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Nature Communications Jun 2024Neurofibromatosis Type II (NFII) is a genetic condition caused by loss of the NF2 gene, resulting in activation of the YAP/TAZ pathway and recurrent Schwann cell tumors,...
Neurofibromatosis Type II (NFII) is a genetic condition caused by loss of the NF2 gene, resulting in activation of the YAP/TAZ pathway and recurrent Schwann cell tumors, as well as meningiomas and ependymomas. Unfortunately, few pharmacological options are available for NFII. Here, we undertake a genome-wide CRISPR/Cas9 screen to search for synthetic-lethal genes that, when inhibited, cause death of NF2 mutant Schwann cells but not NF2 wildtype cells. We identify ACSL3 and G6PD as two synthetic-lethal partners for NF2, both involved in lipid biogenesis and cellular redox. We find that NF2 mutant Schwann cells are more oxidized than control cells, in part due to reduced expression of genes involved in NADPH generation such as ME1. Since G6PD and ME1 redundantly generate cytosolic NADPH, lack of either one is compatible with cell viability, but not down-regulation of both. Since genetic deficiency for G6PD is tolerated in the human population, G6PD could be a good pharmacological target for NFII.
Topics: Schwann Cells; Humans; CRISPR-Cas Systems; Glucosephosphate Dehydrogenase; Neurofibromin 2; Coenzyme A Ligases; Synthetic Lethal Mutations; Animals; Neurofibromatosis 2; NADP; Mice; Oxidation-Reduction
PubMed: 38879607
DOI: 10.1038/s41467-024-49298-7 -
Clinical Proteomics Jun 2024Gliomas are aggressive malignant tumors, with poor prognosis. There is an unmet need for the discovery of new, non-invasive biomarkers for differential diagnosis,...
BACKGROUND
Gliomas are aggressive malignant tumors, with poor prognosis. There is an unmet need for the discovery of new, non-invasive biomarkers for differential diagnosis, prognosis, and management of brain tumors. Our objective is to validate four plasma biomarkers - glial fibrillary acidic protein (GFAP), neurofilament light (NEFL), matrix metalloprotease 3 (MMP3) and fatty acid binding protein 4 (FABP4) - and compare them with established brain tumor molecular markers and survival.
METHODS
Our cohort consisted of patients with benign and malignant brain tumors (GBM = 77, Astrocytomas = 26, Oligodendrogliomas = 23, Secondary tumors = 35, Meningiomas = 70, Schwannomas = 15, Pituitary adenomas = 15, Normal individuals = 30). For measurements, we used ultrasensitive electrochemiluminescence multiplexed immunoassays.
RESULTS
High plasma GFAP concentration was associated with GBM, low GFAP and high FABP4 were associated with meningiomas, and low GFAP and low FABP4 were associated with astrocytomas and oligodendrogliomas. NEFL was associated with progression of disease. Several prognostic genetic alterations were significantly associated with all plasma biomarker levels. We found no independent associations between plasma GFAP, NEFL, FABP4 and MMP3, and overall survival. The candidate biomarkers could not reliably discriminate GBM from primary or secondary CNS lymphomas.
CONCLUSIONS
GFAP, NEFL, FABP4 and MMP3 are useful for differential diagnosis and prognosis, and are associated with molecular changes in gliomas.
PubMed: 38879494
DOI: 10.1186/s12014-024-09492-7 -
Acta Neuropathologica Communications Jun 2024
PubMed: 38877580
DOI: 10.1186/s40478-024-01801-3 -
Asian Journal of Surgery Jun 2024
PubMed: 38876876
DOI: 10.1016/j.asjsur.2024.05.285 -
Turkish Neurosurgery Aug 2023Intradiploic meningiomas are rare neoplasms, often mistaken for metastases or malignant bone tumors. Surgical management can be challenging, considering their diffusive...
AIM
Intradiploic meningiomas are rare neoplasms, often mistaken for metastases or malignant bone tumors. Surgical management can be challenging, considering their diffusive bony invasion. Two main critical decisions need to be taken: the timing for cranial vault reconstruction and the choice of the adequate material for cranioplasty. We believe that this case underscores the complexity of such lesions, the importance of a prompt devascularization, and the pivotal role of an immediate reconstruction to avoid the additional morbidity of a re-do surgery.
MATERIAL AND METHODS
We report a case of 68-year-old men who presented with slow growing right parietal bone swelling he noted many years before, but for which he didn't seek medical attentions, associated with mild contralateral hemiparesis. Neuroradiological examinations revealed a giant extradural intradiploic tumor affecting the right temporo-parietal bone and conditioning significant compression of the underlying brain. We planned a surgical strategy to deafferent the tumor and to reduce the intraoperative bleeding. At first, a circumferential craniectomy centered upon the lesion was performed, then it was devascularized by means of surgical ligation of the ipsilateral superficial temporal artery (STA) and middle meningeal artery (MMA); these steps allowed a subsequent en block tumor excision, despite its large size, without significant blood loss and respecting the oncological principles. At the end, a contextual calvarial reconstruction was performed using a precurved titanium mesh.
RESULTS
Was discharged seven days after surgery with complete recovery of the left-sided motor deficit. Thereafter, he underwent scheduled outpatient evaluations and radiological exams. After 1 year, the Modified Rankin Scale (MRS) was 1, with no evidence of recurrent disease.
CONCLUSION
Surgical complications can be reduced adopting an optimal preoperative work-up and a tailored surgical strategy focused on early tumor deafferentation. Moreover, an immediate cranial vault reconstruction avoids the risks related to a second procedure.
PubMed: 38874243
DOI: 10.5137/1019-5149.JTN.43641-23.2 -
Turkish Neurosurgery Aug 2023The total excision of the tumors is the most effective method for treating meningiomas. However, the absence of an effective medical treatment, especially for high-grade...
AIM
The total excision of the tumors is the most effective method for treating meningiomas. However, the absence of an effective medical treatment, especially for high-grade meningiomas that are inoperable, negatively affects patient survival. We aim to investigate the status of immune checkpoint molecules (CTLA-4 and TIM-3) in meningiomas and thus contribute to the development of new personalized treatment strategies.
MATERIAL AND METHODS
We utilized 402 cases of meningioma for this study. New blocks were prepared using the tissue microarray method, and sections obtained from these blocks were immunohistochemically stained with CTLA-4 and TIM-3 antibodies. Subsequently, statistical analysis were performed.
RESULTS
Our findings revealed that CTLA-4 expression were observed in 25.1% of meningiomas. CTLA-4 expression and the number of expressing lymphocytes were found to be significantly higher in high-grade tumors and in those with brain invasion. Meningiomas with staining of immune cells with TIM-3 are 3.5%, and the tumor grade was correlated with the number of immune cells expressing TIM-3.
CONCLUSION
Immune checkpoint molecules (CTLA-4 and TIM-3) with varying levels of expression can serve as prognostic and predictive biomarkers, as well as important targets for therapy. Drugs developed for CTLA-4 and TIM-3 molecules may prove to be more effective in treating meningiomas with high-grade, brain-invading, spontaneous necrosis, and macronucleolus.
PubMed: 38874241
DOI: 10.5137/1019-5149.JTN.43334-23.2 -
Frontiers in Neurology 2024Falcotentorial meningiomas (FM) are surgical challenges for protecting sinus, and the technique notes on the management of superior sagittal or transverse sinus are...
BACKGROUND
Falcotentorial meningiomas (FM) are surgical challenges for protecting sinus, and the technique notes on the management of superior sagittal or transverse sinus are required for good results.
METHODS
We improved the technique notes on the management of superior sagittal or transverse sinus in three FM patients with signs of increased intracranial pressure or chronic headache.
RESULTS
All patients underwent surgeries in the prone position, and occipital/sup-occipital/sub-occipital craniotomy was performed. In one patient, the skull was removed traditionally with exposure of the confluence of sinuses, superior sagittal, and transverse sinus, while the longitudinal skull bridge was left to suspend the dura for protecting the superior sagittal sinus in one patient, and the transverse skull bridge was left to suspend the dura for protecting the transverse sinus in one patient. The dura was opened infratentorially or supratentorially to spare the sinus and then the "skull bridge" was suspended. The tumor was then removed completely without brain swelling or significant venous bleeding. Complete tumor resection was confirmed by early postoperative imaging, and all patients recovered well without postoperative morbidity.
CONCLUSION
The authors recommend the "skull bridge" to suspend the dura for optimal control of the venous sinuses during FM surgery (less venous bleeding).
PubMed: 38872820
DOI: 10.3389/fneur.2024.1284038 -
SAGE Open Medical Case Reports 2024The management of intracranial malignancies in pregnancy poses unique challenges to the perioperative team. We describe the successful surgical management of a...
The management of intracranial malignancies in pregnancy poses unique challenges to the perioperative team. We describe the successful surgical management of a meningioma in a 28-year-old previously healthy patient, in her third trimester of pregnancy, who first presented with a generalised seizure. Without clear guidelines on the management of intracranial malignancies in pregnancy, a multidisciplinary approach was essential in providing a management plan for the patient's seizures and on the timing of her surgical intervention. Hormone-mediated tumour growth was a significant factor in opting for urgent surgical intervention and we discuss the current evidence linking hormones to tumour growth in pregnancy.
PubMed: 38864029
DOI: 10.1177/2050313X241257193 -
Cureus May 2024Meningeal solitary fibrous tumors (SFTs) are a rare central nervous system neoplastic process, resulting in frequent misdiagnosis as meningioma prior to pathologic...
Meningeal solitary fibrous tumors (SFTs) are a rare central nervous system neoplastic process, resulting in frequent misdiagnosis as meningioma prior to pathologic analysis. Appropriate diagnosis is essential to lowering morbidity and mortality, as Grade II or III SFTs are aggressive neoplasms that possess metastatic potential. The existing data may suggest that intracranial SFTs primarily afflict those in their fourth through sixth decades of life. However, we present the case of a patient outside this demographic presenting with symptoms that we were unable to identify in any prior reports. A 21-year-old male in the United States Navy presented to the emergency department (ED) with a two-month history of progressive headaches, leading to nausea and emesis. The patient also endorsed a daily incidence of the same olfactory hallucination followed by several minutes of palpitations, flushing, and dizziness. His neurologic exam was unremarkable, but imaging in the ED revealed a large mass abutting the right medial sphenoid wing. The radiographic appearance of the mass with a dural tail led to a preoperative diagnosis of meningioma. However, pathologic analysis following gross total resection identified the mass as an SFT. A brief literature review complementary to this case underscored the high variability of intracranial SFT case presentations with a relative scarcity of epidemiologic data due to rarity. This review identified that it was common to initially diagnose SFTs as meningioma, similar to this particular case. This emphasizes the importance of an appropriate pathologic diagnosis. This case adds to the existing literature as anecdotal evidence of SFT occurring in a young patient and a unique symptom profile most notable for olfactory hallucination and dysautonomia as features of focal seizure.
PubMed: 38860106
DOI: 10.7759/cureus.60104 -
Scientific Reports Jun 2024Safe and effective brain tumor surgery aims to remove tumor tissue, not non-tumoral brain. This is a challenge since tumor cells are often not visually distinguishable...
Safe and effective brain tumor surgery aims to remove tumor tissue, not non-tumoral brain. This is a challenge since tumor cells are often not visually distinguishable from peritumoral brain during surgery. To address this, we conducted a multicenter study testing whether the Sentry System could distinguish the three most common types of brain tumors from brain tissue in a label-free manner. The Sentry System is a new real time, in situ brain tumor detection device that merges Raman spectroscopy with machine learning tissue classifiers. Nine hundred and seventy-six in situ spectroscopy measurements and colocalized tissue specimens were acquired from 67 patients undergoing surgery for glioblastoma, brain metastases, or meningioma to assess tumor classification. The device achieved diagnostic accuracies of 91% for glioblastoma, 97% for brain metastases, and 96% for meningiomas. These data show that the Sentry System discriminated tumor containing tissue from non-tumoral brain in real time and prior to resection.
Topics: Humans; Brain Neoplasms; Spectrum Analysis, Raman; Male; Female; Middle Aged; Aged; Meningioma; Glioblastoma; Adult; Machine Learning; Brain
PubMed: 38858389
DOI: 10.1038/s41598-024-62543-9