Faculty Opinions recommendation of Glutamatergic synaptic input to glioma cells drives brain tumour progression.

2020 ◽  
Author(s):  
Alexander Sobolevsky
Keyword(s):  
Brain Tumour ◽  
Synaptic Input ◽  
Tumour Progression ◽  
Glioma Cells

Glutamatergic synaptic input to glioma cells drives brain tumour progression

Nature ◽  
2019 ◽  
Vol 573 (7775) ◽  
pp. 532-538 ◽  
Author(s):  
Varun Venkataramani ◽  
Dimitar Ivanov Tanev ◽  
Christopher Strahle ◽  
Alexander Studier-Fischer ◽  
Laura Fankhauser ◽  
...  
Keyword(s):  
Brain Tumour ◽  
Synaptic Input ◽  
Tumour Progression ◽  
Glioma Cells

scholarly journals TMIC-27. GLUTAMATERGIC NEURON-GLIOMA SYNAPSES DRIVE BRAIN TUMOUR PROGRESSION

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi253-vi253
Author(s):  
Varun Venkataramani ◽  
Dimitar Tanev ◽  
Christopher Strahle ◽  
Alexander Studier-Fischer ◽  
Laura Fankhauser ◽  
...  
Keyword(s):  
Glutamate Receptors ◽  
Brain Tumour ◽  
Neuronal Activity ◽  
Ex Vivo ◽  
Tumour Progression ◽  
Glioma Cells ◽  
Tumour Cells ◽  
Glioma Invasion ◽  
Synaptic Ultrastructure

Abstract A network of communicating tumour cells established by tumour microtubes (TMs) is supposed to mediate relevant aspects of progression and resistance of incurable gliomas. Moreover, neuronal activity has been shown to foster malignant behavior of glioma cells by non-synaptic paracrine and autocrine mechanisms. Here, we report an unexpected direct communication channel between neurons and glioma cells in multiple disease models as well as in astrocytomas and glioblastomas (GBs) of adult patients: functional bona fide chemical synapses formed between presynaptic neurons and postsynaptic glioma cells. These neurogliomal synapses (NGS) show a typical synaptic ultrastructure, are located on TM networks, and produce depolarizing postsynaptic currents mediated by glutamate receptors of the AMPA subtype. AMPA-type glutamate receptors (AMPAR) are expressed by a molecularly and morphologically distinct subpopulation of network-integrated glioma cells. Increased neuronal activity under epileptic conditions ex vivo or neuronal optogenetic stimulation in vivo enhanced, while general anesthesia diminished synchronized calcium transients in TM-connected glioma networks. Accordingly, anesthesia reduced invasiveness of TM-positive tumour cells in mice. Genetic perturbation of AMPAR or chronic AMPAR inhibition by perampanel decreased glioma invasion and proliferation in mice and deletion of GluRII in Drosophila glioma increased survival. These findings reveal a hitherto unappreciated direct synaptic communication between neurons and glioma cells that appears relevant for brain tumour biology, implying new avenues for glioma treatment.

Effects of class-3 semaphorins on brain tumour progression

2011 ◽  
Vol 223 (06) ◽  
Author(s):  
J Bode ◽  
A Sabag ◽  
S Kietz ◽  
G Neufeld ◽  
M Lakomek
Keyword(s):  
Brain Tumour ◽  
Tumour Progression

323 The Subcellular Expression Patterns of Bcl-Xl in Primary Brain Tumour Samples

2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
A Vassiliou ◽  
K Alavian ◽  
M Tsujishita ◽  
H Bae
Keyword(s):  
Brain Tumour ◽  
Tumour Progression ◽  
Expression Patterns ◽  
B Cell Lymphoma ◽  
Nuclear Antigen ◽  
Future Research ◽  
Metabolic Efficiency ◽  
Cell Detection ◽  
Primary Brain Tumour ◽  
Cancerous Cells

Abstract Introduction Primary brain tumours originate from cells within the brain. The commonest malignant types are gliomas which are graded from I-IV. Emerging evidence has elucidated the function of the mitochondrially localised B-cell lymphoma-extra-large (Bcl-xL) protein, and its promotion of tumour progression-associated properties. Our lab has previously established that Bcl-xL-overexpressing neurons increase metabolic efficiency by producing more adenosine triphosphate and consuming less oxygen, which we assumed, fuels cancer cells to proliferate. Method We quantified the subcellular expression patterns of Bcl-xL in primary brain tumour samples through immunohistochemistry on a brain tissue microarray containing 16 glioma cases from Grades II-IV. We used antibodies against Bcl-xL, heat shock protein 60 for mitochondrial detection and proliferating cell nuclear antigen for cancerous cell detection. Results Bcl-xL is overexpressed in cancerous cells of Grade IV gliomas and is significantly greater than cancerous cells of Grade III and Grade II gliomas. Cancerous cells express higher levels of Bcl-xL than non-cancerous cells in all grades of glioma. Conclusions Bcl-xL-overexpressing neurons exhibit enhanced metabolic efficiency, contributing to increased proliferation rates. Future research should focus on the characterisation of ATP levels and oxygen consumption in glioma cells. Conclusively, pharmacological inhibition of Bcl-xL will suppress the proliferation rate in gliomas and cease cancer cell growth.

scholarly journals The Effect of Ginger on the Invasion and Migration of Glioma Cells

2020 ◽  
pp. 38-43
Author(s):  
Manar Zraikat ◽  
Munir Gharaibeh ◽  
Tasneem Alshelleh
Keyword(s):  
Cell Line ◽  
Tumour Progression ◽  
Glioma Cells ◽  
Three Dimension ◽  
Scratch Assay ◽  
Invasion And Migration ◽  
Invasion Model ◽  
Dimension 2 ◽  
And Migration ◽  
U87 Cells

Background: This work studies the effect of different concentrations of soaked ginger on the ability of the U87 glioma cells to invade collagen in a three dimension (3 D) invasion model and compare it with its effect on the ability of the same cell line to migrate in two-dimension (2 D) scratch assay. Methods: The hanging drop spheroids in 3D invasion assay were used to investigate the in invasion of the U87 cells. The 2D scratch assay was used to investigate the migration of the same cell line. Results: Gradual effect of the soaked ginger was noticed on the inhibition of the invasion of U87 in collagen and on the inhibition of the migration of the same cell line in scratch assay. Conclusion: The results in this article are promising and encourage further studies to investigate the effect of ginger active ingredients on tumour progression.

TAMI-52. NEURONAL MECHANISMS OF BRAIN TUMOR INVASION

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi209-vi209
Author(s):  
Varun Venkataramani ◽  
Yvonne Yang ◽  
Marc Schubert ◽  
Carlo Beretta ◽  
Michael Botz ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Neuronal Activity ◽  
Cell Invasion ◽  
Glioma Cell ◽  
Tumour Progression ◽  
Glioma Cells ◽  
Movement Patterns ◽  
Calcium Transients ◽  
High Temporal Resolution ◽  
Branching Points

Abstract Incurable gliomas are characterized by their infiltration into the whole brain. Recently, we described tumor microtubes as a novel structure contributing to glioma cell invasion and uncovered synaptic contacts on glioma cells that drive brain tumour progression. However, the exact effects of neuronal activity on glioma cell motility are yet unclear. Here, we show how a recently described neuronal-like cellular transcription state of glioblastoma cells is correlated to glioma cell invasion in vivo. To unravel the details of neuronal features of glioma invasion in space and time, we established a novel approach of intravital imaging for brain tumor cells with a membrane-bound GFP combined with deep learning algorithms that are used to track glioma cell processes with a high temporal resolution over several hours. This approach uncovers how invading tumor microtubes use Levy-like movement patterns indicative of efficient search patterns often employed by animal predators searching for scarce resources such as food. Neuronal activity is able to accelerate the tumor microtube dynamics, accelerate the Levy-like movement patterns and increase the overall invasion speed of glioma cells. These processes are mediated by local calcium transients in glioma cell somata and tumor microtubes. In accordance, genetic manipulation and pharmacological perturbation of AMPA receptors reduces tumor microtube length, number and branching points by interfering with intracellular calcium transients. All in all, the work here uncovers novel neuronal activity-mediated mechanisms of glioma cell invasion, a hallmark of this yet fatal disease.

scholarly journals BrainApp: Using near-patient sensing through a mobile app and machine learning in brain tumour patients

2021 ◽  
Vol 23 (Supplement_4) ◽  
pp. iv2-iv2
Author(s):  
Nur Aizaan Anwar ◽  
Matthew Williams
Keyword(s):  
Machine Learning ◽  
Healthy Volunteers ◽  
Disease Progression ◽  
Brain Tumour ◽  
Tumour Progression ◽  
Mobile App ◽  
Adult Brain ◽  
Facial Features ◽  
And Performance

Abstract Aims 1. To assess the feasibility, acceptability, and performance of a mobile app, 'BRIAN', developed by The Brain Tumour Charity (BTC), in collecting data on quality of life (QOL), activity and sleep, for predicting disease progression in adult brain tumour patients. 2. To generate a prospectively collected dataset of patient measures obtained through mobile devices in brain tumour patients and healthy volunteers. 3. To assess compliance and performance of micro-challenges (hand coordination, visual memory, speech and facial features) in study participants using a mobile application. 4. To assess differences and systematic variation in micro-challenge performance between healthy volunteers and brain tumour patients. 5. To assess factors associated with micro-challenge performance in brain tumour patients, the relationship between micro-challenges and standard measures of QoL and disease progression. 6. To assess the diagnostic performance of different machine learning models in detecting brain tumour progression. Method This abstract describes the protocol for a multi-centre observational non-randomised phase II trial for adult brain tumour patients and healthy volunteers in the UK. Participants will use the BRIAN mobile app, developed by BTC to help individuals cope with a brain tumour, and share their journey with both researchers and clinicians. Participants will be required to enter information on their medical background, mood, and QOL; have the option to link fitness trackers to the app; as well as perform mini-games which assess speech, coordination, facial features and reaction time. Patients will have their brain imaging and histopathology report submitted to the sponsor. We will then investigate the correlation and temporal relation of these multimodal data with conventional measures of disease progression. We will use traditional statistical methods initially (i.e. descriptive statistics and multilevel modelling), which will then inform the development of a machine learning model in predicting brain tumour progression. Results The BRIAN app is currently being beta-tested by healthy volunteers from the Computational Oncology Lab, Imperial College London. We are in the process of obtaining ethical approval for the trial. Conclusion This study may enable the development of a tool that allows us to detect earlier signs of disease progression, and so offer earlier treatment and preservation of quality of life; and hence the best course of action. Such a tool would also be non-invasive, cheap, quick, and can be used by patients in the comfort of their own homes.

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