Reprogramming tumor-associated macrophages to outcompete endovascular endothelial progenitor cells and suppress tumor neoangiogenesis

Immunity, Journal Year: 2023, Volume and Issue: 56(11), P. 2555 - 2569.e5

Published: Nov. 1, 2023

Language: Английский

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Novel insights into Notch signaling in tumor immunity: potential targets for cancer immunotherapy

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 20, 2024

Notch signaling pathway is a highly conserved system of cell-to-cell communication that participates in various biological processes, such as stem cell maintenance, fate decision, proliferation and death during homeostasis development. Dysregulation has been associated with many aspects cancer biology, maintenance stem-like cells (CSCs), metabolism, angiogenesis tumor immunity. Particularly, can regulate antitumor or pro-tumor immune within the microenvironment (TME). Currently, drawn significant attention therapeutic development treatment. In this review, we focus on role remodeling microenvironment. We describe impact efficacy immunotherapies. Furthermore, summarize results relevant preclinical clinical trials Notch-targeted therapeutics discuss challenges their application therapy. An improved understanding involvement immunity will open door to new options immunotherapy

Language: Английский

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Angiogenesis within Atherosclerotic Plaques: Mechanical Regulation, Molecular Mechanism and Clinical Diagnosis

Mechanobiology in Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 100114 - 100114

Published: Feb. 1, 2025

Language: Английский

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Anti-Angiogenic Potential of Marine Streptomyces-Derived Lucknolide A on VEGF/VEGFR2 Signaling in Human Endothelial Cells

Molecules, Journal Year: 2025, Volume and Issue: 30(5), P. 987 - 987

Published: Feb. 20, 2025

Angiogenesis, primarily driven by the vascular endothelial growth factor (VEGF) and its receptor, VEGFR, plays a key role in various pathological processes such as cancer progression. Here, we investigated anti-angiogenic effects of Lucknolide A (LA), marine Streptomyces-derived compound, evaluated potential VEGFR2 inhibitor. LA selectively inhibited proliferation human cells EA.hy926 HUVEC while exhibiting minimal on normal fibroblasts tumor cells. induced S-phase cell cycle arrest apoptosis cells, increasing apoptotic markers p53, Bax, p21 decreasing anti-apoptotic protein Bcl-2, with these being further enhanced under VEGF stimulation. Additionally, suppressed phosphorylation downstream signaling pathways, including Akt/mTOR/p70S6K, MEK/ERK, Src, FAK, p38 MAPK, which are crucial for survival angiogenesis. Molecular docking studies revealed that binds to both inactive (DFG-out, PDB: 4ASD) active (DFG-in, 3B8R) conformations, significantly stronger affinity state (−107.96 kcal/mol) than (−33.56 kcal/mol), suggesting kinase Functionally, VEGF-induced migration, tube formation, microvessel sprouting vitro ex vivo rat aortic ring assays. reduced tumor-associated formation breast (MDA-MB-231), indicating suppress VEGF-dependent These findings suggest is promising selective agent therapeutic applications angiogenesis-related diseases cancer.

Language: Английский

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Dissecting endothelial cell heterogeneity with new tools

Cell Regeneration, Journal Year: 2025, Volume and Issue: 14(1)

Published: March 23, 2025

Abstract The formation of a blood vessel network is crucial for organ development and regeneration. Over the past three decades, central molecular mechanisms governing growth have been extensively studied. Recent evidence indicates that vascular endothelial cells—the specialized cells lining inner surface vessels—exhibit significant heterogeneity to meet specific needs different organs. This review focuses on current understanding cell heterogeneity, which includes both intra-organ inter-organ heterogeneity. Intra-organ encompasses arterio-venous tip-stalk specialization, while refers organ-specific transcriptomic profiles functions. Advances in single-cell RNA sequencing (scRNA-seq) enabled identification new subpopulations comparison gene expression patterns across subsets cells. Integrating scRNA-seq with other high-throughput technologies promises deepen our at epigenetic level spatially resolved context. To further explore human organoids offer powerful tools studying function three-dimensional culture systems investigating endothelial-tissue interactions using Developing presents unique opportunities unravel its implications disease. Emerging technologies, such as organoids, are poised transform pave way innovative therapeutic strategies address diseases. Graphical

Language: Английский

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The roles of metabolic profiles and intracellular signaling pathways of tumor microenvironment cells in angiogenesis of solid tumors

Cell Communication and Signaling, Journal Year: 2022, Volume and Issue: 20(1)

Published: Nov. 23, 2022

Abstract Innate and adaptive immune cells patrol survey throughout the human body sometimes reside in tumor microenvironment (TME) with a variety of cell types nutrients that may differ from those which they developed. The metabolic pathways metabolites are rooted physiology, not only provide energy for growth survival but also influencing differentiation effector functions. Nowadays, there is growing awareness processes occurring cancer can affect function lead to evasion angiogenesis. In order safely treat patients prevent checkpoint blockade-induced toxicities autoimmunity, we suggest using anti-angiogenic drugs solely or combined Immune blockers (ICBs) boost safety effectiveness therapy. As consequence, significant escalating attention discovering techniques target metabolism as new method this review, summary immune-metabolic their potential role stimulation intracellular signaling TME angiogenesis, therapeutic applications provided.

Language: Английский

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Genome-wide DNA hypermethylation opposes healing in patients with chronic wounds by impairing epithelial-mesenchymal transition

Journal of Clinical Investigation, Journal Year: 2022, Volume and Issue: 132(17)

Published: July 12, 2022

An extreme chronic wound tissue microenvironment causes epigenetic gene silencing. unbiased whole-genome methylome was studied in the wound-edge of patients with wounds. A total 4,689 differentially methylated regions (DMRs) were identified skin compared unwounded human skin. Hypermethylation more frequently observed (3,661 DMRs) hypomethylation (1,028 DMRs). Twenty-six hypermethylated DMRs involved epithelial-mesenchymal transition (EMT). Bisulfite sequencing validated hypermethylation a predicted specific upstream regulator TP53. RNA-Seq analysis performed to qualify findings from analysis. Analysis downregulated genes TP53 signaling pathway as being significantly silenced. Direct comparison and 4 genes, ADAM17, NOTCH, TWIST1, SMURF1, that functionally represent EMT pathway. Single-cell studies revealed these effects on expression limited keratinocyte cell compartment. Experimental murine established ischemia potently induces methylation 5'-azacytidine, inhibitor methylation, improved closure. To specifically address significance keratinocyte-specific editing at edge achieved by nanotransfection-based CRISPR/dCas9 approach. This work reversal methylation-dependent silencing represents productive therapeutic strategy improve

Language: Английский

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Extracellular Vesicles in Breast Cancer: From Biology and Function to Clinical Diagnosis and Therapeutic Management

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 7208 - 7208

Published: April 13, 2023

Breast cancer (BC) is the first worldwide most frequent in both sexes and commonly diagnosed females. Although BC mortality has been thoroughly declining over past decades, there are still considerable differences between women with early when metastatic diagnosed. treatment choice widely dependent on precise histological molecular characterization. However, recurrence or distant metastasis occurs even recent efficient therapies. Thus, a better understanding of different factors underlying tumor escape mainly mandatory. Among leading candidates continuous interplay cells their microenvironment, where extracellular vesicles play significant role. vesicles, smaller ones, also called exosomes, can carry biomolecules, such as lipids, proteins, nucleic acids, generate signal transmission through an intercellular transfer content. This mechanism allows to recruit modify adjacent systemic microenvironment support further invasion dissemination. By reciprocity, stromal use exosomes profoundly cell behavior. review intends cover literature role vesicle production normal cancerous breast tissues. Specific attention paid for diagnosis, follow-up, prognosis because actually under spotlight researchers high-potential source liquid biopsies. Extracellular new targets therapy nanovectors drive drug delivery summarized.

Language: Английский

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Tumor Microenvironment: A Niche for Cancer Stem Cell Immunotherapy

Stem Cell Reviews and Reports, Journal Year: 2023, Volume and Issue: 20(1), P. 3 - 24

Published: Oct. 20, 2023

Language: Английский

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The Role of Stem Cells as Therapeutics for Ischaemic Stroke

Cells, Journal Year: 2024, Volume and Issue: 13(2), P. 112 - 112

Published: Jan. 6, 2024

Stroke remains one of the leading causes death and disability worldwide. Current reperfusion treatments for ischaemic stroke are limited due to their narrow therapeutic window in rescuing penumbra. Stem cell therapy offers a promising alternative. As regenerative medicine, stem cells offer wider range treatment strategies, including long-term intervention chronic patients, through reparation replacement injured via mechanisms differentiation proliferation. The purpose this review is evaluate role stroke. This paper discusses pathology during acute, subacute, phases cerebral injury, highlights involved mesenchymal, endothelial, haematopoietic, neural cell-mediated cerebrovascular regeneration, evaluates pre-clinical clinical data concerning safety efficacy cell-based treatments. patients with different types appears be safe efficacious even at relatively higher concentrations irrespective route timing administration. priming or pre-conditioning prior administration help augment impact. However, larger patient cohorts later-phase trials required consolidate these findings.

Language: Английский

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