Cancer neuroscience and glioma: clinical implications.

In recent years, it has been increasingly recognized that tumor growth relies not only on support from the surrounding microenvironment but also on the tumors capacity to adapt to - and actively manipulate - its niche. While targeting angiogenesis and modulating the local immune environment have been explored as therapeutic approaches, these strategies have yet to yield effective treatments for brain tumors and remain under refinement. More recently, the nervous system itself has been explored as a critical environmental support for cancer, with extensive neuro-tumoral interactions observed both intracranially and in extracranial sites containing neural components.

EANO guideline on molecular testing of meningiomas for targeted therapy selection.

Meningiomas are the most common primary intracranial tumors of adults. For meningiomas that progress or recur despite surgical resection and radiotherapy, additional treatment options are limited due to lack of proven efficacy. Meningiomas show recurring molecular aberrations, which may serve as predictive markers for systemic pharmacotherapies with targeted drugs or immunotherapy, radiotherapy or radioligand therapy.

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.

Circulating Tumor Cells and Thromboembolic Events in Patients with Glioblastoma.

Patients with glioblastoma (GBM) are at increased risk for arterial and venous thromboembolism (TE). Risk factors include surgery, the use of corticosteroids, radiation, and chemotherapy, but also prothrombotic characteristics of the tumor itself such as expression of tissue factor, vascular endothelial growth factor, or podoplanin. Although distant metastases are extremely rare in this tumor entity, circulating tumor cells (CTCs) have been detected in a significant proportion of GBM patients, potentially linking local tumor growth characteristics to systemic hypercoagulability.

SARS-CoV-2-associated T-cell infiltration in the central nervous system.

Objectives: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Although an acute SARS-CoV-2 infection mainly presents with respiratory illness, neurologic symptoms and sequelae are increasingly recognised in the long-term treatment of COVID-19 patients. The pathophysiology and the neuropathogenesis behind neurologic complications of COVID-19 remain poorly understood, but mounting evidence points to endothelial dysfunction either directly caused by viral infection or indirectly by inflammatory cytokines, followed by a local immune response that may include virus-specific T cells.

Temporal change of DNA methylation subclasses between matched newly diagnosed and recurrent glioblastoma.

The longitudinal transition of phenotypes is pivotal in glioblastoma treatment resistance and DNA methylation emerged as an important tool for classifying glioblastoma phenotypes. We aimed to characterize DNA methylation subclass heterogeneity during progression and assess its clinical impact. Matched tissues from 47 glioblastoma patients were subjected to DNA methylation profiling, including CpG-site alterations, tissue and serum deconvolution, mass spectrometry, and immunoassay.

Unclassifiable CNS tumors in DNA methylation-based classification: clinical challenges and prognostic impact.

DNA methylation analysis has become a powerful tool in neuropathology. Although DNA methylation-based classification usually shows high accuracy, certain samples cannot be classified and remain clinically challenging. We aimed to gain insight into these cases from a clinical perspective.

Molecular Determinants of Calcitriol Signaling and Sensitivity in Glioma Stem-like Cells.

Glioblastoma is the most common primary brain cancer in adults and represents one of the worst cancer diagnoses for patients. Suffering from a poor prognosis and limited treatment options, tumor recurrences are virtually inevitable. Additionally, treatment resistance is very common for this disease and worsens the prognosis.

Rhizochalinin Exhibits Anticancer Activity and Synergizes with EGFR Inhibitors in Glioblastoma In Vitro Models.

Rhizochalinin (Rhiz) is a recently discovered cytotoxic sphingolipid synthesized from the marine natural compound rhizochalin. Previously, Rhiz demonstrated high in vitro and in vivo efficacy in various cancer models. Here, we report Rhiz to be highly active in human glioblastoma cell lines as well as in patient-derived glioma-stem like neurosphere models.

Epigenetic profiling reveals a strong association between lack of 5-ALA fluorescence and amplification in -wildtype glioblastoma.

Background: 5-aminolevulinic acid (5-ALA) fluorescence-guided resection increases the percentage of complete CNS tumor resections and improves the progression-free survival of -wildtype glioblastoma patients. A small subset of -wildtype glioblastoma shows no 5-ALA fluorescence. An explanation for these cases is missing.

Epigenetic neural glioblastoma enhances synaptic integration and predicts therapeutic vulnerability.

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

Deep Characterization and Comparison of Different Retrovirus-like Particles Preloaded with CRISPR/Cas9 RNPs.

The CRISPR/Cas system has a broad range of possible medical applications, but its clinical translation has been hampered, particularly by the lack of safe and efficient vector systems mediating the short-term expression of its components. Recently, different virus-like particles (VLPs) have been introduced as promising vectors for the delivery of CRISPR/Cas genome editing components. Here, we characterized and directly compared three different types of retrovirus-based (R) VLPs, two derived from the γ-retrovirus murine leukemia virus (gRVLPs and "enhanced" egRVLPs) and one from the lentivirus human immunodeficiency virus, HIV (LVLPs).

Chimeric Antigen Receptor T Cells in Glioblastoma-Current Concepts and Promising Future.

Glioblastoma (GBM) is a highly aggressive primary brain tumor that is largely refractory to treatment and, therefore, invariably relapses. GBM patients have a median overall survival of 15 months and, given this devastating prognosis, there is a high need for therapy improvement. One of the therapeutic approaches currently tested in GBM is chimeric antigen receptor (CAR)-T cell therapy.

Tumor cell integrin β4 and tumor stroma E-/P-selectin cooperatively regulate tumor growth in vivo.

Background: The immunological composition of the tumor microenvironment has a decisive influence on the biological course of cancer and is therefore of profound clinical relevance. In this study, we analyzed the cooperative effects of integrin β4 (ITGB4) on tumor cells and E-/P-selectin on endothelial cells within the tumor stroma for regulating tumor growth by shaping the local and systemic immune environment.

Methods: We used several preclinical mouse models for different solid human cancer types (xenograft and syngeneic) to explore the role of ITGB4 (shRNA-mediated knockdown in tumor cells) and E-/P-selectins (knockout in mice) for tumor growth; effects on apoptosis, proliferation and intratumoral signaling pathways were determined by histological and biochemical methods and 3D in vitro experiments; changes in the intratumoral and systemic immune cell composition were determined by flow cytometry and immunohistochemistry; chemokine levels and their attracting potential were measured by ELISA and 3D invasion assays.

Circulating tumor cells and extracellular vesicles as liquid biopsy markers in neuro-oncology: prospects and limitations.

For many tumor entities, tumor biology and response to therapy are reflected by components that can be detected and captured in the blood stream. The so called "liquid biopsy" has been stratified over time into the analysis of circulating tumor cells (CTC), extracellular vesicles (EVs), and free circulating components such as cell-free nucleic acids or proteins. In neuro-oncology, two distinct areas need to be distinguished, intrinsic brain tumors and tumors metastatic to the brain.

Clinical determinants impacting overall survival of patients with operable brain metastases from non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is currently the leading cause of cancer-related death worldwide, and the incidence of brain metastases (BM) in NSCLC patients is continuously increasing. The recent improvements of systemic treatment in NSCLC necessitate continuous updates on prognostic subgroups and factors determining overall survival (OS). In order to improve clinical decision-making in tumor boards, we investigated the clinical determinants affecting survival in patients with resectable NSCLC BM.

DNA methylation subclasses predict the benefit from gross total tumor resection in IDH-wildtype glioblastoma patients.

Background: DNA methylation-based tumor classification allows an enhanced distinction into subgroups of glioblastoma. However, the clinical benefit of DNA methylation-based stratification of glioblastomas remains inconclusive.

Methods: Multicentric cohort study including 430 patients with newly diagnosed glioblastoma subjected to global DNA methylation profiling.

Spatially resolved multi-omics deciphers bidirectional tumor-host interdependence in glioblastoma.

Glioblastomas are malignant tumors of the central nervous system hallmarked by subclonal diversity and dynamic adaptation amid developmental hierarchies. The source of dynamic reorganization within the spatial context of these tumors remains elusive. Here, we characterized glioblastomas by spatially resolved transcriptomics, metabolomics, and proteomics.

Diagnostic potential of extracellular vesicles in meningioma patients.

Background: Extracellular vesicles (EVs) play an important role in cell-cell communication, and tumor-derived EVs circulating in patient blood can serve as biomarkers. Here, we investigated the potential role of plasma EVs in meningioma patients for tumor detection and determined whether EVs secreted by meningioma cells reflect epigenetic, genomic, and proteomic alterations of original tumors.

Methods: EV concentrations were quantified in patient plasma (n = 46).

DNA methylation subclass receptor tyrosine kinase II (RTK II) is predictive for seizure development in glioblastoma patients.

Background: Seizures can present at any time before or after the diagnosis of a glioma. Roughly, 25%-30% of glioblastoma (GBM) patients initially present with seizures, and an additional 30% develop seizures during the course of the disease. Early studies failed to show an effect of general administration of antiepileptic drugs for glioblastoma patients, since they were unable to stratify patients into high- or low-risk seizure groups.