An innovative gene expression modulating strategy by converting nucleic acids into HNC therapeutics using carrier-free nanoparticles DOI Creative Commons

Heyuan Liu,

Yinong Huang,

Zongfang Li

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 11, 2024

Cell fate and microenvironmental changes resulting from aberrant expression of specific proteins in tumors are one the major causes inadequate anti-tumor immune response poor prognosis head neck cancer (HNC). Eukaryotic initiation factor 3C (eIF3c) has emerged as a promising therapeutic target for HNC due to its ability regulate protein levels tumor cells, but drug development is difficult achieve by targeting traditional protein-protein interactions. siRNA highly modality eIF3c, while application hindered challenges pertaining stability insufficient concentration specifically within sites. We employed method convert flexible siRNAs into stable biologically active infinite Auric-sulfhydryl coordination supramolecular (IacsRNAs). Through coordinated self-assembly, we successfully transformed eIF3C carrier-free nanotherapeutic agent Iacs-eif3c-RNA. The efficacy this was evaluated vivo using xenograft models, demonstrating antitumor effects. Iacs-eif3c-RNA demonstrated overcome pharmacological obstacle associated with eIF3C, significant reduction tissues, well effective cell proliferating suppression apoptosis promotion. In comparison monotherapy utilizing chemotherapeutic cisplatin, exhibited superior favorable biosafety. utilization presents innovative approach addressing treating challenges. Moreover, strategy demonstrates potential translation clinical drugs, extending applicability treatment other cancers various diseases.

Language: Английский

Targeting Triple NK Cell Suppression Mechanisms: A Comprehensive Review of Biomarkers in Pancreatic Cancer Therapy DOI Open Access
Sara Fanijavadi,

Mads Thomassen,

Lars Henrik Jensen

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 515 - 515

Published: Jan. 9, 2025

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor outcomes due to frequent recurrence, metastasis, and resistance treatment. A major contributor this the tumor's ability suppress natural killer (NK) cells, which are key players in immune system's fight against cancer. In PDAC, tumor microenvironment (TME) creates conditions that impair NK cell function, including reduced proliferation, weakened cytotoxicity, limited infiltration. This review examines how interactions between tumor-derived factors, TME contribute progression treatment resistance. To address these challenges, we propose a new "Triple Cell Biomarker Approach". strategy focuses on identifying biomarkers from three critical areas: characteristics, suppression mechanisms. approach could guide personalized treatments enhance activity. Additionally, highlight potential of combining cell-based therapies conventional repurposed drugs improve for PDAC patients. While progress has been made, more research needed better understand dysfunction develop effective overcome barriers.

Language: Английский

Citations

4
The Impact of Cancer Stem Cells in Colorectal Cancer DOI Open Access
Petru Radu, Mihai Zurzu, Anca Tigora

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4140 - 4140

Published: April 9, 2024

Despite incessant research, colorectal cancer (CRC) is still one of the most common causes fatality in both men and women worldwide. Over time, advancements medical treatments have notably enhanced survival rates patients with cancer. Managing metastatic CRC involves a complex tradeoff between potential benefits adverse effects treatment, considering factors like disease progression, treatment toxicity, drug resistance, overall impact on patient's quality life. An increasing body evidence highlights significance stem cell (CSC) concept, proposing that CSCs occupy central role triggering been focal point extensive research variety types, including CRC. Colorectal cells (CCSCs) play crucial tumor initiation, metastasis, therapy making them targets. Various methods exist for isolating CCSCs, understanding mechanisms resistance associated crucial. This paper offers an overview current pertaining to comprehension

Language: Английский

Citations

9
Cooperative Hedgehog/GLI and JAK/STAT signaling drives immunosuppressive tryptophan/kynurenine metabolism via synergistic induction of IDO1 in skin cancer DOI Creative Commons
Dominik P. Elmer,

Georg Stockmaier,

Sandra Grund‐Gröschke

et al.

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 17, 2025

Pharmacological targeting of Hedgehog (HH)/GLI has proven effective for certain blood, brain and skin cancers including basal cell carcinoma (BCC). However, limited response rates the development drug resistance call improved anti-HH therapies that take synergistic crosstalk mechanisms immune evasion strategies into account. In previous work, we demonstrated cooperation HH/GLI Interleukin 6 (IL6)/STAT3 signaling drives BCC growth. Whether HH-IL6 promotes via activation remained unclear. regulated immunosuppressive genes such as indoleamine 2,3-dioxygenase 1 (IDO1) were identified by gene expression profiling. IDO1 was evaluated in human melanoma models qPCR Western blot analyses. The cis-regulatory region interrogated HH-IL6-regulated GLI STAT transcription factor binding epigenetic modifications targeted chromatin-immunoprecipitation bisulfite pyrosequencing. Functional analyses effects involved HPLC-MS measurements its metabolites assessment T proliferation flow cytometry. Bioinformatic GLI-STAT conducted on published bulk single-cell RNA-seq data patients. We a target cooperative activity melanoma. GLI1 STAT3 factors synergistically enhanced jointly to increasing active chromatin marks at histone level. cells, inhibition prevented induction IL6/STAT3 IFNγ/STAT1 signaling. reduced expression, resulting decreased production metabolite kynurenine. Further, efficacy selective inhibitor epacadostat rescued attenuating IDO1/kynurenine-mediated immunosuppression. Elevated correlated with JAK/STAT cancer patients supporting clinical relevance mechanistic presented. These results identify IDO1-kynurenine pathway novel pro-tumorigenic oncogenic STAT1/STAT3 cooperation. Our suggest simultaneous pharmacological these axes rational combination therapy non-melanoma cancers.

Language: Английский

Citations

1
Stem Cells in Cancer: From Mechanisms to Therapeutic Strategies DOI Creative Commons

Laurence Haddadin,

Xueqin Sun

Cells, Journal Year: 2025, Volume and Issue: 14(7), P. 538 - 538

Published: April 3, 2025

Stem cells have emerged as a pivotal area of research in the field oncology, offering new insights into mechanisms cancer initiation, progression, and resistance to therapy. This review provides comprehensive overview role stem cancer, focusing on (CSCs), their characteristics, implications for We discuss origin identification CSCs, tumorigenesis, metastasis, drug resistance, potential therapeutic strategies targeting CSCs. Additionally, we explore use normal therapy, tissue regeneration delivery vehicles anticancer agents. Finally, highlight challenges future directions cell cancer.

Language: Английский

Citations

1
Targeting GLI1 and GLI2 with small molecule inhibitors to suppress GLI-dependent transcription and tumor growth DOI Creative Commons
Luisa Maresca, Enrica Crivaro, Francesca Migliorini

et al.

Pharmacological Research, Journal Year: 2023, Volume and Issue: 195, P. 106858 - 106858

Published: July 19, 2023

Aberrant activation of Hedgehog (HH) signaling in cancer is the result genetic alterations upstream pathway components (canonical) or other oncogenic mechanisms (noncanonical), that ultimately concur to activate zinc-finger transcription factors GLI1 and GLI2. Therefore, inhibition GLI activity a good therapeutic option suppress both canonical noncanonical HH pathway. However, only few inhibitors are available, none them have profile required for clinical development due poor metabolic stability aqueous solubility, high hydrophobicity. Two promising quinoline were selected by virtual screening subjected hit-to-lead optimization, thus leading identification 4-methoxy-8-hydroxyquinoline derivative JC19. This molecule impaired GLI2 activities several cellular models interfering with binding DNA. JC19 suppressed cell proliferation enhancing apoptosis, inducing strong anti-tumor response lines vitro. Specificity towards was demonstrated lower GLI1- GLI2-depleted cells. showed excellent passive permeability. Notably, inhibited GLI1-dependent melanoma xenograft growth vivo, no evidence toxic effects mice. These results highlight potential as novel anti-cancer agent targeting

Language: Английский

Citations

16
Genomic profiling of intimal sarcoma reveals molecular subtypes with distinct tumor microenvironments and therapeutic implications DOI Creative Commons
Changhee Park, Rathana Kim, Jae Moon Bae

et al.

ESMO Open, Journal Year: 2025, Volume and Issue: 10(1), P. 104097 - 104097

Published: Jan. 1, 2025

Language: Английский

Citations

0
A higher proportion of craniosynostosis genes are cancer driver genes DOI

Suchir Misra,

Andrew Shih,

Xiao‐Jie Yan

et al.

Human Gene, Journal Year: 2025, Volume and Issue: unknown, P. 201378 - 201378

Published: Jan. 1, 2025

Language: Английский

Citations

0
Single-cell RNA sequencing of the carotid artery and femoral artery of rats exposed to hindlimb unloading DOI Creative Commons
Chengfei Li, Yikai Pan,

Yuan Wang

et al.

Cellular and Molecular Life Sciences, Journal Year: 2025, Volume and Issue: 82(1)

Published: Jan. 21, 2025

Prolonged spaceflight is known to cause vascular deconditioning and remodeling. Tail suspension, a widely used analog, reported result in remodeling of rats. However, little about the cellular atlas heterogeneous cells CA FA from hindlimb-unloaded Firstly, we leveraged scRNA-seq perform clustering analysis identify diverse cell populations sub-clusters within rats subjected 3 months hindlimb unloading. The dysregulated genes specific for artery types HU group compared Con were unraveled. Then R package "Cellchat" was reveal ligand-receptor communication. At last, TF network performed using SCENIC predict pivotal TFs rat induced by Clustering identified ECs, SMCs, fibroblasts, spectrum immune cells, as well neuronal stem cells. Notably, an increased percentage ECs diminished proportion SMCs both observed following tail suspension. Intersection type after suspension revealed several gene sets involved ECM remodeling, inflammation, vasoconstriction, etc. Fibroblasts, particular, exhibited most significant expression variability, highlighting their plasticity. Subclustering fibroblasts specialized subsets engaged processes such EndoMT cycle checkpoint regulation. Additionally, enhanced intercellular interactions among major types, especially between SMC fibroblast, underscored importance communication Several potentially influential process under simulated microgravity conditions. This study presents first conductive arteries rats, revealing profiles. identification subclusters transcription factors prediction are also included this work. findings provide reference future research on long-duration spaceflight.

Language: Английский

Citations

0
EPS-8 regulates human malignant melanoma development by activating the Hedgehog pathway via degradation of Ptch1 DOI
Chuan Liu,

Yuan Lin,

Jixiang Zhang

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 150, P. 114231 - 114231

Published: Feb. 19, 2025

Language: Английский

Citations

0
COLEC10: A potential tumor suppressor and prognostic biomarker in hepatocellular carcinoma through modulation of EMT and PI3K-AKT pathways DOI Creative Commons
Ruisheng Ke, Yun Dai, Yixi Tu

et al.

Open Life Sciences, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 1, 2025

Abstract Hepatocellular carcinoma (HCC) is a cancer with poor prognosis, underscoring the urgent need for enhanced detection and management. This study aimed to investigate role of Collectin Subfamily Member 10 (COLEC10) in HCC, which was revealed be associated various diseases. Bioinformatics tools, including GEO, cBioPortal, TCGA, were used identify differentially expressed genes. The prognostic significance COLEC10 assessed two patient cohorts, its functional impact on Hep3B SMMC7721 cells evaluated through CCK-8 Transwell assays. underlying mechanisms HCC progression explored using flow cytometry western blot. downregulated poorer overall survival disease progression. potential interaction COLEC10, CCBE1, FCN3 predicted. identified as indicators HCC. Overexpression inhibited proliferation, migration, invasion cells. overexpression induced G0/G1 cell cycle arrest suppressed epithelial–mesenchymal transition (EMT), regulated protein expression Hedgehog pathway phosphorylation key proteins PI3K-AKT pathway. an independent factor regulates EMT, Hedgehog, pathways, providing new ideas targeted therapy

Language: Английский

Citations

0