scholarly journals Astrocytic Tumor

2020 ◽  
Author(s):  
Keyword(s):  
Astrocytic Tumor

TAMI-70. METABOLIC VULNERABILITY TO GPX4 INHIBITION AND FERROPTOSIS OF QUIESCENT ASTROCYTE-LIKE GLIOMA CELL POPULATIONS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi212-vi213
Author(s):  
Matei Banu ◽  
Athanassios Dovas ◽  
Michael Argenziano ◽  
Wenting Zhao ◽  
Dominique Higgins ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Glioma Cell ◽  
Ex Vivo ◽  
Tricarboxylic Acid Cycle ◽  
Cellular Heterogeneity ◽  
Cell Populations ◽  
Acid Oxidation ◽  
Astrocytic Tumor ◽  
Proliferating Cells ◽  
Novel Treatments

Abstract Diversity is a key feature in the glioma ecosystem. Adaptation to a changing tumor microenvironment is achieved through cellular and metabolic plasticity. Here we show that slow-cycling, astrocyte-like glioma cell subpopulations activate distinct metabolic programs, rendering them susceptible to novel treatments. We performed multi-omics analysis on transgenic murine glioma models to characterize cellular heterogeneity. Bulk RNAseq on targeted time-dependent biopsies combined with scRNAseq uncovered distinct tumor cell populations, including a quiescent, astrocyte-like population relatively insensitive to conventional chemotherapy targeting proliferating cells. Using scRNAseq, we identified a persistently conserved astrocytic population in human IDH1-mt/wt high-grade gliomas. This astrocytic tumor population was more abundant in mouse models with constitutive Notch activation, however it was associated with alterations in several other transcriptional programs, suggesting that targeted therapies would likely be ineffective at eradicating it. Gene ontology analysis revealed enrichment in mitochondrial genes specifically regulating oxidative phosphorylation and tricarboxylic acid cycle. Energetic, lipidomic and metabolomic analyses revealed significant mitochondrial β-fatty acid oxidation and lipid catabolism, with less effective oxygen consumption rate and higher basal oxidative stress. Furthermore, this astrocytic tumor population had depleted levels of basal GSH and was more sensitive to reactive oxygen species. Leveraging this metabolic vulnerability, we performed drug screens and found that therapeutic inhibition of complex I or GPX4 was highly effective and synergistic. GPX4 inhibition induced ferroptosis, a newly-discovered form of programmed non-necroptotic cell death mediated by iron-driven lipid peroxidation. Using scRNAseq and RNAscope on ex vivo slice cultures from murine and human gliomas, we found that GPX4 inhibition and ferroptosis induction in the glioma microenvironment selectively eradicated the quiescent astrocytic subpopulation whereas proliferating glioma were less sensitive. Our data therefore supports a novel treatment paradigm, employing metabolic strategies, such as ferroptosis, in conjunction with chemotherapy and RT to target distinct tumor cell populations with different therapeutic vulnerabilities.

scholarly journals Electrophysiological Properties of Human Astrocytic Tumor Cells In Situ: Enigma of Spiking Glial Cells

1998 ◽  
Vol 79 (5) ◽  
pp. 2782-2793 ◽  
Author(s):  
Angélique Bordey ◽  
Harald Sontheimer
Keyword(s):  
Tumor Cells ◽  
Glial Cells ◽  
Potassium Currents ◽  
Low Grade ◽  
Astrocytic Tumor ◽  
Glial Tumor ◽  
Apparent Lack ◽  
Electrophysiological Properties ◽  
Astrocytoma Cells

Bordey, Angélique and Harald Sontheimer. Electrophysiological properties of human astrocytic tumor cells in situ: enigma of spiking glial cells. J. Neurophysiol. 79: 2782–2793, 1998. To better understand physiological changes that accompany the neoplastic transition of astrocytes to become astrocytoma cells, we studied biopsies of low-grade, pilocytic astrocytomas. This group of tumors is most prevalent in children and the tumor cells maintain most antigenic features typical of astrocytes. Astrocytoma cells were studied with the use of whole cell patch-clamp recordings in acute biopsy slices from 4-mo- to 14-yr-old pediatric patients. Recordings from 53 cells in six cases of low-grade astrocytomas were compared to either noncancerous peritumoral astrocytes or astrocytes obtained from other surgeries. Astrocytoma cells almost exclusively displayed slowly activating, sustained, tetraethylammonium (TEA)-sensitive outward potassium currents (delayed rectifying potassium currents; I DR) and transient, tetrodotoxin (TTX)-sensitive sodium currents ( I Na). By contrast, comparison glial cells from peritumoral regions or other surgeries showed I DR and I Na, but in addition these cells also expressed transient “A”-type K+ currents and inwardly rectifying K+ currents ( I IR), both of which were absent in astrocytoma cells. I IR constituted the predominant conductance in comparison astrocytes and was responsible for a high-resting K+ conductance in these cells. Voltage-activated Na+ currents were observed in 37 of 53 astrocytoma cells. Na+ current densities in astrocytoma cells, on average, were three- to fivefold larger than in comparison astrocytes. Astrocytoma cells expressing I Na could be induced to generate slow action potential-like responses (spikes) by current injections. The threshold for generating such spikes was −34 mV (from a holding potential of −70 mV). The spike amplitude and time width were 52.5 mV and 12 ms, respectively. No spikes could be elicited in comparison astrocytes, although some of them expressed Na+ currents of similar size. Comparison of astrocytes to astrocytoma cells suggests that the apparent lack of I IR, which leads to high-input resistance (>500 MΩ), allows glioma cells to be sufficiently depolarized to generate Na+ spikes, whereas the high resting K+ conductance in astrocytes prevents their depolarization and thus generation of spikes. Consistent with this notion, Na+ spikes could be induced in spinal cord astrocytes in culture when I IR was experimentally blocked by 10 μM Ba2+, suggesting that the absence of I IR in astrocytoma cells is primarily responsible for the unusual spiking behavior seen in these glial tumor cells. It is unlikely that such glial spikes ever occur in vivo.

Hypofractionated radiotherapy boost for dose escalation as a treatment option for high-grade spinal cord astrocytic tumor

2005 ◽  
Vol 78 (1) ◽  
pp. 63-69 ◽  
Author(s):  
Norio Katoh ◽  
Hiroki Shirato ◽  
Hidefumi Aoyama ◽  
Rikiya Onimaru ◽  
Keishiro Suzuki ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Treatment Option ◽  
Dose Escalation ◽  
Hypofractionated Radiotherapy ◽  
High Grade ◽  
Astrocytic Tumor

The influence of gastrin and/or cholecystokinin antagonists on the proliferation of three human astrocytic tumor cell lines

Neuropeptides ◽  
1996 ◽  
Vol 30 (5) ◽  
pp. 433-437 ◽  
Author(s):  
I Camby ◽  
I Salmon ◽  
C Oiry ◽  
J-C Galleyrand ◽  
N Nagy ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Tumor Cell Lines ◽  
Astrocytic Tumor ◽  
Cholecystokinin Antagonists

scholarly journals Histopathological analysis of central nervous system tumor; an observational study

2018 ◽  
Vol 8 (2) ◽  
pp. 1393-1398
Author(s):  
Trishna Kakshapati ◽  
Ranga Bahadur Basnet ◽  
Basant Pant ◽  
Deepti Gautam
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Pituitary Adenoma ◽  
Developed Countries ◽  
Histopathological Analysis ◽  
Central Nervous System Tumor ◽  
Astrocytic Tumor ◽  
Who Grade ◽  
Cns Tumor ◽  
System Tumor

Background:  Though the central nervous system tumor comprises ~2% of all the tumors, an overall increase has been observed especially in less developed countries. This increase in the incidence may be due to exposure of population to various risk factors or improved diagnosis with advancement in the ancillary studies. This study aims to provide a single centre histopathological spectrum of this type of tumor.Materials and Methods: A retrospective cross sectional study on a series of cases was performed in the Department of Pathology, Annapurna Neurological Institute & Allied Science , Maitighar , Kathmandu, Nepal from April 2013 to Jan 2016. Data were analyzed using SPSS version 21.0.Results: A total of 221 brain and CNS tumors (125 females and 96 males) were studied. The mean age at diagnosis was 43.77 years. The most common tumor was meningioma(67 cases, 30.3%), followed by astrocytic tumor (57 cases, 25.7%) and pituitary adenoma(30 cases,13.6%). The frequency of WHO grade I, II,III and IV tumor were 94 cases (55%), 34 cases (19.9%),10 cases (5.8%), and 33 cases (19.3%) respectively. The astrocytic tumor was most frequent tumor in children (7/20 caes, 37 %).Conclusion: This study showed the most common CNS tumor to be meningioma followed by astrocytic tumors and pituitary adenoma. The spectrum of CNS tumor in children showed divergent histologic pattern according to the age. In age group 0-10 years embryonal tumors were common whereas ages group of 12-years showed propensity towards astrocytoma as in adults.  

Desmoplastic non-infantile astrocytic tumor with BRAF V600E mutation

2014 ◽  
Vol 31 (4) ◽  
pp. 282-288 ◽  
Author(s):  
Pinar Karabagli ◽  
Hakan Karabagli ◽  
Dogan Kose ◽  
Nadir Kocak ◽  
Volkan Etus ◽  
...  
Keyword(s):  
Braf V600e Mutation ◽  
Braf V600e ◽  
Astrocytic Tumor

scholarly journals Cavernous Angioma of the Corpus Callosum Mimicking an Astrocytic Tumor. Case Report.

2001 ◽  
Vol 41 (7) ◽  
pp. 349-351 ◽  
Author(s):  
Shunichi HARADA ◽  
Maki NIIMI ◽  
Kenichi MURAKAMI ◽  
Tsuneo NAKAMURA
Keyword(s):  
Case Report ◽  
Corpus Callosum ◽  
Cavernous Angioma ◽  
Astrocytic Tumor

A rare astrocytic tumor with rhabdoid features

2009 ◽  
Vol 26 (1) ◽  
pp. 19-24 ◽  
Author(s):  
Shoichi Nagai ◽  
Masanori Kurimoto ◽  
Shin Ishizawa ◽  
Nakamasa Hayashi ◽  
Hideo Hamada ◽  
...  
Keyword(s):  
Astrocytic Tumor ◽  
Rhabdoid Features
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