Recent advances in 3D bioprinted neural models: A systematic review on the applications to drug discovery

Advanced Drug Delivery Reviews, Год журнала: 2025, Номер 218, С. 115524 - 115524

Опубликована: Фев. 1, 2025

The design of neural tissue models with architectural and biochemical relevance to native tissues opens the way for fundamental study development therapies many disorders limited treatment options. Here, we systematically review most recent literature on 3D bioprinted models, including their potential use in drug screening. Neural that model central nervous system (CNS) from relevant are reviewed comprehensive summaries each study, discussion types, bioinks additives, cell types used, construct shapes culture time, characterization methods used. In this review, accentuate lack standardization among analyze functionality (including chemical, metabolic other pathways) mechanical constructs, discuss as a critical area future exploration. These gaps must be addressed technology applied effective screening applications, despite its enormous rapid efficient biomimetic, printed is promising evaluation vivo multiple levels should sought adequately compare performance develop viable options neurodegenerative diseases, or conditions affect CNS.

Язык: Английский

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Sodium valproate enhances efficacy of NKG2D CAR-T cells against glioblastoma

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 14, 2025

Chimeric antigen receptor T-cell (CAR-T) therapies have shown promise in glioblastoma clinical studies, but responses remain inconsistent due to heterogeneous tumor expression and immune evasion post-treatment. NKG2D CAR-T cells demonstrated a favorable safety profile patients with hematologic tumors, showed robust antitumor efficacy various xenograft models, including glioblastoma. However, malignant glioma evade immunological surveillance by reducing ligands or cleavage. To enhance the effectiveness of therapy, we investigated potential combining approved drugs that cross blood-brain barrier augment cells. We found sodium valproate (VPA), an antiepileptic drug, significantly increased surface on at sublethal concentration. VPA treatment enhanced susceptibility mediated cytotoxicity both 2D monolayer 3D spheroid models vitro. Moreover, VPA-treated stimulated produce higher levels inflammatory cytokines (IL-2, IFN-γ, IL-6). Mechanistically, upregulated via PI3K/Akt signaling pathway. Additionally, augmented activity model vivo. These preclinical results suggest therapy represents promising strategy for improving treatment, warranting further investigation.

Язык: Английский

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The HOX Gene Family’s Role as Prognostic and Diagnostic Biomarkers in Hematological and Solid Tumors

Cancers, Год журнала: 2025, Номер 17(2), С. 262 - 262

Опубликована: Янв. 15, 2025

The HOX gene family encodes for regulatory transcription factors that play a crucial role in embryogenesis and differentiation of adult cells. This highly conserved genes consists thirty-nine humans are located four clusters, A–D, on different chromosomes. While early studies the have been focused embryonic development its related disorders, research has shifted to examine aberrant expression subsequent implication cancer prediction progression. Due their encoding master factors, abnormal shown affect all stages tumorigenesis metastasis. review highlights novel family’s clinical relevance as both prognostic diagnostic biomarkers hematological solid tumors.

Язык: Английский

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Immune Resistance in Glioblastoma: Understanding the Barriers to ICI and CAR-T Cell Therapy

Cancers, Год журнала: 2025, Номер 17(3), С. 462 - 462

Опубликована: Янв. 29, 2025

Background: Glioblastoma (GBM) is the most common primary malignant brain tumor, with fewer than 5% of patients surviving five years after diagnosis. The introduction immune checkpoint inhibitors (ICIs), followed by chimeric antigen receptor (CAR) T-cell therapy, marked major advancements in oncology. Despite demonstrating efficacy other blood and solid cancers, these therapies have yielded limited success clinical trials for both newly diagnosed recurrent GBM. A deeper understanding GBM’s resistance to immunotherapy essential enhancing treatment responses translating results seen cancer models. Objectives: In this review, we examine trial outcomes involving ICIs CAR-T GBM explore evasive mechanisms tumor microenvironment. Findings Discussion: Multiple investigating shown poor outcomes, no significant improvement progression-free survival (PFS) or overall (OS). Results from smaller case studies therapy warranted further investigation. However, large-scale robust yet established immunotherapeutic approaches as definitive strategies. Future research should shift focus addressing scarcity functional T cells exploiting abundant myeloid-derived within Conclusions: Translating into effective treatments glioblastoma humans remains a challenge. highly immunosuppressive nature its microenvironment continue hinder innovative approaches. Targeting compartment may lead more sustained responses.

Язык: Английский

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Integrative analysis of immunogenic PANoptosis and experimental validation of cinobufagin-induced activation to enhance glioma immunotherapy

Journal of Experimental & Clinical Cancer Research, Год журнала: 2025, Номер 44(1)

Опубликована: Фев. 3, 2025

Glioma, particularly glioblastoma (GBM), is a highly aggressive tumor with limited responsiveness to immunotherapy. PANoptosis, form of programmed cell death merging pyroptosis, apoptosis, and necroptosis, plays an important role in reshaping the microenvironment (TME) enhancing immunotherapy effectiveness. This study investigates PANoptosis dynamics glioma explores therapeutic potential its activation, through natural compounds such as cinobufagin. We comprehensively analyzed PANoptosis-related genes (PANoRGs) multiple cohorts, identifying different patterns constructing enrichment score (PANoScore) evaluate relationship patient prognosis immune activity. Cinobufagin, identified activator, was evaluated for ability induce enhance anti-tumor responses both vitro vivo GBM models. Our findings indicate that high PANoScore gliomas showed increased infiltration, effector T cells, enhanced sensitivity immunotherapies. Cinobufagin effectively induced leading immunogenic death, facilitated tumor-associated microglia/macrophages (TAMs) polarization towards M1-like phenotype while augmenting CD4+/CD8 + infiltration activation. Importantly, cinobufagin combined anti-PD-1 therapy exhibited significant synergistic effects prolonged survival These highlight PANoptosis-targeting agents, cinobufagin, combination immunotherapy, offering promising approach convert "cold" tumors into "hot" ones improving treatment outcomes.

Язык: Английский

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Why Do Glioblastoma Treatments Fail?

Future Pharmacology, Год журнала: 2025, Номер 5(1), С. 7 - 7

Опубликована: Фев. 1, 2025

Glioblastoma (GBM) is the most aggressive brain tumor, characterized by high recurrence rates and poor patient outcomes. Treatment failure driven multiple factors, including complex tumor heterogeneity, presence of cancer stem cells, immunosuppressive microenvironment (TME), many others. GBM’s heterogeneity underlines its ability to resist therapies adapt TME. The TME, which highly shaped hypoxia, impairs anti-tumor immunity limits efficacy immunotherapy. blood–brain barrier (BBB) remains a major obstacle delivering sufficient drug concentrations restricting penetration therapeutic agents. Another problem lack reliable biomarkers perform better stratification or even guide personalized treatments, resulting in generalized approaches that do not adequately address GBM complexities. This review highlights multifactorial nature treatment need for paradigm shift innovative, strategies. A deeper understanding biology advances translational research will be crucial developing effective improving outcomes this devastating disease.

Язык: Английский

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Virus-inspired biogenic delivery system for advancing cancer therapy

Biomedical Technology, Год журнала: 2025, Номер 9, С. 100069 - 100069

Опубликована: Фев. 8, 2025

Язык: Английский

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Rapid Isolation of Circulating Tumor Cells from Glioblastoma Patients Using a Lateral Filter Array Microfluidic Device

Chemosensors, Год журнала: 2025, Номер 13(2), С. 64 - 64

Опубликована: Фев. 11, 2025

Glioblastoma is the most common form of brain cancer in adults, representing 35–40% all malignant tumors. This highly aggressive malignancy originates central nervous system, and despite notable advancements treatment strategies, it continues to be an incurable disease. The isolation circulating tumor cells (CTC) at early stage challenging due low probability their presence peripheral blood. Detection enumeration as possible can reportedly lead more effective treatment. study proposes a novel label-free, rapid, continuous CTC separation device based on lateral filter array microfluidic for efficient immunoaffinity CTCs. Our methodology successfully captured isolated (CTCs) from whole blood glioblastoma (GBM) patients prior surgery, achieving over 90% capture efficiency under 40 min analysis. These findings highlight potential this technology enhance our understanding clinical significance CTCs management GBM future research.

Язык: Английский

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Dendritic Cell-Based Glioblastoma Vaccines: Advances and Challenges

IntechOpen eBooks, Год журнала: 2025, Номер unknown

Опубликована: Фев. 14, 2025

Glioblastoma (GBM) is the most aggressive malignancy of central nervous system. Despite advances in standard treatments such as surgery, radiotherapy, and chemotherapy, patients have a very poor prognosis. Tumor vaccines based on dendritic cells (DCs) provide promising new approach for GBM treatment. DCs, effective antigen-presenting cells, initiate adaptive immune responses by activating tumor-specific T cells. However, immunosuppressive microenvironment (characterized regulatory myeloid suppressor factors) physical barrier blood-brain (BBB) greatly limit efficacy DC vaccines. This chapter explores biological basis, preparation process, clinical progress, challenges, future directions DC-based Key aspects antigen selection, vitro culture activation, loading, delivery strategies are analyzed detail. Early trials demonstrated safety potential vaccines, while combination therapies reprogramming being used to overcome existing obstacles. precision personalization highlight their focus immunotherapy research. We believe that with continuous advancement technology interdisciplinary collaboration, can significantly improve survival rate quality life patients.

Язык: Английский

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Advancing Glioblastoma Therapy: Learning From the Past and Innovations for the Future

Cancer Letters, Год журнала: 2025, Номер unknown, С. 217601 - 217601

Опубликована: Март 1, 2025

Язык: Английский

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