-
Turkish Neurosurgery 2024To highlight the diagnosis, follow-up, and treatment options for diffuse leptomeningeal glioneuronal tumor (DLGNT) by examining pediatric patients diagnosed with DLGNT...
AIM
To highlight the diagnosis, follow-up, and treatment options for diffuse leptomeningeal glioneuronal tumor (DLGNT) by examining pediatric patients diagnosed with DLGNT by molecular pathological evaluation and next generation sequencing at our center.
MATERIAL AND METHODS
In this retrospective analysis, patients diagnosed with DLGNT between January 2017 and December 2022 are outlined according to their demographic data, radiological data, pathology results, treatments, and follow-up data.
RESULTS
Four patients were diagnosed with DLGNT. All the patients were male. The mean age was 6.5 years. All but one patient had symptoms of increased intracranial pressure. An open biopsy was obtained from all patients for diagnosis. Three patients received radiotherapy and chemotherapy after the diagnosis. Two patients died during their follow-up, one of them in the early postoperative period. Two patients were clinically and radiologically stable in their follow-up after treatment.
CONCLUSION
Further work with larger cohorts is required to determine a common algorithm for DLGNT treatment and follow-up. This analysis may keep this entity in mind in patients with pediatric communicating hydrocephalus and may present insight into diagnosis, follow-up, and treatment options.
Topics: Humans; Male; Child; Meningeal Neoplasms; Retrospective Studies; Child, Preschool; Follow-Up Studies; Adolescent; Female
PubMed: 38650559
DOI: 10.5137/1019-5149.JTN.43742-23.2 -
BMC Cancer Apr 2024Leptomeningeal metastasis (LM) of small cell lung cancer (SCLC) is a highly detrimental occurrence associated with severe neurological disorders, lacking effective...
BACKGROUND
Leptomeningeal metastasis (LM) of small cell lung cancer (SCLC) is a highly detrimental occurrence associated with severe neurological disorders, lacking effective treatment currently. Proteolysis-targeting chimeric molecules (PROTACs) may provide new therapeutic avenues for treatment of podophyllotoxin derivatives-resistant SCLC with LM, warranting further exploration.
METHODS
The SCLC cell line H128 expressing luciferase were mutated by MNNG to generate H128-Mut cell line. After subcutaneous inoculation of H128-Mut into nude mice, H128-LM and H128-BPM (brain parenchymal metastasis) cell lines were primarily cultured from LM and BPM tissues individually, and employed to in vitro drug testing. The SCLC-LM mouse model was established by inoculating H128-LM into nude mice via carotid artery and subjected to in vivo drug testing. RNA-seq and immunoblotting were conducted to uncover the molecular targets for LM.
RESULTS
The SCLC-LM mouse model was successfully established, confirmed by in vivo live imaging and histological examination. The upregulated genes included EZH2, SLC44A4, VEGFA, etc. in both BPM and LM cells, while SLC44A4 was particularly upregulated in LM cells. When combined with PROTAC EZH2 degrader-1, the drug sensitivity of cisplatin, etoposide (VP16), and teniposide (VM26) for H128-LM was significantly increased in vitro. The in vivo drug trials with SCLC-LM mouse model demonstrated that PROTAC EZH2 degrader-1 plus VM26 or cisplatin/ VP16 inhibited H128-LM tumour significantly compared to VM26 or cisplatin/ VP16 alone (P < 0.01).
CONCLUSION
The SCLC-LM model effectively simulates the pathophysiological process of SCLC metastasis to the leptomeninges. PROTAC EZH2 degrader-1 overcomes chemoresistance in SCLC, suggesting its potential therapeutic value for SCLC LM.
Topics: Animals; Small Cell Lung Carcinoma; Mice; Humans; Lung Neoplasms; Drug Resistance, Neoplasm; Enhancer of Zeste Homolog 2 Protein; Podophyllotoxin; Cell Line, Tumor; Mice, Nude; Meningeal Carcinomatosis; Xenograft Model Antitumor Assays; Proteolysis
PubMed: 38644473
DOI: 10.1186/s12885-024-12244-3 -
Redox Biology Jun 2024The oncogene Aurora kinase A (AURKA) has been implicated in various tumor, yet its role in meningioma remains unexplored. Recent studies have suggested a potential link...
The oncogene Aurora kinase A (AURKA) has been implicated in various tumor, yet its role in meningioma remains unexplored. Recent studies have suggested a potential link between AURKA and ferroptosis, although the underlying mechanisms are unclear. This study presented evidence of AURKA upregulation in high grade meningioma and its ability to enhance malignant characteristics. We identified AURKA as a suppressor of erastin-induced ferroptosis in meningioma. Mechanistically, AURKA directly interacted with and phosphorylated kelch-like ECH-associated protein 1 (KEAP1), thereby activating nuclear factor erythroid 2 related factor 2 (NFE2L2/NRF2) and target genes transcription. Additionally, forkhead box protein M1 (FOXM1) facilitated the transcription of AURKA. Suppression of AURKA, in conjunction with erastin, yields significant enhancements in the prognosis of a murine model of meningioma. Our study elucidates an unidentified mechanism by which AURKA governs ferroptosis, and strongly suggests that the combination of AURKA inhibition and ferroptosis-inducing agents could potentially provide therapeutic benefits for meningioma treatment.
Topics: Ferroptosis; Forkhead Box Protein M1; Aurora Kinase A; Humans; NF-E2-Related Factor 2; Animals; Mice; Meningioma; Piperazines; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Signal Transduction; Kelch-Like ECH-Associated Protein 1; Meningeal Neoplasms; Drug Resistance, Neoplasm
PubMed: 38642502
DOI: 10.1016/j.redox.2024.103137 -
Middle meningeal artery embolization contraindication when it originates from the ophthalmic artery.Arquivos de Neuro-psiquiatria Apr 2024
Topics: Humans; Ophthalmic Artery; Meningeal Arteries; Meningeal Neoplasms; Meningioma; Contraindications; Embolization, Therapeutic
PubMed: 38641341
DOI: 10.1055/s-0044-1786023 -
Journal of Neuroinflammation Apr 2024The notion that the central nervous system is an immunologically immune-exempt organ has changed over the past two decades, with increasing evidence of strong links and... (Review)
Review
The notion that the central nervous system is an immunologically immune-exempt organ has changed over the past two decades, with increasing evidence of strong links and interactions between the central nervous system and the peripheral immune system, both in the healthy state and after ischemic and hemorrhagic stroke. Although primary injury after stroke is certainly important, the limited therapeutic efficacy, poor neurological prognosis and high mortality have led researchers to realize that secondary injury and damage may also play important roles in influencing long-term neurological prognosis and mortality and that the neuroinflammatory process in secondary injury is one of the most important influences on disease progression. Here, we summarize the interactions of the central nervous system with the peripheral immune system after ischemic and hemorrhagic stroke, in particular, how the central nervous system activates and recruits peripheral immune components, and we review recent advances in corresponding therapeutic approaches and clinical studies, emphasizing the importance of the role of the peripheral immune system in ischemic and hemorrhagic stroke.
Topics: Humans; Hemorrhagic Stroke; Brain Ischemia; Brain; Stroke; Brain Injuries; Brain Neoplasms
PubMed: 38637850
DOI: 10.1186/s12974-024-03101-y -
Child's Nervous System : ChNS :... Jul 2024Spinal clear cell meningiomas (CCMs) are a rare histological subtype of meningiomas that pose preoperative diagnostic challenges due to their radiographic similarities... (Review)
Review
Spinal clear cell meningiomas (CCMs) are a rare histological subtype of meningiomas that pose preoperative diagnostic challenges due to their radiographic similarities with other lesions. They are also more aggressive, exhibiting higher rates of recurrence, particularly in pediatric patients. Overcoming diagnostic challenges of these tumors can improve patient outcomes. In this report, we describe a case of a pediatric patient presenting with a lumbar CCM in whom we were able to obtain gross total resection. Our report reviews previously identified predictors of CCM recurrence, including the Ki-67 proliferation index, number of spinal segments involved, and hormonal influences related to age and sex. We describe the characteristic radiographic features that differentiate spinal CCMs from other tumors to improve pre-operative diagnosis. Furthermore, we provide our rationale for adjuvant therapy for pediatric patients to refine treatment protocols for these rare tumors.
Topics: Child; Humans; Magnetic Resonance Imaging; Meningeal Neoplasms; Meningioma
PubMed: 38637336
DOI: 10.1007/s00381-024-06390-z -
European Journal of Histochemistry : EJH Apr 2024Meningioma represents the most frequent tumor of the central nervous system (CNS). Correlations between the presence of mast cells (MCs) and grade or other histological...
Meningioma represents the most frequent tumor of the central nervous system (CNS). Correlations between the presence of mast cells (MCs) and grade or other histological features of meningioma are still debated. Our study aimed to better understand the relationship between mast cells and meningiomas and to compare our results based on specific histological subtypes and novel 2021 CNS WHO grading system. We observed some differences as regards the number of MCs and meningioma grade. In low-grade (grade 1) meningiomas, MCs were observed in 7/22 cases, while they were consistently present in all eight high-grade cases (grade 2 and grade 3). Among the grade 1 meningiomas, we observed two "low-positive", two "intermediate-positive", and three "high-positive" cases. Among the group of high-grade meningiomas, the six cases grade 2 were considered as "low-positive", while the two grade 3 cases showed a higher number of MCs and were included in the "intermediate-positive" group. Even though with no statistical significance, due to the low number of cases, our results seem to confirm a sort of relationship between meningioma grading and the number of MCs, as demonstrated by the higher percentage of high-grade meningiomas showing MCs infiltrates, compared to low-grade meningiomas.
Topics: Humans; Meningioma; Mast Cells; Cell Movement; Meningeal Neoplasms
PubMed: 38634735
DOI: 10.4081/ejh.2024.3973 -
BMC Cancer Apr 2024Meningiomas are among the most common primary tumors of the central nervous system. Previous research into the meningioma histological appearance, genetic markers,...
Meningiomas are among the most common primary tumors of the central nervous system. Previous research into the meningioma histological appearance, genetic markers, transcriptome and epigenetic landscape has revealed that benign meningiomas significantly differ in their glucose metabolism compared to aggressive lesions. However, a correlation between the systemic glucose metabolism and the metabolism of the tumor hasn't yet been found. We hypothesized that chronic levels of glycaemia (approximated with glycated hemoglobin (HbA1c)) are different in patients with aggressive and benign meningiomas. The study encompassed 71 patients with de novo intracranial meningiomas, operated on in three European hospitals, two in Croatia and one in Spain. Our results show that patients with WHO grade 2 meningiomas had significantly higher HbA1c values compared to patients with grade 1 lesions (P = 0.0290). We also found a significant number of patients (19/71; 26.7%) being hyperglycemic, harboring all the risks that such a condition entails. Finally, we found a significant correlation between our patients' age and their preoperative HbA1c levels (P = 0.0008, ρ(rho) = 0.388), suggesting that older meningioma patients are at a higher risk of having their glycaemia severely dysregulated. These findings are especially important considering the current routine and wide-spread use of corticosteroids as anti-edematous treatment. Further research in this area could lead to better understanding of meningiomas and have immediate clinical impact.
Topics: Humans; Meningioma; Glycated Hemoglobin; Meningeal Neoplasms; Hyperglycemia; Glucose
PubMed: 38632533
DOI: 10.1186/s12885-024-12243-4 -
International Wound Journal Apr 2024To analyse the risk factors affecting wound healing and infection after spinal meningioma resection surgery. The surgical incision healing of 137 patients who underwent...
To analyse the risk factors affecting wound healing and infection after spinal meningioma resection surgery. The surgical incision healing of 137 patients who underwent spinal meningioma resection at our hospital from January 2021 to January 2024 was analysed. The data collected included physical examination findings, haematological and biochemical measurements, and various scales assessed upon admission and after surgery. These data were then analysed. The surgical wound healing, infection and postoperative complications were statistically analysed. Multiple logistic regression analysis method was used to conduct risk factor analysis on corresponding indicators; the odds ratio and p value of 95% confidence interval were calculated. Factors such as age and smoking history were significantly negatively correlated with wound healing after meningioma resection (odds ratio < 1.000, p < 0.05), while preoperative albumin and platelet count were significantly positively correlated with wound healing (odds ratio > 1.000, p < 0.05). Age, WHO Meningioma Grading, preoperative albumin and preoperative platelet were significantly negatively correlated with wound infection after meningioma resection (odds ratio < 1.000, p < 0.05). The history of virus infection and history of neurological disorders were significantly positively correlated with wound infection (odds ratio > 1.000, p < 0.05). The influence of each factor is different. Age, smoking history, WHO Meningioma Grading, preoperative albumin, preoperative platelets, history of virus infection and history of neurological disorders had the greatest influence on wound healing and infection after meningioma resection.
Topics: Humans; Meningioma; Retrospective Studies; Risk Factors; Surgical Wound; Wound Healing; Wound Infection; Meningeal Neoplasms; Albumins; Virus Diseases
PubMed: 38629599
DOI: 10.1111/iwj.14870 -
BMC Cancer Apr 2024While surgical resection remains the primary treatment approach for symptomatic or growing meningiomas, radiotherapy represents an auspicious alternative in patients...
BACKGROUND
While surgical resection remains the primary treatment approach for symptomatic or growing meningiomas, radiotherapy represents an auspicious alternative in patients with meningiomas not safely amenable to surgery. Biopsies are often omitted in light of potential postoperative neurological deficits, resulting in a lack of histological grading and (molecular) risk stratification. In this prospective explorative biomarker study, extracellular vesicles in the bloodstream will be investigated in patients with macroscopic meningiomas to identify a biomarker for molecular risk stratification and disease monitoring.
METHODS
In total, 60 patients with meningiomas and an indication of radiotherapy (RT) and macroscopic tumor on the planning MRI will be enrolled. Blood samples will be obtained before the start, during, and after radiotherapy, as well as during clinical follow-up every 6 months. Extracellular vesicles will be isolated from the blood samples, quantified and correlated with the clinical treatment response or progression. Further, nanopore sequencing-based DNA methylation profiles of plasma EV-DNA will be generated for methylation-based meningioma classification.
DISCUSSION
This study will explore the dynamic of plasma EVs in meningioma patients under/after radiotherapy, with the objective of identifying potential biomarkers of (early) tumor progression. DNA methylation profiling of plasma EVs in meningioma patients may enable molecular risk stratification, facilitating a molecularly-guided target volume delineation and adjusted dose prescription during RT treatment planning.
Topics: Humans; Meningioma; Meningeal Neoplasms; Prospective Studies; Liquid Biopsy; Biomarkers; Extracellular Vesicles
PubMed: 38605332
DOI: 10.1186/s12885-024-12170-4