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EBioMedicine Jun 2024External radiation therapy (RT) is often a primary treatment for inoperable meningiomas in the absence of established chemotherapy. Histone deacetylase 6 (HDAC6)...
BACKGROUND
External radiation therapy (RT) is often a primary treatment for inoperable meningiomas in the absence of established chemotherapy. Histone deacetylase 6 (HDAC6) overexpression, commonly found in cancer, is acknowledged as a driver of cellular growth, and inhibiting HDACs holds promise in improving radiotherapeutic efficacy. Downregulation of HDAC6 facilitates the degradation of β-catenin. This protein is a key element in the Wnt/β-catenin signalling pathway, contributing to the progression of meningiomas.
METHODS
In order to elucidate the associations and therapeutic potential of HDAC6 inhibitors (HDAC6i) in conjunction with RT, we administered Cay10603, HDAC6i, to both immortalised and patient-derived meningioma cells prior to RT in this study.
FINDINGS
Our findings reveal an increase in HDAC6 expression following exposure to RT, which is effectively mitigated with pre-treated Cay10603. The combination of Cay10603 with RT resulted in a synergistic augmentation of cytotoxic effects, as demonstrated through a range of functional assays conducted in both 2D as well as 3D settings; the latter containing syngeneic tumour microenvironment (TME). Radiation-induced DNA damage was augmented by pre-treatment with Cay10603, concomitant with the inhibition of β-catenin and minichromosome maintenance complex component 2 (MCM2) accumulation within the nucleus. This subsequently inhibited c-myc oncogene expression.
INTERPRETATION
Our findings demonstrate the therapeutic potential of Cay10603 to improve the radiosensitisation and provide rationale for combining HDAC6i with RT for the treatment of meningioma.
FUNDING
This work was funded by Brain Tumour Research Centre of Excellence award to C Oliver Hanemann.
PubMed: 38917510
DOI: 10.1016/j.ebiom.2024.105211 -
PloS One 2024Meningiomas, the most prevalent primary benign intracranial tumors, often exhibit complicated levels of adhesion to adjacent normal tissues, significantly influencing...
Meningiomas, the most prevalent primary benign intracranial tumors, often exhibit complicated levels of adhesion to adjacent normal tissues, significantly influencing resection and causing postoperative complications. Surgery remains the primary therapeutic approach, and when combined with adjuvant radiotherapy, it effectively controls residual tumors and reduces tumor recurrence when complete removal may cause a neurologic deficit. Previous studies have indicated that slip interface imaging (SII) techniques based on MR elastography (MRE) have promise as a method for sensitively determining the presence of tumor-brain adhesion. In this study, we developed and tested an improved algorithm for assessing tumor-brain adhesion, based on recognition of patterns in MRE-derived normalized octahedral shear strain (NOSS) images. The primary goal was to quantify the tumor interfaces at higher risk for adhesion, offering a precise and objective method to assess meningioma adhesions in 52 meningioma patients. We also investigated the predictive value of MRE-assessed tumor adhesion in meningioma recurrence. Our findings highlight the effectiveness of the improved SII technique in distinguishing the adhesion degrees, particularly complete adhesion. Statistical analysis revealed significant differences in adhesion percentages between complete and partial adherent tumors (p = 0.005), and complete and non-adherent tumors (p<0.001). The improved technique demonstrated superior discriminatory ability in identifying tumor adhesion patterns compared to the previously described algorithm, with an AUC of 0.86 vs. 0.72 for distinguishing complete adhesion from others (p = 0.037), and an AUC of 0.72 vs. 0.67 for non-adherent and others. Aggressive tumors exhibiting atypical features showed significantly higher adhesion percentages in recurrence group compared to non-recurrence group (p = 0.042). This study validates the efficacy of the improved SII technique in quantifying meningioma adhesions and demonstrates its potential to affect clinical decision-making. The reliability of the technique, coupled with potential to help predict meningioma recurrence, particularly in aggressive tumor subsets, highlights its promise in guiding treatment strategies.
Topics: Humans; Meningioma; Elasticity Imaging Techniques; Female; Middle Aged; Male; Meningeal Neoplasms; Aged; Adult; Magnetic Resonance Imaging; Neoplasm Recurrence, Local; Tissue Adhesions; Algorithms
PubMed: 38917107
DOI: 10.1371/journal.pone.0305247 -
Scientific Reports Jun 2024Variations in the biomechanical stiffness of brain tumors can not only influence the difficulty of surgical resection but also impact postoperative outcomes. In a...
Variations in the biomechanical stiffness of brain tumors can not only influence the difficulty of surgical resection but also impact postoperative outcomes. In a prospective, single-blinded study, we utilize pre-operative magnetic resonance elastography (MRE) to predict the stiffness of intracranial tumors intraoperatively and assess the impact of increased tumor stiffness on clinical outcomes following microsurgical resection of vestibular schwannomas (VS) and meningiomas. MRE measurements significantly correlated with intraoperative tumor stiffness and baseline hearing status of VS patients. Additionally, MRE stiffness was elevated in patients that underwent sub-total tumor resection compared to gross total resection and those with worse postoperative facial nerve function. Furthermore, we identify tumor microenvironment biomarkers of increased stiffness, including αSMA + myogenic fibroblasts, CD163 + macrophages, and HABP (hyaluronic acid binding protein). In a human VS cell line, a dose-dependent upregulation of HAS1-3, enzymes responsible for hyaluronan synthesis, was observed following stimulation with TNFα, a proinflammatory cytokine present in VS. Taken together, MRE is an accurate, non-invasive predictor of tumor stiffness in VS and meningiomas. VS with increased stiffness portends worse preoperative hearing and poorer postoperative outcomes. Moreover, inflammation-mediated hyaluronan deposition may lead to increased stiffness.
Topics: Humans; Meningioma; Neuroma, Acoustic; Elasticity Imaging Techniques; Female; Male; Middle Aged; Biomarkers, Tumor; Aged; Prospective Studies; Adult; Meningeal Neoplasms; Treatment Outcome; Tumor Microenvironment; Magnetic Resonance Imaging
PubMed: 38914647
DOI: 10.1038/s41598-024-64597-1 -
The Indian Journal of Radiology &... Jul 2024Arterial spin labeling (ASL) perfusion imaging is widely used since its main advantage is that no intravenous contrast is needed. Given that perfusion is a crucial...
Arterial spin labeling (ASL) perfusion imaging is widely used since its main advantage is that no intravenous contrast is needed. Given that perfusion is a crucial biological characteristic for identifying tumor lesions, the qualitative noncontrast perfusion characteristics of these lesions were examined. We attempted utilizing the three-dimensional (3D) ASL technique to characterize skull base lesions and to highlight its crucial role in differentiating lesions. 3D ASL imaging of 20 patients with posterior skull base lesions was performed in a 3-T magnetic resonance (MR) system (Siemens Healthineers, Skyra, Erlangen, Germany). The common differential diagnoses of skull base lesions could be distinguished based on this qualitative evaluation. Glomus tumor has a strikingly increased perfusion when compared to meningiomas. The perfusion characteristics of metastasis depends on the primary tumor. Chondrosarcomas have a heterogeneously increased perfusion. Chordomas have variable perfusion, which helps in prognosticating the tumors. ASL benefits pediatric patients and in renal failure as well since it avoids the ethical ambiguity associated with contrast agents.
PubMed: 38912234
DOI: 10.1055/s-0044-1778727 -
The Indian Journal of Radiology &... Jul 2024
PubMed: 38912230
DOI: 10.1055/s-0043-1777743 -
Acta Medica Okayama Jun 2024Organized chronic subdural hematoma (OCSDH) is a relatively rare condition that forms over a longer period of time compared to chronic subdural hematoma and is sometimes...
Organized chronic subdural hematoma (OCSDH) is a relatively rare condition that forms over a longer period of time compared to chronic subdural hematoma and is sometimes difficult to diagnose with preoperative imaging. We resected an intracranial lesion in a 37-year-old Japanese man; the lesion had been increasing in size for >17 years. The preoperative diagnosis based on imaging findings was meningioma; however, pathological findings revealed OCSDH. Clinicians should be aware that OCSDH mimics other tumors and consider surgical strategies for this disease.
Topics: Humans; Male; Meningioma; Hematoma, Subdural, Chronic; Adult; Meningeal Neoplasms; Diagnosis, Differential; Tomography, X-Ray Computed; Magnetic Resonance Imaging
PubMed: 38902217
DOI: 10.18926/AMO/67204 -
World Journal of Clinical Cases Jun 2024Meningioma in the cerebellopontine angle (CPA) without dural attachment is extremely rare. We report a unique case of meningioma derived from the superior petrosal vein...
BACKGROUND
Meningioma in the cerebellopontine angle (CPA) without dural attachment is extremely rare. We report a unique case of meningioma derived from the superior petrosal vein without dural attachment.
CASE SUMMARY
A 44-year-old right-handed woman presented with a two-month history of headache and tinnitus. Brain magnetic resonance imaging showed a well-defined contrast-enhancing lesion in the right CPA without a dural tail sign. Tumor resection was performed using a right retro sigmoid approach. A dural attachment was not seen at the tentorium or posterior surface of the petrous pyramid. The tumor was firmly adherent to the superior petrosal vein. The origin site was cauterized and resected with the preservation of the superior petrosal vein. A diagnosis of meningothelial meningioma was made. The patient's headache and tinnitus gradually disappeared, and a recurrence was not observed five years after the surgery.
CONCLUSION
The rare occurrence of meningioma without dural attachment makes it difficult to determine dural attachment before surgery. The absence of dural attachment makes it easy to completely resect such tumors. Vessels related to tumors should be removed carefully, considering the possible presence of tumor stem cells in the microvessels.
PubMed: 38898871
DOI: 10.12998/wjcc.v12.i17.3156 -
Scientific Reports Jun 2024This study examined the association between hearing loss in sporadic vestibular schwannoma patients and the proteome of perilymph (PL), cerebrospinal fluid (CSF), and...
This study examined the association between hearing loss in sporadic vestibular schwannoma patients and the proteome of perilymph (PL), cerebrospinal fluid (CSF), and vestibular schwannoma. Intraoperative sampling of PL and of CSF, and biopsy of vestibular schwannoma tissue, was performed in 32, 32, and 20 patients with vestibular schwannoma, respectively. Perilymph and CSF in three patients with meningioma and normal hearing were also sampled. The proteomes were identified by liquid chromatography coupled to high-resolution tandem mass spectrometry. Preoperative hearing function of the patients was evaluated with pure tone audiometry, with mean values at frequencies of 500, 1000, 2000, and 4000 Hz (PTA4) in the tumor-affected ear used to delineate three hearing groups. Analysis of the PL samples revealed significant upregulation of complement factor H-related protein 2 (CFHR2) in patients with severe to profound hearing loss after false discovery rate correction. Pathway analysis of biofunctions revealed higher activation scores in the severe/profound hearing loss group of leukocyte migration, viral infection, and migration of cells in PL. Upregulation of CFHR2 and activation of these pathways indicate chronic inflammation in the cochlea of vestibular schwannoma patients with severe to profound hearing loss compared with patients with normal hearing or mild hearing loss.
Topics: Humans; Neuroma, Acoustic; Female; Male; Middle Aged; Proteome; Perilymph; Hearing Loss; Adult; Aged; Cerebrospinal Fluid; Audiometry, Pure-Tone
PubMed: 38898156
DOI: 10.1038/s41598-024-64352-6 -
Neurologia Medico-chirurgica Jun 2024NF2-related schwannomatosis (NF2; previously termed neurofibromatosis type 2) is a tumor-prone disorder characterized by development of multiple schwannomas and...
NF2-related schwannomatosis (NF2; previously termed neurofibromatosis type 2) is a tumor-prone disorder characterized by development of multiple schwannomas and meningiomas. The diagnostic criteria of NF2 have been regularly revised. Clinical criteria for NF2 were first formulated at the National Institutes of Health Consensus Conference in 1987 and revised in 1990. Revised criteria were also proposed by the Manchester group in 1992 and by the National Neurofibromatosis Foundation (NNFF) in 1997. The 2011 Baser criteria improved the sensitivity of diagnostic criteria, particularly for patients without bilateral vestibular schwannomas. Revisions to the Manchester criteria were published in 2019, with replacement of "glioma" by "ependymoma," removal of "neurofibroma," addition of an age limit of 70 years for development of vestibular schwannomas, and introduction of molecular criteria, which led to the most widely used criteria. In 2022, the criteria were reviewed and updated by the international committee of NF experts. In addition to changes in diagnostic criteria, the committee recommended the use of "schwannomatosis" as an umbrella term for conditions that predispose to schwannomas. Each type of schwannomatosis was classified by the gene containing the disease-causing pathogenic variant. Molecular data from NF2 patients led to further clarification of the diagnostic criteria for NF2 mosaic phenotypes. Given all these changes, the diagnostic criteria of NF2 may be confusing. Herein, to help healthcare professionals who diagnose NF2 conditions in the clinical setting, we review the historical development of diagnostic criteria.
PubMed: 38897938
DOI: 10.2176/jns-nmc.2024-0067 -
Cancers Jun 2024Surgery stands as the primary treatment for spheno-orbital meningiomas, following a symptoms-oriented approach. We discussed the decision-making process behind surgical...
Surgery stands as the primary treatment for spheno-orbital meningiomas, following a symptoms-oriented approach. We discussed the decision-making process behind surgical strategies through a review of medical records from 80 patients who underwent surgical resection at the University of Naples Federico II. Different surgical approaches were employed based on the tumor's location relative to the optic nerve's long axis, categorized into lateral (type I), medial (type II), and diffuse (type III). We examined clinical, neuroradiological, surgical, pathological, and outcome factors. Proptosis emerged as the most frequent symptom (97%), followed by visual impairment (59%) and ocular motility issues (35%). Type I represented 20%, type II 43%, and type III 17%. Growth primarily affected the optic canal (74%), superior orbital fissure (65%), anterior clinoid (60%), and orbital apex (59%). The resection outcomes varied, with Simpson grades I and II achieved in all type I cases, 67.5% of type II, and 18% of type III. Recurrence rates were highest in type II (41.8%) and type III (59%). Improvement was notable in proptosis (68%) and visual function (51%, predominantly type I). Surgery for spheno-orbital meningiomas should be tailored to each patient, considering individual characteristics and tumor features to improve quality of life by addressing primary symptoms like proptosis and visual deficits.
PubMed: 38893267
DOI: 10.3390/cancers16112148