Neuro-oncology

BACKGROUND: Diffuse intrinsic pontine gliomas (DIPG/DMG) are devastating pediatric brain tumors with extraordinarily limited treatment options and uniformly fatal prognosis. Histone H3K27M mutation is a common recurrent alteration in DIPG and disrupts epigenetic regulation. We hypothesize that genome-wide H3K27M-induced epigenetic dysregulation makes tumors vulnerable to epigenetic targeting. METHODS: We performed a screen of compounds targeting epigenetic enzymes to identify potential inhibitors for the growth of patient-derived DIPG cells...

Glioblastoma (GBM)'s median overall survival is almost 21 months. Six phase 3 immunotherapy clinical trials have recently been published, yet 5/6 did not meet approval by regulatory bodies. For the sixth, approval is uncertain. Trial failures result from multiple factors, ranging from intrinsic tumor biology to clinical trial design. Understanding the clinical and basic science of these 6 trials is compelled by other immunotherapies reaching the point of advanced phase 3 clinical trial testing. We need to understand more of the science in human GBMs in early trials: the "window of opportunity" design may not be best to understand complex changes brought about by immunotherapeutic perturbations of the GBM microenvironment...

BACKGROUND: Metastatic spine disease (MSD) occurs commonly in cancer patients causing pain, spinal instability, devastating neurological compromise and decreased quality of life. Oncological patients are often medically complex and frail, precluding them form invasive procedures. To address this issue, minimally invasive spinal surgery (MISS) techniques are desirable. The aim of this study is to review published peer-reviewed literature and ongoing clinical trials to provide current state of the art...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

The most common childhood central nervous system (CNS) tumor is pediatric low-grade glioma (pLGG), representing 30%-40% of all CNS tumors in children. Although there is high associated morbidity, tumor-related mortality is relatively rare. pLGG is now conceptualized as a chronic disease, underscoring the importance of functional outcomes and quality-of-life measures. A wealth of data has emerged about these tumors, including a better understanding of their natural history and their molecular drivers, paving the way for the use of targeted inhibitors...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

BACKGROUND: Myeloid cells comprise up to 50% of the total tumor mass in glioblastoma (GBM) and have been implicated in promoting tumor progression and immunosuppression. Modulating the response of myeloid cells to the tumor has emerged as a promising new approach for cancer treatment. In this regard, we focus on the Triggering Receptor Expressed on Myeloid cells 2 (TREM2), which has recently emerged as a novel immune modulator in peripheral tumors. METHODS: We studied the TREM2 expression profile in various patient tumor samples and conducted single-cell transcriptomic analysis in both glioblastoma patients and the GL261 mouse glioma model...

BACKGROUND: Glioblastomas have highly infiltrative growth patterns that contribute to recurrence and poor survival. Despite infiltration being a critical therapeutic target, no clinically useful therapies exist which counter glioblastoma invasion. Here, we report that inhibition of Ataxia telangiectasia and Rad 3 related kinase (ATR) reduces invasion of glioblastoma cells through dysregulation of cytoskeletal networks and subsequent integrin trafficking. METHODS: Glioblastoma motility and invasion were assessed in vitro and in vivo in response to ATR inhibition (ATRi) and ATR over-expression using timelapse microscopy, two orthotopic glioblastoma models and intravital imaging...

BACKGROUND: Pediatric high-grade gliomas (PHGG) are aggressive brain tumors with five-year survival rates ranging from less than 2% to 20% depending upon subtype. PHGG presents differently from patient to patient and is intratumorally heterogeneous, posing challenges in designing therapies. We hypothesized that heterogeneity occurs because PHGG comprises multiple distinct tumor and immune cell types in varying proportions, each of which may influence tumor characteristics. METHODS: We obtained 19 PHGG samples from our institution's pediatric brain tumor bank...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

BACKGROUND: Patients with low-grade gliomas (LGG) treated with surgery, generally function well and have a favourable prognosis. However, LGG can affect neurocognitive functioning. To date, little is known about social cognition (SC) in these patients, although impaired SC is related to social-behavioral problems and poor societal participation. Frontal brain areas are important for SC and LGG frequently have a frontal location. Therefore, the aim of the present study was to investigate whether emotion recognition, a key component of SC, was impaired, and related to general cognition, tumor location laterality, tumor volume and histopathological characteristics in patients with LGG, post-surgery and before start of adjuvant therapy...

BACKGROUND: There is an urgent need to better understand the mechanisms associated with the development, progression, and onset of recurrence after initial surgery in glioblastoma (GBM). The use of integrative phenotype-focused -omics technologies such as proteomics and lipidomics provides an unbiased approach to explore the molecular evolution of the tumor and its associated environment. METHODS: We assembled a cohort of patient-matched initial (iGBM) and recurrent (rGBM) specimens of resected GBM...

No abstract text is available yet for this article.

BACKGROUND: GBM is an aggressive grade 4 primary brain tumor (BT), with a 5%-13% 5-year survival. Most human GBMs manifest as immunologically "cold" tumors, or "immune deserts", yet the promoting or suppressive roles of specific lymphocytes within the GBM tumor microenvironment (TME) is of considerable debate. PATIENTS AND METHODS: We used meticulous multiparametric flow cytometry (FC) to determine the lymphocytic frequencies in 102 GBMs, lower-grade gliomas, brain metastases, and non-tumorous brain specimen...

BACKGROUND: Antibody-drug conjugates (ADCs) enhance the specificity of cytotoxic drugs by directing them to cells expressing target antigens. Multiple ADCs are FDA-approved for solid and hematologic malignancies, including those expressing HER2, TROP2, and NECTIN4. Recently, an ADC targeting HER2 (Trastuzumab-Deruxtecan) increased survival and reduced growth of brain metastases in treatment-refractory metastatic breast cancer, even in tumors with low HER2 expression. Thus, low-level expression of ADC targets may be sufficient for treatment responsiveness...

BACKGROUND: Vestibular schwannoma (VS) is the most common benign tumor in the cerebellopontine angle and internal auditory canal. Illustrating the heterogeneous cellular components of VS could provide insights into its various growth patterns. METHODS: Single-cell RNA sequencing was used to profile transcriptomes from 7 VS samples and 2 normal nerves. Multiplex immunofluorescence was employed to verify the dataset results. Bulk RNA sequencing was conducted on 5 normal nerves and 44 VS samples to generate a prediction model for VS growth...

BACKGROUND: To investigate the prognostic value of spatial features from whole-brain MRI using a three-dimensional (3D) convolutional neural network (CNN) for adult-type diffuse gliomas. METHODS: In a retrospective, multicenter study, 1,925 diffuse glioma patients were enrolled from five datasets: SNUH (n=708), UPenn (n=425), UCSF (n=500), TCGA (n=160), and Severance (n=132). The SNUH and Severance datasets served as external test sets. Pre- and postcontrast 3D T1-weighted, T2-weighted, and T2-FLAIR images were processed as multichannel 3D images...