Treatment Of Gliomas Research Articles

In-patient neurosurgical tumor treatments for malignant glioma patients in Germany.

Treatment for malignant gliomas involves multiple disciplines, including neurosurgery, radiation therapy, medical and neuro-oncology, and palliative medicine, with function-preserving neurosurgical tumor removal being crucial. However, real-world data on hospital cases, treatment types, especially regarding surgical approaches, and the associated complication and mortality rates in Germany are lacking. We analyzed data on hospital cases involving malignant gliomas (ICD-10-GM code C71) from the German §21 Hospital Remuneration Act, provided by the Institute for the Hospital Remuneration System (InEK GmbH), from 2019 to 2022. Our focus was on neuro-oncological operations defined by the German Cancer Society (DKG) and included specific operation and procedure (OPS) codes. From 2019 to 2022, there were 101,192 hospital cases involving malignant gliomas in Germany. Neurosurgical tumor removal was performed in 27,193 cases (26.9%). Microsurgical techniques were used in 95% of surgeries, intraoperative navigation systems in 84%, fluorescence-guided surgeries in 45.6%, and intraoperative neurophysiological monitoring (IONM) in 46.4%. Surgical or medical complications occurred in 2903 cases (10.7%). The hospital mortality rate was 2.7%. Mortality was significantly higher in patients aged 65 and older (Odds ratio 2.9, p < 0.0001), and lower in cases using fluorescence-guided procedures (Odds ratio 0.8, p = 0.015) and IONM (Odds ratio 0.5, p < 0.0001). Over the course of 4years, over 100,000 hospital cases involving adult patients diagnosed with malignant gliomas were treated in Germany, with 27,193 cases undergoing tumor removal using various modern surgical techniques. The hospital mortality rate was 2.7%.

Functional germline variants in DNA damage repair pathways are associated with altered survival in adults with glioma treated with temozolomide.

Temozolomide (TMZ) treatment has demonstrated, but variable, impact on glioma prognosis. This study examines associations of survival with DNA repair gene germline polymorphisms among glioma patients who did and did not have TMZ treatment. Identifying genetic markers which sensitize tumor cells to TMZ could personalize therapy and improve outcomes. We evaluated TMZ-related survival associations of pathogenic germline SNPs and genetically predicted transcript levels within 34 DNA repair genes among 1504 glioma patients from the UCSF Adult Glioma Study and Mayo Clinic whose diagnoses spanned pre- and post-TMZ eras within the major known glioma prognostic molecular subtypes. Among those who received TMZ, 5 SNPs were associated with overall survival, but not in those who did not receive TMZ. Only rs2308321-G, in MGMT , was associated with decreased survival (HR=1.21, p=0.019) for all glioma subtypes. Rs73191162-T (near UNG ), rs13076508-C (near PARP3 ), rs7840433-A (near NEIL2 ), and rs3130618-A (near MSH5 ) were only associated with survival and TMZ treatment for certain subtypes, suggesting subtype-specific germline chemo-sensitization. Genetically predicted elevated compared to normal brain expression of PNKP was associated with dramatically worse survival for TMZ-treated patients with IDH -mutant and 1p/19q non-codeleted gliomas (p=0.015). Similarly, NEIL2 and TDG expressions were associated with altered TMZ-related survival only among certain subtypes. Functional germline alterations within DNA repair genes were associated with TMZ sensitivity, measured by overall survival, among adults with glioma, these variants should be evaluated in prospective analyses and functional studies. We observed SNPs associated with glioma survival, specific to cases receiving TMZ An MGMT variant may reduce glioma survival indirectly through myelosuppression Decreased genetic PNKP expression in the brain may sensitize cells to TMZ. The introduction of temozolomide (TMZ) as a part of standard-of-care in the treatment of gliomas marked the last notable increase in patient survival. However, the effectiveness of TMZ is not universal, and can result in serious complications. The mechanism of action behind the drug is the introduction of damaging methyl groups across the tumor genome and leveraging of DNA damage repair (DDR) mechanisms to signal programmed cell death. Previous literature has identified that defects in DDR mechanisms can alter TMZ sensitivity. Using a unique dataset that spans the pre- and post-TMZ eras, we demonstrate that germline variation in DDR-related genes may have significant impact on overall survival for patients treated with TMZ, with no effects observed in the pre-TMZ era. This suggests that germline variants in these DDR genes could be used to personalize TMZ therapy to improve patient survival.

Exploring the significance and potential mechanisms of hippo pathway-associated genes in prognosis of glioma patients

PurposeDespite the efforts of countless researchers to develop glioma treatment strategies, the current therapeutic effect of glioma is still not ideal, and it is necessary to further explore the mechanism to guide treatment. Thus, this study aims to introduce a novel approach for predicting patient prognosis and guiding further treatment interventions.MethodsInitially, we conducted a differential gene expression analysis to identify Hippo pathway-associated genes overexpressed in tumors and determined genes correlated with prognosis. Subsequently, employing cluster analysis, we categorized samples into two groups and performed further analyses including prediction, immune cell infiltration abundance, and drug response rates. We utilized weighted gene co-expression analysis to reveal gene sets with high co-variation, delineate inter-sample gene correlation patterns, and conduct enrichment analysis. Prognostic models were built using ten machine learning algorithms combined in 101 different combinations, followed by evaluation and validation. Immune infiltration analysis, differential expression analysis of depleted T cell-related markers, drug sensitivity analysis, and exploration of pathway dysregulation were performed for different risk groups. Quality control and batch integration were performed, and single-cell data were analyzed using dimensionality reduction clustering algorithms and annotation tools to evaluate the activity of the prognostic model in malignant cells.ResultsWe conducted data filtering to identify genes overexpressed in tumors, intersecting these genes with Hippo pathway-related genes, identifying 62 genes correlated with prognosis, and performing cluster analysis to divide tumor tissues into two groups. Cluster 2 exhibited a poorer prognosis and demonstrated differences in immune cell infiltration. Utilizing weighted gene co-expression analysis on Cluster 2, we identified gene modules, conducted functional enrichment analysis, and delineated pathways. Employing a combined model based on ten machine learning algorithm combinations, we selected the optimal prognostic model system and validated the model’s predictive ability within the dataset. Through immune-related analysis and drug sensitivity analysis, we uncovered differences in immune infiltration and varying sensitivities to chemotherapy drugs. Additionally, the enrichment analysis of gene set revealed discrepancies in upregulation within relevant pathways between the high and low-risk groups. Finally, annotation and evaluation of malignant cells via single-cell analysis showed increased activity of the prognostic model and variations in distribution across different prognostic levels in malignant cells.ConclusionThis study introduces a novel approach utilizing the Hippo pathway and associated genes for glioma prognosis research, demonstrating the potential and significance of this method in evaluating the outcome for patients with glioma. These findings hold substantial clinical significance in guiding therapy and predicting outcomes for individuals diagnosed with glioma, offering significant clinical utility.

Chinese expert consensus on diagnosis and treatment of spinal cord glioma

Spinal cord glioma is a group of tumors originated from spinal cord glial cells. They typically have an insidious onset, with early symptoms in patients including sensory disturbances, motor disorder, and sphincter dysfunction. When the course of disease develops to a certain extent, it can lead to paralysis, dyspnea, and even result in death. The spinal cord bears the role of nerve conduction, and acts as a lower central hub for somatic and visceral activities and primary neural reflexes. Because the self-repair ability after injury is limited, spinal cord injury caused by tumor and treatment may be permanent, potentially causing huge economic and social burden. To further standardize the diagnosis and treatment of spinal cord glioma, the expert group formulated The Chinese Expert Consensus on the Diagnosis and Treatment of Spinal Cord Glioma according to the current situation of diagnosis and treatment of spinal cord glioma at home and abroad. This consensus elaborates the epidemiology, natural course, clinical manifestations, diagnosis, treatment, follow-up, and prognosis of spinal gliomas and formulates 17 recommendations. It aims to offer reference for medical personnel and other related individuals.

Development of a prognostic model related to homologous recombination deficiency in glioma based on multiple machine learning.

Despite advances in neuro-oncology, treatments of glioma and tools for predicting the outcome of patients remain limited. The objective of this research is to construct a prognostic model for glioma using the Homologous Recombination Deficiency (HRD) score and validate its predictive capability for glioma. We consolidated glioma datasets from TCGA, various cancer types for pan-cancer HRD analysis, and two additional glioma RNAseq datasets from GEO and CGGA databases. HRD scores, mutation data, and other genomic indices were calculated. Using machine learning algorithms, we identified signature genes and constructed an HRD-related prognostic risk model. The model's performance was validated across multiple cohorts. We also assessed immune infiltration and conducted molecular docking to identify potential therapeutic agents. Our analysis established a correlation between higher HRD scores and genomic instability in gliomas. The model, based on machine learning algorithms, identified seven key genes, significantly predicting patient prognosis. Moreover, the HRD score prognostic model surpassed other models in terms of prediction efficacy across different cancers. Differential immune cell infiltration patterns were observed between HRD risk groups, with potential implications for immunotherapy. Molecular docking highlighted several compounds, notably Panobinostat, as promising for high-risk patients. The prognostic model based on the HRD score threshold and associated genes in glioma offers new insights into the genomic and immunological landscapes, potentially guiding therapeutic strategies. The differential immune profiles associated with HRD-risk groups could inform immunotherapeutic interventions, with our findings paving the way for personalized medicine in glioma treatment.

CuO nanoparticles for glioma treatment in vitro and in vivo.

Glioma is the most prevalent malignant brain tumor in adults. The development of engineered nanomaterials (ENMs) has led to the emergence of innovative therapeutic strategies for gliomas. Therefore, our aim is to investigate the therapeutic effect of CuO nanoparticles (NPs) on glioma and provide data support for future research. The therapeutic effect of CuO NPs on glioma rats was explored through the detection of inflammatory factors, oxidase, pathological sections, immunofluorescence, neurotransmitter, glioma biomarker proteins and genes, and rat behavioral tests. Additionally, the application prospect of CuO NPs was evaluated by treating U87MG human glioma cell line. In this study, it was found that CuO NPs can alleviate the inflammatory reaction in the hippocampus tissue of glioma rats, promote the production of ·OH and lead to the up-regulation of catalase (CAT) and superoxide dismutase (SOD) enzyme activities. Treatment with CuO NPs also inhibited the expression of matrix metalloproteinase-9 (MMP-9) biomarkers in model rats and glioma cells. Moreover, it enhanced the release of neurotransmitters, which subsequently improved spatial recognition and memory ability of glioma rats. In conclusion, CuO NPs is a potential glioma treatment for ENMs, but still needs modification and modification strategies to improve its biocompatibility and targeted delivery.

T7 Peptide-modified macrophage membrane-coated nanoplatform for enhanced glioma treatment

The efficient and secure delivery of intravenous chemotherapeutic agents across the blood–brain barrier (BBB) to the precise location of a brain tumor is a crucial element in glioma treatment. Herein, we introduce a biomimetic nanoplatform (T7-M-C/S) comprising a core made up of irinotecan hydrochloride (CPT11) and its bioactive metabolite, 7-Ethyl-10-hydroxycamptothecin (SN38), surrounded by a layer of T7-peptide-modified macrophage membrane. CPT11 spontaneously assembles with SN38 into stable and water-dispersible nanoparticles (C/S), greatly enhancing the water solubility of SN38. The integration of the modified peptide with the inherent proteins expressed by macrophage cells confers the nanoplatform with enhanced bioavailability and robust glioma-targeting abilities, ultimately resulting in superior therapeutic outcomes. These discoveries highlight a drug delivery system characterized by a high drug loading capacity, leveraging the macrophage membrane, and promising significant potential for glioma treatment.

A near-infrared triggered multi-functional indocyanine green nanocomposite with NO gas release function inducing improved photothermal therapy

The integration of photothermal and near-infrared (NIR) imaging capabilities of indocyanine green (ICG) small molecules has attracted considerable attention in tumor diagnosis and treatment. However, the abnormal upregulation of cellular heat shock proteins (HSPs) induced by photothermal therapy (PTT) enhances cellular heat resistance, thereby severely affecting the efficacy of PTT. In this study, to address the impact of HSPs on the efficacy of PTT while obtaining high-quality NIR fluorescence imaging in the NIR region, we designed a targeted peptide@ICG nanofluorescent probe encapsulated in liposomes. The introduced cRGD targeting peptide not only possesses tumor-targeting capabilities but also features LA as the last amino acid in the targeting peptide, which can generate nitric oxide (NO) under reactive oxygen species (ROS) triggering. It can happen under 808 nm single-light source NIR light, and the guanidine group in the peptide decomposes and combines with singlet oxygen molecules to generate NO gas molecules, thereby exerting an elevated photothermal effect by inhibiting the expression of HSP70. In addition, the nanoprobes enable deep imaging and treatment of glioma in situ and can be combined with a laser speckle contrast imaging (LSCI) system for multimodal imaging. This composite probe demonstrates synergistic tumor therapeutic effects of photodynamic therapy (PDT), PTT, and gas therapy, offering a promising strategy for cancer treatment.

Proapoptotic and antimigration properties of osthole in combination with LY294002 against human glioma cells.

Anaplastic astrocytoma and glioblastoma multiforme are infiltrating and vascularized gliomas with a high degree of chemoresistance and metastasis. Our previous studies have shown that osthole may be of great importance in the treatment of gliomas. Therefore, in this work, for the first time, coumarin was used in combination with LY294002-an inhibitor of the PI3K-Akt/PKB-mTOR pathway, which is overly active in gliomas. MOGGCCM and T98G cells were incubated with osthole and LY294002, alone and in combination. Staining with specific fluorochromes was used to visualize cell death and the scratch test to assess the migration. The level of proteins was estimated by immunoblotting. Forming protrusions were visualized by SEM, and immunocytochemistry was used to determine the localization of proteins. Additionally, the expression of Bcl-2, beclin 1 and Raf kinase was silenced using specific siRNA. The obtained results showed that osthole in combination with LY294092 effectively inhibited the migration of glioma cells by reducing the level of metaloproteinases and Rho family proteins, as well as decreasing the level of N-cadherin. In addition, the combination of compounds induced apoptosis. New combination of compounds shows a high pro-apoptotic potential and also inhibits the migration of gliomas cells.

Interference of FZD2 suppresses proliferation, vasculogenic mimicry and stemness in glioma cells via blocking the Notch/NF‑κB signaling pathway.

Frizzled family protein 2 (FZD2) is widely associated with tumor development and metastasis. The present study aimed to gain an insight into the role and regulatory mechanism of FZD2 in glioma. The expression level of FZD2 in normal astrocyte and glioma cells was determined by reverse transcription-quantitative PCR and western blotting, and cell transfection was conducted for FZD2 expression knockdown. Malignant behaviors including cell proliferation, migration and invasion, vasculogenic mimicry (VM) and cell stemness were determined using Cell Counting Kit-8, 5-Ethynyl-2'-deoxyuridine (EdU) staining, colony formation, wound healing, Transwell, 3D culturing and sphere formation assays. The expression levels of proteins related to stemness, epithelial-mesenchymal transition (EMT) and Notch/NF-κB signaling were measured by western blotting. Then, the Notch agonist, Jagged-1 (JAG), was adopted for rescue experiments. The results demonstrated that FZD2 was highly expressed in glioma cells. Interference of FZD2 expression suppressed the proliferation of glioma cells, as evidenced by the reduced cell viability and the number of EdU+ cells and colonies. Meanwhile, the reduced sphere formation ability and decreased protein expression of Nanog, Sox2 and Oct4 following FZD2 knockdown confirmed that FZD2 repressed cell stemness in glioma. Additionally, FZD2 knockdown suppressed the migration, invasion, EMT and VM formation capabilities of glioma cells, and also blocked the Notch/NF-κB signaling pathway. Furthermore, activation of Notch by JAG treatment partially reversed the aforementioned FZD2 knockdown-mediated changes in glioma cell malignant behaviors. In conclusion, FZD2 may contribute to glioma progression through activating the Notch/NF-κB signaling pathway, providing a plausible therapeutic target for the treatment of glioma.

Decoding the immune microenvironment: unveiling CD8 + T cell-related biomarkers and developing a prognostic signature for personalized glioma treatment

BackgroundGliomas are aggressive brain tumors with poor prognosis. Understanding the tumor immune microenvironment (TIME) in gliomas is essential for developing effective immunotherapies. This study aimed to identify TIME-related biomarkers in glioma using bioinformatic analysis of RNA-seq data.MethodsIn this study, we employed weighted gene co-expression network analysis (WGCNA) on bulk RNA-seq data to identify TIME-related genes. To identify prognostic genes, we performed univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. Based on these genes, we constructed a prognostic signature and delineated risk groups. To validate the prognostic signature, external validation was conducted.ResultsCD8 + T cell infiltration was strongly correlated with glioma patient prognosis. We identified 115 CD8 + T cell-related genes through integrative analysis of bulk-seq data. CDCA5, KIF11, and KIF4A were found to be significant immune-related genes (IRGs) associated with overall survival in glioma patients and served as independent prognostic factors. We developed a prognostic nomogram that incorporated these genes, age, gender, and grade, providing a reliable tool for clinicians to predict patient survival probabilities. The nomogram’s predictions were supported by calibration plots, further validating its accuracy.ConclusionIn conclusion, our study identifies CD8 + T cell infiltration as a strong predictor of glioma patient outcomes and highlights the prognostic value of genes. The developed prognostic nomogram, incorporating these genes along with clinical factors, provides a reliable tool for predicting patient survival probabilities and has important implications for personalized treatment decisions in glioma.

The Role of Systemic Therapies in the Treatment of Grades 1-4 Gliomas.

The primary treatment for gliomas typically involves tumor resection followed by adjuvant radiotherapy, with increasing emphasis on chemotherapy and molecularly targeted drugs. This study aimed to review and summarize the literature on the systemic therapy of malignant gliomas.Chemotherapy may be considered in grades 2 and 3 gliomas, especially when mutations in 1p19q-codeletion are detected. The beneficial impact of adding chemotherapy to radiotherapy (PCV: procarbazine, lomustine, vincristine) has also been demonstrated. In grade 4 glioblastoma multiforme (GBM), wild-type isocitrate dehydrogenase (IDH) status showed the best treatment outcomes with temozolomide (TMZ) in patients with O-6-methylguanine-DNA methyltransferase (MGMT)promoter methylation. Prolonging adjuvant TMZ therapy improves treatment outcomes compared to the standard 6-cycle adjuvant therapy. Bevacizumab (BEV) monotherapy can improve progression-free survival and maintain the initial quality of life. Despite advancements in GBM treatment, outcomes remain unsatisfactory, with a median survival of 14-16 months. Further research is still needed regarding the systemic treatment of central nervous system gliomas.

Fotemustine in recurrent high‑grade glioma: MRI neuro‑radiological findings.

The use of fotemustine (FTM) has been authorized in certain countries for the treatment of recurrent high-grade gliomas (HGG) after Stupp therapy. However, to the best of our knowledge, no studies have assessed changes in magnetic resonance imaging (MRI) during treatment with FTM monotherapy. The aim of the present study was to assess the neuroradiological findings in a cohort of patients with recurrent HGG treated with FTM monotherapy. Patients with HGG already undergoing the Stupp protocol were retrospectively included. MRIs (pre- and post-FTM treatment) were analyzed by two neuroradiologists in consensus: Volume and diffusion values of the contrast-enhanced component were measured on T1-weighted volumetric sequences after gadolinium injection and on apparent diffusion coefficient (ADC) maps, respectively. A total of 19 patients [median age, 49 years; interquartile range (IQR), 43-57 years] were included, 17 of whom had glioblastoma and 2 had astrocytoma isocitrate dehydrogenase-mutated grade 4. The median duration of FTM therapy was 4 months (IQR, 2-6 months). The median tumor volume measured on the contrast-enhanced component was 2,216 mm3 (IQR, 768-13,169 mm3) at baseline and 9,217 mm3 (IQR, 3,455-16,697 mm3) at the end of treatment, with a median change of +38% (IQR, -45-+574%). A total of seven patients showed a volume decrease. ADC value analysis of the enhancement area demonstrated no significant difference between the pre- and the post-FTM treatment periods (P=0.36); however, in three patients, the decreases in ADC levels were particularly marked. In conclusion, the present study described a series of patients with recurrent HGG treated with FTM in monotherapy, demonstrating a prevalent increase in lesion enhancement and three cases of marked restrictions on diffusion-weighted imaging. Further prospective studies are required to corroborate such preliminary results.

PP2 suppresses proliferation and migration of C6 Glioma and MDA-MB-231 cells by targeting both fibroblast growth factor receptor 1 and Src

Fibroblast growth factor (FGF) is involved in the progression of glioma, a most common type of brain tumor, and breast tumors. In this study, we aim to evaluate the effects of the inhibitor PP2 on cell proliferation and migration in glioma and breast tumor cells, and to characterize the molecular mechanisms involved in these processes. The inhibitory effect of PP2 on the tumorigenic potential of C6 glioma and MDA-MB-231 cells was examined by proliferation, migration, and invasion assays, and apoptotic analysis. The molecular mechanism behind the anti-glioma activity of PP2 was investigated by immunoblotting, immunoprecipitation, phosphoprotein assay, cellular thermal shift assay (CETSA), and molecular docking modeling. PP2 suppressed the proliferation and migration of C6 glioma and MDA-MB-231 cells via FGF2. Moreover, PP2 directly blocked the enzyme activity of FGF receptor 1 (FGFR1) and Src, subsequently affecting the nuclear factor-κB and activator protein-1 signaling pathways. CETSA analysis and the docking model indicated that the TK1 domains (Val 492 ad Glu 486) of FGFR2 could be binding sites of PP2. Collectively, therefore, our findings suggest that PP2 mediates antitumor effects by targeting both FGFR1 and Src and may have applications as a therapeutic inhibitor for the treatment of glioma.

The role of trimethylation on histone H3 lysine 27 (H3K27me3) in temozolomide resistance of glioma

Temozolomide (TMZ) is the first-line chemotherapeutic agent for malignant glioma, but its resistance limited the benefits of the treated patients. In this study, the role and significance of trimethylation of histone H3 lysine 27 (H3K27me3) in TMZ resistance were investigated. Data from twenty advanced glioma patients were collected, and their pathological samples were analyzed for H3K27me3 levels. TMZ sensitivity was compared between glioma cells U87 and TMZ-resistant cells U87TR, with H3K27me3 levels determined in both cells. The effects of H3K27me3 demethylases inhibitor GSK-J4, combined with TMZ, were assessed on the proliferation and migration of U87TR cells. The results indicated that a high level of H3K27me3 predicts longer disease free survival (DFS) and overall survival (OS) in glioma patients receiving TMZ treatment. The H3K27me3 level was lower in U87TR cells compared to U87 cells. GSK-J4 increased the H3K27me3 level in U87TR cells and decreased their resistance to TMZ. In summary, this study identified a novel marker of TMZ resistance in glioma and provided a new strategy to address this challenge. These findings are significant for improving the clinical treatment of glioma in the future.

The Role of Mutant IDH Inhibitors in the Treatment of Glioma.

The identification of isocitrate dehydrogenase (IDH) mutations has led to a transformation in our understanding of gliomas and has paved the way to a new era of targeted therapy. In this article, we review the classification of IDH-mutant glioma, standard of care treatment options, clinical evidence for mutant IDH (mIDH) inhibitors, and practical implications of the recent landmark INDIGO trial. In the phase 3 randomized placebo-controlled INDIGO trial, mIDH1/2 inhibitor vorasidenib increased progression-free survival among non-enhancing grade 2 IDH-mutant gliomas following surgery. This marks the first positive randomized trial of targeted therapy in IDH-mutant glioma, and led to the US Food and Drug Administration's approval of vorasidenib in August 2024 for grade 2 IDH-mutant glioma. Vorasidenib is a well-tolerated treatment that can benefit a subset of patients with IDH-mutant glioma. Targeting mIDH also remains a promising strategy for select groups of patients excluded from the INDIGO trial. Ongoing and future studies, including with new agents and with combination therapy approaches, may expand the benefit and unlock the potential of mIDH inhibitors.

Lipid-Conjugated Reduced Haloperidol in Association with Glucose-Based Nanospheres: A Strategy for Glioma Treatment.

Aggressive glioma exhibits a poor survival rate. Increased tumor aggression is linked to both tumor cells and tumor-associated macrophages (TAMs), which induce pro-aggression, invasion, and metastasis. Imperatively, for effective treatment, it is important to target both glioma cells and TAMs. Haloperidol, a neuropsychotic drug, avidly targets the sigma receptor (SR), which is expressed in higher levels in both the cell types. Herein, we present the development of a novel cationic lipid-conjugated reduced haloperidol (±RHPC8), which aims to mediate the SR-targeted antiglioma effect. Hypothetically, ±RHPC8 would act simultaneously as an SR-targeting ligand and anticancer agent. As the blood-brain barrier (BBB) obstructs direct targeting of in situ glioma, we used BBB-crossing glucose-based carbon nanospheres (CSPs) to deliver ±RHPC8 within the glioma tumor-bearing mouse brain. The resultant ±RHPC8-CSP nanoconjugate targeted SR-expressing glioma cells. In both orthotopic and subcutaneous mouse tumor models, ±RHPC8-CSP prolonged survival and regressed tumors compared to other treated groups. Notably, ±RHPC8-CSP was significantly taken up by SR-expressing TAMs thus resulting in macrophage polarization from M2 to M1, as exhibited by markedly reduced expression of immunosuppressive cytokines released by TAMs, including TGF-β, IL-10, and VEGF. In conclusion, the designed ±RHPC8-CSP nanoconjugate presented an effective nanodrug delivery system for brain cancer treatment.

Beyond surgical resection: evaluating stereotactic brachytherapy iodine-125 for low-grade gliomas: a systematic review and meta-analysis.

Stereotactic Brachytherapy Iodine-125 (SBT I-125) has been investigated by some studies for the treatment of lowgrade gliomas. We performed a meta-analysis to assess the efficacy and safety of SBT I-125 Brachytherapy for treatment of patients with Low-Grade Gliomas. PubMed, Cochrane, Web of Science, and EMBASE databases were searched for randomized and observational studies. This systematic review and meta-analysis was conducted according to the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines. We used relative risk (RR) with 95% confidence intervals and random effects model to compare the effects of I-125 SBT treatment on the interest outcomes. We evaluated heterogeneity using I2 statistics; we considered heterogeneity to be significant if the p-value was less than 0.05 and I2 was higher than 35%. We performed statistical analysis using the software R (version 4.2.3). A total of 20 studies with a cohort of 988 patients with low grade gliomas who received SBT I-125 as a treatment option. The pooled analysis evidenced: (1) Complication rate of 10% (95% CI: 7-12%; I² = 60%); (2) 5-year PFS of 66% (99% CI: 45-86%; I²= 98%); (3) 10-year PFS was 66% (99% CI: 45-86%; I²= 98%); (4) Malignant transformation rate of 26% (95% CI: 8-45%; I²=0); (5) Mortality of 33% (95% CI: 15-51%; I² = 0%). Our systematic review and meta-analysis of SBT I-125 for low-grade gliomas have revealed significant concerns regarding its safety and efficacy. Despite a proportion of patients remaining progression-free, elevated rates of complications and mortality cast doubt on the intervention's reliability. Future research should prioritize long-term follow-up studies, standardized protocols, and comparative effectiveness research.

Unlocking the potential of LHPP: Inhibiting glioma growth and cell cycle via the MDM2/p53 pathway

The recurrence of glioma after treatment has remained an intractable problem for many years. Recently, numerous studies have explored the pivotal role of the mouse double minute 2 (MDM2)/p53 pathway in cancer treatment. Lysine phosphate phosphohistidine inorganic pyrophosphate phosphatase (LHPP), a newly discovered tumor suppressor, has been confirmed in numerous studies on tumors, but its role in glioma remains poorly understood. Expression matrices in The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases were analyzed using gene set enrichment analysis (GSEA), revealing significant alterations in the p53 pathway among glioma patients with high LHPP expression. The overexpression of LHPP in glioma cells resulted in a reduction in cell proliferation, migration, and invasive ability, as well as an increase in apoptosis and alterations to the cell cycle. The present study has identified a novel inhibitory mechanism of LHPP against glioma, both in vivo and in vitro. The results demonstrate that LHPP exerts anti-glioma effects via the MDM2/p53 pathway. These findings may offer a new perspective for the treatment of glioma in the clinic.

Andrographolide sensitizes glioma to temozolomide by inhibiting DKK1 expression.

Temozolomide (TMZ) is the first-line chemotherapeutic drug for gliomas treatment. However, the clinical efficacy of TMZ in glioma patients was very limited. Therefore, it is urgently needed to discover a novel approach to increase the sensitivity of glioma cells to TMZ. Western blot, immunohistochemical staining, and qRT-PCR assays were used to explore the mechanisms underlying TMZ promoting DKK1 expression and andrographolide (AND) inhibiting DKK1 expression. HPLC was used to detect the ability of andrographolide (AND) to penetrate the blood-brain barrier. MTT assay, bioluminescence images, magnetic resonance imaging (MRI) and H&E staining were employed to measure the proliferative activity of glioma cells and the growth of intracranial tumors. TMZ can promote DKK1 expression in glioma cells and brain tumors of an orthotopic model of glioma. DKK1 could promote glioma cell proliferation and tumor growth in an orthotopic model of glioma. Mechanistically, TMZ increased EGFR expression and subsequently induced the activation of its downstream MEK-ERK and PI3K-Akt pathways, thereby promoting DKK1 expression in glioma cells. Andrographolide inhibited TMZ-induced DKK1 expression through inactivating MEK-ERK and PI3K-Akt pathways. Andrographolide can cross the blood-brain barrier, the combination of TMZ and andrographolide not only improved the anti-tumor effects of TMZ but also showed a survival benefit in an orthotopic model of glioma. Andrographolide can enhance anti-tumor activity of TMZ against glioma by inhibiting DKK1 expression.