scholarly journals Metabolic Heterogeneity of Brain Tumor Cells of Proneural and Mesenchymal Origin

2020 ◽  
Author(s):  
Corinna Seliger ◽  
Verena Leidgens ◽  
Anne-Louise Meyer ◽  
Lisa Rauer ◽  
Sylvia Moeckel ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Tumor Cells ◽  
Pentose Phosphate ◽  
Tumor Initiating Cells ◽  
Mesenchymal Origin ◽  
Brain Tumor Cells ◽  
Current Therapies ◽  
Brain Tumor Initiating Cells ◽  
Metabolic Heterogeneity ◽  
Pentose Phosphate Pathways

Abstract Background: Brain-tumor-initiating cells (BTICs) of proneural and mesenchymal origin contribute to the highly malignant phenotype of glioblastoma (GB) and resistance to current therapies. Methods: BTICs of different subtypes representing tumor heterogeneity were challenged with OXPHOS (oxidative phosphorylation) inhibition to assess the differential effects of metabolic intervention on key resistance features. Results: Whereas mesenchymal BTICs were more invasive, more glycolytic and less responsive to OXPHOS-inhibition, proneural BTICs were less invasive, catabolized glucose more via the pentose phosphate pathways, and responded better to OXPHOS inhibition. Conclusion: Targeting glycolysis may be a promising approach to inhibit highly invasive tumor cells of mesenchymal origin, whereas proneural cells are more responsive to OXPHOS inhibition. Future clinical trials exploring metabolic interventions should account for metabolic heterogeneity of brain tumors to overcome resistance to current treatments.

scholarly journals Brain Tumor Treatment: 2017 Update

2018 ◽  
Vol 7 (1) ◽  
pp. 30
Author(s):  
Adri Chakraborty ◽  
Jennifer Han ◽  
Cristina Faltas ◽  
Natalia Coleman
Keyword(s):  
Stem Cells ◽  
Brain Tumor ◽  
Brain Tumors ◽  
Tumor Cells ◽  
Cell Types ◽  
High Recurrence Rate ◽  
Tumor Initiating Cells ◽  
Malignant Brain Tumors ◽  
Current Therapies ◽  
Adults And Children

Malignant brain tumors are a heterogeneous group of diseases arising from different cell types that affect both adults and children. The high recurrence rate of malignant brain tumors typically is due to reappearance of focal masses, indicating that a sub population of tumor cells are insensitive to current therapies and may be responsible for reinitiating tumor growth. It is generally agreed that the resistant tumor cells are comprised of cancer stem cells or tumor-initiating cells. While brain tumor stem cells (BTSCs) were first isolated within the last decade, much of the early research has been focused on identifying the BTSC markers and therapeutic targets. The challenge however, is to translate this knowledge to therapeutics. In the current review, we survey the remedial strategies to target BTSCs, which includes diagnostic, pharmacologic, immunologic, viral, and post-transcriptional approaches.

scholarly journals ETS-Domain Transcription Factor Elk-1 Regulates Stemness Genes in Brain Tumors and CD133+ BrainTumor-Initiating Cells

2021 ◽  
Vol 11 (2) ◽  
pp. 125
Author(s):  
Melis Savasan Sogut ◽  
Chitra Venugopal ◽  
Basak Kandemir ◽  
Ugur Dag ◽  
Sujeivan Mahendram ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Brain Tumor ◽  
Brain Tumors ◽  
System Development ◽  
Nervous System Development ◽  
Stem Cell Population ◽  
Tumor Initiating Cells ◽  
Specific Domain ◽  
Brain Tumor Initiating Cells ◽  
Ets Domain

Elk-1, a member of the ternary complex factors (TCFs) within the ETS (E26 transformation-specific) domain superfamily, is a transcription factor implicated in neuroprotection, neurodegeneration, and brain tumor proliferation. Except for known targets, c-fos and egr-1, few targets of Elk-1 have been identified. Interestingly, SMN, SOD1, and PSEN1 promoters were shown to be regulated by Elk-1. On the other hand, Elk-1 was shown to regulate the CD133 gene, which is highly expressed in brain-tumor-initiating cells (BTICs) and used as a marker for separating this cancer stem cell population. In this study, we have carried out microarray analysis in SH-SY5Y cells overexpressing Elk-1-VP16, which has revealed a large number of genes significantly regulated by Elk-1 that function in nervous system development, embryonic development, pluripotency, apoptosis, survival, and proliferation. Among these, we have shown that genes related to pluripotency, such as Sox2, Nanog, and Oct4, were indeed regulated by Elk-1, and in the context of brain tumors, we further showed that Elk-1 overexpression in CD133+ BTIC population results in the upregulation of these genes. When Elk-1 expression is silenced, the expression of these stemness genes is decreased. We propose that Elk-1 is a transcription factor upstream of these genes, regulating the self-renewal of CD133+ BTICs.

Synchronization of 9L rat brain tumor cells by centrifugal elutriation

1980 ◽  
Vol 2 (3) ◽  
pp. 191-206 ◽  
Author(s):  
P. C. Keng ◽  
C. K. N. Li ◽  
K. T. Wheeler
Keyword(s):  
Brain Tumor ◽  
Rat Brain ◽  
Tumor Cells ◽  
Centrifugal Elutriation ◽  
Brain Tumor Cells ◽  
Rat Brain Tumor

Development and estimation of brain tumor cells culture flask with acoustic window film for ultrasound exposure

2014 ◽  
Vol 53 (7S) ◽  
pp. 07KF12 ◽  
Author(s):  
Sakino Iwasiro ◽  
Akiko Watanabe ◽  
Yoshifumi Onozuka ◽  
Masatsune Minai ◽  
Hiroyuki Nishimura ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Tumor Cells ◽  
Ultrasound Exposure ◽  
Acoustic Window ◽  
Culture Flask ◽  
Brain Tumor Cells ◽  
Window Film

scholarly journals CS-14 * NEUROTROPHIN RECEPTORS TrkB AND TrkC ARE REQUIRED FOR SURVIVAL OF BRAIN TUMOR INITIATING CELLS

2014 ◽  
Vol 16 (suppl 5) ◽  
pp. v54-v54
Author(s):  
R. Kenchappa ◽  
S. Lawn ◽  
N. Krishna ◽  
X. Qu ◽  
D. Fenstermacher ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Neurotrophin Receptors ◽  
Tumor Initiating Cells ◽  
Brain Tumor Initiating Cells

BCNU-modification of the in vitro radiation response in 9L brain tumor cells of rats

1977 ◽  
Vol 2 (1-2) ◽  
pp. 79-88 ◽  
Author(s):  
Kenneth T. Wheeler ◽  
Dennis F. Deen ◽  
Charles B. Wilson ◽  
Mary E. Williams ◽  
Sandra Sheppard
Keyword(s):  
Brain Tumor ◽  
Tumor Cells ◽  
Radiation Response ◽  
Brain Tumor Cells

scholarly journals Elevation of osteopontin levels in brain tumor cells reduces burden and promotes survival through the inhibition of cell dispersal

2007 ◽  
Vol 86 (3) ◽  
pp. 285-296 ◽  
Author(s):  
Stephen M. Selkirk ◽  
Jay Morrow ◽  
Tara A. Barone ◽  
Alan Hoffer ◽  
Jeffrey Lock ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Tumor Cells ◽  
Brain Tumor Cells

Monoclonal antibody 2C5-mediated binding of liposomes to brain tumor cells in vitro and in subcutaneous tumor model in vivo

2005 ◽  
Vol 13 (6) ◽  
pp. 337-343 ◽  
Author(s):  
Bhawna Gupta ◽  
Tatiana S. Levchenko ◽  
Dmitry A. Mongayt ◽  
Vladimir P. Torchilin
Keyword(s):  
Monoclonal Antibody ◽  
Brain Tumor ◽  
Tumor Cells ◽  
Tumor Model ◽  
Subcutaneous Tumor ◽  
Brain Tumor Cells

scholarly journals Multiplexed RNAi therapy against brain tumor-initiating cells via lipopolymeric nanoparticle infusion delays glioblastoma progression

2017 ◽  
Vol 114 (30) ◽  
pp. E6147-E6156 ◽  
Author(s):  
Dou Yu ◽  
Omar F. Khan ◽  
Mario L. Suvà ◽  
Biqin Dong ◽  
Wojciech K. Panek ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Therapeutic Potential ◽  
Therapy Resistance ◽  
Tumor Initiating Cells ◽  
Convection Enhanced Delivery ◽  
Individual Gene ◽  
Brain Tumor Initiating Cells ◽  
Novel Therapeutic Strategies

Brain tumor-initiating cells (BTICs) have been identified as key contributors to therapy resistance, recurrence, and progression of diffuse gliomas, particularly glioblastoma (GBM). BTICs are elusive therapeutic targets that reside across the blood–brain barrier, underscoring the urgent need to develop novel therapeutic strategies. Additionally, intratumoral heterogeneity and adaptations to therapeutic pressure by BTICs impede the discovery of effective anti-BTIC therapies and limit the efficacy of individual gene targeting. Recent discoveries in the genetic and epigenetic determinants of BTIC tumorigenesis offer novel opportunities for RNAi-mediated targeting of BTICs. Here we show that BTIC growth arrest in vitro and in vivo is accomplished via concurrent siRNA knockdown of four transcription factors (SOX2, OLIG2, SALL2, and POU3F2) that drive the proneural BTIC phenotype delivered by multiplexed siRNA encapsulation in the lipopolymeric nanoparticle 7C1. Importantly, we demonstrate that 7C1 nano-encapsulation of multiplexed RNAi is a viable BTIC-targeting strategy when delivered directly in vivo in an established mouse brain tumor. Therapeutic potential was most evident via a convection-enhanced delivery method, which shows significant extension of median survival in two patient-derived BTIC xenograft mouse models of GBM. Our study suggests that there is potential advantage in multiplexed targeting strategies for BTICs and establishes a flexible nonviral gene therapy platform with the capacity to channel multiplexed RNAi schemes to address the challenges posed by tumor heterogeneity.

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