfering with function

Язык: Английский

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Identification of the Molecular Subtype and Prognostic Characteristics of Breast Cancer Based on Tumor‐Infiltrating Regulatory T Cells

The Breast Journal, Год журнала: 2025, Номер 2025(1)

Опубликована: Янв. 1, 2025

Background: T regulatory cells (Tregs) are essential for preserving immune tolerance. They present in large numbers many tumors, hindering potentially beneficial antitumor responses. However, their predictive significance breast cancer (BC) remains ambiguous. This study aimed to explore genes associated with Tregs and develop a prognostic signature Tregs. Methods: The gene expression clinical data on BC were obtained from Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) databases. integration of CIBERSORT weighted correlation network analysis (WGCNA) algorithms was utilized identify modules consensus cluster algorithm create molecular subtypes determined by Then, constructed its relationship tumor immunity the prognosis evaluated. Results: blue module exhibited most significant Tregs, 1080 related acquired. A total 93 TCGA dataset found have impact patient prognosis. Samples categorized into two clusters analysis. overall survival, checkpoint genes, subtype, biological behaviors varied significantly between these subtypes. 10-gene developed differentially expressed demonstrated consistent accuracy both GEO datasets. It functioned as standalone marker individuals BC. In addition, patients low risk more inclined exhibit increased cell infiltration, TME score, mutation burden (TMB). Meanwhile, Individuals classified within low-risk group showed better responses immunotherapies compared counterparts high-risk group. Conclusions: model derived Tregs-related could aid assessing prognosis, guiding personalized treatment, enhancing outcomes

Язык: Английский

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Clusterin-mediated polarization of M2 macrophages: a mechanism of temozolomide resistance in glioblastoma stem cells

Stem Cell Research & Therapy, Год журнала: 2025, Номер 16(1)

Опубликована: Март 24, 2025

Glioblastoma remains one of the most lethal malignancies, largely due to its resistance standard chemotherapy such as temozolomide. This study investigates a novel mechanism involving glioblastoma stem cells (GSCs) and polarization M2-type macrophages, mediated by extracellular vesicle (EV)-based transfer Clusterin. Using 6-week-old male CD34+ humanized huHSC-(M-NSG) mice (NM-NSG-017) cell lines (T98G U251), we demonstrated that GSC-derived EVs enriched with Clusterin induce M2 macrophage polarization, thereby enhancing temozolomide in cells. Single-cell transcriptome sequencing revealed close interactions between GSCs highlighting key mediator. Our findings indicate Clusterin-rich from drive proliferation modulating phenotypes. Targeting this pathway could potentially reverse mechanisms, offering promising therapeutic approach for glioblastoma. not only sheds light on critical underpinning but also lays groundwork developing therapies targeting tumor microenvironment. results suggest paradigm shift understanding resistance, emphasizing potential disrupting EV-mediated communication

Язык: Английский

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Exosome‐related lncRNA score: A value‐based individual treatment strategy for predicting the response to immunotherapy in clear cell renal cell carcinoma

Cancer Medicine, Год журнала: 2024, Номер 13(11)

Опубликована: Май 29, 2024

Abstract Background Exosomes play a crucial role in intercellular communication clear cell renal carcinoma (ccRCC), while the long non‐coding RNAs (lncRNAs) are implicated tumorigenesis and progression. Aims The purpose of this study is to construction exosomes‐related lncRNA score ceRNA network predict response immunotherapy potential targeted drug ccRCC. Methods Data ccRCC patients were obtained from TCGA database. Pearson correlation analysis was used identify eExosomes‐related lncRNAs (ERLRs) Top10 genes that have been screened. entire cohort randomly divided into training validation equal scale. LASSO regression multivariate cox construct ERLRs‐based score. Differences clinicopathological characteristics, immune microenvironment, checkpoints, susceptibility between high‐ low‐risk groups also investigated. Finally, relevant constructed by machine learning analyze their targets use patients. Results A consisting 4ERLRs identified, with higher tended worse prognosis than those lower ROC curves Cox demonstrated could be considered as risk factor for both cohorts. Moreover, high scores predisposed experience poor overall survival, larger prevalence advanced stage (III‐IV), greater tumor mutational burden, infiltration immunosuppressive cells, likelihood responding favorably immunotherapy. importance EMX2OS determined mechanical learning, constructed, may therapeutic target, possibly exerting its function through EMX2OS/hsa‐miR‐31‐5p/TLN2 axis. Conclusions Based on novel predicting survival promising independent prognostic closely correlated microenvironment characteristics. Meanwhile, we screened out key lncRNAEMX2OS identified axis, which provide new clues therapy

Язык: Английский

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Drug-device-field Integration for Mitochondria-targeting Dysfunction and Tumor Therapy by Home-tailored Pyroelectric Nanocomposites

Biomaterials, Год журнала: 2024, Номер 316, С. 122990 - 122990

Опубликована: Дек. 2, 2024

Язык: Английский

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Nano‐Engineering Strategies for Tumor‐Specific Therapy

ChemMedChem, Год журнала: 2024, Номер 19(10)

Опубликована: Фев. 15, 2024

Nanodelivery systems (NDSs) provide promising prospects for decreasing drug doses, reducing side effects, and improving therapeutic effects. However, the bioapplications of NDSs are still compromised by their fast clearance, indiscriminate biodistribution, limited tumor accumulation. Hence, engineering modification aiming at promoting tumor-specific therapy avoiding systemic toxicity is usually needed. An NDS integrating various functionalities, including flexible camouflage, specific biorecognition, sensitive stimuli-responsiveness, into one sequence would be "smart" highly effective. Herein, we systematically summarize related principles, methods, progress. At end review, predict obstacles to precise nanoengineering future application NDSs.

Язык: Английский

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Design of a prodrug photocage for cancer cells detection and anticancer drug release

Talanta, Год журнала: 2024, Номер 274, С. 126002 - 126002

Опубликована: Март 27, 2024

Язык: Английский

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