Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 13, 2025

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.

Language: Английский

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Brd7 loss reawakens dormant metastasis initiating cells in lung by forging an immunosuppressive niche

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 5, 2025

Metastasis in cancer is influenced by epigenetic factors. Using an vivo screen, we demonstrate that several subunits of the polybromo-associated BAF (PBAF) chromatin remodeling complex, particularly Brd7, are required for maintaining breast metastatic dormancy lungs female mice. Brd7 loss induces reawakening, along with modifications epigenomic landscapes and upregulated oncogenic signaling. Breast cells harboring inactivation also reprogram surrounding immune microenvironment downregulating MHC-1 expression promoting a pro-metastatic cytokine profile. Flow cytometric single-cell analyses reveal increased levels pro-tumorigenic inflammatory transitional neutrophils, CD8+ exhausted T cells, CD4+ stress response from mice Brd7-deficient metastases. Finally, attenuating this immunosuppressive milieu neutrophil depletion, extracellular trap (NET) inhibition, or checkpoint therapy abrogates outgrowth. These findings implicate PBAF triggering outgrowth cancer, pointing to targetable underlying mechanisms involving specific cell compartments. Metastasis-initiating can reawaken dormant state initially allowed them survive, Here, authors show promotes tumor drives reawakening lung.

Language: Английский

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Mast cells: key players in digestive system tumors and their interactions with immune cells

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 15, 2025

Abstract Mast cells (MCs) are critical components of both innate and adaptive immune processes. They play a significant role in protecting human health the pathophysiology various illnesses, including allergies, cardiovascular diseases autoimmune diseases. Recent studies tumor-related research have demonstrated that mast exert substantial influence on tumor cell behavior microenvironment, exhibiting pro- anti-tumor effects. Specifically, not only secrete mediators related to pro-tumor function such as trypsin-like enzymes, chymotrypsin, vascular endothelial growth factor histamine, but also progression cystatin C IL-17F. This dual renders them an under-recognized very promising target for immunotherapy. Digestive system tumors, characterized by high morbidity associated mortality rates globally, increasingly recognized healthcare burden. paper examines cell-derived development tumors digestive system. It explores prognostic significance patients with gastrointestinal cancers at different stages disease. Additionally, article investigates interactions between cells, well potential relationships among intratumoral bacteria, within microenvironment. The aim is propose new strategies immunotherapy targeting cells.

Language: Английский

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Immature forms of low density granulocytes are increased in acute myeloid leukemia and myelodysplastic syndromes

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 13, 2025

Neutrophils can promote or suppress tumor growth. These different immunological functions mirror a great heterogenicity of neutrophil maturation and activation status: low-density granulocytes (LDGs) normal-density neutrophils (NDNs). LDGs participate in immune dysregulation during autoimmune disorders with an activated phenotype, while NDNs might exert immunosuppressive activities. Here, we investigated variations distribution benign malignant hematological conditions using optimized 10-color flow cytometry staining for immunophenotyping the main circulating populations. A total 102 consecutive subjects diagnosed malignancies was enrolled by cytometry. We showed impaired subset myelodysplastic syndromes (MDS) acute myeloid leukemia (AML) patients compared to healthy individuals, intermediate mature significantly reduced, also displaying good diagnostic sensitivity MDS (AUC, 0.793 P = 0.0013; AUC, 0.7319 0.0109, respectively) AML 0.9059 0.0069; 0.9176 0.00057, respectively). In conclusion, LDG NDN subsets could be altered MDS, favor more immature forms, suggesting that emergency hemopoiesis first mechanism sustain peripheral blood counts, maintaining pro-inflammatory microenvironment.

Language: Английский

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Emerging Path Promoting Neovascularization in Chronic Ischemia

JVS-Vascular Insights, Journal Year: 2025, Volume and Issue: unknown, P. 100190 - 100190

Published: Jan. 1, 2025

Language: Английский

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Construction of Tandem Multimers with Different Combinatorial Forms of BmSPI38 and BmSPI39 and Analysis of Their Expression and Activity in Escherichia coli

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1788 - 1788

Published: Feb. 20, 2025

It was found that the serine protease inhibitors BmSPI38 and BmSPI39 in silkworm can strongly inhibit activity of porcine pancreatic elastase, which has potential applicational value drug research development lung diseases, inflammatory skin aging caused by excessive release elastase. Previous studies have shown homotypic multimers obtained tandem expression significantly enhance antifungal structural homogeneity BmSPI39, while effect these two inhibitors, with different combinations, on total levels remains unclear. The aim this study is to explore whether it possible obtain combination strong protein engineering. In study, 40 multimer vectors combinatorial forms were constructed isocaudomer method, recombinant proteins prokaryotic system. target separated SDS-PAGE analyze forms. products investigated using in-gel staining technique inhibitors. results show containing module at carboxyl terminus generally higher Escherichia coli supernatant than terminus. indicate compared multimers, some stronger. Furthermore, level relatively when a module, such as dimers SPIAB SPIaB trimers SPIabB, SPIaaB, SPIbaB. fusion combinations E. successfully achieved. confirmed forms, based engineering, an effective way improve their levels. Additionally, number high exogenous also screened, for example, SPIbaA, SPIbbA, SPIbbB, This not only lays foundation production but provides reference construction multimerization exploration other

Language: Английский

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Neutrophil Extracellular Traps: Emerging Biomarker and Prototype of Functional Materials

Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown

Published: March 30, 2025

Abstract Functional biomaterials composed of multiple biomacromolecules have significant advantages over those made from a single type. However, harmoniously integrating various remains challenging. Neutrophil extracellular traps (NETs), an emerging biological structure released neutrophils, serve as natural prototype worth investigating and learning from. NETs consist intricate exhibit web‐like microstructure, endowing them with multifaceted roles in both physiological pathological processes. In this review, research progress is systematically examined on materials science perspective. First, the origin transformation are introduced, their functional mechanisms NET components thoroughly dissected rather than conventionally treating entity. Second, given complex functions, revealed potential biomarker for disease prediction. Third, typical characterization technologies analysis summarized. Fourth, artificial inspired by discussed. addition, regulatory processes provide bio‐inspired prototypes design advanced materials. Finally, perspectives opportunities challenges advancing presented biomarkers models development

Language: Английский

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Neutrophil Elastase and Elafin in Inflammatory Bowel Diseases: Urinary Biomarkers Reflecting Intestinal Barrier Dysfunction and Proteolytic Activity

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(7), P. 2466 - 2466

Published: April 4, 2025

Background: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's (CD), is a chronic inflammatory disorder driven by complex interplay of immune proteolytic mechanisms. Neutrophil elastase (NE), released at sites inflammation, plays central role promoting degrading the extracellular matrix (ECM), disturbing intestinal barrier integrity via NF-κB activation E-cadherin degradation. Elafin, an endogenous NE inhibitor, mitigates damage, reinforces barrier, exerts anti-inflammatory effects suppressing reducing pro-inflammatory cytokines. Since NE/elafin balance critical in IBD, assessing their ratio may provide more precise measure dysregulation. This study aimed to evaluate diagnostic prognostic utility urinary NE, elafin, IBD patients. Methods: Urinary concentrations elafin were measured immunoassay 88 subjects patients healthy individuals. The accuracy these biomarkers was assessed using receiver operating characteristic (ROC) curve analysis. Results: levels significantly elevated both UC CD compared controls, with 17-fold increase 28-fold (p < 0.0001). Elafin also increased groups, 4.5-fold 5.6-fold controls. ROC analysis demonstrated that most effective biomarker for distinguishing from individuals (AUC = 0.896), high sensitivity (92.9%) specificity (69.7%), making it strong tool. showed excellent performance 0.842) 0.880). profile had value, better 0.772) than 0.674), though inferior NE/elafin. Conclusions: Our findings indicate have significant value differentiating proved be reliable diagnosis, predictive discriminatory power.

Language: Английский

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Neutrophil elastase as a promising biomarker of low-grade inflammation in chronic non-communicable diseases

Russian Journal of Preventive Medicine, Journal Year: 2025, Volume and Issue: 28(4), P. 142 - 142

Published: April 28, 2025

The pathogenesis of many chronic non-communicable diseases (NCDs) is associated with low-grade (low-intensity) inflammation. One the most important mechanisms in development inflammation activation proteolysis system, which regulates biological processes through post-translational modification proteins. A clinically significant proteolytic enzyme neutrophil elastase (NE), belongs to GASPIDs (Granule-Associated Serine Peptidases Immune Defense). In inflammation, NE exerts its catalytic activity and damaging potential, acting on a wide range structural regulatory proteins, thus participating several NCDs. commonly used scientific clinical laboratory methods for assessing NE, both circulating complexed an inhibitor, are reviewed. Objective. To analyze Russian foreign publications relationship between prospects using as biomarker these diseases. Materials methods. literature search was performed eLibrary.ru PubMed databases keywords elastase, biomarkers, analysis methods, Results. biochemical structure analyzed, main functions NE-mediated regulation NCDs presented. test level possibilities conditions their use practice discussed. Conclusion. role non-infectious change level/activity blood serum patients compared those control groups support this promising predicting risk complications.

Language: Английский

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Neutrophil extracellular traps in diseases of the female reproductive organs

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: May 5, 2025

Neutrophil extracellular traps (NETs) are physiologically released in response to pathogens, serving as a defense mechanism. However, excessive NET production has been implicated various pathological conditions, including diseases of the female reproductive system. Recent studies highlight significant role neutrophils and NETs cancer pathogenesis. Overproduction creates sites for tumor cell adhesion, promoting proliferation, immune escape, progression. formation is associated with many diseases, cancers organs. Detection can be used prognostic tool patients characterized by higher rates formation, such cancer. In order use diagnosis, it possible determine them directly or components: DNA, citrullinated histones, NE MPO. This review explores pathogenesis, diagnosis treatment breast, ovarian, cervical endometrial cancer, premature lapse ovarian function, cervicitis, endometriosis, pregnancy pregnancy-related diseases.

Language: Английский

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