The role of exosomes in liver cancer: comprehensive insights from biological function to therapeutic applications

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Окт. 21, 2024

In recent years, cancer, especially primary liver cancer (including hepatocellular carcinoma and intrahepatic cholangiocarcinoma), has posed a serious threat to human health. the field of exosomes play an important role in initiation, metastasis interaction with tumor microenvironment. Exosomes are class nanoscale extracellular vesicles (EVs)secreted by most cells rich bioactive molecules, including RNA, proteins lipids, that mediate intercellular communication during physiological pathological processes. This review reviews multiple roles progression, as well their effects on angiogenesis, epithelial-mesenchymal transformation (EMT), immune evasion, drug resistance. have great potential biomarkers for diagnosis prognosis because they carry specific molecular markers facilitate early detection evaluation treatment outcomes. addition, exosomes, new type delivery vector, unique advantages targeted therapy provide strategy cancer. The challenges prospects exosome-based immunotherapy were also discussed. However, such standardization isolation techniques scalability therapeutic applications remain significant hurdles.

Язык: Английский

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Heat-Induced Phosphatidylserine Changes Drive HSPA1A's Plasma Membrane Localization

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 2, 2024

Abstract Heat shock protein A1A (HSPA1A) is a molecular chaperone crucial in cell survival. In addition to its cytosolic functions, HSPA1A translocates heat-shocked and cancer cells’ plasma membrane (PM). cancer, PM-localized (mHSPA1A) associated with increased tumor aggressiveness therapeutic resistance, suggesting that preventing localization could have value. This translocation depends on HSPA1A’s interaction PM phospholipids, including phosphatidylserine (PS). Although PS binding regulates localization, the exact trigger for this movement remains unclear. Given lipid modifications are hallmark, we hypothesized driving heat-induced changes levels response heat stress. We tested hypothesis using pharmacological inhibition RNA interference (RNAi) targeting synthesis, combined confocal microscopy, lipidomics, western blotting. Lipidomic analysis PS-specific biosensors confirmed shock-induced increase, peaking immediately post-stress. Inhibition of synthesis fendiline RNAi significantly reduced while depletion cholesterol or fatty acids had minimal effects, confirming specificity PS. Further experiments showed saturation elongation did not impact indicating total rather than specific species, critical factor. These findings reshape current models trafficking, demonstrating regulator during response. work offers new insights into lipid-regulated trafficking highlights importance controlling cellular responses

Язык: Английский

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A highly sensitive and reusable magnetic nano-electrochemical biosensor for the detection of the liver cancer biomarker heat shock protein 70

Chemical Engineering Journal, Год журнала: 2025, Номер unknown, С. 159860 - 159860

Опубликована: Янв. 1, 2025

Язык: Английский

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Exosome: an overview on enhanced biogenesis by small molecules

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 25, 2025

Язык: Английский

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The Role of HSP70 in Regulation of Breast Cancer Stem Cells and Apoptotic Pathway

IntechOpen eBooks, Год журнала: 2025, Номер unknown

Опубликована: Март 25, 2025

HSP70 is a molecular chaperone that plays critical role in normal physiology of the cell and highly activated under pathological conditions such as cancer. It has been well established implicated breast cancer development progression. Highly linked to processes, proliferation, metastasis, drug resistance, driving anti-apoptotic pathways. In Luminal A subtype, stabilizes ESR1 (estrogen receptor 1) PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) pathways, supporting survival, while B its interaction with Cyclin D1 TP53 contributes treatment resistance. HER2 (+) triggers aggressive tumor growth by increasing human epidermal factor 2 (HER2) signaling via stabilizing protein. triple-negative (TNBC), it supports stem cell-like properties interacting neurogenic locus notch homolog protein 1 (NOTCH1) nuclear factor-kappa (NF-κB) suppressing The effect on cells (CSCs) an important limiting therapeutic response initiating potential metastasis. turn, inhibits apoptosis, preventing death through B-cell lymphoma (BCL-2) stabilization suppression caspase activity. This review aims provide integrative view biology addressing functions subtypes, interactions apoptosis.

Язык: Английский

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H3K9/18 lactylation regulates DNA damage due to nickel exposure in human bronchial epithelial cells

Toxicology and Applied Pharmacology, Год журнала: 2025, Номер 499, С. 117347 - 117347

Опубликована: Апрель 16, 2025

Язык: Английский

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The Confluence of Nanotechnology and Heat Shock Protein 70 in Pioneering Glioblastoma Multiforme Therapy: Forging Pathways Towards Precision Targeting and Transformation

Advances in Pharmacological and Pharmaceutical Sciences, Год журнала: 2025, Номер 2025(1)

Опубликована: Янв. 1, 2025

Heat-shock protein 70 (HSP70) and nanotechnology have emerged as promising avenues in glioblastoma multiforme (GBM) therapy, addressing the critical challenges posed by its aggressive nature therapeutic resistance. HSP70's dual role cellular stress response tumour survival emphasises potential both a biomarker target. This review explores innovative integration of HSP70 with nanotechnology, emphasising advancements imaging, drug delivery combination therapies. Nanoparticles, including SPIONs, liposomes, gold nanoparticles metal-organic frameworks, demonstrate enhanced targeting efficacy through modulation. Functionalized nanocarriers exploit tumour-specific overexpression to improve delivery, minimise off-target effects overcome blood-brain barrier. Emerging strategies such chemophototherapy, immunotherapy photothermal therapy leverage interactions within microenvironment, enabling synergistic treatment modalities. The also highlights translational challenges, heterogeneity GBM, regulatory hurdles variability permeability retention (EPR) effect. Integrating computational modelling, personalised approaches adaptive trial designs is crucial for clinical translation. By bridging molecular biology, HSP70-targeted hold transformative redefine GBM diagnosis treatment, offering hope improved quality life. Trial Registration: ClinicalTrials.gov identifier: NCT00054041 NCT04628806.

Язык: Английский

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Extracellular RNAs (exRNAs): Functions, Crosstalks, and Therapeutic Potential

Опубликована: Янв. 1, 2025

Язык: Английский

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Mixtures of Three Mortaparibs with Enhanced Anticancer, Anti-Migration, and Antistress Activities: Molecular Characterization in p53-Null Cancer Cells

Cancers, Год журнала: 2024, Номер 16(12), С. 2239 - 2239

Опубликована: Июнь 17, 2024

Mortalin, a member of the Hsp70 family proteins, is commonly enriched in many types cancers. It promotes carcinogenesis and metastasis multiple ways which inactivation tumor suppressor activity p53 has been firmly established. The downregulation mortalin and/or disruption mortalin–p53 interactions by small molecules earlier shown to activate function yielding growth arrest/apoptosis cancer cells. Mortaparibs (Mortaparib, MortaparibPlus, MortaparibMild) are chemical inhibitors isolated cell-based two-way screening involving (i) shift staining pattern from perinuclear (characteristics cells) pancytoplasmic normal (ii) nuclear enrichment p53. They have similar structures also cause inhibition PARP1 hence were named Mortaparibs. In present study, we report anticancer anti-metastasis MortaparibMild (4-[(4-amino-5-thiophen-2-yl-1,2,4-triazol-3-yl)sulfanylmethyl]-N-(4-methoxyphenyl)-1,3-thiazol-2-amine) p53-null By extensive molecular analyses cell proliferation, arrest, apoptosis pathways, demonstrate that although it causes relatively weaker cytotoxicity compared Mortaparib its lower concentrations equally potent inhibit migration. We developed combinations (called MortaparibMix-AP, MortaparibMix-AM, MortaparibMix-AS) consisting different ratios three for specifically enhancing their anti-proliferation, anti-migration, antistress activities, respectively. Based on control treated cells, suggest mixtures may be considered further laboratory clinical studies validating use treatment as well prevention relapse metastasis.

Язык: Английский

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Lysis of Extracellular Vesicles and Multiplexed Protein Detection via a Reverse Phase Immunoassay Using a Gold-Nanoparticle-Embedded Membrane Platform

Langmuir, Год журнала: 2024, Номер 40(42), С. 22177 - 22189

Опубликована: Окт. 10, 2024

Extracellular vesicles (EVs) are cell-derived membrane-bound particles with molecular cargo reflective of their cell origin. Analysis disease-related EVs and associated from biofluids is a promising tool for disease management. To facilitate the analysis intravesicular molecules, EV lysis needed. Moreover, highly sensitive multiplexed detection methods required to achieve early diagnostics. While approaches have been well studied, effects on downstream lacking. In this work, we analyzed chemical, thermal, mechanical determined efficiency based particle concentration immunoassay activity. We, first time, discovered that vortex was an efficient method used it surface markers in reverse phase gold-nanoparticle-embedded membrane. phosphate-buffered saline, limits up 3 orders magnitude lower than enzyme-linked immunosorbent assay were achieved. spiked human plasma, as low 7.27 × 104 EVs/mL achieved, making suitable These results demonstrated effective pipeline lysing complex biofluids, paving way broad applications biomedicine.

Язык: Английский

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