Tumor Metastasis: Mechanistic Insights and Therapeutic Intervention

MedComm – Oncology, Год журнала: 2025, Номер 4(1)

Опубликована: Фев. 17, 2025

ABSTRACT Metastasis remains a leading cause of cancer‐related deaths, defined by complex, multi‐step process in which tumor cells spread and form secondary growths distant tissues. Despite substantial progress understanding metastasis, the molecular mechanisms driving this development effective therapies remain incompletely understood. Elucidating pathways governing metastasis is essential for discovery innovative therapeutic targets. The rapid advancements sequencing technologies expansion biological databases have significantly deepened our drivers associated drug resistance. This review focuses on particularly roles genetic mutations, epigenetic changes, post‐translational modifications progression. We also examine how microenvironment influences metastatic behavior explore emerging strategies, including targeted immunotherapies. Finally, we discuss future research directions, stressing importance novel treatment approaches personalized strategies to overcome improve patient outcomes. By integrating contemporary insights into basis innovation, provides comprehensive framework guide clinical cancer.

Язык: Английский

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An adoptive cell therapy with TREM2‐overexpressing macrophages mitigates the transition from acute kidney injury to chronic kidney disease

Clinical and Translational Medicine, Год журнала: 2025, Номер 15(3)

Опубликована: Фев. 25, 2025

Abstract Background Macrophages have been shown to contribute renal injury and fibrosis as well repair. Recently, Triggering Receptor Expressed on Myeloid Cells 2 (TREM2)‐positive macrophages play important roles in regulating tissue inflammation However, it remains unclear whether they can mitigate the transition from acute kidney chronic disease (the AKI–CKD transition). Methods The was generated by unilateral ischaemia–reperfusion (UIRI) wild‐type (WT) Trem2 knockout mice. F4/80 magnetic beads were used isolate macrophages. Flow cytometry determine levels of TREM2 CD11b levels. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR), Western blotting histological staining performed expression cytokines fibrotic markers. RNA‐seq investigate transcriptomic changes between WT bone marrow‐derived (BMDMs). TREM2‐overexpressing using lentivirus transferred intravenously UIRI Results exhibited a strong protective effect transition. Genetic deletion resulted increased exacerbated Interestingly, we found that hypoxia could increase via HIF‐1α. Upregulated enhanced macrophage phagocytosis suppressed pro‐inflammatory cytokines, resulting lower apoptosis tubular epithelial cells. Using analysis, showed regulatory effects orchestrated PI3K‐AKT pathway. Pharmacological regulation pathway modulate macrophage‐mediated phagocytosis. In addition, an adoptive cell therapy effectively reduced immune infiltration, Conclusion Our study not only provides valuable mechanistic insights into role but also offers new avenue for macrophage‐based treat diseases. Key points worsens accelerates is upregulated HIF1α An reduces fibrosis.

Язык: Английский

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Targeting endometrial inflammation in intrauterine adhesion ameliorates endometrial fibrosis by priming MSCs to secrete C1INH

iScience, Год журнала: 2023, Номер 26(7), С. 107201 - 107201

Опубликована: Июнь 25, 2023

Intrauterine adhesion (IUA) is a common cause of uterine infertility and its histopathologic characteristic endometrial fibrosis. A shortage stem cells in the basalis has been recognized as IUA development because approximately 90% patients suffer from after injury. In this study, we provide evidence that persistent inflammation main contributor to fibrosis patients. We further found treating an IUA-like mouse model with ITI-hUC-MSCs (hUC-MSCs reprogrammed by IL-1β, TNF-α IFN-γ) significantly decreased Mechanistically, high levels complement 1 inhibitor (C1INH) secreted prevented inducing profibrotic CD301+ macrophage polarization downregulating JAK-STAT signaling pathway. conclusion, endometria provides niche promote fibrosis, powerful immunomodulatory effects improve immune microenvironment regeneration.

Язык: Английский

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Chondroitin sulfate-modified tragacanth gum–gelatin composite nanocapsules loaded with curcumin nanocrystals for the treatment of arthritis

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Май 20, 2024

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disease of yet undetermined etiology that accompanied by significant oxidative stress, inflammatory responses, and damage to joint tissues. In this study, we designed chondroitin sulfate (CS)-modified tragacanth gum–gelatin composite nanocapsules (CS-Cur-TGNCs) loaded with curcumin nanocrystals (Cur-NCs), which rely on the ability CS target CD44 accumulate drugs in inflamed joints. Cur was encapsulated form into (TGNCs) using an inborn microcrystallization method, produced CS-Cur-TGNCs particle size approximately 80 ± 11.54 nm drug loading capacity 54.18 5.17%. vitro release assay, showed MMP-2-responsive properties. During treatment RA, significantly inhibited promoted polarization M2-type macrophages M1-type macrophages, decreased expression factors (TNF-α, IL-1β, IL-6). addition, it also exerted excellent anti-inflammatory effects, alleviated swelling joints during gouty (GA). Therefore, CS-Cur-TGNCs, as novel delivery system, could lead new ideas for clinical therapeutic regimens RA GA. Graphical

Язык: Английский

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Boosting Antitumor Immunity via a Tumor Microenvironment‐Responsive Transformable Trifecta Nanovaccine

Advanced Functional Materials, Год журнала: 2024, Номер 34(26)

Опубликована: Янв. 9, 2024

Abstract In situ tumor vaccines (ISTVs) hold great potential in immunotherapy, however, three major obstacles, including inadequate endogenous antigen uptake by dendritic cells (DCs), weak T‐cell immune responses, and stubborn immunosuppressive microenvironment (TME), still need to be fully addressed. Herein, a trifecta nanovaccine (TriNV) with TME‐responsive transformable ability is developed tri‐boost antitumor immunity. First, sufficient tumor‐associated antigens (TAAs) are liberated after immunogenic cell death induced via TriNV‐based photoimmunotherapy. the TME, soft‐transformed TriNV improves of TAAs DCs enhance acquired Second, self‐adjuvating released Mn 2+ synergistically promote DC maturation macrophage M1 polarization augmenting stimulator interferon genes activation further amplify responses. Moreover, decomposition MnO 2 within core exhausts glutathione facilitates O release alleviate hypoxia thereby overcoming chemical obstacles TME mitigate immunosuppression. Thus, remarkably eradicates primary tumors inhibits distant metastasis, thus demonstrating as feasible effective ISTV nanoplatform for combating poorly solid tumors.

Язык: Английский

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Spermidine synthase promotes liver cancer progression in a paracrine manner by altering the macrophage immunometabolic state

Bioorganic Chemistry, Год журнала: 2025, Номер 155, С. 108135 - 108135

Опубликована: Янв. 7, 2025

Язык: Английский

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Macrophage metabolism in nonalcoholic fatty liver disease

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Окт. 4, 2023

Nonalcoholic fatty liver disease (NAFLD) and its inflammatory often progressive subtype nonalcoholic steatohepatitis (NASH), have emerged as significant contributors to hepatic morbidity worldwide. The pathophysiology of NAFLD/NASH is multifaceted, variable, remains incompletely understood. pivotal role liver-resident recruited macrophages in the pathogenesis NAFLD NASH widely acknowledged a crucial factor innate immunity. remarkable plasticity enables them assume diverse activation polarization states, dictated by their immunometabolism microenvironment functional requirements. Recent studies field elucidated that alterations metabolic profile can profoundly influence state functionality, thereby influencing various pathological processes. This review primarily focuses on elucidating states macrophages, highlighting correlation between characteristics transition from pro-inflammatory anti-inflammatory phenotypes. Additionally, we explore potential targeting macrophage metabolism promising therapeutic approach for management NAFLD/NASH.

Язык: Английский

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Protozoan‐Derived Cytokine‐Transgenic Macrophages Reverse Hepatic Fibrosis

Advanced Science, Год журнала: 2024, Номер 11(13)

Опубликована: Янв. 21, 2024

Abstract Macrophage therapy for liver fibrosis is on the cusp of meaningful clinical utility. Due to heterogeneities macrophages, it urgent develop safer macrophages with a more stable and defined phenotype treatment fibrosis. Herein, new macrophage‐based immunotherapy using stably expressing pivotal cytokine from Toxoplasma gondii , parasite that infects ≈ 2 billion people developed. It found macrophage migration inhibitory factor‐transgenic (Mφ tgmif ) shows fibrinolysis strong chemotactic capacity. Mφ effectively ameliorates deactivates aHSCs by recruiting Ly6C hi via paracrine CCL2 polarizing them into restorative lo through secretion CX3CL1. Remarkably, exhibits even higher potential, lower grade inflammation, better therapeutic effects than LPS/IFN‐γ‐treated making immune efficient safer. Mechanistically, Tg MIF promotes expression activating ERK/HMGB1/NF‐κB pathway, this event associated endogenous liver. The findings do not merely identify viable but also suggest strategy based evolutionarily designed immunomodulator treat human diseases modifying microenvironment.

Язык: Английский

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The Interface of Tumour-Associated Macrophages with Dying Cancer Cells in Immuno-Oncology

Cells, Год журнала: 2022, Номер 11(23), С. 3890 - 3890

Опубликована: Дек. 2, 2022

Tumour-associated macrophages (TAMs) are essential players in the tumour microenvironment (TME) and modulate various pro-tumorigenic functions such as immunosuppression, angiogenesis, cancer cell proliferation, invasion metastasis, along with resistance to anti-cancer therapies. TAMs also mediate important anti-tumour can clear dying cells via efferocytosis. Thus, not surprisingly, exhibit heterogeneous activities functional plasticity depending on type context of death that they faced with. This ultimately governs both anti-tumorigenic activity TAMs, making interface between very for modulating growth efficacy chemo-radiotherapy or immunotherapy. In this review, we discuss from perspectives pathways, TME-driven variations, TAM heterogeneity cell-death-inducing We believe a better understanding how influence lead improved combinatorial therapies, especially combination TAM-targeting immunotherapies.

Язык: Английский

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Mechanisms regulating wound healing: Functional changes in biology mediated by lactate and histone lactylation

Journal of Cellular Physiology, Год журнала: 2023, Номер 238(10), С. 2243 - 2252

Опубликована: Сен. 24, 2023

Abstract The high incidence, low healing rate and huge economic burden of wounds (especially chronic wounds) worldwide remain a great challenge for clinical staff patients. various stages wound are regulated by paracrine or autocrine cytokines growth factors, the study their intrinsic mechanisms is prerequisite better treatment. Lactate, end product glycolysis, plays role in all healing, recent studies have identified lactate as an epigenetic regulator that regulates gene expression through histone lysine lactylation stimulates posttranslational modifications to regulate related expression, thereby causing series biological functional changes. This article reviews progress research on during diseases, including its involvement immune regulation, inflammation control, proliferative remodeling, finally describes prospects therapy regarding healing.

Язык: Английский

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