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
2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
A Vassiliou ◽  
K Alavian ◽  
M Tsujishita ◽  
H Bae

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.


2021 ◽  
Vol 23 (Supplement_4) ◽  
pp. iv2-iv2
Author(s):  
Nur Aizaan Anwar ◽  
Matthew Williams

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.


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi253-vi253
Author(s):  
Varun Venkataramani ◽  
Dimitar Tanev ◽  
Christopher Strahle ◽  
Alexander Studier-Fischer ◽  
Laura Fankhauser ◽  
...  

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.


2003 ◽  
Vol 145 (11) ◽  
pp. 1023-1023
Author(s):  
N. Levicar ◽  
R.K. Nutall ◽  
T.T. Lah

2003 ◽  
Vol 145 (9) ◽  
pp. 825-838 ◽  
Author(s):  
N. Levicar ◽  
R. K. Nutall ◽  
T. T. Lah

Nature ◽  
2019 ◽  
Vol 573 (7775) ◽  
pp. 532-538 ◽  
Author(s):  
Varun Venkataramani ◽  
Dimitar Ivanov Tanev ◽  
Christopher Strahle ◽  
Alexander Studier-Fischer ◽  
Laura Fankhauser ◽  
...  

Nature ◽  
1992 ◽  
Vol 355 (6363) ◽  
pp. 846-847 ◽  
Author(s):  
David Sidransky ◽  
Tom Mikkelsen ◽  
Karl Schwechheimer ◽  
Mark L. Rosenblum ◽  
Web Cavanee ◽  
...  

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