Topic: glioblastoma

Gladstone-UCSF Institute of Genomic Immunology Seminar by Christine Brown, PhD (Deputy Director, T Cell Therapeutics Research Laboratories) on developing and refining redirected CAR T cells for malignant brain tumors, including glioblastoma, tumor heterogeneity, immunosuppressive microenvironments, delivery routes, and manufacturing.

Astrocytes release glutamate by regulated exocytosis in health and disease Vladimir Parpura, International Translational Neuroscience Research Institute, Zhejiang Chinese Medical University, Hangzhou, P.R. China Parpura will present you with the evidence that astrocytes, a subtype of glial cells in the brain, can exocytotically release the neurotransmitter glutamate and how this release is regulated. Spatiotemporal characteristic of vesicular fusion that underlie glutamate release in astrocytes will be discussed. He will also present data on a translational project in which this release pathwa

Glioblastoma cells trigger pharmacoresistant seizures that may promote tumor growth and diminish the quality of remaining life. To define the relationship between growth of glial tumors and their neuronal microenvironment, and to identify genomic biomarkers and mechanisms that may point to better prognosis and treatment of drug resistant epilepsy in brain cancer, we are analyzing a new generation of genetically defined CRISPR/in utero electroporation inborn glioblastoma (GBM) tumor models engineered in mice. The molecular pathophysiology of glioblastoma cells and surrounding neurons and untra

Orthotopic xenograft studies strongly promote the development of personalized and targeted cancer therapies to increase the still very poor life expectancy of glioblastoma (GBM) patients. As the tumor microenvironment (TME) plays an active role in cancer progression, the TME has increasingly become subject of investigations recently.We aimed to assess the metabolome from interstitial fluid (ISF) collected with Open Flow Microperfusion (cOFM) from the TME and compare it to the metabolome from cerebrospinal fluid (CSF). This was done via atraumatic access that has been generated by inoculating m

Alzheimer's disease (AD) is a progressive degenerative disorder characterized by memory loss and cognitive decline. However, there are limited studies on preventing or stopping the advanced neuronal loss that occurs during or before the disease. Our project aims to provide a prophylactic application against AD and similar neurodegenerative diseases. Exosomes are small particles that can cross biological membranes like the blood-brain barrier. They are being used as drug carrier systems and have attracted attention recently. In AD and similar diseases, exposure to oxidant molecules increases in

Coffee consumption is ubiquitous, and the age of coffee drinking has been declining worldwide. Drinking coffee has often been discouraged especially for youngsters, due to its association with negative effects, mainly attributed to caffeine. Despite the “bad reputation” related to coffee, it has been increasingly demonstrated that it offers more health benefits than possible negative effects.Findings from epidemiological studies and clinical research indicate that coffee consumption is associated with a significant decrease in the risk of developing many different types of cancer, including br

Understanding the mechanisms underlying neurological disorders and offering fresh viewpoints and remedies, neuroscientists must bridge the gap between emerging technology and experimental research. We computed the cell migration ratio of confocal pictures of astrocytes and glioblastoma (GBM) in our recent study. The primary goal is to comprehend how astrocyte placement in the 3D cell culture model influences GBM migration. For image processing applications, there are numerous computational tools available. MATLAB provides an extensive library and the ability to create new, bespoke funct

Diaphanous-related formin (DIAPH) 3 is a key regulator of fundamental processes such as division, adhesion, motility and polarity. Diaph3 is exclusively expressed in neural progenitors in the developing mouse brain and its deficiency causes aberrant cell division and aneuploidy, resulting in the loss of neural progenitor cells. Errors in mitosis often lead to mitotic catastrophe and subsequent cell death, impeding the proliferation of aneuploid cells. Nevertheless, aneuploidy is a hallmark of highly proliferative cancer cells and is generally associated with poor prognosis and therapeutic resi

Proliferation of malignant cell also depends on high rate of protein synthesis that increases demands on protein quality control mechanisms. Quality of intracellular proteins are controlled at the level of both endoplasmic reticulum (ER) and 26S proteasome. Disturbances in the functions of either ER or proteasome are associated with particular stress responses. The cellular response to ER stress involves translation inhibition, expression of ER chaperones and degradation of aberrant protein. Elevated expression of HSP70 that binds aberrant proteins or supports their translocation to lysosomes

Glioblastoma is the most lethal brain tumor, partly because of its high intra-tumoral heterogeneity. There are four different glioblastoma subtypes (proneural, mesenchymal, classical and neural) based on their molecular profiles. Distinguishing between each of them is important for physicians in order to choose the appropriate clinical response. For example, proneural glioblastomas are more sensitive to chemotherapy than mesenchymal ones. Since the subtype profiling largely depends on transcriptome analysis, it is not financially practical to perform subtype profiling for every patient. The pr

Glioblastoma is an aggressive primary brain cancer with poor prognosis and limited therapeutic options. In tumors, glioblastoma cells control their microenvironment through the secretion of proteins and other factors. Work from our lab has identified a new unconventional secretion mechanism that is dependent on VAMP7, a tetanus neurotoxin insensitive v-SNARE. We have shown that Endoplasmic Reticulum (ER) and mitochondrial fragments can be incorporated into late endosomes and can later be released by an unconventional secretory mechanism. This process is more efficient in the absence of degrada

In rodent models with intracranial tumor formation, severity assessment and humane endpoint determination are fundamental for ethical and legal reasons. We here evaluated whether voluntary wheel running (VWR) would enable classification of severity after surgery for subcutaneous transmitter-implantation, intracranial tumor-cell-injection and resection, as well as humane endpoint detection. VWR behavior was compared to body weight, clinical state, together with heart rate (HR) and activity (Act) generated via transmitter. Male BDIX rats (n=14) were single-housed in cages equipped with a running

Gliomas, the heterogeneous primary brain tumors lacking efficient treatment, interact with their tumor microenvironment (TME) and the central nervous system (CNS) resident cells to support their own survival and growth. Deeper knowledge on these interactions is needed to improve treatment, and therefore glioma models incorporating components of human TME are of great interest. The aim of this work was to develop a three-dimensional (3D) in vitro coculture model for assessing physical and functional neuro-glioma interactions. For that, human glioblastoma cell line LN229/GFP-derived spheroids we

VPS10P domain receptors are intracellular sorting receptors which direct their protein cargo to destined subcellular localizations. Although it seemed that functions of VPS10P receptors in the brain are restricted to neurons, it turned out they are also relevant for glial cells, including microglia, which dependently on pathological context may acquire different functional properties. For instance, during glioblastoma progression, microglia along with infiltrating macrophages are reprogrammed, so instead of fighting with glioma they support it, mainly through secretion of pro-tumorigenic facto

Gliomas constitute a heterogeneous group of primary brain cancers, being glioblastoma (GBM) the most prevalent and aggressive form. Despite intensive research, current biomarkers and therapies are still not applied in a personalized manner, and do not prevent recurrency. H3.3 is a non-canonical, replication-independent histone H3 variant which alterations have gain- and loss-of-function effects in pediatric and adult GBM, respectively. The canonical replication-dependent H3.1/H3.2 variants remain largely unexplored in gliomas. We examined these variants in surgical resections of two independen

Glioblastoma is a highly aggressive brain tumour that creates an immunosuppressive microenvironment.Microglia, the brain's resident immune cells, play a crucial role in this environment. Glioblastoma cells canreprogram microglia to create a supportive niche that promotes tumour growth. However, the mechanismscontrolling the acquisition of a transcriptome-associated with a tumour-supportive microglial reactive state arenot fully understood. In this study, we investigated changes in the transcriptional profile of BV2 microgliaexposed to C6 glioma cells. RNA sequencing analysis revealed a signifi

Glioblastoma (GBM) is the most aggressive primary brain tumor in humans, characterized by the presence of stem cells, responsible for drug resistance and recurrence. For this reason, the identification of a new therapeutic target for GBM may be a promising challenge in tumor treatment.Many reports suggest that M2 muscarinic receptors (M2Rs) inhibit cell proliferation, survival and migration in several tumor types. Previous data demonstrated that the activation of M2R by orthosteric agonist Arecaidine-Propargyl-Ester (APE) and dualsteric agonist N8-Iper decreased cell proliferation and survival

The microtubule-associated protein tau plays a critical role in many neurodegenerative diseases, including Alzheimer’s disease. Abnormal hyperphosphorylation of tau (pTau) generates pathological paired helical filaments (PHF) that aggregate into neurofibrillary tangles, which leads to a cascade of changes including neuroinflammation and network excitability. Abnormal pTau, neuroinflammation, and seizures also occur in patients with glioblastoma (GBM) and recent work suggests pTau may be a potential a link between neurodegenerative changes and glioblastoma.Using live adult human cortical tissue

Glioblastoma (GBM) tumors rely on neovascularization, driven by specific tumor signals that stimulate endothelial cell (EC) proliferation, migration, and differentiation. Moreover, extracellular vesicles (EVs) has emerged as a key mediator in tumor angiogenesis. This in vitro study assesses glioblastoma-derived EVs' (GD-EV) potential in endothelial cell remodelling (ECR). Glioblastoma cell (U87 MG) conditioned media, treated with the chemotherapeutic drug, Temozolomide (TMZ), EV inhibitor (GW4869), or TMZ+EV inhibitor, were incubated with endothelial cells, HUVEC. Dose-& time-dependent stu

Glioblastoma (GBM) patients have a poor prognosis due to glioblastoma stem cells (GSCs) that resist current treatments. Leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins, particularly Lrig1, play a role in growth factor signaling in various stem cells. In this study, the function of Lrig1 in glioblastoma stem cells was investigated using gain- and loss-of-function experiments. Removing Lrig1 in cultured GBM stem cells increased proliferation and reduced quiescence, while overexpression of Lrig1 enhanced quiescence and reduced proliferation. Mice transplanted with Lrig1-defic

Glioblastoma (GBM) is a cancer of the brain that has a high mortality and morbidity rate. In the current study, we aimed to find potential small molecules (50-1500 Dalton) with antiproliferative effects on the human U-87 GBM cell line using a machine learning (ML) based screening tool. A list of 519 small molecules that have been tested regarding their antiproliferative effect on the U-87 cell line in MTT assay after 72 hours was obtained from the ChEMBL database. Then feature extraction was conducted using Molecular ACCess Systems keys (MACCS) and Morgan fingerprints. Then, molecules in the l

Glioblastoma is the most common and aggressive primary brain tumour. Cancer hijacks developmental pathways and several studies have identified a stem cell-like population in glioblastoma following neurodevelopmental trajectories. In the foetal neocortex, a type of neural stem cell called basal progenitor is thought to be responsible for neocortical expansion. Basal progenitors exist in different morphotypes, and greater morphological complexity underlies their increased proliferation. We thus propose that cell morphology also plays a role in the proliferation of glioblastoma stem cells. Throug

Glioblastoma, highly aggressive neoplasms, deliver a devastating diagnosis and induce severe symptoms, notably sleep disturbances. Disrupted sleep triggers systemic pro-tumor effects in various cancers. Our research explores the pro-tumor impact of disturbed sleep and potential pathophysiological effects of the brain lesion on sleep ability in our patients, and as indicated by the available literature. To assess sleep quality of patients with neuroradiologically proven brain tumors, participants completed The Pittsburgh Sleep Quality Index questionnaire. After obtaining the pathological diagno

Metabolic regulation in the nervous system plays a pivotal role in orchestrating neuronal function and maintaining cellular homeostasis. Utilizing our RNAseq data from gain- and loss-of-function studies of embryonic neural tissue and neuronal cells, we demonstrate that the nuclear receptor NR5A2 regulates hypoxia response, glycolysis, and fatty acid metabolism. Consistently, we have previously shown that NR5A2 inhibits the proliferation and growth of glioblastoma cells and tumors, respectively. Here, we elucidate a novel mechanism whereby NR5A2 functions as a potent suppressor of HIF-1α (Hypox