Malignant meningioma metastasizes systemically, primarily due to its role in epithelial-mesenchymal transition. Although the prognosis is extremely poor, drug development efforts have been limited, because this tumor is categorized as a rare form.

To examine growth suppressive effect of GO-Y030, a diarylpentanoid curcumin analog, (1E,4E)-1,5-bis [3,5-bis (methoxymethoxy) phenyl] penta-1,4-dien-3-one against the malignant meningioma.

The growth suppression of malignant meningioma cells by GO-Y022 and GO-Y030 were examined, using IOMM-Lee and HKBMM cell lines. Male nude mice aged eight weeks, specifically BALB/cSlc-nu/nu mice received a subcutaneous inoculation of IOMM-Lee (10⁷ cells/site) on their back and 30 μg/kg of recombinant hepatocellular growth factor (HGF) was injected into the tumor every three days. After confirmed the growth tumor mass, 500 μL of GO-Y030 diluted with PBS were administrated intraperitoneally daily at doses of 1 mg/kg and 2 mg/kg, respectively.

GO-Y030 exhibits a growth inhibitory effect on malignant meningioma cell lines, IOMM-Lee and HKBMM ranging from 0.8-2.0 μM in vitro. Notably, GO-Y030’s inhibitory effect is about 10 to 16^th times more potent than that of curcumin, which has previously demonstrated potential in combating malignant meningioma. In mouse models, the intraperitoneal administration of GO-Y030 effectively suppresses the growth of malignant meningioma tumors that have been inoculated in the back (P = 0.002). High-performance liquid chromatography analysis has confirmed the distribution of GO-Y030 in the bloodstream and brain tissue. Moreover, GO-Y030 demonstrates the ability to significantly suppress HGF (P < 0.01), nuclear factor kappa B (P < 0.001), and N-cadherin (P < 0.001), all of which contribute to the epithelial-mesenchymal transition.

GO-Y030 holds promise as a potent compound for the systemic inhibition of malignant meningioma. GO-Y030 has higher tumor growth inhibitory effect against meningiomas than curcumin, which is known to have antitumor activity through multi-molecular target control resulting in apoptosis induction. GO-Y030 controls at least three molecules of HGF, nuclear factor kappa B, and N-cadherin.

• Malignant meningioma
• Curcumin
• Diarylpentanoid curcumin analog
• Hepatocellular growth factor
• Nuclear factor kappa B
• N-cadherin

• Exosome drug delivery system
• Exosome-based targeted therapy
• Exosome-based vaccines
• Meningioma
• Targeted therapy
• Therapeutic drugs

• Humans
• Exosomes/metabolism
• Meningioma/drug therapy
• Meningioma/metabolism
• Clinical Relevance
• Drug Delivery Systems
• Meningeal Neoplasms/drug therapy
• Meningeal Neoplasms/metabolism

• Genetically engineered model
• Meningioma animal model
• Meta-analysis
• Systematic review
• Xenograft

• Animals
• Humans
• Meningeal Neoplasms
• Meningioma
• Reproducibility of Results
• Disease Models, Animal

• University Library of Southern Denmark

• cancer genomics
• molecular medicine
• cns cancer

• Humans
• Hedgehog Proteins/genetics
• Hedgehog Proteins/metabolism
• Meningioma/genetics
• Ligands
• Signal Transduction
• Meningeal Neoplasms/genetics

• R01 NS120547 NINDS NIH HHS
• F30 CA213666 NCI NIH HHS
• UL1 TR001863 NCATS NIH HHS
• P30 CA060553 NCI NIH HHS
• T32 GM007205 NIGMS NIH HHS
• S10 OD030363 NIH HHS
• F30 CA183530 NCI NIH HHS
• P50 CA221747 NCI NIH HHS

• NF2
• SWI/SNF
• Schwann cell precursors
• Smarcb1
• rhabdoid
• schwannoma

• Adult
• Animals
• Mice
• Humans
• Neural Crest
• Cell Differentiation/genetics
• Aggression
• Homozygote
• Mice, Transgenic
• Mammals

• Mice
• Animals
• Humans
• Female
• Meningioma/genetics
• Meningioma/pathology
• Meningeal Neoplasms/genetics
• Meningeal Neoplasms/pathology
• Cyproterone Acetate
• Mutation
• Cell Transformation, Neoplastic
• Class I Phosphatidylinositol 3-Kinases/genetics
• Breast Neoplasms

• Emerging treatments
• Meningiomas
• Preclinical models
• Subclassification

• Animals
• Humans
• Meningioma/therapy
• Meningeal Neoplasms/therapy
• Artificial Intelligence
• Disease Progression

• Anticancer drugs
• Cell lines
• Ex vivo
• Heterotopic
• Orthotopic
• Preclinical
• Xenograft

• Humans
• Animals
• Mice
• Meningioma/genetics
• Meningioma/therapy
• Disease Models, Animal
• Organoids
• Meningeal Neoplasms/genetics
• Meningeal Neoplasms/therapy

Meningiomas are the most common intracranial primary tumor in adults. Surgery is the predominant therapeutic modality for symptomatic meningiomas. Although the majority of meningiomas are benign, there exists a subset of meningiomas that are clinically aggressive. Recent advances in genetics and epigenetics have uncovered molecular alterations that drive tumor meningioma biology with prognostic and therapeutic implications. In this review, we will discuss the advances on molecular determinants of therapeutic response in meningiomas to date and discuss findings of targeted therapies in meningiomas.

Brain tumors are a large and heterogeneous group of neoplasms that affect the central nervous system and include some of the deadliest cancers. Almost all the conventional and new treatments fail to hinder tumoral growth of the most malignant brain tumors. This is due to multiple factors, such as intra-tumor heterogeneity, the microenvironmental properties of the human brain, and the lack of reliable models to test new therapies. Therefore, creating faithful models for each tumor and discovering tailored treatments pose great challenges in the fight against brain cancer. Over the years, different types of models have been generated, and, in this review, we investigated the advantages and disadvantages of the models currently used.

• Associazione Italiana per la Ricerca sul Cancro

The influence of exposure to hormonal treatments, particularly cyproterone acetate (CPA), has been posited to contribute to the growth of meningiomas. Given the widespread use of CPA, this systematic review and meta-analysis attempted to assess real-world evidence of the association between CPA and the occurrence of intracranial meningiomas. Systematic searches of Ovid MEDLINE, Embase and Cochrane Controlled Register of Controlled Trials, were performed from database inception to 18th December 2021. Four retrospective observational studies reporting 8,132,348 patients were included in the meta-analysis. There was a total of 165,988 subjects with usage of CPA. The age of patients at meningioma diagnosis was generally above 45 years in all studies. The dosage of CPA taken by the exposed group (n = 165,988) was specified in three of the four included studies. All studies that analyzed high versus low dose CPA found a significant association between high dose CPA usage and increased risk of meningioma. When high and low dose patients were grouped together, there was no statistically significant increase in risk of meningioma associated with use of CPA (RR = 3.78 [95% CI 0.31–46.39], p = 0.190). Usage of CPA is associated with increased risk of meningioma at high doses but not when low doses are also included. Routine screening and meningioma surveillance by brain MRI offered to patients prescribed with CPA is likely a reasonable clinical consideration if given at high doses for long periods of time. Our findings highlight the need for further research on this topic.

• Genomic subgroups
• Meningioma
• Precision medicine
• Sporadic

• DNA Copy Number Variations
• Genomics
• Humans
• Meningeal Neoplasms/diagnosis
• Meningeal Neoplasms/genetics
• Meningeal Neoplasms/therapy
• Meningioma/diagnosis
• Meningioma/genetics
• Meningioma/therapy

• UL1 TR001863 NCATS NIH HHS
• National Brain Tumor Society

• Animals
• Class I Phosphatidylinositol 3-Kinases/genetics
• Disease Models, Animal
• Female
• Humans
• Intracranial Arteriovenous Malformations/genetics
• Intracranial Arteriovenous Malformations/pathology
• KRIT1 Protein/genetics
• Male
• Meningioma/genetics
• Mice
• Mice, Inbred Strains
• Mutation
• Proto-Oncogene Proteins c-akt/genetics

• R21 NS105001 NINDS NIH HHS

• GEMM
• meningioma
• mouse model
• xenograft

• GAB1
• SMO
• hedgehog
• meningioma
• skull base

Certain driver mutations and pathological diagnoses are associated with the anatomical site of meningioma, based on which the meninges have different embryological origins. We hypothesized that mutations and pathological diagnoses of meningiomas are associated with different embryological origins. We comprehensively evaluated associations among tumor location, pathological diagnosis (histological type), and genetic alterations including AKT1, KLF4, SMO, POLR2A, and NF2 mutations and 22q deletion in 269 meningioma cases. Based on the embryological origin of meninges, the tumor locations were as follows: neural crest, paraxial mesodermal, and dorsal mesodermal origins. Tumors originating from the dura of certain embryologic origin displayed a significantly different pathological diagnoses and genetic abnormality ratio. For instance, driver genetic mutations with AKT1, KLF4, SMO, and POLR2A, were significantly associated with the paraxial mesodermal origin (p = 1.7 × 10⁻¹⁰). However, meningiomas with NF2-associated mutations were significantly associated with neural crest origin (p = 3.9 × 10^–12). On analysis of recurrence, no difference was observed in embryological origin. However, POLR2A mutation was a risk factor for the tumor recurrence (p = 1.7 × 10⁻², Hazard Ratio 4.08, 95% Confidence Interval 1.28–13.0). Assessment of the embryological origin of the meninges may provide novel insights into the pathomechanism of meningiomas.

• Falx
• Meningioma
• Recurrence
• Simpson grade

• cancer genetics
• differentiation

• Genotype
• Hedgehog Proteins/genetics
• Humans
• Kruppel-Like Factor 4
• Kruppel-Like Transcription Factors/genetics
• Meningeal Neoplasms/genetics
• Meningeal Neoplasms/pathology
• Meningioma/genetics
• Meningioma/pathology
• Mutation/genetics
• Phenotype
• Phosphatidylinositol 3-Kinases/genetics
• Proto-Oncogene Proteins c-akt/genetics
• Signal Transduction/genetics

• Cyproterone acetate
• Hirsutism
• Meningioma
• Polycystic ovary syndrome
• Progestative

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Androgen Antagonists/adverse effects
• Cohort Studies
• Cyproterone Acetate/adverse effects
• Female
• France/epidemiology
• Humans
• Male
• Meningeal Neoplasms/epidemiology
• Meningeal Neoplasms/therapy
• Meningioma/epidemiology
• Meningioma/therapy
• Middle Aged
• Neurosurgical Procedures
• Radiotherapy
• Retrospective Studies
• Young Adult

Meningiomas are the most common primary intracranial tumors, but treatment options for meningioma patients are limited due to incomplete understanding of tumor biology. A small percentage of meningiomas harbor somatic variants in the Hedgehog pathway, a conserved gene expression program that is essential for development and adult stem cell homeostasis. Hedgehog signals are transduced through primary cilia, and misactivation of the Hedgehog pathway is known to underlie cancer. Nevertheless, the mechanisms of Hedgehog signaling in meningioma are unknown. Here, we investigate mechanisms of ciliary Hedgehog signaling in meningioma using tissue microarrays containing 154 human meningioma samples, NanoString transcriptional profiling, primary meningioma cells, pharmacology, and CRISPR interference. Our results reveal that meningiomas of all grades can express primary cilia, but that cilia are less prevalent among anaplastic tumors. Moreover, we find that expression of Smoothened alleles that are oncogenic in other contexts fail to activate the Hedgehog transcriptional program or promote proliferation in primary meningioma cells. These data reveal that meningiomas can express the subcellular structure necessary for canonical Hedgehog signaling, but suggest that they do not transduce ciliary Hedgehog signals.

• Cilia
• Hedgehog
• Meningioma
• Primary cilium
• Smoothened
• Vismodegib

Objective: Surgical removal of anterior clinoidal meningiomas (ACMs) remains a challenge because of its complicated relationship with surrounding meninges, major arteries and cranial nerves. This study aims to define the meningeal structures around the anterior clinoid process (ACP) and its surgical implications.

Methods: Five dry skulls and 19 cadavers were used in the anatomical study. Cadavers were prepared as transverse, coronal, and sagittal plastinated sections, and the meningeal architecture around the ACP was studied with dissecting and confocal microscopies. The database of meningiomas in one single center was retrospectively reviewed, and the patients with ACMs were collected for clinical analysis.

Results: The superior, lateral, medial surfaces, and the tip of ACP were covered by different layers and types of meninges. The ACMs were classified into four main types based on the sites of origin, possible extending pathways following meningeal dura. In the retrospective cohort of 131 ACMs, the percentage of types I, IIa, IIb, III, and IV were 42.0% (55/131), 19.8% (26/131), 9.2% (12/131), 16.8% (22/131), and 12.2% (16/131), respectively. We found that types IIa and I had higher chances for achieving Simpson grade 1–2 resection (92.3 and 85.4%, respectively), followed by type III (54.5%) and type IV (31.3%), while type IIb showed little chance of Simpson grade 1–2 resection. Univariate and multivariate analyses revealed ACM classification and tumor size (<3 cm) to be independent risk factors for achieving more extensive resection.

Conclusion: The meningeal architecture around the ACP may guide and determine the origin and extension of ACMs. The classification based on the meningeal architecture helps to understand surgical anatomy as well as predicting surgical outcomes.

• anterior clinoid process
• anterior clinoidal meningioma
• carotid artery
• cavernous sinus
• classification
• meninges
• surgical anatomy

Background: With a prevalence of 170 000 adults in the US alone, meningiomas are the most common primary intracranial tumors. The management of skull base meningiomas is challenging due to their complexity and proximity to crucial nearby structures. The identification of oncogenic mutations has provided further insights into the tumorigenesis of meningioma and the possibility of targeted therapy.

This study aimed to further investigate the association of mutational profiles with anatomical distribution, histological subtype, WHO grade, and recurrence in patients with meningioma.

Methods: Tissue samples were collected from 71 patients diagnosed with meningioma from 2008 to 2016. A total of 51 cases were skull based. Samples were subjected to targeted sequencing using a next generation customized cancer gene panel (n = 66 genes analyzed).

Results: We detected genomic alterations (GAs) in 68 tumors, averaging 1.56 ± 1.07 genomic alterations (GAs) per sample. NF2 was the most frequently altered gene (36/71 cases). Interestingly, we identified a number of mutations in non-NF2 genes, including a hotspot TERTp c.−124: G > A mutation that may be related to poor prognosis and FGFR3 mutations that may represent biomarkers of a favorable prognosis as reported in other cancers.

Conclusions: We demonstrate that comprehensive genomic profiling in our population can reveal a potential new prognostic biomarkers of skull base meningioma. These mutations can enhance diagnostic accuracy and clinical decision-making. Among our findings were the identification of a TERTp mutation and the first report of FGFR3 mutations that may represent biomarkers for the identification of skull base meningioma patients with a favorable prognosis.

• CNS
• FGFR3
• NGS
• genomics
• meningioma

Meningiomas are the most common primary brain tumor of adults. The majority are benign (WHO grade I), with a mostly indolent course; 20% of them (WHO grade II and III) are, however, considered aggressive and require a more complex management. WHO grade II and III tumors are heterogeneous and, in some cases, can develop from a prior lower grade meningioma, although most arise de novo. Mechanisms leading to progression or implicated in de novo grade II and III tumorigenesis are poorly understood. RNA-seq was used to profile the transcriptome of grade I, II, and III meningiomas and to identify genes that may be involved in progression. Bioinformatic analyses showed that grade I meningiomas that progress to a higher grade are molecularly different from those that do not. As such, we identify GREM2, a regulator of the BMP pathway, and the snoRNAs SNORA46 and SNORA48, as being significantly reduced in meningioma progression. Additionally, our study has identified several novel fusion transcripts that are differentially present in meningiomas, with grade I tumors that did not progress presenting more fusion transcripts than all other tumors. Interestingly, our study also points to a difference in the tumor immune microenvironment that correlates with histopathological grade.

• Immune infiltration
• Meningioma
• Progression
• Transcriptome
• snoRNAs

• neurofibromatosis 1
• neurofibromatosis 2
• schwannomatosis