scholarly journals Metabolic Drivers of Invasion in Glioblastoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Joseph H. Garcia ◽  
Saket Jain ◽  
Manish K. Aghi
Keyword(s):  
Driving Forces ◽  
Tumor Metabolism ◽  
Nucleotide Metabolism ◽  
Metabolic Reprogramming ◽  
Dynamic Nature ◽  
Cellular Invasion ◽  
The Poor ◽  
The Brain ◽  
The Warburg Effect ◽  
Tumor Growth And Invasion

Glioblastoma is a primary malignant brain tumor with a median survival under 2 years. The poor prognosis glioblastoma caries is largely due to cellular invasion, which enables escape from resection, and drives inevitable recurrence. While most studies to date have focused on pathways that enhance the invasiveness of tumor cells in the brain microenvironment as the primary driving forces behind GBM’s ability to invade adjacent tissues, more recent studies have identified a role for adaptations in cellular metabolism in GBM invasion. Metabolic reprogramming allows invasive cells to generate the energy necessary for colonizing surrounding brain tissue and adapt to new microenvironments with unique nutrient and oxygen availability. Historically, enhanced glycolysis, even in the presence of oxygen (the Warburg effect) has dominated glioblastoma research with respect to tumor metabolism. More recent global profiling experiments, however, have identified roles for lipid, amino acid, and nucleotide metabolism in tumor growth and invasion. A thorough understanding of the metabolic traits that define invasive GBM cells may provide novel therapeutic targets for this devastating disease. In this review, we focus on metabolic alterations that have been characterized in glioblastoma, the dynamic nature of tumor metabolism and how it is shaped by interaction with the brain microenvironment, and how metabolic reprogramming generates vulnerabilities that may be ripe for exploitation.

Metabolic reprogramming for cancer cells and their microenvironment: Beyond the Warburg Effect

2018 ◽  
Vol 1870 (1) ◽  
pp. 51-66 ◽  
Author(s):  
Linchong Sun ◽  
Caixia Suo ◽  
Shi-ting Li ◽  
Huafeng Zhang ◽  
Ping Gao
Keyword(s):  
Cancer Cells ◽  
Warburg Effect ◽  
Metabolic Reprogramming ◽  
The Warburg Effect

scholarly journals Current Trends in Non-Invasive Imaging of Interactions in the Liver Tumor Microenvironment Mediated by Tumor Metabolism

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3645
Author(s):  
Isabel Theresa Schobert ◽  
Lynn Jeanette Savic
Keyword(s):  
Tumor Microenvironment ◽  
Liver Cancer ◽  
Cancer Cells ◽  
Imaging Techniques ◽  
Treatment Strategies ◽  
Tumor Metabolism ◽  
Resistance Mechanisms ◽  
Metabolic Reprogramming ◽  
Non Invasive

With the increasing understanding of resistance mechanisms mediated by the metabolic reprogramming in cancer cells, there is a growing clinical interest in imaging technologies that allow for the non-invasive characterization of tumor metabolism and the interactions of cancer cells with the tumor microenvironment (TME) mediated through tumor metabolism. Specifically, tumor glycolysis and subsequent tissue acidosis in the realms of the Warburg effect may promote an immunosuppressive TME, causing a substantial barrier to the clinical efficacy of numerous immuno-oncologic treatments. Thus, imaging the varying individual compositions of the TME may provide a more accurate characterization of the individual tumor. This approach can help to identify the most suitable therapy for each individual patient and design new targeted treatment strategies that disable resistance mechanisms in liver cancer. This review article focuses on non-invasive positron-emission tomography (PET)- and MR-based imaging techniques that aim to visualize the crosstalk between tumor cells and their microenvironment in liver cancer mediated by tumor metabolism.

BAI1 acts as a tumor suppressor in lung cancer A549 cells by inducing metabolic reprogramming via the SCD1/HMGCR module

2020 ◽  
Author(s):  
Lei Liu ◽  
Li Chai ◽  
Jingjing Ran ◽  
Ying Yang ◽  
Li Zhang
Keyword(s):  
Lung Cancer ◽  
Tumor Suppressor ◽  
Colony Formation ◽  
Warburg Effect ◽  
Poor Prognosis ◽  
A549 Cells ◽  
Angiogenesis Inhibitor ◽  
Metabolic Reprogramming ◽  
The Warburg Effect

Abstract Brain-specific angiogenesis inhibitor 1 (BAI1) is an important tumor suppressor in multiple cancers. However, the mechanisms behind its anti-tumor activity, particularly the relationship between BAI1 and metabolic aberrant of a tumor, remained unveiled. This study aimed to investigate whether BAI1 could inhibit biological functions in lung cancer A549 cells and the critical regulating molecules that induce metabolic reprogramming. Immunohistochemistry staining was performed to analyze whether variations in the expression of BAI1 in tumor tissues contributes to poor prognosis of lung cancer. Overexpressed BAI1 (BAI1-OE-A549) and control (Vector-NC-A549) were generated by lentiviral transfection. Biological function assays (proliferation, apoptosis, colony formation, invasion and in vivo metastasis), as well as metabolic reprogramming (by the Warburg effect and the glycolytic rate), were performed in both groups. Our results indicated that lower levels of BAI1 contributed to poor prognosis of lung cancer patients. Furthermore, overexpressed of BAI1 dramatically inhibited proliferation, migration, invasion, colony formation and in vivo metastasis of A549 cells. The Warburg effect and the Seahorse assay revealed that BAI1-OE induced metabolism reprogramming by inhibiting the Warburg effect and glycolysis. Further exploration indicated that BAI1 induced metabolic reprogramming by upregulating stearoyl-CoA desaturase 1 (SCD1) and inhibited 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Our study revealed a novel mechanism through which BAI1 acted as tumor suppressor by inducing metabolic reprogramming via the SCD1 and HMGCR module.

Trail Making Test Performance in Relation to Certain Experimenter, Test and Subject Variables

1964 ◽  
Vol 19 (1) ◽  
pp. 199-206 ◽  
Author(s):  
Oscar A. Parsons ◽  
Harriet I. Maslow ◽  
Freda Morris ◽  
J. Peter Denny
Keyword(s):  
Test Performance ◽  
Screening Test ◽  
Poor Performance ◽  
Trail Making Test ◽  
Psychiatric Disturbance ◽  
The Poor ◽  
Subject Variables ◽  
Trail Making ◽  
The Brain ◽  
Order Of Administration

The Trail Making Test, previously reported highly effective in differentiating brain-damaged from non-brain-damaged Ss, was administered to 21 brain-damaged Ss and 63 non-brain-damaged Ss. Since the latter Ss performed at a level indistinguishable from that of the brain-damaged Ss, several studies were designed in an attempt to “explain” the poor performance of the non-brain-damaged Ss. The possible effects of behavioral agitation, anxiety, examiner differences, facility with letters of the alphabet, order of administration, and ego-involvement were investigated. Only anxiety was found to be significantly related to performance. However, in other analyses age, education, vocabulary, and degree of psychiatric disturbance were significantly related to performance. Until these variables are considered in the scoring system, it seems unlikely that the TMT will be effective as a general screening test for brain-damage.

scholarly journals The Key Role of the WNT/β-Catenin Pathway in Metabolic Reprogramming in Cancers under Normoxic Conditions

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5557
Author(s):  
Alexandre Vallée ◽  
Yves Lecarpentier ◽  
Jean-Noël Vallée
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Warburg Effect ◽  
Target Genes ◽  
Glucose Transporter ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Metabolic Reprogramming ◽  
Pyruvate Dehydrogenase Kinase ◽  
The Warburg Effect

The canonical WNT/β-catenin pathway is upregulated in cancers and plays a major role in proliferation, invasion, apoptosis and angiogenesis. Nuclear β-catenin accumulation is associated with cancer. Hypoxic mechanisms lead to the activation of the hypoxia-inducible factor (HIF)-1α, promoting glycolytic and energetic metabolism and angiogenesis. However, HIF-1α is degraded by the HIF prolyl hydroxylase under normoxia, conditions under which the WNT/β-catenin pathway can activate HIF-1α. This review is therefore focused on the interaction between the upregulated WNT/β-catenin pathway and the metabolic processes underlying cancer mechanisms under normoxic conditions. The WNT pathway stimulates the PI3K/Akt pathway, the STAT3 pathway and the transduction of WNT/β-catenin target genes (such as c-Myc) to activate HIF-1α activity in a hypoxia-independent manner. In cancers, stimulation of the WNT/β-catenin pathway induces many glycolytic enzymes, which in turn induce metabolic reprogramming, known as the Warburg effect or aerobic glycolysis, leading to lactate overproduction. The activation of the Wnt/β-catenin pathway induces gene transactivation via WNT target genes, c-Myc and cyclin D1, or via HIF-1α. This in turn encodes aerobic glycolysis enzymes, including glucose transporter, hexokinase 2, pyruvate kinase M2, pyruvate dehydrogenase kinase 1 and lactate dehydrogenase-A, leading to lactate production. The increase in lactate production is associated with modifications to the tumor microenvironment and tumor growth under normoxic conditions. Moreover, increased lactate production is associated with overexpression of VEGF, a key inducer of angiogenesis. Thus, under normoxic conditions, overstimulation of the WNT/β-catenin pathway leads to modifications of the tumor microenvironment and activation of the Warburg effect, autophagy and glutaminolysis, which in turn participate in tumor growth.

Abstract 48: Dysregulated Glucose Metabolism Pathway Specific Genes in Aged and Post-stroke Rat Brains: Implicating Hexokinase 3 in Glucose Regulation

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Umadevi V Wesley ◽  
Vijesh J Bhute ◽  
Sean P Palecek ◽  
Robert J Dempsey
Keyword(s):  
Glucose Metabolism ◽  
Fold Increase ◽  
Nucleotide Metabolism ◽  
Metabolic Reprogramming ◽  
Mrna Levels ◽  
Stroke Incidence ◽  
Post Stroke ◽  
Metabolism Pathway ◽  
Aged Brain ◽  
Old Rats

Background: Metabolic dysregulation associated with aging impacts stroke incidence and outcome. Hyperglycemia occurs in 30% of patients with ischemic stroke, and is associated with poor stroke recovery. On the other hand, depletion of glucose within the brain prevents production of ATP, leading to energy reduction and neuronal death. Thus, balanced glucose metabolism is critical for normal brain function. However, our understanding of the regulation of genes involved in glucose metabolism and relationship to age in the post-stroke brain is elusive. Methods: Using transcriptomic and metabolomics approach, we examined the expression pattern of glucose metabolism pathway specific genes in the naïve and post-stroke brains of 3 month, and 12 month old rats subjected to focal cerebral ischemia by middle cerebral artery occlusion and 2 days re-perfusion. Metabolites were analyzed using Nuclear Magnetic Resonance (NMR) spectroscopy. Results: Our data shows substantial alterations in the glucose metabolism pathway in aged, and particularly in post stroke rat brain. Brains from 12 month old rats showed about 15 fold increase in phosphoenolpyruvate carboxykinase (PCK1), and 2 fold increase in phosphorylase kinase (PHKG1) mRNA as compared to 3 month old rats. In the post-stroke brain, mRNA levels of hexokinase 3 (HK3) was upregulated 9 fold in 3 month old rats. However, HK3 mRNA substantially increased to 26 fold in 12 month old post-stroke brain as compared to control brains. The PCK1 gene was down regulated 2-4 fold in post-stroke brain. Metabolomics studies indicated significant alterations in nucleotide metabolism and decreased antioxidants in the aged brain. Metabolic changes in post-stroke brains included depletion of ADP and AMP, and accumulation of fumarate, O-phospho-ethanolamine, glycerol, glycine, leucine, lysine and malate. Conclusion: Upregulation of PCK1, a key gluconeogenic enzyme may contribute to excess glucose production in aged brain, leading to increased risk of obesity and stroke. The inducible expression of HK3 in post-stroke brain suggests its adaptive role in metabolic responses to stress in the ischemic environment. Overall, HK3 by modulating glycolysis pathway, may lead to metabolic reprogramming in aged and post stroke brain.

scholarly journals Heart rate variability, the dynamic nature of the retinal microvasculature and cardiac stress: providing insight into the brain–retina–heart link: the SABPA study

Eye ◽  
2019 ◽  
Vol 34 (5) ◽  
pp. 835-846
Author(s):  
Annemarie Wentzel ◽  
Leoné Malan ◽  
Roland von Känel ◽  
Wayne Smith ◽  
Nicolaas T. Malan
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Dynamic Nature ◽  
Cardiac Stress ◽  
Retinal Microvasculature ◽  
The Brain ◽  
Insight Into

Neutrophil affinity for PGP and HAIYPRH (T7) peptide dual-ligand functionalized nanoformulation enhances the brain delivery of tanshinone IIA and exerts neuroprotective effects against ischemic stroke by inhibiting proinflammatory signaling pathways

2018 ◽  
Vol 42 (23) ◽  
pp. 19043-19061
Author(s):  
Yutao Li ◽  
Chiying An ◽  
Danan Han ◽  
Yanxin Dang ◽  
Xin Liu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Physicochemical Properties ◽  
Signaling Pathways ◽  
Blood Brain Barrier ◽  
Tanshinone Iia ◽  
Brain Barrier ◽  
Brain Delivery ◽  
Neuroprotective Effects ◽  
The Poor ◽  
The Brain

A great challenge to the therapy of ischemic stroke is the poor physicochemical properties and inability of the drug to cross the blood–brain barrier (BBB).

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