A mitochondria-related genes associated neuroblastoma signature - based on bulk and single-cell transcriptome sequencing data analysis, and experimental validation DOI Creative Commons
Chaoyu Wang, Jiaxiong Tan, Yan Jin

et al.

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

Published: June 19, 2024

Background Neuroblastoma (NB), characterized by its marked heterogeneity, is the most common extracranial solid tumor in children. The status and functionality of mitochondria are crucial regulating NB cell behavior. While significance mitochondria-related genes (MRGs) still missing key knowledge. Materials methods This study leverages consensus clustering machine learning algorithms to construct validate an MRGs-related signature NB. Single-cell data analysis experimental validation were employed characterize pivotal role FEN1 within cells. Results MRGs facilitated classification patients into 2 distinct clusters with considerable differences. constructed quantitative indicators, mtScore mtRisk, effectively patient clusters. Notably, outperformed MYCN predicting prognosis was adept at representing microenvironment (TME), stemness, sensitivity chemotherapeutic agents Cisplatin, Topotecan, Irinotecan. FEN1, identified as contributory gene signature, found play a communication between cells TME, developmental trajectory Experimental validations confirmed FEN1’s significant influence on proliferation, apoptosis, cycle, invasiveness. Conclusion developed this offers novel predictive tool for assessing prognosis, immune infiltration, sensitivity. Our findings unveil critical function NB, suggesting potential therapeutic target.

Language: Английский

A New Oxoaporphine and Liriodenine's Anti-Neuroblastoma Potential from the Roots of Polyalthia bullata King DOI Open Access
Phoebe Sussana Primus, Carol Hsin‐Yi Wu, Chai‐Lin Kao

et al.

Sains Malaysiana, Journal Year: 2024, Volume and Issue: 53(2), P. 359 - 367

Published: Feb. 29, 2024

Polyalthia bullata King’s root yielded a new compound named 5-methylliridine (1) in addition to six previously identified compounds. These known compounds include liriodenine (2), 11-methoxyliriodenine (3), lysicamine (4), onychine (5), 5-hydroxy-6-methoxyonychine (6), and 8-methoxyeupolauridine (7). The structures of 1-7 were determined through spectroscopic analysis. Liriodenine (2) exhibited remarkable ability decrease the cell viability cancerous N2A cells 22% within 24 h timeframe, indicating its potential as an anti-neuroblastoma agent. Molecular docking results additionally suggested that oxoaporphines (1-4) have act inhibitors protein kinases. findings highlight therapeutic P. constituents cancer treatment, particularly neuroblastoma, contribute understanding medicinal properties.

Language: Английский

Citations

6
Targeting CD93 on monocytes revitalizes antitumor immunity by enhancing the function and infiltration of CD8+T cells DOI Creative Commons
Da Jiang, Ai-Qi Huang,

Baixue Zhu

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(10), P. e010148 - e010148

Published: Oct. 1, 2024

Limited activation and infiltration of CD8

Language: Английский

Citations

6
Adaptation of Natural Killer Cells to Hypoxia: A Review of the Transcriptional, Translational, and Metabolic Processes DOI Creative Commons
Teding Chang,

Yu-Jie Chen,

Jialiu Luo

et al.

ImmunoTargets and Therapy, Journal Year: 2025, Volume and Issue: Volume 14, P. 99 - 121

Published: Feb. 1, 2025

As important innate immune cells, natural killer (NK) cells play an essential role in resisting pathogen invasion and eliminating transformed cells. However, the hypoxic microenvironment caused by disease conditions is physicochemical factor that impairs NK cell function. With increasing prominence of immunotherapy, there has been a surge interest developing biological means through which may overcome inhibition hypoxia conditions. Although effects shaping functions have increasingly recognized investigated, reviews scantly. A comprehensive understanding how adapt to can provide valuable insights into functional capacity be restored. This review focuses on alterations response hypoxia. It delineates mechanisms at transcriptional, metabolic, translational levels. Furthermore, given complexity microenvironment, we also elucidated key metabolites Finally, this discusses current clinical therapies derived from targeting The study adaptation yielded new immunotherapy. These lead development novel strategies improve treatment infectious diseases cancer.

Language: Английский

Citations

0
Mechanisms and molecular characterization of relapsed/refractory neuroblastomas DOI Creative Commons
Chong Chen, Zixuan Wei

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: March 6, 2025

Relapsed/refractory neuroblastoma is a type of malignant solid tumor with very poor prognosis in children. Its pathogenesis complex, involving multiple molecular pathways and genetic alterations. Recent studies have shown that MYCN amplification, ALK mutation, TERT promoter p53 pathway inactivation, chromosomal instability are the key mechanisms characteristics relapsed/refractory neuroblastoma. Precision treatment strategies targeting these certain prospects preclinical clinical practice. This review focuses on relevant neuroblastoma, explores its relationship response prognosis, briefly introduces current to provide theoretical basis for development novel personalized therapeutic regimens improve

Language: Английский

Citations

0
Identification and verification of international neuroblastoma staging system (INSS) stage-related genes as potential biomarkers for neuroblastoma prognostic models DOI Creative Commons

Can Qi,

Ziwei Zhao, Weiqi Yan

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: April 15, 2025

Background Neuroblastoma (NB), one of the most common malignant extracranial solid tumors in children, is highly invasive and lethal with limited treatment efficacy. This study aimed to establish a prognostic model advanced-stage NB. Methods Differentially expressed genes were screened validated using two training datasets validation dataset from Therapeutically Applicable Research Generate Effective Treatments Gene Expression Omnibus databases. Protein–protein interaction networks developed MCode plug-in, top three key clusters used produce candidate genes. We performed gene set enrichment analysis (GSEA), ontology (GO), Kyoto Encyclopedia Genes Genomes (KEGG) analysis, immune cell infiltration, drug sensitivity further understand functions these Kaplan–Meier (K–M) receiver operating characteristic (ROC) curves check their prognosis value. Real-time quantitative polymerase chain reaction (qPCR), Western blot (WB), immunohistochemistry (IHC) employed verify mRNA protein levels clinical samples. Results A total 699 differentially identified, including 294 upregulated 405 downregulated CNR1, PRKACB, CDKN3 , PCLAF found significantly affect overall survival event-free neuroblastoma patients positively correlated INSS advanced stages. The functional four revealed cancer-promoting effects correlations immune-inflammatory, cycle, p53 signaling pathways. After stratifying established containing above genes, different patterns observed terms infiltrating proportion, sensitivity, expression checkpoints. Finally, both verification assays demonstrated that upregulated, while PRKACB was tissue Conclusion can serve as new biomarker for predicting neuroblastoma. Findings on infiltration checkpoints provide novel insights immunotherapy

Language: Английский

Citations

0
Principles of Immunotherapy and Novel Immunotherapeutic Agents for Pediatric Cancer Management DOI
Zachary Morrison, Ali Suliman

Published: Jan. 1, 2025

Language: Английский

Citations

0
Interplay Between the Epigenome, the Microenvironment, and the Immune System in Neuroblastoma DOI Open Access

Valentina Andrade-Pérez,

Noël J.‐M. Raynal

Cancers, Journal Year: 2025, Volume and Issue: 17(11), P. 1812 - 1812

Published: May 29, 2025

Neuroblastoma (NB) is the most prevalent extracranial childhood tumor and third leading cause of death from cancer in children. Despite having a high overall survival rate for low- intermediate-risk patients, rates high-risk cases remain unsatisfactory. The current standard treatment NB involves surgery, chemotherapy, radiotherapy, autologous stem cell transplantation, immunotherapy with anti-ganglioside GD2, differentiation therapy isotretinoin. Besides not being enough to achieve these treatments are associated significant side effects. With next-generation sequencing technologies, better understanding genetic epigenetic landscapes has been achieved. This led study novel improve reduce toxicity conventional treatments. Current research focusing on development targeted drugs alterations, protein degraders. Moreover, enhance anticancer immune responses by using cell-engineering techniques chimeric antigen receptor (CAR) T NK cells explored target cells. Here, we review promising strategies NB, which genetics, epigenetics, microenvironment, landscape, highlighting preclinical studies ongoing clinical trials.

Language: Английский

Citations

0
Natural killer cells in neuroblastoma: immunological insights and therapeutic perspectives DOI Creative Commons
Magdalena Radoš,

Anna Landegger,

Lukas Schmutzler

et al.

Cancer and Metastasis Reviews, Journal Year: 2024, Volume and Issue: 43(4), P. 1401 - 1417

Published: Sept. 18, 2024

Language: Английский

Citations

2
CAR-iNKT cell therapy: mechanisms, advantages, and challenges DOI
Zixuan Wang, Guangji Zhang

Current Research in Translational Medicine, Journal Year: 2024, Volume and Issue: 73(1), P. 103488 - 103488

Published: Dec. 4, 2024

Language: Английский

Citations

2
Opaganib Downregulates N-Myc Expression and Suppresses In Vitro and In Vivo Growth of Neuroblastoma Cells DOI Open Access

Lynn W. Maines,

Staci N. Keller,

Ryan A. Smith

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(9), P. 1779 - 1779

Published: May 5, 2024

Neuroblastoma (NB), the most common cancer in infants and solid tumor outside brain children, grows aggressively responds poorly to current therapies. We have identified a new drug (opaganib, also known as ABC294640) that modulates sphingolipid metabolism by inhibiting synthesis of sphingosine 1-phosphate (S1P) kinase-2 elevating dihydroceramides inhibition dihydroceramide desaturase. The present studies sought determine potential therapeutic activity opaganib cell culture xenograft models NB. Cytotoxicity assays demonstrated NB cells, including cells with amplified MYCN, are effectively killed concentrations well below those accumulate tumors vivo. Opaganib was shown cause dose-dependent decreases S1P hexosylceramide levels Neuro-2a while concurrently dihydroceramides. As other reduced c-Myc Mcl-1 protein expression N-Myc protein. vivo growth xenografts human SK-N-(BE)2 MYCN suppressed oral administration at doses tolerated mice. Combining temozolomide plus irinotecan, considered backbone for therapy relapsed or refractory NB, resulted increased antitumor compared irinotecan alone. Mice did not lose additional weight when combined indicating combination is tolerated. has additive toward checkpoint inhibitor anti-CTLA-4 antibody; however, anti-PD-1 anti-PD-L1 antibodies provide over seen Overall, data demonstrate intracellular signaling inhibits alone anticancer drugs. Amplified does confer resistance opaganib, and, fact, attenuates both N-Myc. safety been established clinical trials adults advanced severe COVID-19, so excellent treating patients particularly antibody.

Language: Английский

Citations

1