Intracranial Malignancies Research Articles

Leptomeningeal metastatic disease: new frontiers and future directions.

Leptomeningeal metastatic disease (LMD), encompassing entities of 'meningeal carcinomatosis', neoplastic meningitis' and 'leukaemic/lymphomatous meningitis', arises secondary to the metastatic dissemination of cancer cells from extracranial and certain intracranial malignancies into the leptomeninges and cerebrospinal fluid. The clinical burden of LMD has been increasing secondary to more sensitive diagnostics, aggressive local therapies for discrete brain metastases, and improved management of extracranial disease with targeted and immunotherapeutic agents, resulting in improved survival. However, owing to drug delivery challenges and the unique microenvironment of LMD, novel therapies against systemic disease have not yet translated into improved outcomes for these patients. Underdiagnosis and misdiagnosis are common, response assessment remains challenging, and the prognosis associated with this disease of whole neuroaxis remains extremely poor. The dearth of effective therapies is further challenged by the difficulties in studying this dynamic disease state. In this Review, a multidisciplinary group of experts describe the emerging evidence and areas of active investigation in LMD and provide directed recommendations for future research. Drawing upon paradigm-changing advances in mechanistic science, computational approaches, and trial design, the authors discuss domain-specific and cross-disciplinary strategies for optimizing the clinical and translational research landscape for LMD. Advances in diagnostics, multi-agent intrathecal therapies, cell-based therapies, immunotherapies, proton craniospinal irradiation and ongoing clinical trials offer hope for improving outcomes for patients with LMD.

ZNF503-AS2 is a promising therapeutic target and is associated with the immune microenvironment in glioma.

Glioma is the most common intracranial malignancy, and the available treatment options are poor. Long noncoding RNAs (lncRNAs) have been reported to be involved in the malignant progression of glioma. The role of ZNF503-AS2 in glioma has not been reported. We screened ZNF503-AS2 with upregulated expression in glioblastoma (GBM) by analyzing the TCGA, CGGA and GTEx databases. Single sample gene set enrichment analysis (ssGSEA) was used to calculate the enrichment of immune cells and signaling pathways in glioma samples. Single-cell datasets were used to analyze the distribution of ZNF503-AS2. In vitro experiments were used to investigate the biological function of ZNF503-AS2. ZNF503-AS2 was highly expressed in glioma and was associated with poor prognosis, malignant progression and infiltration of immunosuppressive cells. Single-cell transcriptomic analysis showed that ZNF503-AS2 was mainly expressed in macrophages and tumor cells. Further analysis revealed that immunotherapy may have better efficacy in patients with low ZNF503-AS2 expression. In vitro experiments showed that knockdown of ZNF503-AS2 reduced the proliferation, invasion and migration ability of glioma cells, induced G2/M cell cycle arrest and promoted apoptosis. ZNF503-AS2 might be a valuable biomarker for predicting the prognosis of glioma patients and a potential target for glioma therapy.

The 5-factor modified frailty index as a prognostic factor for stereotactic radiosurgery in meningioma management.

Meningiomas are the most frequent primary intracranial malignancy. While surgical resection can confer long term tumor control, stereotactic radiosurgery (SRS) is often used for small, asymptomatic tumors in the adjuvant setting. Frailty has been associated with increased rates of peri-operative morbidity but has yet to be defined in the setting of SRS for meningiomas. We therefore sought to examine the relationship between frailty and clinical/radiographic outcomes of patients with meningiomas who have undergone SRS. A single-center, retrospective cohort study classified patients by their 5-factor modified frailty index (mFI-5) score into pre-frail (0-1) and frail (2-5) at the time of SRS treatment. Evaluations of overall survival (OS), progression free survival (PFS), local control (LC), and distant control (DC) were performed using Kaplan-Meier analysis. Cox proportional hazards regression analysis was used to further define factors associated with OS/PFS. 94 patients met inclusion criteria and underwent SRS for meningioma treatment from 2019 to 2023. Analyses compared prefrail (0-1) and frail (2-5) individuals. Kaplan-Meier analysis demonstrated a near significant association between frailty and OS (HR 3.66, 95% CI 0.49-26.8 p = 0.05) with 3-year OS rates of 75.4% in the pre-frail versus 36.6% in the frail group. However, a significant relationship was demonstrated between frailty and PFS (HR: 2.95 95% CI 1.12-7.81, p = 0.02) with 3-year PFS rates of 90.5% in the pre-frail group versus 49.2% in the frail group. Univariable regression analysis demonstrated that frailty, prior surgical excision, and cumulative tumor volume predicted PFS. Frailty, as assessed by the mFI-5, did not independently predict OS but did predict PFS in individuals with meningioma undergoing SRS.

Immunotherapy-Related Neurotoxicity in the Central Nervous System of Children with Cancer.

Significant gaps remain in our understanding of immunotherapy-related neurotoxicity in pediatric patients, largely because much of our knowledge comes from studies in adults. Accurately identifying the adverse effects of immunotherapy in children is also challenging, owing to variations in terminology and grading systems. Moreover, the manifestation of immunotherapy-related neurotoxicity differs greatly across different diseases, various modalities, dosages, and delivery methods. Combining immunotherapy with other treatments might improve outcomes but introduces new complexities and potential for increased toxicities. Additionally, pediatric patients with intracranial malignancy have unique responses to immunotherapies and distinct neurotoxicity compared to those with extracranial malignancy. Consequently, we must enhance our understanding of the pathophysiology, prevalence, severity, and management of immunotherapy's neurotoxic effects in this vulnerable group. This review consolidates the current knowledge of immunotherapy-related neurotoxicity in pediatric oncology, highlighting various types of neurotoxicity including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and tumor inflammation-associated neurotoxicity (TIAN), among others. Furthermore, we examine the unique features of neurotoxicity associated with adoptive cellular therapy (ACT), antibody-based therapies, immune checkpoint inhibitors (ICIs), oncolytic viruses (OV), and cancer vaccines.

IMMU-09. REVERSING SYSTEMIC T CELL DYSFUNCTION TO LICENSE IMMUNOTHERAPY IN INTRACRANIAL TUMORS

Abstract Intracranial tumors present unique challenges for immunotherapy. These can include both local and systemic modes of immune suppression, the mechanistic underpinnings of which are incompletely understood. Our work reveals that intracranial tumors elicit systemic increases in circulating catecholamine levels, and that this chronic sympathetic hyperactivity results in T cell dysfunction that impedes immunotherapeutic efficacy. We show that treatment with b-adrenergic blockade can partially overcome the negative impacts of chronic sympathetic hyperactivity by increasing NF-kB activity in immune cells, restoring T cell polyfunctionality, favorably modifying the tumor microenvironment, and extending survival in murine models of glioblastoma treated with immune-based therapies. Furthermore, we demonstrate that extended survival is also observed in glioblastoma patients receiving b-adrenergic blockade, as well as in patients with melanoma and lung cancer brain metastases who received b-blockade alongside concomitant immune checkpoint inhibition. Importantly, while local sympathetic hyperactivity in the tumor microenvironment and b-blockade also impact the anti-tumor immune response in the context of extracranial disease, these effects are markedly more pronounced in intracranial disease. Taken together, these data reveal that sympathetic hyperactivity facilitates systemic immune dysfunction in the setting of intracranial tumors and highlight a novel role for the application of b-adrenergic blockade to license immunotherapy in intracranial malignancies.

Initial feasibility cohort of temporally modulated pulsed proton re-irradiation (TMPPR) for recurrent high-grade intracranial malignancies

Recurrent high-grade intracranial malignancies have a grim prognosis and uniform management guidelines are lacking. Re-irradiation is underused due to concerns about irreversible side effects. Pulsed-reduced dose rate radiotherapy (PRDR) aims to reduce toxicity while improving tumor control by exploiting dose-rate effects. We share our initial experience with temporally modulated pulsed proton re-irradiation (TMPPR), focusing on workflow, safety, feasibility, and outcomes for the first patient cohort. TMPPR was administered to patients with recurrent or progressive central nervous system malignancies using intensity modulated proton therapy with three fields. Patient and treatment data were collected, responses categorized using RANO assessment, and toxicities graded using CTCAE v5.0. Five patients received TMPPR between October 2022 and May 2023, with a median age of 54 years (Range: 32–72), and a median time from initial radiotherapy to re-RT of 23 months (Range 14–40). Treatment was completed without delay, with a median dose of 60 GyRBE in 30 fractions. Initial treatment response assessment showed complete (n = 1) or partial (n = 3) responses. Limited toxicity was observed, primarily grade 2 alopecia and one case of radiation necrosis graded at 2. This early experience demonstrates the feasibility of TMPPR delivery, highlighting the importance of prospective evaluations in the re-irradiation setting.

Comprehensive gene set enrichment and variation analyses identify SUV39H1 as a potential prognostic biomarker for glioblastoma immunorelevance

Glioblastoma (GBM) is the most common intracranial malignancy. SUV39H1 encodes a histone H3 lysine 9 methyltransferase that acts as an oncogene in several cancers; however, its role in GBM remains unknown. We obtained GBM transcriptome and clinical data from The Cancer Genome Atlas (TCGA) database on the UCSC Xena platform to perform differential and enrichment analyses of genes in the SUV39H1 high- and low-expression groups to construct a prognostic risk model. Analysis of SUV39H1 related biological processes in GBM was performed by gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA). High- and low-risk subgroup mutation signatures were analyzed using maftools. Immune infiltration was evaluated using IOBR and CIBERSORT algorithms. We analyzed the cell types and intercellular communication networks in glioma stem cells (GSCs) using scRNA-seq. The effects on GBM cells and GSCs after inhibition of SUV39H1 were investigated in vitro. SUV39H1 was significantly overexpressed in GBM and associated with poor prognosis. SUV39H1-related differentially expressed genes were enriched in immune and inflammation related pathways, and GSEA revealed that these genes were significantly enriched in signaling pathways such as IL-18, oxidative phosphorylation, and regulation of TP53 activity. Mutational analysis revealed frequent alterations in TP53 and PTEN expression. In addition, the infiltration abundances of the five immune cell types were significantly different between the high- and low-expression groups. Analysis of cellular communication networks by scRNA-seq revealed a strong interaction between CRYAB-GSC and PTPRZ1-GSC in GSCs. In vitro experiments verified that knockdown of SUV39H1 inhibited the viability and proliferation of U87 and U251 glioblastoma cells and downregulated the expression of stemness markers Nestin and SOX2 in CSC1589 and TS576 GSC lines. Increased SUV39H1 expression is associated with immune cell infiltration and poor prognosis in patients with GBM. Inhibition of SUV39H1 restrains GBM growth and reduces the stem cell properties of GSC. Thus, SUV39H1 might be a prognostic predictor and immunotherapeutic target in patients with GBM.

Rare presentations of glioblastoma multiforme in the septum pellucidum: illustrative case.

Glioblastoma multiforme (GBM), a high-grade primary brain tumor, presents a formidable challenge in neuro-oncology because of its aggressive nature, infiltrative growth, and limited response to treatment. The septum pellucidum represents an uncommon and unexpected location for GBM, adding complexity to the diagnosis and management of this rare intracranial malignancy. A 69-year-old male with a previous history of prostate carcinoma presented to an outside hospital with a 2-week history of a "trance-like state" and cognitive decline. Initial head computed tomography showed prominent ventricles without distinct mass lesions. Upon admission, magnetic resonance imaging demonstrated a mass within the inferior septum pellucidum extending to the third and both lateral ventricles. Biopsy findings indicated a GBM, World Health Organization central nervous system tumor grade 4, with immunopositivity for glial fibrillary acidic protein and a Ki-67 labeling index of 60%-70%. Identifying only 5 cases in more than 60 years of literature, this systematic review illustrates the diverse clinical presentations, diagnostic advancements, and management approaches for septum pellucidum GBM. https://thejns.org/doi/10.3171/CASE23770.

Margin derivation from intrafraction patient motion of multi-target, single isocentre, brain stereotactic radiosurgery treatments.

Brain metastases are the most common intracranial malignancy and remain a substantial source of morbidity and mortality in cancer patients. Linear accelerator based stereotactic radiosurgery (SRS) is widely used and is frequently delivered by hypo-fractionnated volumetric modulated arc therapy using non-coplanar beams, where geometric accuracy and planning margins are a majorconcern. To give a practical analysis of intrafraction patient motion for multi-target, single isocentre, brain SRS treatments and to derive adapted GTV-to-PTV margins. Data of 154 lesions, spread over 85 fractions from 56 patients treated in our institution with the Varian HyperArc SRS solution was processed. Intrafraction patient motion were recorded using an Optical Surface Monitoring System during irradiation. The present study focuses on small tumor volumes, roughly equal or inferior to 1.5 , and frameless mask-based immobilization. For each treatment session, a tumor displacement vector matrix was calculated from the patient drifts as a function of time. Data were combined together into a representative treatment scenario and the dosimetric impact of GTV displacement was calculated. Recommended margins due to patient motion range between 0.3 and 1mm, depending on the distance tumor-isocentre, and the desired GTV edge dose coverage. Those values should be added quadratically with other sources of uncertainty, such as mechanical isocentre and kV-MVmisalignment. Thorough analysis of intrafraction patient motion was performed, the dosimetric impact was calculated for different scenarios, and adequate GTV-to-PTV margins were derived. These values vary according to the distance isocentre-to-GTV, as well as the desired dose coverage, and should be chosenadequately.

Aberrant overexpression of myosin 1b in glioblastoma promotes angiogenesis via VEGF-myc-myosin 1b-Piezo1 axis

Glioblastoma (GBM) is the most aggressive intracranial malignancy with poor prognosis. Enhanced angiogenesis is an essential hallmark of GBM, which demonstrates extensive microvascular proliferation and abnormal vasculature. Here, we uncovered the key role of myosin 1b in angiogenesis and vascular abnormality in GBM. Myosin 1b is upregulated in GBM endothelial cells (ECs) compared to the paired non-malignant brain tissue. In our study, we found that myosin 1b promotes migration, proliferation and angiogenesis of human/mouse brain ECs. We also found that myosin 1b expression in ECs can be regulated by vascular endothelial growth factor (VEGF) signaling through myc. Moreover, myosin 1b promotes angiogenesis via Piezo1 by enhancing Ca2+ influx, in which process VEGF can be the trigger. In conclusion, our results identified myosin 1b as a key mediator in promoting angiogenesis via mechanosensitive ion channel component 1 (Piezo1) and suggested that VEGF/myc signaling pathway could be responsible for driving the changes of myosin 1b overexpression in GBM ECs.

Step-by-step Stereotactic Radiotherapy Planning of Pituitary Adenoma: A ROSE (Radiation Oncology from Simulation to Execution) Guide to Radiation Oncologists

Introduction Pituitary adenoma accounts for 10%–20% of all intracranial malignancies. The primary modality of treatment is surgery, while pituitary radiation is indicated in residual or recurrent setting post-surgery. Currently, stereotactic radiotherapy (SRT) is one of the main modalities of radiation treatment. The objective of this article is to describe the procedural steps for radiation planning of SRT of pituitary adenoma Methods The step-by-step procedure for stereotactic planning of pituitary adenoma has been described using a clinical scenario of pituitary adenoma. Results The stereotactic radiation planning of pituitary adenoma starts with the basic history and relevant clinical evaluation that is visual testing. Magnetic resonance imaging (MRI) of the brain is the imaging modality of choice. Evaluation of surgical notes and post-operative histopathology confirmation of diagnosis should also be done. The radiation planning of pituitary adenoma starts with Computed tomography (CT) simulation and MRI of brain that should be done in prescribed format to achieve uniformity in radiation planning. After CT and MRI image fusion, contouring of target, organs at risk (OAR) and radiation planning should be done. The plan evaluation includes target and OAR coverage index, conformity, homogeneity and gradient index and beam arrangement. After radiation plan evaluation, treatment is delivered after quality assurance and dry run. Conclusion The article highlights the sequential process of radiation planning for SRT—starting from simulation, planning, evaluation of plan and treatment.

Unveiling the role of PSMA5 in glioma progression and prognosis

Glioma is the most aggressive intracranial malignancy and is associated with poor survival rates and limited quality of life, impairing neuropsychological function and cognitive competence in survivors. The Proteasome Subunit Alpha Type-5 (PSMA5) is a multicatalytic proteinase complex that has been linked with tumor progression but is rarely reported in glioma. This study investigates the expression pattern, prognostic characteristics, and potential biological functions of PSMA5 in glioma. PSMA5 was significantly overexpressed in 28 types of cancer when compared to normal tissue. Furthermore, elevated levels of PSMA5 were observed in patients with wild-type isocitrate dehydrogenase 1 and exhibited a positive correlation with tumor grade. It was also found to be a standalone predictor of outcomes in glioma patients. Additionally, inhibiting PSMA5-induced cell cycle arrest may provide a therapeutic option for glioma.

Exposed Phosphatidylserine as a Biomarker for Clear Identification of Breast Cancer Brain Metastases in Mouse Models.

Brain metastasis is the most common intracranial malignancy in adults. The prognosis is extremely poor, partly because most patients have more than one brain lesion, and the currently available therapies are nonspecific or inaccessible to those occult metastases due to an impermeable blood-tumor barrier (BTB). Phosphatidylserine (PS) is externalized on the surface of viable endothelial cells (ECs) in tumor blood vessels. In this study, we have applied a PS-targeting antibody to assess brain metastases in mouse models. Fluorescence microscopic imaging revealed that extensive PS exposure was found exclusively on vascular ECs of brain metastases. The highly sensitive and specific binding of the PS antibody enables individual metastases, even micrometastases containing an intact BTB, to be clearly delineated. Furthermore, the conjugation of the PS antibody with a fluorescence dye, IRDye 800CW, or a radioisotope, 125I, allowed the clear visualization of individual brain metastases by optical imaging and autoradiography, respectively. In conclusion, we demonstrated a novel strategy for targeting brain metastases based on our finding that abundant PS exposure occurs on blood vessels of brain metastases but not on normal brain, which may be useful for the development of imaging and targeted therapeutics for brain metastases.

CLEC7A regulates M2 macrophages to suppress the immune microenvironment and implies poorer prognosis of glioma.

Gliomas constitute a category of malignant tumors originating from brain tissue, representing the majority of intracranial malignancies. Previous research has demonstrated the pivotal role of CLEC7A in the progression of various cancers, yet its specific implications within gliomas remain elusive. The primary objective of this study was to investigate the prognostic significance and immune therapeutic potential of CLEC7A in gliomas through the integration of bioinformatics and clinical pathological analyses. This investigation involved examining and validating the relationship between CLEC7A and glioma using samples from Hospital, along with data from TCGA, GEO, GTEx, and CGGA datasets. Subsequently, we explored its prognostic value, biological functions, expression location, and impact on immune cells within gliomas. Finally, we investigated its potential impact on the chemotaxis and polarization of macrophages. The expression of CLEC7A is upregulated in gliomas, and its levels escalate with the malignancy of tumors, establishing it as an independent prognostic factor. Functional enrichment analysis revealed a significant correlation between CLEC7A and immune function. Subsequent examination of immune cell differential expression demonstrated a robust association between CLEC7A and M2 macrophages. This conclusion was further substantiated through single-cell analysis, immunofluorescence, and correlation studies. Finally, the knockout of CLEC7A in M2 macrophages resulted in a noteworthy reduction in macrophage chemotaxis and polarization factors. CLEC7A expression is intricately linked to the pathology and molecular characteristics of gliomas, establishing its role as an independent prognostic factor for gliomas and influencing macrophage function. It could be a promising target for immunotherapy in gliomas.

Hsa_circ_0004872 mitigates proliferation, metastasis and immune escape of meningioma cells by suppressing PD-L1

Meningioma is a prevalent intracranial malignancy known for its aggressive growth. Circular RNAs (circRNAs) play a crucial role in the development of various cancers. However, their involvement in meningioma remains understudied. This study aimed to investigate the function and underlying mechanism of hsa_circ_0004872 in meningioma. The molecular expression of hsa_circ_0004872, PD-L1 and EIF4A3 was identified by RT-qPCR and/or western blot assays. Cell viability, migration, and invasion were assessed through CCK-8 and Transwell assays, respectively. Cytotoxicity was determined using an LDH assay, and cell apoptosis was monitored by flow cytometry. The RNA and protein interactions were assessed through RNA-protein immunoprecipitation (RIP) and RNA pull down analyses. Our findings revealed that hsa_circ_0004872 expression was significantly downregulated in both meningioma tissue samples and cells. Overexpression of hsa_circ_0004872 inhibited the proliferation, metastasis, and immune escape of meningioma cells, as well as enhanced the cytotoxicity of CD8+ T cells by suppressing PD-L1. Furthermore, hsa_circ_0004872 directly interacted with EIF4A3, leading to the degradation of PD-L1 mRNA. Finally, inhibiting EIF4A3 improved the proliferation, metastasis, and immune escape of meningioma cells, as well as the cytotoxicity of CD8+ T cells. Our study demonstrated that hsa_circ_0004872 mitigated the proliferation, metastasis,and immune escape of meningioma cells by targeting the EIF4A3/PD-L1 axis. These findings suggested that hsa_circ_0004872 and EIF4A3 might serve as promising biological markers and therapeutic targets for meningioma treatment.

The prognostic utility of temporalis thickness measured on MRI scans in patients with intra-axial malignant brain tumours: a systematic review and meta-analysis

Sarcopenia is associated with worsened outcomes in solid cancers [1].Temporalis muscle thickness (TMT) has emerged as a measure of sarcopenia[2]. Hence, this study aims to evaluate the relationship between TMTand outcome measures in patients with malignant intra-axial neoplasms.We searched Medline, Embase, Scopus, and Cochrane databases for relevantstudies. Event ratios with 95% confidence intervals (CI) were analysedusing the RevMan 5.4 software. Where meta-analysis was impossible, votecounting was used to determine the effect of TMT on outcomes. TheGRADE framework was used to determine the certainty of the evidence. Four outcomes were reported for three conditions across 17 studiesinvolving 4430 patients. Glioblastoma: thicker TMT was protective foroverall survival (OS) (HR 0.59; 95% CI 0.46–0.76) (GRADE low), progressionfree survival (PFS) (HR 0.40; 95% CI 0.26–0.62) (GRADE high),and early discontinuation of treatment (OR 0.408; 95% CI 0.168–0.989)(GRADE high); there was no association with complications (HR 0.82;95% CI 0.60–1.10) (GRADE low). Brain Metastases: thicker TMTwas protective for OS (HR 0.73; 95% CI 0.67–0.78) (GRADE moderate);there was no association with PFS (GRADE low). Primary CNSlymphoma: TMT was protective for overall survival (HR 0.34; 95%CI 0.19–0.60) (GRADE moderate) and progression free survival (HR0.23; 95% CI 0.09–0.56) (GRADE high).Across various intracranial intra-axial malignancies, patients withthicker TMT have better survival outcomes and are less prone to discontinuingtreatment secondary to drug toxicity. TMT has the potential tobe a valuable prognostic tool for risk-benefit considerations in the managementof these patients.

Disappearance of "Elongated Pony Tail Sign" Following Chemoradiotherapy in a Case of Primary Cerebellopontine Angle Ependymoma With Spinal Drop Metastasis: 18 F-FDG PET/CT Scan Findings.

Ependymomas are rare glial tumors that commonly arise from the lining cells of ventricular system and constitute ~10% of intracranial pediatric malignancies. The incidence of ependymoma in adults is rare. Due to close approximation with the ventricular system, subtentorial ependymomas are more prone to show cerebrospinal fluid metastasis compared with supratentorial ependymomas. We present a case of subtentorial cerebellopontine angle ependymoma with diffuse spinal drop metastases showing "elongated pony tail appearance" in a 69-year-old man with complete metabolic response on 18 F-FDG PET/CT imaging following chemoradiotherapy.

Safety profile of growth hormone replacement (GHr) in GH deficient patients during transition period treated for intracranial tumors and malignancy in childhood- Single center expirence

Safety profile of growth hormone replacement (GHr) in GH deficient patients during transition period treated for intracranial tumors and malignancy in childhood- Single center expirence

Dual-modified brain-targeting lipid polymer micelle delivery of anti-miRNA-21 for achieving oral treatment of glioma

Glioma represents a predominant intracranial malignancy, with fewer than 40 % of patients surviving beyond five years. MiRNA-21 antisense oligonucleotides (anti-miR-21) hold considerable promise for managing aggressive intracranial gliomas. Yet, challenges such as in vivo degradation, suboptimal brain targeting, and inadequate tumor penetration compromise the therapeutic efficacy of unmodified miRNA-21 inhibitors. To overcome these obstacles, we designed an orally-administered, brain-targeted anti-miRNA-21 lipid polymer micelle system (BTMLPMS), dually modified with Ang-2 and TAT. This modification ensures the stable delivery of anti-miR-21, leveraging the protective capacities of lipid polymer micelles to effectively impede glioma growth in vivo. In vitro studies confirmed that these micelles were efficiently uptaken by glioma cells, resulting in induced apoptosis. Importantly, in an orthotopic glioma xenograft model using nude mice, oral administration of these micelles activated pro-apoptotic proteins p53 and Caspase-3, effectively inducing apoptosis in tumor tissues and curbing tumor progression. Hematoxylin-eosin staining further validated the biocompatibility of the micelles. Collectively, our findings underscore the potential of the anti-miR-21 lipid polymer micelle system as a significant advancement in glioma gene therapy, paving the way for groundbreaking transformations in miRNA clinical applications.

Metastases and Primary Brain Tumors Affecting the Fornix of the Brain.

Background The aim of this study is to evaluate the clinical and radiological findings of metastatic tumors and primary brain tumors affecting the fornix. Methods Between January 2015 and March 2023, we retrospectively evaluated 1087 patients of both sexes who underwent cranial magnetic resonance imaging (MRI) for a preliminary diagnosis of intracranial malignancy in the radiology department of our hospital. Two radiologists with six and 10 years of experience in MRI examination assessed the relationship between primary and metastatic tumors and the fornix. Results Involvement of the fornix was diagnosed in 29 of the 1087 patients (2.66%), of which fornix was affected by metastatic lesions in 14 patients (48.2%) and primary tumors in 15 patients (51.7%).The majority of metastatic lesions were from lung and breast cancers, with other tumor types including osteosarcoma, renal cell carcinoma, pancreatic adenocarcinoma, pleomorphic sarcoma, and diffuse large B-cell lymphoma. Among all primary tumors, glioblastoma was the most common primary brain tumor invading the fornix, with other diagnoses including diffuse astrocytoma, medulloblastoma, and anaplastic oligodendroglioma.Metastatic and primary brain tumors affecting the fornix were detected over a broad timeline, from the time of diagnosis up to 120 months after diagnosis. A retrospective evaluation of medical records revealed memory deficits in four patients. Conclusion The fornix can be affected by both metastatic and primary brain tumors. It is crucial to understand the relevant neuroanatomical relationships when evaluating lesions that affect the fornix.