TERT-Promoter Mutational Status in Glioblastoma – Is There an Association With Amino Acid Uptake on Dynamic 18F-FET PET?

ObjectiveThe mutation of the ‘telomerase reverse transcriptase gene promoter’ (TERTp) has been identified as an important factor for individual prognostication and tumorigenesis and will be implemented in upcoming glioma classifications. Uptake characteristics on dynamic 18F-FET PET have been shown to serve as additional imaging biomarker for prognosis. However, data on the correlation of TERTp-mutational status and amino acid uptake on dynamic 18F-FET PET are missing. Therefore, we aimed to analyze whether static and dynamic 18F-FET PET parameters are associated with the TERTp-mutational status in de-novo IDH-wildtype glioblastoma and whether a TERTp-mutation can be predicted by dynamic 18F-FET PET.MethodsPatients with de-novo IDH-wildtype glioblastoma, WHO grade IV, available TERTp-mutational status and dynamic 18F-FET PET scan prior to any therapy were included. Here, established clinical parameters maximal and mean tumor-to-background-ratios (TBRmax/TBRmean), the biological-tumor-volume (BTV) and minimal-time-to-peak (TTPmin) on dynamic PET were analyzed and correlated with the TERTp-mutational status.ResultsOne hundred IDH-wildtype glioblastoma patients were evaluated; 85/100 of the analyzed tumors showed a TERTp-mutation (C228T or C250T), 15/100 were classified as TERTp-wildtype. None of the static PET parameters was associated with the TERTp-mutational status (median TBRmax 3.41 vs. 3.32 (p=0.362), TBRmean 2.09 vs. 2.02 (p=0.349) and BTV 26.1 vs. 22.4 ml (p=0.377)). Also, the dynamic PET parameter TTPmin did not differ in both groups (12.5 vs. 12.5 min, p=0.411). Within the TERTp-mutant subgroups (i.e., C228T (n=23) & C250T (n=62)), the median TBRmax (3.33 vs. 3.69, p=0.095), TBRmean (2.08 vs. 2.09, p=0.352), BTV (25.4 vs. 30.0 ml, p=0.130) and TTPmin (12.5 vs. 12.5 min, p=0.190) were comparable, too.ConclusionUptake characteristics on dynamic 18F-FET PET are not associated with the TERTp-mutational status in glioblastoma However, as both, dynamic 18F-FET PET parameters as well as the TERTp-mutation status are well-known prognostic biomarkers, future studies should investigate the complementary and independent prognostic value of both factors in order to further stratify patients into risk groups.

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Action of growth hormone in vitro on the net uptake and incorporation into protein of amino acids in muscle from intact rabbits given protein-deficient diets

British Journal Of Nutrition ◽

10.1079/bjn19760003 ◽

1976 ◽

Vol 35 (1) ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

M. R. Turner ◽

P. J. Reeds ◽

K. A. Munday

Keyword(s):

Amino Acids ◽

Growth Hormone ◽

Protein Synthesis ◽

Amino Acid ◽

De Novo ◽

Amino Acid Uptake ◽

Acid Uptake ◽

Amino Acid Incorporation ◽

Acid Incorporation

1. Net amino acid uptake, and incorporation into protein have been measured in vitro in the presence and absence of porcine growth hormone (GH) in muscle from intact rabbits fed for 5 d on low-protein (LP), protein-free (PF) or control diets.2. In muscle from control and LP animals GH had no effect on the net amino acid uptake but stimulated amino acid incorporation into protein, although this response was less in LP animals than in control animals.3. In muscle from PF animals, GH stimulated both amino acid incorporation into protein and the net amino acid uptake, a type of response which also occurs in hypophysectomized animals. The magnitude of the effect of GH on the incorporation of amino acids into protein was reduced in muscle from PF animals.4. The effect of GH on the net amino acid uptake in PF animals was completely blocked by cycloheximide; the uptake effect of GH in these animals was dependent therefore on de novo protein synthesis.5. It is proposed that in the adult the role of growth hormone in protein metabolism is to sustain cellular protein synthesis when there is a decrease in the level of substrate amino acids, similar to that which occurs during a short-term fast or when the dietary protein intake is inadequate.

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Differential regulation of T-cell growth by IL-2 and IL-15

Blood ◽

10.1182/blood-2005-12-4827 ◽

2006 ◽

Vol 108 (2) ◽

pp. 600-608 ◽

Cited By ~ 101

Author(s):

Georgina H. Cornish ◽

Linda V. Sinclair ◽

Doreen A. Cantrell

Keyword(s):

T Cells ◽

Protein Synthesis ◽

Amino Acid ◽

T Cell ◽

Cell Growth ◽

De Novo ◽

Cell Mass ◽

Interleukin 2 ◽

Amino Acid Uptake ◽

Acid Uptake

Although interleukin 2 (IL-2) and IL-15 signal through the common gamma chain (γc) and through IL-2 receptor β–chain (CD122) subunits, they direct distinct physiologic and immunotherapeutic responses in T cells. The present study provides some insight into why IL-2 and IL-15 differentially regulate T-cell function by revealing that these cytokines are strikingly distinct in their ability to control protein synthesis and T-cell mass. IL-2 and IL-15 are shown to be equivalent mitogens for antigen-stimulated CD8+ T cells but not for equivalent growth factors. Antigen-primed T cells cannot autonomously maintain amino acid incorporation or de novo protein synthesis without exogenous cytokine stimulation. Both IL-2 and IL-15 induce amino acid uptake and protein synthesis in antigen-activated T cells; however, the IL-2 response is strikingly more potent than the IL-15 response. The differential action of IL-2 and IL-15 on amino acid uptake and protein synthesis is explained by temporal differences in signaling induced by these 2 cytokines. Hence, the present results show that cytokines that are equivalent mitogens can have different potency in terms of regulating protein synthesis and cell growth.

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NI-37 * INCREASED CEREBRAL AMINO ACID UPTAKE DURING AND AFTER EPILEPTIC DISORDERS MIMICS BRAIN TUMOR IN 18F-FET PET

Neuro-Oncology ◽

10.1093/neuonc/nou264.35 ◽

2014 ◽

Vol 16 (suppl 5) ◽

pp. v146-v146 ◽

Cited By ~ 2

Author(s):

M. Hutterer ◽

Y. Krenn ◽

A. Kunz ◽

M. McCoy ◽

B. Egger ◽

...

Keyword(s):

Brain Tumor ◽

Amino Acid ◽

Amino Acid Uptake ◽

Acid Uptake ◽

Fet Pet

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Faculty Opinions recommendation of Light enhanced amino acid uptake by dominant bacterioplankton groups in surface waters of the Atlantic Ocean.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1126015.583128 ◽

2008 ◽

Author(s):

John Hobbie

Keyword(s):

Amino Acid ◽

Atlantic Ocean ◽

Surface Waters ◽

Amino Acid Uptake ◽

Acid Uptake

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Molecular Imaging of Brain Tumor-Associated Epilepsy

Diagnostics ◽

10.3390/diagnostics10121049 ◽

2020 ◽

Vol 10 (12) ◽

pp. 1049

Author(s):

Csaba Juhász ◽

Sandeep Mittal

Keyword(s):

Brain Tumor ◽

Amino Acid ◽

Brain Tumors ◽

Treatment Strategies ◽

Amino Acid Uptake ◽

Seizure Outcome ◽

Acid Uptake ◽

Positron Emission ◽

Oncology Practice ◽

Glioneuronal Tumors

Epilepsy is a common clinical manifestation and a source of significant morbidity in patients with brain tumors. Neuroimaging has a pivotal role in neuro-oncology practice, including tumor detection, differentiation, grading, treatment guidance, and posttreatment monitoring. In this review, we highlight studies demonstrating that imaging can also provide information about brain tumor-associated epileptogenicity and assist delineation of the peritumoral epileptic cortex to optimize postsurgical seizure outcome. Most studies focused on gliomas and glioneuronal tumors where positron emission tomography (PET) and advanced magnetic resonance imaging (MRI) techniques can detect metabolic and biochemical changes associated with altered amino acid transport and metabolism, neuroinflammation, and neurotransmitter abnormalities in and around epileptogenic tumors. PET imaging of amino acid uptake and metabolism as well as activated microglia can detect interictal or peri-ictal cortical increased uptake (as compared to non-epileptic cortex) associated with tumor-associated epilepsy. Metabolic tumor volumes may predict seizure outcome based on objective treatment response during glioma chemotherapy. Advanced MRI, especially glutamate imaging, can detect neurotransmitter changes around epileptogenic brain tumors. Recently, developed PET radiotracers targeting specific glutamate receptor types may also identify therapeutic targets for pharmacologic seizure control. Further studies with advanced multimodal imaging approaches may facilitate development of precision treatment strategies to control brain tumor-associated epilepsy.

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Polyribonucleotide Synthesis and Bacterial Amino Acid Uptake: the Work of Leon A. Heppel

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)47471-0 ◽

2007 ◽

Vol 282 (18) ◽

pp. e13-e15

Author(s):

Nicole Kresge ◽

Robert D. Simoni ◽

Robert L. Hill

Keyword(s):

Amino Acid ◽

Amino Acid Uptake ◽

Acid Uptake

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Amino Acid Transporters on the Guard of Cell Genome and Epigenome

Cancers ◽

10.3390/cancers13010125 ◽

2021 ◽

Vol 13 (1) ◽

pp. 125

Author(s):

Uğur Kahya ◽

Ayşe Sedef Köseer ◽

Anna Dubrovska

Keyword(s):

Amino Acid ◽

Cancer Metabolism ◽

Tumor Imaging ◽

Redox Homeostasis ◽

Amino Acid Uptake ◽

Metabolic Reprogramming ◽

Tumor Evolution ◽

Amino Acid Transporters ◽

Acid Uptake ◽

Growth And Survival

Tumorigenesis is driven by metabolic reprogramming. Oncogenic mutations and epigenetic alterations that cause metabolic rewiring may also upregulate the reactive oxygen species (ROS). Precise regulation of the intracellular ROS levels is critical for tumor cell growth and survival. High ROS production leads to the damage of vital macromolecules, such as DNA, proteins, and lipids, causing genomic instability and further tumor evolution. One of the hallmarks of cancer metabolism is deregulated amino acid uptake. In fast-growing tumors, amino acids are not only the source of energy and building intermediates but also critical regulators of redox homeostasis. Amino acid uptake regulates the intracellular glutathione (GSH) levels, endoplasmic reticulum stress, unfolded protein response signaling, mTOR-mediated antioxidant defense, and epigenetic adaptations of tumor cells to oxidative stress. This review summarizes the role of amino acid transporters as the defender of tumor antioxidant system and genome integrity and discusses them as promising therapeutic targets and tumor imaging tools.

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