Blood–brain barrier-crossing dendrimers for glioma theranostics

Biomaterials Science, Journal Year: 2024, Volume and Issue: 12(6), P. 1346 - 1356

Published: Jan. 1, 2024

Blood–brain barrier-crossing dendrimers for glioma imaging diagnostics, chemotherapy, gene therapy, or imaging-guided therapy have been concisely reviewed with perspectives briefly discussed.

Language: Английский

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Identifying predictors of glioma evolution from longitudinal sequencing

Science Translational Medicine, Journal Year: 2023, Volume and Issue: 15(716)

Published: Oct. 4, 2023

Clonal evolution drives cancer progression and therapeutic resistance. Recent studies have revealed divergent longitudinal trajectories in gliomas, but early molecular features steering posttreatment remain unclear. Here, we collected sequencing clinical data of initial-recurrent tumor pairs from 544 adult diffuse gliomas performed multivariate analysis to identify predictors three glioma subtypes. We found that CDKN2A deletion at initial diagnosis preceded necrosis microvascular proliferation occur later stages IDH-mutant glioma. Ki67 expression was positively correlated with acquiring hypermutation recurrence the IDH-wild-type In all subtypes, MYC gain or MYC-target activation associated treatment-induced recurrence. To predict evolution, constructed CELLO2 (Cancer EvoLution for LOngitudinal version 2), a machine learning model integrating forecast after treatment. successfully stratified patients into subgroups distinct prognoses identified high-risk patient group featured by worse post-progression survival, low-grade IDH-mutant-noncodel subtype. then chronic temozolomide-induction experiments cell lines isogenic patient-derived gliomaspheres demonstrated temozolomide resistance promoting hypermutation. Mechanistically, that, binding open chromatin transcriptionally active genomic regions, c-MYC increases vulnerability key mismatch repair genes mutagenesis, thus triggering This study reveals under therapy provides resource precision oncology targeting dynamics gliomas.

Language: Английский

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Single-cell RNA sequencing identifies a subtype of FN1 + tumor-associated macrophages associated with glioma recurrence and as a biomarker for immunotherapy

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Oct. 7, 2024

Abstract Background Glioma is the most common primary malignant tumor in brain, and even with standard treatments including surgical resection, radiotherapy, chemotherapy, long-term survival rate of patients remains unsatisfactory. Recurrence one leading causes death glioma patients. The molecular mechanisms underlying recurrence remain unclear. Methods Our study utilized single-cell sequencing, spatial transcriptomics, RNA-seq data to identify a subtype FN1 + tumor-associated macrophages (FN1 TAMs) associated recurrence. Results This revealed an increased abundance TAMs recurrent gliomas, indicating their potential involvement as critical factor A negative correlation was observed between gliomas interval time recurrence, suggesting poor prognosis for high levels TAMs. Further investigation showed that were enriched hypoxic regions, implying metabolic changes tumors drive production recruitment Additionally, found contribute regulation immunosuppressive microenvironment might serve indicator patients’ sensitivity immunotherapy. Finally, we developed user-friendly website, PRIMEG ( http://www.szflab.site/PRIMEG/ ), exploring immune gliomas. Conclusion findings highlight providing new insights into therapeutic targets. Moreover, hold promise predicting therapy response aiding more precise risk stratification

Language: Английский

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Integrating Multiplex Immunohistochemistry and Machine Learning for Glioma Subtyping and Prognosis Prediction

MedComm, Journal Year: 2025, Volume and Issue: 6(5)

Published: April 22, 2025

ABSTRACT Glioma subtyping is crucial for treatment decisions, but traditional approaches often fail to capture tumor heterogeneity. This study proposes a novel framework integrating multiplex immunohistochemistry (mIHC) and machine learning glioma prognosis prediction. 185 patient samples from the Huashan hospital cohort were stained using multi‐label mIHC panel analyzed with an AI‐based auto‐scanning system calculate cell ratios determine proportion of positive cells various markers. Patients divided into two cohorts (training: N = 111, testing: 74), model was then developed validated subtype classification The identified distinct subtypes significant differences in prognosis, clinical characteristics, molecular profiles. high‐risk subtype, associated older age, poorer outcomes, astrocytoma/glioblastoma, higher grades, elevated mesenchymal scores, inhibitory immune microenvironment, exhibited IDH wild‐type, 1p19q non‐codeletion, MGMT promoter unmethylation, suggesting chemotherapy resistance. Conversely, low‐risk characterized by younger better astrocytoma/oligodendroglioma, lower favorable profiles (IDH mutation, codeletion, methylation), indicated sensitivity. mIHC‐based enables rapid classification, facilitating tailored strategies accurate prediction, potentially improving management outcomes.

Language: Английский

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Single-cell sequencing elucidates the mechanism of NUSAP1 in glioma and its diagnostic and prognostic significance

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 5, 2025

Background Personalized precision medicine (PPPM) in cancer immunology and oncology is a rapidly advancing field with significant potential. Gliomas, known for their poor prognosis, rank among the most lethal brain tumors. Despite advancements, there remains critical need precise, individualized treatment strategies. Methods We conducted comprehensive analysis of RNA-seq microarray data from TCGA GEO databases, supplemented by single-cell RNA sequencing (scRNA-seq) glioma patients. By integrating foundational experiments, we investigated molecular variations cellular interactions within neural cell subpopulations during tumor progression. Results Our revealed distinct gene expression patterns across subpopulations. Notably, differentiation trajectory identified NUSAP1 as key marker terminal subpopulation. found that elevated correlated prompting further investigation its functional role through both animal studies. Conclusions NUSAP1-based risk models hold potential predictive therapeutic tools personalized treatment. In-depth exploration NUSAP1’s mechanisms glioblastoma could enhance our understanding response to immunotherapy, suggesting targeting may offer benefits

Language: Английский

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Exosomes in the Chemoresistance of Glioma: Key Point in Chemoresistance

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(4)

Published: Feb. 1, 2025

ABSTRACT Gliomas are the most ordinary primary virulent brain tumours and commonly used clinical treatments include tumour resection, radiation therapy chemotherapy. Although significant progress has been made in recent years progression‐free survival (PFS) overall (OS) for patients with high‐grade gliomas, prognosis remains poor. Chemoresistance refers to phenomenon of decreased sensitivity cells drugs, resulting reduced or ineffective drug efficacy, is an important cause failure Exosomes, a type extracellular vesicle, secreted by cancer various stromal microenvironment (TME) transfer their inclusions cells, increasing chemoresistance. Furthermore, depletion exosomes reverses certain detrimental effects on metabolism restores chemotherapeutic agents. Here, we summarised correlation between resistance agents glioma patients, mechanisms action involved value. We aimed afford new thoughts research, diagnosis intervention chemoresistance patients.

Language: Английский

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A pathogenic subpopulation of human glioma associated macrophages linked to glioma progression

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Summary Malignant gliomas follow two distinct natural histories: de novo high grade tumors such as glioblastoma, or lower with a propensity to transform into disease. Despite differences in tumor genotype, both entities converge on common histologically aggressive phenotype, and the basis for this progression is unknown. Glioma associated macrophages (GAM) have been implicated process, however GAMs are ontologically transcriptionally diverse, rendering isolation of pathogenic subpopulations challenging. Since macrophage contextual gene programs orchestrated by transcription factors acting cis -acting promoters enhancers regulatory networks (GRN), we hypothesized that functional populations can be resolved through GRN inference. Here show via parallel single cell RNA ATAC sequencing subpopulation human defined centered around Activator Protein-1 factor FOSL2 preferentially enriched tumors. Using nominate ANXA1 HMOX1 surrogate surface markers activation, thus permitting prospective validation GAMs. These cells, termed malignancy (mGAMs) pro-invasive, pro-angiogenic, pro-proliferative, possess intact antigen presentation but skew T-cells towards CD4+FOXP3+ phenotype under hypoxia. Ontologically, mGAMs share somatic mitochondrial mutations peripheral blood monocytes, their presence correlates disease irrespective underlying mutation status. Furthermore, spatio-temporally occupy metabolic niches; directly induce proliferation mesenchymal transition low glioma cells accelerate growth vivo upon co-culture. Finally patients newly transformed regions gliomas, supporting view play pivotal role may represent plausible therapeutic target high-grade glioma.

Language: Английский

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Basic mechanism of mobilizing cell movement during invasion of glioblastoma and target selection of targeted therapy

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Glioblastoma (GBM), also known as glioblastoma multiforme, is a rapidly growing and highly invasive malignant tumor. Due to the inability clearly distinguish between normal tissue, surgery cannot achieve safe resection, often leading poor patient prognosis inevitable tumor recurrence. According previous studies, GBM invasion related intercellular adhesion, matrix degradation, extracellular its adhesion molecules, well molecular of protein hydrolases in microenvironment cells stromal cells. The aim enhance our understanding mechanisms underlying advance research on targeted therapies for inhibiting invasion. This article describes that may affect cell invasion, changes cytoskeleton during motility, regulatory intracellular signaling pathways In addition, we explored possibility therapy against molecules GBM.

Language: Английский

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Glioma hexokinase 3 positively correlates with malignancy and macrophage infiltration

Metabolic Brain Disease, Journal Year: 2024, Volume and Issue: 39(5), P. 719 - 729

Published: April 30, 2024

Language: Английский

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Single‐cell transcriptomics reveals IRF7 regulation of the tumor microenvironment in isocitrate dehydrogenase wild‐type glioma

MedComm, Journal Year: 2024, Volume and Issue: 5(11)

Published: Nov. 1, 2024

Abstract Mutations in isocitrate dehydrogenase (IDH) are important markers of glioma prognosis. However, few studies have examined the gene expression regulatory network (GRN) IDH‐mutant and wild‐type gliomas. In this study, single‐cell RNA sequencing spatial transcriptome were used to analyze GRN cell subsets patients with Through transcriptional regulation analysis, we identified M4 module, whose transcription factor activity is highly expressed IDH gliomas compared IDH‐mutants. Enrichment analysis revealed that these genes predominantly microglia macrophages, significant enrichment interferon‐related signaling pathways. Interferon 7 (IRF7), a within pathway, showed highest percentage was primarily localized core region tumors. A machine‐learning prognostic model novel subgroups population. Additionally, IRF7 shown promote proliferation migration T98G U251 cells vitro, its knockdown affected vivo. This study systematically established mechanism at level drew corresponding map. The presents map for gliomas, involving transcriptomics identify networks, machine learning models subtyping, experimental validation, highlighting role progression.

Language: Английский

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