Mossy Fiber Sprouting in Temporal Lobe Epilepsy: The Impact of Netrin-1, DCC, and Gene Expression Changes.

Background: Temporal lobe epilepsy (TLE) is the most common form of drug-resistant epilepsy, often associated with hippocampal sclerosis (HS), which involves selective neuronal loss in the Cornu Ammonis subregion 1 CA1 and CA4 regions of the hippocampus. Granule cells show migration and mossy fiber sprouting, though the mechanisms remain unclear. Microglia play a role in neurogenesis and synaptic modulation, suggesting they may contribute to epilepsy.

DNA methylation-based analysis reveals accelerated epigenetic aging in giant cell-enriched adult-type glioblastoma.

Background: Giant cell (gc)-enriched glioblastoma (gcGB) represents a distinct histological variant of isocitrate dehydrogenase wild-type adult-type glioblastoma with notable enlarged mono- or multinuclear tumor cells. While some studies suggest a survival advantage for gcGB patients, the underlying causes remain elusive. GcGBs are associated with TP53 mutations, and gcs were shown to accumulate DNA double-strand breaks and show deficient mitosis, potentially triggering cellular senescence programs.

Measurable disease as baseline criterion for response assessment in glioblastoma: A comparison of PET -based (PET RANO 1.0) and MRI-based (RANO) assessments.

Background: Recently, criteria based on amino acid positron emission tomography (PET) have been proposed for response assessment in diffuse gliomas (PET RANO 1.0). In this study, we compare the prevalence of measurable disease according to PET RANO 1.

An AMP-activated protein kinase-PGC-1α axis mediates metabolic plasticity in glioblastoma.

Glioblastoma, the most frequent primary malignant brain tumour in adults, is characterised by profound yet dynamic hypoxia and nutrient depletion. To sustain survival and proliferation, tumour cells are compelled to acquire metabolic plasticity with the induction of adaptive metabolic programs. Here, we interrogated the pathways necessary to enable processing of nutrients other than glucose.

Dual MAPK Inhibition Triggers Pro-inflammatory Signals and Sensitizes BRAF Glioma to T Cell-Mediated Checkpoint Therapy.

BRAF pediatric low-grade gliomas frequently transform into high-grade gliomas (HGG) and poorly respond to chemotherapy, resulting in high mortality. Although combined BRAF and MEK inhibition (BRAFi+MEKi) outperforms chemotherapy, ∼70% of BRAF HGG patients are therapy resistant and undergo unbridled tumor progression. BRAF glioma have an immune-rich microenvironment suggesting that they could be responsive to immunotherapy but effects of BRAFi+MEKi on anti-tumor immunity are unclear.

PD-1 blockade does not improve efficacy of EpCAM-directed CAR T-cell in lung cancer brain metastasis.

Background: Lung cancer brain metastasis has a devastating prognosis, necessitating innovative treatment strategies. While chimeric antigen receptor (CAR) T-cell show promise in hematologic malignancies, their efficacy in solid tumors, including brain metastasis, is limited by the immunosuppressive tumor environment. The PD-L1/PD-1 pathway inhibits CAR T-cell activity in the tumor microenvironment, presenting a potential target to enhance therapeutic efficacy.

Determinants of long-term survival in patients with IDH-mutant gliomas.

Background: Survival times of patients with IDH-mutant gliomas are variable and can extend to decades. Many studies provide progression-free rather than overall survival times and prognostic factors remain ill-defined. Here we explored characteristics of short- and long-term survivors within a cohort of patients with extended follow-up.

Epigenetic profiling of prostate cancer reveals potential prognostic signatures.

Purpose: While epigenetic profiling discovered biomarkers in several tumor entities, its application in prostate cancer is still limited. We explored DNA methylation-based deconvolution of benign and malignant prostate tissue for biomarker discovery and the potential of radiomics as a non-invasive surrogate.

Methods: We retrospectively included 30 patients (63 [58-79] years) with prostate cancer (PCa) who had a multiparametric MRI of the prostate before radical prostatectomy between 2014 and 2019.

Disturbance in cerebral blood microcirculation and hypoxic-ischemic microenvironment are associated with the development of brain metastasis.

Background: Brain metastases (BM) constitute an increasing challenge in oncology due to their impact on neurological function, limited treatment options, and poor prognosis. BM occurs through extravasation of circulating tumor cells across the blood-brain barrier. However, the extravasation processes are still poorly understood.

A prognostic neural epigenetic signature in high-grade glioma.

Neural-tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is limited. We present an epigenetically defined neural signature of glioblastoma that independently predicts patients' survival. We use reference signatures of neural cells to deconvolve tumor DNA and classify samples into low- or high-neural tumors.

Fatty acid-binding protein 5 is a functional biomarker and indicator of ferroptosis in cerebral hypoxia.

The progression of human degenerative and hypoxic/ischemic diseases is accompanied by widespread cell death. One death process linking iron-catalyzed reactive species with lipid peroxidation is ferroptosis, which shows hallmarks of both programmed and necrotic death in vitro. While evidence of ferroptosis in neurodegenerative disease is indicated by iron accumulation and involvement of lipids, a stable marker for ferroptosis has not been identified.

Perifocal edema is a risk factor for preoperative seizures in patients with meningioma WHO grade 2 and 3.

Background: Patients with intracranial meningiomas frequently suffer from tumor-related seizures prior to resection, impacting patients' quality of life. We aimed to elaborate on incidence and predictors for seizures in a patient cohort with meningiomas WHO grade 2 and 3.

Methods: We retrospectively searched for patients with meningioma WHO grade 2 and 3 according to the 2021 WHO classification undergoing tumor resection.

EpiDiP/NanoDiP: a versatile unsupervised machine learning edge computing platform for epigenomic tumour diagnostics.

DNA methylation analysis based on supervised machine learning algorithms with static reference data, allowing diagnostic tumour typing with unprecedented precision, has quickly become a new standard of care. Whereas genome-wide diagnostic methylation profiling is mostly performed on microarrays, an increasing number of institutions additionally employ nanopore sequencing as a faster alternative. In addition, methylation-specific parallel sequencing can generate methylation and genomic copy number data.

Molecular refinement of pilocytic astrocytoma in adult patients.

Aim: Pilocytic astrocytomas (PA) in adults are rare and may be challenging to identify based only on histomorphology. Compared to their paediatric counterparts, they are reportedly molecularly more diverse and associated with a worse prognosis. We aimed to describe the characteristics of adult PAs more precisely by comprehensively profiling a series of 79 histologically diagnosed adult cases (≥18 years).

The impact of referring patients with drug-resistant focal epilepsy to an epilepsy center for presurgical diagnosis.

Background: Epilepsy surgery is an established treatment for drug-resistant focal epilepsy (DRFE) that results in seizure freedom in about 60% of patients. Correctly identifying an epileptogenic lesion in magnetic resonance imaging (MRI) is challenging but highly relevant since it improves the likelihood of being referred for presurgical diagnosis. The epileptogenic lesion's etiology directly relates to the surgical intervention's indication and outcome.

Wnt/β-Catenin-Signaling Modulates Megakaryopoiesis at the Megakaryocyte-Erythrocyte Progenitor Stage in the Hematopoietic System.

The bone marrow (BM) hematopoietic system (HS) gives rise to blood cells originating from hematopoietic stem cells (HSCs), including megakaryocytes (MKs) and red blood cells (erythrocytes; RBCs). Many steps of the cell-fate decision remain to be elucidated, being important for cancer treatment. To explore the role of Wnt/β-catenin for MK and RBC differentiation, we activated β-catenin signaling in platelet-derived growth factor b (Pdgfb)-expressing cells of the HS using a Cre-lox approach (Ctnnb1).

Gliomatosis cerebri (GC) growth pattern: A single-center analysis of clinical, histological, and molecular characteristics of GC and non-GC glioblastoma.

Background: The biological understanding of glioblastoma (GB) with gliomatosis cerebri (GC) pattern is poor due to the absence of GC-specific studies. Here, we aimed to identify molecular or clinical parameters that drive GC growth.

Methods: From our methylome database of IDH (isocitrate dehydrogenase)-wildtype GB, we identified 158 non-GC and 65 GC cases.

DistSNE: Distributed computing and online visualization of DNA methylation-based central nervous system tumor classification.

The current state-of-the-art analysis of central nervous system (CNS) tumors through DNA methylation profiling relies on the tumor classifier developed by Capper and colleagues, which centrally harnesses DNA methylation data provided by users. Here, we present a distributed-computing-based approach for CNS tumor classification that achieves a comparable performance to centralized systems while safeguarding privacy. We utilize the t-distributed neighborhood embedding (t-SNE) model for dimensionality reduction and visualization of tumor classification results in two-dimensional graphs in a distributed approach across multiple sites (DistSNE).