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The fight against Glioblastoma multiforme (GBM) is ongoing and the long-term outlook for GBM remains challenging due to low prognosis but every breakthrough brings us closer to improving patient outcomes. Significant hurdles in GBM are heterogeneity, fortified tumor location, and blood-brain barrier (BBB), hindering adequate drug concentrations within functioning brain regions, thus leading to low survival rates. The nasal passageway has become an appealing location to commence the course of cancer therapy. Utilization of the nose-to-brain (N2B) route for drug delivery takes a sidestep from the BBB to allow therapeutics to directly access the central nervous system (CNS) and enhance drug localization in the vicinity of the tumor. This comprehensive review provides insights into pertinent anatomy and cellular organization of the nasal cavity, present-day diagnostic tools, intracranial invasive therapies, and advancements in intranasal (IN) therapies in GBM models for better clinical outcomes. Also, this review highlights groundbreaking carriers and delivery techniques that could revolutionize GBM management such as biomimetics, image guiding-drug delivery, and photodynamic and photothermal therapies for GBM management.

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PURPOSE: To construct a comprehensive model for predicting the prognosis of patients with glioblastoma (GB) using a radiomics method and integrating clinical risk factors, tumor microenvironment (TME), and imaging characteristics. MATERIALS AND METHODS: In this retrospective study, we included 148 patients (85 males and 63 females; median age 53 years) with isocitrate dehydrogenase-wildtype GB between January 2016 and April 2022. Patients were randomly divided into the training (n = 104) and test (n = 44) sets. The best feature combination related to GB overall survival (OS) was selected using LASSO Cox regression analyses. Clinical, radiomics, clinical-radiomics, clinical-TME, and clinical-radiomics-TME models were established. The models' concordance index (C-index) was evaluated. The survival curve was drawn using the Kaplan-Meier method, and the prognostic stratification ability of the model was tested. RESULTS: LASSO Cox analyses were used to screen the factors related to OS in patients with GB, including MGMT (hazard ratio [HR] = 0.642; 95% CI 0.414-0.997; P = 0.046), TERT (HR = 1.755; 95% CI 1.095-2.813; P = 0.019), peritumoral edema (HR = 1.013; 95% CI 0.999-1.027; P = 0.049), tumor purity (TP; HR = 0.982; 95% CI 0.964-1.000; P = 0.054), CD163 + tumor-associated macrophages (TAMs; HR = 1.049; 95% CI 1.021-1.078; P < 0.001), CD68 + TAMs (HR = 1.055; 95% CI 1.018-1.093; P = 0.004), and the six radiomics features. The clinical-radiomics-TME model had the best survival prediction ability, the C­index was 0.768 (0.717-0.819). The AUC of 1­, 2­, and 3­year OS prediction in the test set was 0.842, 0.844, and 0.795, respectively. CONCLUSION: The clinical-radiomics-TME model is the most effective for predicting the survival of patients with GB. Radiomics features, TP, and TAMs play important roles in the prognostic model.

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Overcoming temozolomide (TMZ)-resistance is a major challenge in glioblastoma therapy. Therefore, identifying the key molecular player in chemo-resistance becomes urgent. We previously reported the downregulation of PDCD10 in primary glioblastoma patients and its tumor suppressor-like function in glioblastoma cells. Here, we demonstrate that the loss of PDCD10 causes a significant TMZ-resistance during treatment and promotes a rapid regrowth of tumor cells after treatment. PDCD10 knockdown upregulated MGMT, a key enzyme mediating chemo-resistance in glioblastoma, accompanied by increased expression of DNA mismatch repair genes, and enabled tumor cells to evade TMZ-induced cell-cycle arrest. These findings were confirmed in independent models of PDCD10 overexpressing cells. Furthermore, PDCD10 downregulation led to the dedifferentiation of glioblastoma cells, as evidenced by increased clonogenic growth, the upregulation of glioblastoma stem cell (GSC) markers, and enhanced neurosphere formation capacity. GSCs derived from PDCD10 knockdown cells displayed stronger TMZ-resistance and regrowth potency, compared to their parental counterparts, indicating that PDCD10-induced stemness may independently contribute to tumor malignancy. These data provide evidence for a dual role of PDCD10 in tumor suppression by controlling both chemo-resistance and dedifferentiation, and highlight PDCD10 as a potential prognostic marker and target for combination therapy with TMZ in glioblastoma.

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Proteínas Reguladoras de la Apoptosis , Resistencia a Antineoplásicos , Glioblastoma , Temozolomida , Humanos , Glioblastoma/patología , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/tratamiento farmacológico , Temozolomida/farmacología , Resistencia a Antineoplásicos/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Línea Celular Tumoral , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Reguladoras de la Apoptosis/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Células Madre Neoplásicas/efectos de los fármacos , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/tratamiento farmacológico , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas/genética , Proliferación Celular/efectos de los fármacos , Metilasas de Modificación del ADN/metabolismo , Metilasas de Modificación del ADN/genética , Proteínas Supresoras de Tumor/metabolismo , Proteínas Supresoras de Tumor/genética , Enzimas Reparadoras del ADN/metabolismo , Enzimas Reparadoras del ADN/genética

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PURPOSE: Tumor-associated macrophages (TAMs) are important biomarkers of tumor invasion and prognosis in patients with glioblastoma. We combined the imaging and radiomics features of preoperative MRI to predict CD68+ macrophage infiltration. METHODS: Clinical, MRI image, and pathology data of 188 patients with glioblastoma were analyzed. Overall, 143 patients were included in the training (n = 101) and validation (n = 42) sets, whereas 45 patients were included in an independent test set. The optimal cut-off value (14.8%) was based on the minimum p-value formed by the Kaplan-Meier survival analysis and log-rank tests which divided patients into groups with high CD68+ TAMs (≥ 14.8%) and low CD68+ TAMs (< 14.8%). Regions of interest and radiomics features extraction were based on contrast-enhanced T1-weighted images (CE-T1WI) and T2WI. Multi-parameter stepwise regression was used to create the clinical, radiomics, and combined models, each evaluated using the receiver operating characteristic curve. Decision curve analysis was used to assess the clinical applicability of the nomogram. RESULTS: A clinical model based on the minimum apparent diffusion coefficient (ADCmin) revealed an area under the curve (AUC) of 0.768, 0.764, and 0.624 for the training set, validation set, and test set, respectively. The 2D radiomics model, based on two features, revealed an AUC of 0.783, 0.724, and 0.789 for the training, validation, and test sets, respectively. The 3D radiomics model, based on three features, revealed AUCs of 0.823, 0.811, and 0.787 for the training, validation, and test sets, respectively. The combined model, with ADCmin and radiomics features, showed the best performance, with AUCs of 0.865, 0.822, and 0.776 for the training, validation, and test sets, respectively. The calibration curve of the combined model nomogram showed good agreement between the estimated and actual probabilities. CONCLUSION: The combined model constructed using ADCmin, a quantitative imaging parameter, combined with five key radiomics features can be used to evaluate the extent of CD68+ macrophages before surgery.

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Glioblastoma remains a fatal diagnosis despite continuous efforts to improve upon the current standard backbone management paradigm of surgery, radiation therapy, systemic therapy and Tumor Treating Fields. Radiation therapy (RT) plays a pivotal role, with progress recently achieved in multiple key areas of research. The evolving landscape of dose and fractionation schedules and dose escalation options for different patient populations is explored, offering opportunities to better tailor treatment to a patient's overall status and preferences; novel efforts to modify treatment volumes are presented, such as utilizing state-of-the-art MRI-based linear accelerators to deliver adaptive therapy, hoping to reduce normal tissue exposure and treatment-related toxicity; specialized MR techniques and functional imaging using novel PET agents are described, providing improved treatment accuracy and the opportunity to target areas at risk of disease relapse; finally, the role of particle therapy and new altered dose-rate photon and proton therapy techniques in the treatment paradigm of glioblastoma is detailed, aiming to improve tumor control and patient outcome by exploiting novel radiobiological pathways. Improvements in each of these aforementioned areas are needed to make the critical necessary progress and allow for new approaches combining different advanced treatment modalities. This plethora of multiple new treatment options currently under investigation provides hope for a new outlook for patients with glioblastoma in the near future.

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The stiffness of human cancers may be correlated with their pathology, and can be used as a biomarker for diagnosis, malignancy prediction, molecular expression, and postoperative complications. Neurosurgeons perform tumor resection based on tactile sensations. However, it takes years of surgical experience to appropriately distinguish brain tumors from surrounding parenchymal tissue. Haptics is a technology related to the touch sensation. Haptic technology can amplify, transmit, record, and reproduce real sensations, and the physical properties (e.g., stiffness) of an object can be quantified. In the present study, glioblastoma (SF126-firefly luciferase-mCherry [FmC], U87-FmC, U251-FmC) and malignant meningioma (IOMM-Lee-FmC, HKBMM-FmC) cell lines were transplanted into nude mice, and the stiffness of tumors and normal brain tissues were measured using our newly developed surgical forceps equipped with haptic technology. We found that all five brain tumor tissues were stiffer than normal brain tissue (p < 0.001), and that brain tumor pathology (three types of glioblastomas, two types of malignant meningioma) was significantly stiffer than normal brain tissue (p < 0.001 for all). Our findings suggest that tissue stiffness may be a useful marker to distinguish brain tumors from surrounding parenchymal tissue during microsurgery, and that haptic forceps may help neurosurgeons to sense minute changes in tissue stiffness.

Asunto(s)

Neoplasias Encefálicas , Glioblastoma , Meningioma , Ratones Desnudos , Microcirugia , Animales , Humanos , Microcirugia/métodos , Microcirugia/instrumentación , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Glioblastoma/cirugía , Glioblastoma/patología , Ratones , Meningioma/cirugía , Meningioma/patología , Línea Celular Tumoral , Instrumentos Quirúrgicos

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Malignant gliomas present great difficulties in treatment, with little change over the past 30 years in the median survival time of 15 months. Current treatment options include surgery, radiotherapy (RT), and chemotherapy. New therapies aimed at suppressing the formation of new vasculature (antiangiogenic treatments) or destroying formed tumor vasculature (vascular disrupting agents) show promise. This study summarizes the existing knowledge regarding the processes by which glioblastoma (GBM) tumors acquire resistance to antiangiogenic treatments. The discussion encompasses the activation of redundant proangiogenic pathways, heightened tumor cell invasion and metastasis, resistance induced by hypoxia, creation of vascular mimicry channels, and regulation of the tumor immune microenvironment. Subsequently, we explore potential strategies to overcome this resistance, such as combining antiangiogenic therapies with other treatment methods, personalizing treatments for each patient, focusing on new therapeutic targets, incorporating immunotherapy, and utilizing drug delivery systems based on nanoparticles. Additionally, we would like to discuss the limitations of existing methods and potential future directions to enhance the beneficial effects of antiangiogenic treatments for patients with GBM. Therefore, this review aims to enhance the research outcome for GBM and provide a more promising opportunity by thoroughly exploring the mechanisms of resistance and investigating novel therapeutic strategies.

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The most common type of primary brain tumour in adults is gliomas although rare. Glioblastomas are a subtype of gliomas with the worst prognosis having the ability to rapidly increase in size, even doubling within days to weeks. Patients can present with varied presentations depending on the site of the involvement, thus misleading in diagnosis due to vagueness. The most common clinical presentations include headaches, seizures, and focal neurological signs. However, there can be atypical presentations like personality changes and back pain due to meningeal irritation which may be the only presenting complaint in the early stages. Magnetic resonance imaging (MRI) is usually considered the only investigation required for the diagnosis of the illness. However, it can mislead in the early stages. Therefore, brain biopsy remains the gold standard in the diagnosis of glioblastoma multiforme. It is important to identify the subtype to decide on the prognosis and plan the management thereafter. Here, we present a 49-year-old woman with prominent personality changes, depressive symptoms, and atypical brain imaging findings. The definitive diagnosis was made with the brain biopsy as two MRI findings were contradictory. This article highlights the importance of suspicion of primary brain tumours in adults presenting with atypical neuropsychiatric manifestations.

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BACKGROUND: Astrocytoma, the most common type of glioma, can histologically be low or high grade. Treatment recommendations for astrocytic tumors are based on the histopathological and molecular phenotype. For grade 2 astrocytoma, the combination of radiotherapy and adjuvant chemotherapy with procarbazine, lomustine, and vincristine (PCV) is better than radiotherapy alone. Temozolomide (TMZ) is being increasingly recognized as a replacement for PCV in brain tumor therapy, due to the lower myelotoxicity. TMZ is currently a well-established first-line treatment for grade 3 astrocytoma, grade 4 astrocytoma, and glioblastoma and it is also sporadically used for grade 2 astrocytoma. However, TMZ faces multiple challenges such as adverse effects and drug resistance. METHODS: In this study, we compared the cytotoxic effect induced by TMZ and doxorubicin (DOXO), alone and in combination, on a low-grade astrocytoma cell line (AC1B) and a high-grade glioma cell line (GB1B). RESULTS: We found that TMZ and DOXO, each produced a cytotoxic effect in monotherapy. GB1B cell line was more sensitive to the treatment than AC1B cells, at a 7- and 10-day exposure to the DOXO. However, when the duration of the treatment was extended to 14 days, GB1B cells became more resistant to DOXO treatment, compared to AC1B cells. Regarding the treatment with TMZ, GB1B exhibited greater resistance to TMZ compared to AC1B, across all studied intervals and the resistance to treatment of GB1B increased with longer exposure time. However, in combined therapy, the drugs did not exert a synergistic effect on any astrocytic cell line. CONCLUSIONS: The current data suggest that both TMZ and DOXO exhibit efficient therapeutic effects on low- and high-grade glioma cells. However, no synergistic effect was observed for combined therapy.

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Atypical meningioma is a type of intermediate-grade meningioma (grade 2) according to the WHO classification. The occurrence of glioblastomas at the same site of resection of a meningioma is extremely rare and the causes of this type of mutations should be investigated. We present a case of a 54-year-old patient who five years after resection of a left parietooccipital atypical meningioma presented with a glioblastoma at the same site.

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Introduction: Lobectomy has recently been employed in the management of glioblastoma (GB). Compared to subtotal, gross total and supramarginal resection, lobectomy provides maximum cytoreduction and improves overall survival (OS). Research question: The primary aim of this study is to compare lobectomy to other techniques for managing GB in terms of OS and progression-free survival (PFS). This study evaluated the association of the available surgical techniques for GB management with the reported relevant seizure outcome, operation time, length of stay, complication incidence, and Karnofsky performance status. Materials and methods: A PRISMA-compliant systematic review and meta-analysis was performed. We searched PubMed, Scopus, and Web of Science from January 2013 until April 2023. Random-effects models were employed. The Newcastle-Ottawa scale (NOS) and the GRADE approach were used for estimating risk of bias and quality of evidence. Results: We included six studies. Lobectomy demonstrated a mean OS of 25 months, compared to 13.72 months for gross total resection (GTR), and a PFS of 16.13 months, compared to 8.77 months for GTR. Comparing lobectomy to GTR, no statistically significant differences were observed regarding seizure management, length of stay, operation time, complications, and KPS due to limited amount of data. Discussion and conclusion: Our analysis demonstrated that lobectomy compared to GTR has a tremendous impact on the OS and the PFS, which seems to be improved almost by a year. Lobectomy, while demanding from a technical standpoint, constitutes a safe surgical procedure but further studies should assess its exact role in the management of GB patients.

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Glioblastoma (GB) is the most common type of malignant tumor of the central nervous system, responsible for significant morbidity and with a 5-year overall relative survival of only 6.8%. Without advances in treatment in the last twenty years, the standard of care continues to be maximum safe resection, Temozolomide (TMZ), and radiotherapy. Many new trials are ongoing, and despite showing increased progression-free survival, these trials did not improve overall survival. They did not consider the adverse effects of these therapies. Therefore, an increasing number of bioprospecting studies have used snake venom molecules to search for new strategies to attack GB selectively without producing side effects. The present review aims to describe GB characteristics and current and new approaches for treatment considering their side effects. Besides, we focused on the antitumoral activity of snake venom proteins from the Viperidae family against GB, exploring the potential for drug design based on in vitro and in vivo studies. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. In January 2024, a systematic search was performed in the PubMed, EMBASE, and Web of Science databases from January 2000 to December 2023. Search terms were selected based on the population/exposure/outcome (PEO) framework and combined using Boolean operators ("AND", "OR"). The search strategy used these terms: glioblastoma, glioma, high-grade glioma, WHO IV glioma, brain cancer, snake venom, Viperidae, and bioprospection. We identified 10 in vivo and in vitro studies with whole and isolated proteins from Viperidae venom that could have antitumor activity against glioblastoma. Studies in bioprospecting exploring the advantage of snake venom proteins against GB deserve to be investigated due to their high specificity, small size, inherent bioactivity, and few side effects to cross the blood-brain barrier (BBB) to reach the tumor microenvironment.

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While glioblastoma (GBM) progression is associated with extensive extracellular matrix (ECM) secretion, the causal contributions of ECM secretion to invasion remain unclear. Here we investigate these contributions by combining engineered materials, proteomics, analysis of patient data, and a model of bevacizumab-resistant GBM. We find that GBM cells cultured in engineered 3D hyaluronic acid hydrogels secrete ECM prior to invasion, particularly in the absence of exogenous ECM ligands. Proteomic measurements reveal extensive secretion of collagen VI, and collagen VI-associated transcripts are correspondingly enriched in microvascular proliferation regions of human GBMs. We further show that bevacizumab-resistant GBM cells deposit more collagen VI than their responsive counterparts, which is associated with marked cell-ECM stiffening. COL6A3 deletion in GBM cells reduces invasion, ß-catenin signaling, and expression of mesenchymal markers, and these effects are amplified in hypoxia. Our studies strongly implicate GBM cell-derived collagen VI in microenvironmental remodeling to facilitate invasion.

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Aims: Mesenchymal stem cells (MSCs) are key components in promoting glioblastoma (GBM) progression. This study aimed to explore new therapeutic targets and related pathogenic mechanisms based on different MSCs infiltration levels in GBM patients. Methods: We estimated the relationship between cell infiltration and prognosis of GBM. Subsequently, key risk genes were identified and prognostic models were constructed by LASSO-Cox analysis. The risk genes were validated by five independent external cohorts, single-cell RNA analysis, and immunohistochemistry of human GBM tissues. TIDE analysis predicted responsiveness to immune checkpoint inhibitors in different risk groups. Results: The MSCs infiltration level was negatively associated with survival in GBM patients. LOXL1, LOXL4, and GUCA1A are key risk genes that promote GBM progression and may act through complex intercellular communication. Conclusion: This research has provided a comprehensive study for exploring the MSCs infiltration environment on GBM progression, which could shed light on novel biomarkers and mechanisms involved in GBM progression.

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Glioblastoma (GBM), a grade IV brain tumor, presents a severe challenge in treatment and eradication due to its high genetic variability and the existence of stem-like cells with self-renewal potential. Conventional therapies fall short of preventing recurrence and fail to extend the median survival of patients significantly. However, the emergence of gene therapy, which has recently obtained significant clinical outcomes, brings hope. It has the potential to be a suitable strategy for the treatment of GBM. Notably, microRNAs (miRNAs) have been noticed as critical players in the development and progress of GBM. The combined usage of hsa-miR-34a and Cytosine Deaminase (CD) suicide gene and 5-fluorocytosine (5FC) prodrug caused cytotoxicity against U87MG Glioma cells in vitro. The apoptosis and cell cycle arrest rates were measured by flow cytometry. The lentiviral vector generated overexpression of CD/miR-34a in the presence of 5FC significantly promoted apoptosis and caused cell cycle arrest in U87MG cells. The expression level of the BCL2, SOX2, and P53 genes, target genes of hsa-miR-34a, was examined by quantitative real-time PCR. The treatment led to a substantial downregulation of Bcl2 and SOX2 genes while elevating the expression levels of Caspase7 and P53 genes compared to the scrambled control. The hsa-miR-34a hindered the proliferation of GBM cancer cells and elevated apoptosis through the P53-miR-34a-Bcl2 axis. The CD suicide gene with 5FC treatment demonstrated similar results to miR-34a in the apoptosis, cell cycle, and real-time assays. The combination of CD and miR-34a produced a synergistic effect. In vivo, anti-GBM efficacy evaluation in rats bearing intracranial C6 Glioma cells revealed a remarkable induction of apoptosis and a significant inhibition of tumor growth compared with the scrambled control. The simultaneous use of CD/miR-34a with 5FC almost entirely suppressed tumor growth in rat models. The combined application of hsa-miR-34a and CD suicide gene against GBM tumors led to significant induction of apoptosis in U87MG cells and a considerable reduction in tumor growth in vivo.

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Targeting nucleotide enzymes emerges as a promising avenue for impeding tumor proliferation and fortifying anti-tumor immunogenicity. The non-canonical role of nucleotide enzymes remains poorly understood. In this study, we have identified that Phosphoglucomutase 2 (PGM2) rapidly accumulates at the DNA damage site to govern the DNA damage response mediated by the phosphorylation at Serine 165 and by forming a complex with Rho-associated coiled-coil-containing protein kinase 2 (ROCK2). Silencing PGM2 in Glioblastoma Multiforme (GBM) cells heightens DNA damage in vitro and enhances the sensitivity of temozolomide (TMZ) treatment by activating anti-tumor immunity in vivo. Furthermore, we demonstrate that pharmacological inhibition of ROCK2 synergistically complements TMZ treatment and pembrolizumab (PD-L1) checkpoint immunotherapy, augmenting anti-tumor immunity. This study reveals the non-canonical role of the nucleotide enzyme PGM2 in the regulation of DNA damage response and anti-tumor immunity, with implications for the development of therapeutic approaches in cancer treatment.

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Lanthanum (La)-based nanotherapeutics are therapeutically advantageous due to cytoplasmic oxygen species (ROS) levels for mediating intrinsic and extrinsic tumor cell apoptosis. While they have not been extensively explored for their potential to suppress malignancies in vivo. Correspondingly, we have formulated a unique lanthanum nanocarrier with high specific surface area, dendritic-divergent mesopores, importantly, exposing more active lanthanum sites. After surface PEGlytion and ICG loading in mesoporous channels, this fantastic nanoplatform can efficaciously enrich in malignant glioblastoma regions. Meaningfully, it can be sensitively dissociated for La ions release under weak acid (pH = 6.5) tumor microenvironment. Upon 808 nm light irradiation, high light-heat conversion efficiency is further proved, then this satisfied thermal in the tumor site progressively enhances ROS production by La ions. Owing to the synergistic oxidative therapy and photothermal therapy of our dendritic La nanoplatform, glioblastoma is efficaciously and synergistically prevented both in vitro and in vivo. All outcomes highlight the therapeutic potency of La based nanoplatform with radial mesopores to treat malignant cancer in vivo and encourage future translational exploration.

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The goal of surgery for patients with newly diagnosed glioblastoma (GBM) is maximum safe resection of the contrast-enhancing (CE) lesion on magnetic resonance imaging. However, there is no consensus on the efficacy of FLAIRectomy, which is defined as the possible resection of fluid-attenuated inversion recovery (FLAIR)-hyperintense lesions surrounding the CE lesion. Although retrospective analyses suggested the potential benefits of FLAIRectomy, such outcomes have not been confirmed by prospective studies. Therefore, we planned a multicenter, open-label, randomized controlled phase III trial to evaluate the efficacy of FLAIRectomy compared with gross total resection of CE lesions in patients with newly diagnosed GBM. The primary endpoint is overall survival. In total, 130 patients will be enrolled from 47 institutions over 5 years. This trial has been registered at the Japan Registry of Clinical Trials (study number jRCT1031230245).

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Glioblastoma organoids (GBOs) serve as a powerful and reliable tool to study glioblastoma stem cells (GSCs) and glioblastoma (GBM). GBOs can be derived from different materials using different methods. To identify the predominant generation methods and the most applications of GBOs, we searched four databases (PubMed, Embase, Web of Science, and Wiley Online Laboratory) from August 2021 to August 2023. After screening, 42 out of 295 articles were included and analyzed. GBOs in these articles were generated using only one material, such as tumor tissues, tumor cells, and gene-edited multifunctional stem cells, or simultaneously using two materials, such as tumor cells and normal organoids. Methodologically, direct cultivation of GBM cells or tissues was the most commonly used method to generate GBOs. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) were the frequently used multifunctional stem cells to generate GBOs by simultaneously silencing P53, NF1, and PTEN using CRISPR/Cas9. In terms of applications, GBOs generated by direct cultivation of GBM tissue had the most applications, including molecular mechanisms, therapy, and culture technique. This review provides a theoretical reference for selecting an appropriate method to generate GBOs when studying GSCs and GBM.

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Postoperative radiotherapy currently stands as the cornerstone of glioblastoma (GBM) treatment. Nevertheless, low-dose radiotherapy has been proven ineffective for GBM, due to hypoxia in the GBM microenvironment, which renders the resistance to radiation-induced cell death. Moreover, the overexpression of the PLK1 gene in glioma cells enhances GBM proliferation, invasion, metastasis, and resistance to radiation. This study introduced a hybrid membrane-camouflaged biomimetic lipid nanosensitizer (CNL@miPA), which efficiently encapsulated gold nanoclusters (PA) and miR-593-5p by a chimeric membrane derived from lipids, cancer cells, and natural killer cells. CNL@miPA exhibited exceptional blood-brain barrier and tumor tissue penetration, effectively ameliorating hypoxia and synergizing with radiotherapy. By enabling prolonged miRNA circulation in the bloodstream and achieving high enrichment at the tumor site, CNL@miPA significantly suppressed tumor growth in combination treatment, thereby significantly extending the survival period of treated mice. Overall, the developed biomimetic nanosensitizer represented an efficient and multifunctional targeted delivery system, offering a novel strategy for gene-radiotherapy of GBM.