Biochemistry (Moscow), Journal Year: 2024, Volume and Issue: 89(12-13), P. 2274 - 2286
Published: Dec. 1, 2024
Language: Английский
Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)
Published: May 8, 2024
Abstract Glioblastoma (GBM), the predominant and primary malignant intracranial tumor, poses a formidable challenge due to its immunosuppressive microenvironment, thereby confounding conventional therapeutic interventions. Despite established treatment regimen comprising surgical intervention, radiotherapy, temozolomide administration, exploration of emerging modalities such as immunotherapy integration medicine engineering technology therapy, efficacy these approaches remains constrained, resulting in suboptimal prognostic outcomes. In recent years, intensive scrutiny inhibitory milieu within GBM has underscored significance cellular constituents microenvironment their interactions with cells neurons. Novel immune targeted therapy strategies have emerged, offering promising avenues for advancing treatment. One pivotal mechanism orchestrating immunosuppression involves aggregation myeloid-derived suppressor (MDSCs), glioma-associated macrophage/microglia (GAM), regulatory T (Tregs). Among these, MDSCs, though constituting minority (4–8%) CD45 + GBM, play central component fostering evasion propelling tumor progression, angiogenesis, invasion, metastasis. MDSCs deploy intricate mechanisms that adapt dynamic (TME). Understanding interplay between provides compelling basis This review seeks elucidate inherent explore existing targets, consolidate insights into MDSC induction contribution immunosuppression. Additionally, comprehensively surveys ongoing clinical trials potential strategies, envisioning future where targeting could reshape landscape GBM. Through synergistic other modalities, this approach can establish multidisciplinary, multi-target paradigm, ultimately improving prognosis quality life patients
Language: Английский
Citations
70
Glia, Journal Year: 2024, Volume and Issue: 72(5), P. 857 - 871
Published: Jan. 17, 2024
Abstract Tumor‐associated astrocytes (TAAs) in the glioblastoma microenvironment play an important role tumor development and malignant progression initiated by glioma stem cells (GSCs). In current study, normal human (NHAs) were cultured continuously treated with GSC‐derived exosomes (GSC‐EXOs) induction to explore mechanism which GSCs affect astrocyte remodeling. This study revealed that GSC‐EXOs can induce transformation of NHAs into TAAs, relatively swollen cell bodies multiple extended processes. addition, high proliferation, elevated resistance temozolomide (TMZ), increased expression TAA‐related markers (TGF‐β, CD44, tenascin‐C) observed TAAs. Furthermore, exosomal miR‐3065‐5p could be delivered NHAs, levels significantly as verified miRNA profile sequencing Reverse transcription polymerase chain reaction. Overexpression also enhanced NHA TMZ, markers. both GSC‐EXO‐induced miR‐3065‐5p‐overexpressing promoted tumorigenesis vivo. Discs Large Homolog 2 (DLG2, downregulated glioblastoma) is a direct downstream target DLG2 overexpression partially reverse Collectively, these data demonstrate TAAs via miR‐3065‐5p/DLG2 signaling axis further promote GSCs. Thus, precisely blocking interactions between may novel strategy inhibit development, but more in‐depth mechanistic studies are still needed.
Language: Английский
Citations
6
CNS Neuroscience & Therapeutics, Journal Year: 2023, Volume and Issue: 29(9), P. 2690 - 2704
Published: April 17, 2023
Abstract Background The recent development of dendritic cell (DC)‐based immunotherapy has resulted in advances glioblastoma multiforme (GBM) treatment. However, the fate DCs GBM microenvironment, especially microenvironments which glioma stem (GSCs)‐mediated remodeling highly immunosuppressive conditions, not yet been fully investigated. Methods Observed interaction between GSCs and primary cultured a dual‐color tracing model, monoclonal continuously passaged proliferative DCs, named transformed (t‐DCs). expression DC‐specific surface markers was analyzed using RT‐PCR, chromosome karyotype, flow cytometry. long pentraxin 3 (PTX3) its transcription factor zinc finger protein 148 (ZNF148) t‐DCs detected qRT‐PCR western blot. CCK8 transwell assays were conducted to assess effect ZNF148 PTX3 on proliferation, migration, invasion t‐DCs. Bioinformatics analysis, dual‐luciferase reporter assay, chromatin immunoprecipitation (ChIP)‐qPCR assay used explore relation PTX3. Results Transformed (t‐DCs) still expressed markers, namely, CD80 CD11c, immune‐related costimulatory molecules, CD80, CD86, CD40, ICAM‐1. levels these molecules decreased moderately compared those naive DCs. Stable overexpression further promoted proliferation migration vitro, increased tumorigenicity vivo. directly bound promoter region enhanced expression. Downregulation significantly reduced Overexpression t‐DCs, achieving same biological effects as Simultaneously, downregulation partially reversed Conclusion ZNF148/PTX3 axis played an important role regulating malignant transformation after cross‐talk with GSCs, this may serve new target for sensitizing DC‐based immunotherapy.
Language: Английский
Citations
13
PLoS ONE, Journal Year: 2025, Volume and Issue: 20(2), P. e0316552 - e0316552
Published: Feb. 4, 2025
Glioblastoma (GBM) is the most lethal primary tumor of central nervous system, with its resistance to treatment posing significant challenges. This study aims develop a comprehensive prognostic model identify biomarkers associated temozolomide (TMZ) resistance. We employed multifaceted approach, combining differential expression and univariate Cox regression analyses screen for TMZ resistance-related differentially expressed genes (TMZR-RDEGs) in GBM. Using LASSO analysis, we selected 12 TMZR-RDEGs construct risk score model, which was evaluated performance through survival time-dependent ROC, stratified analyses. Functional enrichment mutation were conducted explore underlying mechanisms relationship immune cell infiltration levels The based on TMZR-RDEGs, demonstrated high efficacy predicting GBM patient outcomes emerged as an independent predictive factor. Additionally, focused molecule TSPAN13, whose role not well understood. assessed proliferation, migration, invasion capabilities vitro assays (including CCK-8, Edu, wound healing, transwell assays) quantitatively analyzed TSPAN13 clinical glioma samples using tissue microarray immunohistochemistry. impact cells validated experiments mouse orthotopic xenograft model. Notably, upregulated correlated poorer prognosis. Knockdown inhibited invasion, enhanced sensitivity treatment. provides valuable tool identifies critical target therapeutic intervention.
Language: Английский
Citations
0
Virology Journal, Journal Year: 2024, Volume and Issue: 21(1)
Published: Jan. 31, 2024
Abstract Background Progressive hepatitis B virus (HBV) infection can result in cirrhosis, hepatocellular cancer, and chronic hepatitis. While antiviral drugs that are now on the market efficient controlling HBV infection, finding a functional cure is still quite difficult. Identifying host factors involved regulating life cycle will contribute to development of new strategies. Zinc finger proteins have significant function replication, according earlier studies. protein 148 (ZNF148), zinc transcription factor, regulates expression various genes by specifically binding GC-rich sequences within promoter regions. The ZNF148 replication was investigated this study. Methods HepG2-Na + /taurocholate cotransporting polypeptide (HepG2-NTCP) cells Huh7 were used evaluate vitro. Northern blotting real-time PCR quantify amount viral RNA. Southern DNA. Viral levels elevated, Western blot results. Dual-luciferase reporter assays examine transcriptional activity promoters. ZNF148’s impact vivo using an established rcccDNA mouse model. Results overexpression significantly decreased RNAs core DNA HBV-infected HepG2-NTCP expressing prcccDNA. Silencing exhibited opposite effects both cell lines. Furthermore, inhibited ENII/Cp cccDNA. Mechanistic studies revealed attenuated retinoid X receptor alpha (RXRα) RXRα sequence. site mutation or abolished suppressive effect replication. inhibitory also observed Conclusions downregulating transcription. Our findings reveal may be target for anti-HBV
Language: Английский
Citations
3
CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(2)
Published: Feb. 1, 2024
Abstract Background Glioblastoma is the most malignant primary brain tumor in adults. Temozolomide (TMZ) stands for first‐line chemotherapeutic agent against glioblastoma. Nevertheless, therapeutic efficacy of TMZ appears to be remarkably limited, because low cytotoxic efficiency Besides, various mechanical studies and corresponding strategies fail enhancing curative effect clinical practice. Our previous have disclosed remodeling glial cells by GSCs, but roles these transformed on promoting resistance never been explored. Methods Exosomes were extracted from GSCs culture through standard centrifugation procedures, which can activate transformation normal human astrocytes (NHAs) totumor‐associated (TAAs) 3 days detect level TGF‐β, CD44 tenascin‐C. The secretive protein ALKBH7 TAAs was determined ELISA kit. APNG GBM Western blot. Cell‐based assays triggered drug performed flow cytometric assay, blotting colony formation assay respectively. A xenograft model applied investigate function vivo. Finally, ALKBH7/APNG signaling evaluated functional experiments. Results derived (NHAs)to tumor‐associated (TAAs), as well up‐regulation ALKBH7expression TAAs. regulate gene expression cells. After co‐culturing with 5 days, elevated. Furthermore, Knocking‐down increased inhibitory survival. Conclusion present study illustrated a new mechanism glioblastoma TMZ, based GSCs‐exo educated delivering enhance cells, implied that targeting regulation network may provide strategy effects
Language: Английский
Citations
3
Cancers, Journal Year: 2024, Volume and Issue: 16(9), P. 1637 - 1637
Published: April 24, 2024
Brain tumors are a heterogeneous group of brain neoplasms that highly prevalent in individuals all ages worldwide. Within this pathological framework, the most and aggressive type primary tumor is glioblastoma (GB), subtype glioma falls within IV-grade astrocytoma group. The death rate for patients with GB remains high, occurring few months after diagnosis, even gold-standard therapies now available, such as surgery, radiation, or pharmaceutical approach Temozolomide. For reason, it crucial to continue looking cutting-edge therapeutic options raise patients’ survival chances. Pentraxin 3 (PTX3) multifunctional protein has variety regulatory roles inflammatory processes related extracellular matrix (ECM). An increase PTX3 blood levels considered trustworthy factor associated beginning inflammation. Moreover, scientific evidence suggested sensitive earlier inflammation-related marker compared short pentraxin C-reactive (CRP). In several tumoral subtypes, via regulating complement-dependent macrophage-associated tumor-promoting inflammation, been demonstrated may function promoter cancer metastasis, invasion, stemness. Our review aims deeply evaluate context GB, considering its pivotal biological activities possible role molecular target future therapies.
Language: Английский
Citations
2
Upsala Journal of Medical Sciences, Journal Year: 2024, Volume and Issue: 129, P. e10627 - e10627
Published: April 12, 2024
Dendritic cells (DCs) possess a specialized function in presenting antigens and play pivotal roles both innate adaptive immune responses. Their ability to cross-present from tumor naïve T is instrumental generating specific T-cell-mediated antitumor responses, crucial for controlling growth preventing cell dissemination. However, within microenvironment (TIME), the functions of DCs can be significantly compromised. This review focuses on profile, function, activation DCs, leveraging recent studies that reveal insights into their phenotype acquisition, transcriptional state, functional programs through single-cell RNA sequence (scRNA-seq) analysis. Additionally, therapeutic potential DC-mediated antigen sensing priming immunity discussed.
Language: Английский
Citations
2
Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown
Published: Aug. 1, 2024
With the gradual understanding of glioma development and immune microenvironment, many cells have been discovered. Despite growing comprehension cell functions clinical application immunotherapy, precise roles characteristics subtypes, how induces subtype transformation its impact on progression yet to be understood. In this review, we comprehensively center four major within particularly neutrophils, macrophages, lymphocytes, myeloid-derived suppressor (MDSCs), other significant cells. We discuss (1) markers, (2) glioma-induced transformation, (3) mechanisms each influencing chemotherapy resistance, (4) therapies targeting cells, (5) cell-associated single-cell sequencing. Eventually, identified subtypes in glioma, summarized exact mechanism concluded progress sequencing exploring glioma. conclusion, analyzed resistance detailly, discovered prospective immunotherapy targets, excavating potential novel immunotherapies approach that synergistically combines radiotherapy, chemotherapy, surgery, thereby paving way for improved immunotherapeutic strategies against enhanced patient outcomes.
Language: Английский
Citations
2
Cancer Management and Research, Journal Year: 2024, Volume and Issue: Volume 16, P. 1109 - 1130
Published: Sept. 1, 2024
This study aimed to explore the roles of cell-in-cell (CIC)-related genes in glioblastoma (GBM) using bioinformatics and experimental strategies.
Language: Английский
Citations
1