Tetraspanin CD81 promotes leukemia stem cell function and represents a new therapeutic vulnerability in acute myeloid leukemia DOI Open Access
Fanny Gonzales,

Pauline Peyrouze,

Thomas D. Boyer

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 26, 2023

Abstract Despite important progress over the last decade, acute myeloid leukemia (AML) is still associated with poor clinical outcome. Novel potent therapies ideally effective against AML stem cells (LSC), a major driver of initiation and progression, are urgently needed. In particular, targeting common AML-associated antigens at progenitor cell level represents an attractive therapeutic strategy to achieve deep long-term remissions currently subject intensive research efforts. this study, we identified tetraspanin CD81, surface antigen frequently expressed on including LSC, as new determinant relapse prognosis. CD81 expression was higher in compared normal bone marrow cells, more markedly relapse. We further showed that modulation using gain- loss-of-function approaches affected aggressiveness, tumor burden, LSC-homing - xenoengraftment well mouse survival. Finally, anti-hCD81 monoclonal antibody-treatment combined standard chemotherapy mice pre-established not only reduced burden but also prolonged relapse-free overall Collectively, these results efficacious safe pharmacological for opening up novel avenues improve Key points LSC aggressive disease Anti-hCD81 xenografts improved survival rates.

Language: Английский

Immunoassays for Extracellular Vesicle Detection via Transmembrane Proteins Using Surface Plasmon Resonance Biosensors DOI
Jesus M. Lopez Baltazar, Wenchao Gu, Markéta Bocková

et al.

ACS Sensors, Journal Year: 2024, Volume and Issue: 9(7), P. 3594 - 3603

Published: June 24, 2024

Extracellular vesicles (EVs) are preeminent carriers of biomarkers and have become the subject intense biomedical research for medical diagnostics using biosensors. To create effective EV-based immunoassays, it is imperative to develop surface chemistry approaches with optimal EV detection targeting transmembrane protein that not affected by cell-to-cell variability. Here, we developed a series immunoassays EVs derived from mouse monocyte cells plasmon resonance (SPR) We chemically immobilized antibodies onto mixed self-assembled monolayers oligo ethylene glycol (OEG) alkanethiolates carboxylic hydroxylic terminal groups. The effects antibody clonality (monoclonal vs polyclonal) coverage in via CD81 tetraspanins were investigated. determined binding kinetic parameters, establishing trends steric hindrance epitope recognition properties antibodies. Our results indicate 40% polyclonal covalently linked SAM 10% terminated −COOH groups yields promising approach linear range 1.9 × 108–1.9 109 EVs/mL limit 5.9 106 EVs/mL. This immunoassay exhibits 1.92 nM equilibrium dissociation constant bound EVs, suggesting high affinity when targeted. study provides important insights into development targeted antibodies, which has applications disease diagnostics.

Language: Английский

Citations

4
An updated review on the development of a nanomaterial-based field-effect transistor-type biosensors to detect exosomes for cancer diagnosis DOI
Jeongyun An, Hyunjun Park,

Minyoung Ju

et al.

Talanta, Journal Year: 2024, Volume and Issue: 279, P. 126604 - 126604

Published: July 22, 2024

Language: Английский

Citations

4
Ziziphus mauritiana Leaf Extract Induces ROS-dependent Apoptosis by Downregulation of CD81 in MDA- MB 231 Triple Negative Breast Cancer Cells DOI Creative Commons
Dian Lestari, Gondo Mastutik, Indri Safitri Mukono

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Abstract Background. Breast cancer (BC) is the most prevalent among women, with triple-negative breast (TNBC) representing a particularly aggressive subtype. Current treatments often have limited efficacy and significant toxicity, highlighting need for alternative therapeutic strategies. Ziziphus mauritiana (ZM) leaf extract contains triterpenoids which been proven to be used as anticancer agents, but not studied in TNBC cells. Aim. To examine triterpenoid content ZM, especially BA OA, ZM cytotoxicity, intracellular ROS levels, amount of apoptosis, CD81 expression on MDA-MB 231 cells after being given ZM. Material Methods. The was prepared using sequential extraction method. presence confirmed via HPLC LC-MS analysis. cytotoxicity assessed CCK-8 assay, while flow cytometry employed analyze levels. Apoptosis quantified an Annexin V-FITC/PI detection kit. Results. Based HPLC, 28.3 µg/ml, OA 13.4 µg/ml. significantly reduced cell viability by 28.28% at 400 µg/ml 48 hours. Flow revealed notable downregulation (p < 0.0001) increase levels 0.0001). Furthermore, induced early late apoptosis treated cells, increases 2.34-fold 2.66-fold, respectively. Conclusion. exhibits potent cytotoxic effects against through ROS-dependent downregulation, suggesting its potential novel agent treatment.

Language: Английский

Citations

0
Mesenchymal stromal cell exosomes for drug delivery of prostate cancer treatments: a review DOI Creative Commons

Chengran Wang,

Yanling Feng,

Xianfang Rong

et al.

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 23, 2025

Interest in prostate cancer as a research topic has gradually increased. As result, series of innovative treatment strategies have emerged with an in-depth understanding the disease. Owing to their unique biological characteristics, mesenchymal stromal cell exosomes (MSC-Exos) garnered significant attention for potential deliver targeted drugs and enable precise treatment. Herein, MSC-Exos drug-delivery systems is reviewed. This review provides comprehensive introduction advantages these systems, current trends progress, well analysis challenges future directions. Moreover, this lays solid foundation continued development application MSC-Exos.

Language: Английский

Citations

0
Distinctive function of Tetraspanins: Implication in viral infections DOI Creative Commons

Yuzhi Zhang,

Chengwei Pan, Sijie Wang

et al.

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

Published: March 7, 2025

Harboring four transmembrane domains in their structural hallmark, Tetraspanins (Tspans) are a family of glycoproteins with pivotal functions variety biological and cellular processes. Through interacting laterally each other or specific membrane proteins, Tspans organize tetraspanin-enriched microdomains (TEMs), modulating signaling, adhesion, fusion, proliferation. An abundance evidence has identified the multiple progression cancer as well underlying molecular mechanisms. Recently, plenty studies have focused on utilities by pathogens for infection, especially infection viruses. The expression correlates phase viral type virus, targeted therapies. In particular, perturbations host cells can affect attachment, intracellular trafficking, translation, virus assembly, release. this review, we summarize provide historical overview discovery characterization various kinds highlight diversity complexity, along life cycle. Furthermore, examined current understanding how involved regulatory mechanisms infection. This review aims to offer comprehensive targeting therapeutic intervention infections caused diverse pathogens.

Language: Английский

Citations

0
The State of the Art of Pediatric Multiple Sclerosis DOI Open Access
Raluca Ioana Teleanu, Adelina-Gabriela Niculescu,

Oana Aurelia Vladâcenco

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 8251 - 8251

Published: May 4, 2023

Multiple sclerosis (MS) represents a chronic immune-mediated neurodegenerative disease of the central nervous system that generally debuts around age 20-30 years. Still, in recent years, MS has been increasingly recognized among pediatric population, being characterized by several peculiar features compared to adult-onset disease. Unfortunately, etiology and mechanisms are poorly understood, rendering already limited treatment options with uncertain efficacy safety patients. Thus, this review aims shed some light on progress therapeutic strategies specifically addressed children adolescents. In regard, present paper briefly discusses etiology, risk factors, comorbidities, diagnosis possibilities for pediatric-onset (POMS), further moving detailed presentation current strategies, clinical trials, emerging alternatives. Particularly, promising care solutions indicated, including new formulations, stem cell therapies, cognitive training methods.

Language: Английский

Citations

10
A Synopsis of Hepatitis C Virus Treatments and Future Perspectives DOI Creative Commons
Christian Medina, Alexis García,

Francis Isamarg Crespo

et al.

Current Issues in Molecular Biology, Journal Year: 2023, Volume and Issue: 45(10), P. 8255 - 8276

Published: Oct. 11, 2023

Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic with HCV can lead to liver cirrhosis or cancer. Although some immune-competent individuals clear the virus, others develop chronic disease due viral mutations an impaired immune response. IFNs type I and III signal transduction induced by them are essential for proper antiviral effect. Research on cycle escape mechanisms has formed basis of therapeutic strategies achieve sustained virological response (SVR). The first therapies were based IFNα; then, IFNα plus ribavirin (IFN–RBV); pegylated-IFNα-RBV (PEGIFNα-RIV) improve cytokine pharmacokinetics. However, maximum SVR was 60%, several significant side effects observed, decreasing patients’ treatment adherence. development direct-acting antivirals (DAAs) significantly enhanced (>90%), compounds able inhibit replication without effects, even in paediatric populations. management coinfected HBV–HCV HCV–HIV patients also improved DAA PEG-IFNα-RBV (HBV–HCV). CD4 cells crucial effective IFNλ3, IL28B, TNF-α, IL-10, TLR-3, TLR-9 gene polymorphisms involved clearance, responses, hepatic pathologies. Future research should focus searching circumvent resistance-associated substitution (RAS) DAAs, new schemes different medical conditions, including organ transplant, vaccines long-lasting cellular humoral responses cross-protection against genotypes. goal minimise probability infection, chronicity carcinoma.

Language: Английский

Citations

5
Common carp (Cyprinus carpio) CD81 promoting CyHV-3 virus replication via regulating autophagy and RLRs-interferon signaling pathway DOI
Xuezhu Lee,

Zihan Fan,

Zhihong Huang

et al.

Fish & Shellfish Immunology, Journal Year: 2023, Volume and Issue: 143, P. 109181 - 109181

Published: Oct. 21, 2023

Language: Английский

Citations

4
Targeting Tetraspanins at Cell Interfaces: Functional Modulation and Exosome‐Based Drug Delivery for Precise Disease Treatment DOI
Kun Xu, Huixia Feng, Rui Zhao

et al.

ChemMedChem, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 17, 2024

Abstract Tetraspanins are key players in various physiological and pathological processes, including malignancy, immune response, fertilization, infectious disease. Affinity ligands targeting the interactions between tetraspanins partner proteins promising for modulating downstream signaling pathways, thus emerging as attractive candidates interfering related biological functions. Due to involvement vesicle biogenesis cargo trafficking, also regarded exosome markers, become molecular targets drug loading delivery. Given rapid development these areas, this minireview focuses on recent advances design engineering of affinity binders toward CD63, CD81, CD9. Their mechanism actions protein at cell interfaces treatment malignant diseases discussed. Strategies constructing exosome‐based delivery platforms reviewed, with emphasis important roles ligands. Finally, challenges future tetraspanin‐targeting therapy exosomal

Language: Английский

Citations

1
Betulinic acid and oleanolic acid modulate CD81 expression and induce apoptosis in triple-negative breast cancer cells through ROS generation DOI
Dian Lestari, Gondo Mastutik, Indri Safitri Mukono

et al.

Medical Oncology, Journal Year: 2024, Volume and Issue: 42(1)

Published: Dec. 7, 2024

Language: Английский

Citations

1