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Glutamine cancer

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https://www.readbyqxmd.com/read/29473879/in-silico-based-repositioning-of-phosphinothricin-as-a-novel-technetium-99m-imaging-probe-with-potential-anti-cancer-activity
#1
Tamer M Sakr, Mohammed A Khedr, Hassan M Rashed, Maged E Mohamed
l-Phosphinothricin (glufosinate or 2-amino-4-((hydroxy(methyl) phosphinyl) butyric acid ammonium salt (AHPB)), which is a structural analog of glutamate, is a recognized herbicide that acts on weeds through inhibition of glutamine synthetase. Due to the structural similarity between phosphinothricin and some bisphosphonates (BPs), this study focuses on investigating the possibility of repurposing phosphinothricin as a bisphosphonate analogue, particularly in two medicine-related activities: image probing and as an anti-cancer drug...
February 23, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29467657/effects-of-sodium-and-amino-acid-substrate-availability-upon-the-expression-and-stability-of-the-snat2-slc38a2-amino-acid-transporter
#2
Thorsten M Hoffmann, Emma Cwiklinski, Dinesh S Shah, Clare Stretton, Russell Hyde, Peter M Taylor, Harinder S Hundal
The SNAT2 (SLC38A2) System A amino acid transporter mediates Na+ -coupled cellular uptake of small neutral α-amino acids (AAs) and is extensively regulated in response to humoral and nutritional cues. Understanding the basis of such regulation is important given that AA uptake via SNAT2 has been linked to activation of mTORC1; a major controller of many important cellular processes including, for example, mRNA translation, lipid synthesis, and autophagy and whose dysregulation has been implicated in the development of cancer and conditions such as obesity and type 2 diabetes...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29466723/small-molecule-screen-identifies-de-novo-nucleotide-synthesis-as-a-vulnerability-of-cells-lacking-sirt3
#3
Karina N Gonzalez Herrera, Elma Zaganjor, Yoshinori Ishikawa, Jessica B Spinelli, Haejin Yoon, Jia-Ren Lin, F Kyle Satterstrom, Alison Ringel, Stacy Mulei, Amanda Souza, Joshua M Gorham, Craig C Benson, Jonathan G Seidman, Peter K Sorger, Clary B Clish, Marcia C Haigis
Sirtuin 3 (SIRT3) is a NAD+ -dependent deacetylase downregulated in aging and age-associated diseases such as cancer and neurodegeneration and in high-fat diet (HFD)-induced metabolic disorders. Here, we performed a small-molecule screen and identified an unexpected metabolic vulnerability associated with SIRT3 loss. Azaserine, a glutamine analog, was the top compound that inhibited growth and proliferation of cells lacking SIRT3. Using stable isotope tracing of glutamine, we observed its increased incorporation into de novo nucleotide synthesis in SIRT3 knockout (KO) cells...
February 20, 2018: Cell Reports
https://www.readbyqxmd.com/read/29463059/glutamine-synthetase-localization-dictates-outcome
#4
REVIEW
Alessandra Castegna, Alessio Menga
Glutamine synthetase (GS) is the adenosine triphosphate (ATP)-dependent enzyme that catalyses the synthesis of glutamine by condensing ammonium to glutamate. In the circulatory system, glutamine carries ammonia from muscle and brain to the kidney and liver. In brain reduction of GS activity has been suggested as a mechanism mediating neurotoxicity in neurodegenerative disorders. In cancer, the delicate balance between glutamine synthesis and catabolism is a critical event. In vitro evidence, confirmed in vivo in some cases, suggests that reduced GS activity in cancer cells associates with a more invasive and aggressive phenotype...
February 19, 2018: Genes
https://www.readbyqxmd.com/read/29459886/dna-damage-repair-and-cancer-metabolism
#5
REVIEW
Marc-Olivier Turgeon, Nicholas J S Perry, George Poulogiannis
Although there has been a renewed interest in the field of cancer metabolism in the last decade, the link between metabolism and DNA damage/DNA repair in cancer has yet to be appreciably explored. In this review, we examine the evidence connecting DNA damage and repair mechanisms with cell metabolism through three principal links. (1) Regulation of methyl- and acetyl-group donors through different metabolic pathways can impact DNA folding and remodeling, an essential part of accurate double strand break repair...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29455869/overexpression-of-slc1a5-in-lymph-node-metastases-outperforms-assessment-in-the-primary-as-a-negative-prognosticator-in-non-small-cell-lung-cancer
#6
Agnes Csanadi, Annika Oser, Konrad Aumann, Vera Gumpp, Justyna Rawluk, Ursula Nestle, Claudia Kayser, Sebastian Wiesemann, Martin Werner, Gian Kayser
Despite recent advances in therapeutic options, lung cancer is the leading cause of death among malignant diseases worldwide. Glutamine-dependence is an established attribute in cancer tissue with emerging importance as a diagnostic and therapeutic target. We analysed the expression of SLC1a5, a major glutamine transporter, in the primary tumour and corresponding nodal metastasis of non-small cell lung cancer (NSCLC) to investigate its biological impact. Expression of SLC1a5 was analysed by immunohistochemistry in 259 NSCLC and in 142 nodal metastases and correlated with clinicopathological parameters including overall survival...
February 15, 2018: Pathology
https://www.readbyqxmd.com/read/29445172/rational-cell-culture-optimization-enhances-experimental-reproducibility-in-cancer-cells
#7
Marina Wright Muelas, Fernando Ortega, Rainer Breitling, Claus Bendtsen, Hans V Westerhoff
Optimization of experimental conditions is critical in ensuring robust experimental reproducibility. Through detailed metabolomic analysis we found that cell culture conditions significantly impacted on glutaminase (GLS1) sensitivity resulting in variable sensitivity and irreproducibility in data. Baseline metabolite profiling highlighted that untreated cells underwent significant changes in metabolic status. Both the extracellular levels of glutamine and lactate and the intracellular levels of multiple metabolites changed drastically during the assay...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29441565/metabolomics-and-transcriptomics-profiles-reveal-the-dysregulation-of-the-tricarboxylic-acid-cycle-and-related-mechanisms-in-prostate-cancer
#8
Yaping Shao, Guozhu Ye, Shancheng Ren, Hai-Long Piao, Xinjie Zhao, Xin Lu, Fubo Wang, Ma Wang, Jia Li, Peiyuan Yin, Tian Xia, Chuanliang Xu, Jane J Yu, Yinghao Sun, Guowang Xu
Genetic alterations drive metabolic reprogramming to meet increased biosynthetic precursor and energy demands for cancer cell proliferation and survival in unfavorable environments. A systematic study of gene-metabolite regulatory networks and metabolic dysregulation should reveal the molecular mechanisms underlying prostate cancer (PCa) pathogenesis. Herein, we performed gas chromatography-mass spectrometry (GC-MS)-based metabolomics and RNA-seq analyses in prostate tumors and matched adjacent normal tissues (ANTs) to elucidate the molecular alterations and potential underlying regulatory mechanisms in PCa...
February 14, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29436167/sestrin2-facilitates-glutamine-dependent-transcription-of-pgc-1%C3%AE-and-survival-of-liver-cancer-cells-under-glucose-limitation
#9
Ashish Kumar, Sagnik Giri, Chandrima Shaha
Differential utilization of metabolites and metabolic plasticity can confer adaptation to cancer cells under metabolic stress. Glutamine is one of the vital and versatile nutrients which cancer cells consume avidly for their proliferation, therefore, mechanisms related to glutamine metabolism has been identified as targets. Recently, SESN2 (sestrin2), a stress inducible protein has been reported to regulate survival in glutamine depleted cancer cells, based on this, we explored if SESN2 could regulate glutamine metabolism during glucose starvation...
February 12, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29435734/targeting-of-glutamine-transporter-asct2-and-glutamine-synthetase-suppresses-gastric-cancer-cell-growth
#10
Jianxin Ye, Qiang Huang, Jie Xu, Jinsheng Huang, Jinzhou Wang, Wenjing Zhong, Wannan Chen, Xinjian Lin, Xu Lin
PURPOSE: Glutamine (Gln) is essential for the proliferation of most cancer cells, making it an appealing target for cancer therapy. However, the role of Gln in gastric cancer (GC) metabolism is unknown and Gln-targeted therapy against GC remains scarce. The aim of this study was to investigate the relevance of Gln in GC growth and targeting. METHODS: Expression of Gln transporter ASCT2 and glutamine synthetase (GS) in the parental and molecularly engineered GC cells or in human GC specimens was determined by RT-PCR and western blot analysis or immunohistochemistry...
February 12, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29434187/glutamine-metabolism-regulates-flip-expression-and-sensitivity-to-trail-in-triple-negative-breast-cancer-cells
#11
Marta Mauro-Lizcano, Abelardo López-Rivas
Glutamine plays an important role in the metabolism of tumor cells through its contribution to redox homeostasis, bioenergetics, synthesis of macromolecules, and signaling. Triple-negative breast cancers (TNBC) are highly metastatic and associated with poor prognosis. TNBC cells show a marked dependence on extracellular glutamine for growth. Herein we demonstrate that TNBC cells are markedly sensitized to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis upon glutamine deprivation...
February 12, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29416026/sirtuin5-contributes-to-colorectal-carcinogenesis-by-enhancing-glutaminolysis-in-a-deglutarylation-dependent-manner
#12
Yun-Qian Wang, Hao-Lian Wang, Jie Xu, Juan Tan, Lin-Na Fu, Ji-Lin Wang, Tian-Hui Zou, Dan-Feng Sun, Qin-Yan Gao, Ying-Xuan Chen, Jing-Yuan Fang
Reversible post-translational modifications represent a mechanism to control tumor metabolism. Here we show that mitochondrial Sirtuin5 (SIRT5), which mediates lysine desuccinylation, deglutarylation, and demalonylation, plays a role in colorectal cancer (CRC) glutamine metabolic rewiring. Metabolic profiling identifies that deletion of SIRT5 causes a marked decrease in 13C-glutamine incorporation into tricarboxylic-acid (TCA) cycle intermediates and glutamine-derived non-essential amino acids. This reduces the building blocks required for rapid growth...
February 7, 2018: Nature Communications
https://www.readbyqxmd.com/read/29414301/palmatine-suppresses-glutamine-mediated-interaction-between-pancreatic-cancer-and-stellate-cells-through-simultaneous-inhibition-of-survivin-and-col1a1
#13
Divya Chakravarthy, Amanda R Muñoz, Angel Su, Rosa F Hwang, Brian R Keppler, Daniel E Chan, Glenn Halff, Rita Ghosh, Addanki P Kumar
Reciprocal interaction between pancreatic stellate cells (PSCs) and cancer cells (PCCs) in the tumor microenvironment (TME) promotes tumor cell survival and progression to lethal, therapeutically resistant pancreatic cancer. The goal of this study was to test the ability of Palmatine (PMT) to disrupt this reciprocal interaction in vitro and examine the underlying mechanism of interaction. We show that PSCs secrete glutamine into the extracellular environment under nutrient deprivation. PMT suppresses glutamine-mediated changes in GLI signaling in PCCs resulting in the inhibition of growth and migration while inducing apoptosis by inhibition of survivin...
January 31, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29405021/-effect-of-oral-glutamine-on-chemotherapy-induced-peripheral-neuropathy-in-cancer-patients-an-evidence-based-appraisal
#14
Wan-Na Sun, Jing-Wei Su, Zih-Ping Shen, Hsin-Tien Hsu
BACKGROUND: Chemotherapy may induce peripheral neuropathy, which often results in the chemotherapy dose being reduced or the chemotherapy regimen being stopped. At present, there are no treatment guidelines for chemotherapy-induced peripheral neuropathy. Glutamine is one of the treatment strategies currently applied in practice. This strategy is expensive and lacks clear evidence as to its efficacy. PURPOSE: To evaluate the effect of oral glutamine on CIPN in cancer patients...
February 2018: Hu Li za Zhi the Journal of Nursing
https://www.readbyqxmd.com/read/29402740/synthesis-of-novel-multivalent-fluorescent-inhibitors-with-high-affinity-to-prostate-cancer-and-their-biological-evaluation
#15
Young-Do Kwon, Hea-Jong Chung, Sun Joo Lee, Sun-Hwa Lee, Byung-Hoon Jeong, Hee-Kwon Kim
Prostate-specific membrane antigen (PSMA) is an important biological target for therapy and diagnosis of prostate cancer. In this study, novel multivalent PSMA inhibitors with glutamate-urea-lysine structures were designed to improve inhibition characteristics. Precursors of the novel inhibitors were prepared from glutamic acid with di-tert-butyl ester. A near-infrared molecular dye, sulfo-Cy5.5, was introduced into the precursors to generate the final PSMA fluorescent inhibitors, compounds 12-14, to visualize prostate cancer...
January 31, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29399334/dysregulated-metabolic-enzymes-and-metabolic-reprogramming-in-cancer-cells
#16
Annapoorna Sreedhar, Yunfeng Zhao
Tumor cells carry various genetic and metabolic alterations, which directly contribute to their growth and malignancy. Links between metabolism and cancer are multifaceted. Metabolic reprogramming, such as enhanced aerobic glycolysis, mutations in the tricarboxylic acid (TCA) cycle metabolic enzymes, and dependence on lipid and glutamine metabolism are key characteristics of cancer cells. Understanding these metabolic alterations is crucial for development of novel anti-cancer therapeutic strategies. In the present review, the broad importance of metabolism in tumor biology is discussed, and the current knowledge on dysregulated metabolic enzymes involved in the vital regulatory steps of glycolysis, the TCA cycle, the pentose phosphate pathway, and lipid, amino acid, and mitochondrial metabolism pathways are reviewed...
January 2018: Biomedical Reports
https://www.readbyqxmd.com/read/29388903/in-vivo-pet-assay-of-tumor-glutamine-flux-and-metabolism-in-human-trial-of-18f-2s-4r-4-fluoroglutamine
#17
Mark P S Dunphy, James J Harding, Sriram Venneti, Hanwen Zhang, Eva M Burnazi, Jacqueline Bromberg, Antonio M Omuro, James J Hsieh, Ingo K Mellinghoff, Kevin Staton, Christina Pressl, Bradley J Beattie, Pat B Zanzonico, John F Gerecitano, David P Kelsen, Wolfgang Weber, Serge K Lyashchenko, Hank F Kung, Jason S Lewis
Purpose To assess the clinical safety, pharmacokinetics, and tumor imaging characteristics of fluorine 18-(2S,4R)-4-fluoroglutamine (FGln), a glutamine analog radiologic imaging agent. Materials and Methods This study was approved by the institutional review board and conducted under a U.S. Food and Drug Administration-approved Investigational New Drug application in accordance with the Helsinki Declaration and the Health Insurance Portability and Accountability Act. All patients provided written informed consent...
January 31, 2018: Radiology
https://www.readbyqxmd.com/read/29383096/hypoxia-inducible-factor-1%C3%AE-promotes-cell-survival-during-ammonia-stress-response-in-ovarian-cancer-stem-like-cells
#18
Shojiro Kitajima, Kian Leong Lee, Hiroki Hikasa, Wendi Sun, Ruby Yun-Ju Huang, Henry Yang, Shinji Matsunaga, Takehiro Yamaguchi, Marito Araki, Hiroyuki Kato, Lorenz Poellinger
Ammonia is a toxic by-product of metabolism that causes cellular stresses. Although a number of proteins are involved in adaptive stress response, specific factors that counteract ammonia-induced cellular stress and regulate cell metabolism to survive against its toxicity have yet to be identified. We demonstrated that the hypoxia-inducible factor-1α (HIF-1α) is stabilized and activated by ammonia stress. HIF-1α activated by ammonium chloride compromises ammonia-induced apoptosis. Furthermore, we identified glutamine synthetase (GS) as a key driver of cancer cell proliferation under ammonia stress and glutamine-dependent metabolism in ovarian cancer stem-like cells expressing CD90...
December 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29371936/lncrna-tug1-sponges-mir-145-to-promote-cancer-progression-and-regulate-glutamine-metabolism-via-sirt3-gdh-axis
#19
Bing Zeng, Huilin Ye, Jianming Chen, Di Cheng, Canfeng Cai, Guoxing Chen, Xiang Chen, Haiyang Xin, Chaoming Tang, Jun Zeng
Long noncoding RNAs (lncRNAs) are important regulators in cancer progression. Deregulation of the lncRNA taurine upregulated gene 1 (TUG1) predicts poor prognosis and is implicated in the development of several cancers. In this study, we investigated the role of TUG1 in the pathogenesis of intrahepatic cholangiocarcinoma (ICC). We found that TUG1 is upregulated in ICC samples, which correlates with poor prognosis and adverse clinical pathological characteristics. Knockdown of TUG1 inhibited the proliferation, motility, and invasiveness of cultured ICC cells, and decreased tumor burden in a xenograft mouse model...
December 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/29371926/a-natural-inhibitor-of-kidney-type-glutaminase-a-withanolide-from-physalis-pubescens-with-potent-anti-tumor-activity
#20
Canrong Wu, Mengzhu Zheng, Suyu Gao, Shanshan Luan, Li Cheng, Liqing Wang, Jiachen Li, Lixia Chen, Hua Li
Kidney-type glutaminase (KGA), a mitochondrial enzyme converting glutamine to glutamate for energy supply, was over-expressed in many cancers and had been regarded as a promising therapeutic target in recent years. Structure-based virtual ligand screening predicted physapubescin K, a new withanolide from Physalis pubescens, to be potential KGA inhibitor. Enzyme activity inhibition assays and microscale thermophoresis experiments had demonstrated the efficiency and specificity of physapubescin K targeting KGA...
December 26, 2017: Oncotarget
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