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Glutamine cancer

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https://www.readbyqxmd.com/read/29047383/a-novel-small-molecule-inhibitor-of-p32-mitochondrial-protein-overexpressed-in-glioma
#1
Venkata Yenugonda, Natsuko Nomura, Valentina Kouznetsova, Igor Tsigelny, Valentina Fogal, Elmar Nurmemmedov, Santosh Kesari, Ivan Babic
BACKGROUND: The mitochondrial protein p32 is a validated therapeutic target of cancer overexpressed in glioma. Therapeutic targeting of p32 with monoclonal antibody or p32-binding LyP-1 tumor-homing peptide can limit tumor growth. However, these agents do not specifically target mitochondrial-localized p32 and would not readily cross the blood-brain barrier to target p32-overexpressing gliomas. Identifying small molecule inhibitors of p32 overexpressed in cancer is a more rational therapeutic strategy...
October 18, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29046333/the-p53-inducible-long-noncoding-rna-trings-protects-cancer-cells-from-necrosis-under-glucose%C3%A2-starvation
#2
Muhammad Riaz Khan, Shaoxun Xiang, Zhiyin Song, Mian Wu
The tumor suppressor p53 is activated in response to cellular stress to prevent malignant transformation. However, several recent studies have shown that p53 can play protective roles in tumor cell survival under adversity. Whether p53-regulated long noncoding RNAs are involved in this process remains to be fully understood. Here, we show that under glucose starvation condition, p53 directly upregulates a novel lncRNA named TRINGS (Tp53-regulated inhibitor of necrosis under glucose starvation) in human tumor cells...
October 18, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29045397/glucose-feeds-the-tca-cycle-via-circulating-lactate
#3
Sheng Hui, Jonathan M Ghergurovich, Raphael J Morscher, Cholsoon Jang, Xin Teng, Wenyun Lu, Lourdes A Esparza, Tannishtha Reya, Le Zhan, Jessie Yanxiang Guo, Eileen White, Joshua D Rabinowitz
Mammalian tissues are fuelled by circulating nutrients, including glucose, amino acids, and various intermediary metabolites. Under aerobic conditions, glucose is generally assumed to be burned fully by tissues via the tricarboxylic acid cycle (TCA cycle) to carbon dioxide. Alternatively, glucose can be catabolized anaerobically via glycolysis to lactate, which is itself also a potential nutrient for tissues and tumours. The quantitative relevance of circulating lactate or other metabolic intermediates as fuels remains unclear...
October 18, 2017: Nature
https://www.readbyqxmd.com/read/29044214/limits-of-aerobic-metabolism-in-cancer-cells
#4
Jorge Fernandez-de-Cossio-Diaz, Alexei Vazquez
Cancer cells exhibit high rates of glycolysis and glutaminolysis. Glycolysis can provide energy and glutaminolysis can provide carbon for anaplerosis and reductive carboxylation to citrate. However, all these metabolic requirements could be in principle satisfied from glucose. Here we investigate why cancer cells do not satisfy their metabolic demands using aerobic biosynthesis from glucose. Based on the typical composition of a mammalian cell we quantify the energy demand and the OxPhos burden of cell biosynthesis from glucose...
October 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29038291/cystine-uptake-through-the-cystine-glutamate-antiporter-xct-triggers-glioblastoma-cell-death-under-glucose-deprivation
#5
Takeo Goji, Kazuhiko Takahara, Manabu Negishi, Hironori Katoh
Oncogenic signaling in cancer cells alters glucose uptake and utilization to supply sufficient energy and biosynthetic intermediates for survival and sustained proliferation. Oncogenic signaling also prevents oxidative stress and cell death caused by increased production of reactive oxygen species (ROS). However, elevated glucose metabolism in cancer cells, especially in glioblastoma, results in the cells becoming sensitive to glucose deprivation (i.e. in high glucose dependence), which rapidly induces cell death...
October 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29037738/peptides-derived-from-in-vitro-gastrointestinal-digestion-of-germinated-soybean-proteins-inhibit-human-colon-cancer-cells-proliferation-and-inflammation
#6
Marcela González-Montoya, Blanca Hernández-Ledesma, Jose Manuel Silván, Rosalva Mora-Escobedo, Cristina Martínez-Villaluenga
The aim was to investigate the potential of germinated soybean proteins asa source of peptides with anticancer and anti-inflammatory activities produced after simulated gastrointestinal digestion. Protein concentrate from germinated soybean was hydrolysed with pepsin/pancreatin and fractionated by ultrafiltration. Whole digest and fractions>10, 5-10, and<5kDa caused cytotoxicity to Caco-2, HT-29, HCT-116 human colon cancer cells, and reduced inflammatory response caused by lipopolysaccharide in macrophages RAW 264...
March 1, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29029389/a-ketogenic-diet-supplemented-with-medium-chain-triglycerides-enhances-the-anti-tumor-and-anti-angiogenic-efficacy-of-chemotherapy-on-neuroblastoma-xenografts-in-a-cd1-nu-mouse-model
#7
Sepideh Aminzadeh-Gohari, René Günther Feichtinger, Silvia Vidali, Felix Locker, Tricia Rutherford, Maura O'Donnel, Andrea Stöger-Kleiber, Johannes Adalbert Mayr, Wolfgang Sperl, Barbara Kofler
Neuroblastoma (NB) is a pediatric malignancy characterized by a marked reduction in aerobic energy metabolism. Recent preclinical data indicate that targeting this metabolic phenotype by a ketogenic diet (KD), especially in combination with calorie restriction, slows tumor growth and enhances metronomic cyclophosphamide (CP) therapy of NB xenografts. Because calorie restriction would be contraindicated in most cancer patients, the aim of the present study was to optimize the KD such that the tumors are sensitized to CP without the need of calorie restriction...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29027024/studies-on-the-constituents-of-helleborus-purpurascens-analysis-and-biological-activity-of-the-aqueous-and-organic-extracts
#8
M Heiko Franz, Roxana Birzoi, Catalin-Vasile Maftei, Elena Maftei, Gerhard Kelter, Heinz-Herbert Fiebig, Ion Neda
In Southeast Europe, the ethnomedicinal use of Helleborus species has a very long tradition. Cardiac steroids (Hellebrin), cysteine-rich proteins (Hellethionins) and several steroidal saponins have been identified in these plants. Aim of the present work was to investigate the amino acid composition of native extracts from the root and rootstock of Helleborus purpurascens. The amino acids have been identified by the GC-MS technique on the previously derivatised (Phenomenex Faast Kit) extract samples by comparison with the mass spectra and retention-time of the standards...
October 12, 2017: Amino Acids
https://www.readbyqxmd.com/read/29021138/glutamine-addiction-in-kidney-cancer-suppresses-oxidative-stress-and-can-be-exploited-for-real-time-imaging
#9
Omran Abu Aboud, Samy Habib, Josephine F Trott, Benjamin Stewart, Sitai Liang, Abhijit J Chaudhari, Julie L Sutcliffe, Robert H Weiss
Many cancers appear to activate intrinsic antioxidant systems as a means to counteract oxidative stress. Some cancers, such as clear cell renal cell carcinoma (ccRCC), require exogenous glutamine for growth and exhibit reprogrammed glutamine metabolism, at least in part due to the glutathione pathway, an efficient cellular buffering system that counteracts reactive oxygen species (ROS) and other oxidants. We show here that ccRCC xenograft tumors under the renal capsule exhibit enhanced oxidative stress compared to adjacent normal tissue and the contralateral kidney...
October 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/28993139/rapid-quantification-of-glutaminase-2-gls2-related-metabolites-by-hilic-ms-ms
#10
Guan-Yuan Chen, Hsi-Chun Chao, Hsiao-Wei Liao, I-Lin Tsai, Ching-Hua Kuo
Glutamine, glutamate and glutathione are key modulators of excessive oxidative stress in tumor cells. In this study, we developed a rapid and accurate HILIC-MS/MS method to simultaneously determine concentrations of cellular glutamine, glutamate and glutathione. A bared silica HILIC column was employed to analyze these polar metabolites. The LC-MS parameters were optimized to achieve high sensitivity and selectivity. The analysis can be completed within 4 min under optimal conditions. The method was validated in terms of accuracy, precision, and linearity...
October 6, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28982757/another-case-for-diet-restriction-tap73-expressing-medulloblastomas-are-stunted-by-glutamine-withdrawal
#11
REVIEW
Marco Napoli, Elsa R Flores
Medulloblastomas are among the most common malignant brain cancers in the pediatric population and consist of at least four distinct subgroups with unique molecular and genetic features and clinical outcomes. In this issue of Genes & Development, Niklison-Chirou and colleagues (pp. 1738-1753) identify the p53 family member and p73 isoform TAp73 as a crucial factor causing glutamine addiction in aggressive medulloblastomas. Their findings pave the way for the use of glutamine restriction as an adjuvant treatment for TAp73-expressing medulloblastomas...
September 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28978620/de-novo-myc-addiction-as-an-adaptive-response-of-cancer-cells-to-cdk4-6-inhibition
#12
Míriam Tarrado-Castellarnau, Pedro de Atauri, Josep Tarragó-Celada, Jordi Perarnau, Mariia Yuneva, Timothy M Thomson, Marta Cascante
Cyclin-dependent kinases (CDK) are rational cancer therapeutic targets fraught with the development of acquired resistance by tumor cells. Through metabolic and transcriptomic analyses, we show that the inhibition of CDK4/6 leads to a metabolic reprogramming associated with gene networks orchestrated by the MYC transcription factor. Upon inhibition of CDK4/6, an accumulation of MYC protein ensues which explains an increased glutamine metabolism, activation of the mTOR pathway and blunting of HIF-1α-mediated responses to hypoxia...
October 4, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28969664/perspective-on-the-dynamics-of-cancer
#13
REVIEW
Youcef Derbal
BACKGROUND: The genetic diversity of cancer and the dynamic interactions between heterogeneous tumor cells, the stroma and immune cells present daunting challenges to the development of effective cancer therapies. Although cancer biology is more understood than ever, this has not translated into therapies that overcome drug resistance, cancer recurrence and metastasis. The future development of effective therapies will require more understanding of the dynamics of homeostatic dysregulation that drives cancer growth and progression...
October 3, 2017: Theoretical Biology & Medical Modelling
https://www.readbyqxmd.com/read/28969010/dual-inhibition-of-glycolysis-and-glutaminolysis-as-a-therapeutic-strategy-in-the-treatment-of-ovarian-cancer
#14
Li Sun, Yajie Yin, Leslie H Clark, Wenchuan Sun, Stephanie A Sullivan, Arthur-Quan Tran, Jianjun Han, Lu Zhang, Hui Guo, Esther Madugu, Tommy Pan, Amanda L Jackson, Joshua Kilgore, Hannah M Jones, Timothy P Gilliam, Chunxiao Zhou, Victoria L Bae-Jump
Cancer cell metabolism is required to support the biosynthetic demands of cell growth and cell division, and to maintain reduction oxidaton (redox) homeostasis. This study was designed to test the effects of glucose and glutamine on ovarian cancer cell growth and explore the inter-relationship between glycolysis and glutaminolysis. The SKOV3, IGROV-1 and Hey ovarian cancer cell lines were assayed for glucose, pyruvate and glutamine dependence by analyzing cytotoxicity, cell cycle progression, apoptosis and ATP production...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28967864/activation-of-the-nrf2-antioxidant-program-generates-an-imbalance-in-central-carbon-metabolism-in-cancer
#15
Volkan I Sayin, Sarah E LeBoeuf, Simranjit X Singh, Shawn M Davidson, Douglas Biancur, Betul S Guzelhan, Samantha W Alvarez, Warren L Wu, Triantafyllia R Karakousi, Anastasia Maria Zavitsanou, Julian Ubriaco, Alexander Muir, Dimitris Karagiannis, Patrick J Morris, Craig J Thomas, Richard Possemato, Matthew G Vander Heiden, Thales Papagiannakopoulos
During tumorigenesis, the high metabolic demand of cancer cells results in increased production of reactive oxygen species. To maintain oxidative homeostasis, tumor cells increase their antioxidant production through hyperactivation of the NRF2 pathway, which promotes tumor cell growth. Despite the extensive characterization of NRF2-driven metabolic rewiring, little is known about the metabolic liabilities generated by this reprogramming. Here, we show that activation of NRF2, in either mouse or human cancer cells, leads to increased dependency on exogenous glutamine through increased consumption of glutamate for glutathione synthesis and glutamate secretion by xc(-) antiporter system...
October 2, 2017: ELife
https://www.readbyqxmd.com/read/28957320/a-metabolic-core-model-elucidates-how-enhanced-utilization-of-glucose-and-glutamine-with-enhanced-glutamine-dependent-lactate-production-promotes-cancer-cell-growth-the-warburq-effect
#16
Chiara Damiani, Riccardo Colombo, Daniela Gaglio, Fabrizia Mastroianni, Dario Pescini, Hans Victor Westerhoff, Giancarlo Mauri, Marco Vanoni, Lilia Alberghina
Cancer cells share several metabolic traits, including aerobic production of lactate from glucose (Warburg effect), extensive glutamine utilization and impaired mitochondrial electron flow. It is still unclear how these metabolic rearrangements, which may involve different molecular events in different cells, contribute to a selective advantage for cancer cell proliferation. To ascertain which metabolic pathways are used to convert glucose and glutamine to balanced energy and biomass production, we performed systematic constraint-based simulations of a model of human central metabolism...
September 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28950000/glutaminase-is-essential-for-the-growth-of-triple-negative-breast-cancer-cells-with-a-deregulated-glutamine-metabolism-pathway-and-its-suppression-synergizes-with-mtor-inhibition
#17
Michael Lampa, Heike Arlt, Timothy He, Beatriz Ospina, Jason Reeves, Bailin Zhang, Joshua Murtie, Gejing Deng, Claude Barberis, Dietmar Hoffmann, Hong Cheng, Jack Pollard, Christopher Winter, Victoria Richon, Carlos Garcia-Escheverria, Francisco Adrian, Dmitri Wiederschain, Lakshmi Srinivasan
Tumor cells display fundamental changes in metabolism and nutrient uptake in order to utilize additional nutrient sources to meet their enhanced bioenergetic requirements. Glutamine (Gln) is one such nutrient that is rapidly taken up by tumor cells to fulfill this increased metabolic demand. A vital step in the catabolism of glutamine is its conversion to glutamate by the mitochondrial enzyme glutaminase (GLS). This study has identified GLS a potential therapeutic target in breast cancer, specifically in the basal subtype that exhibits a deregulated glutaminolysis pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28947392/glutaminase-inhibition-improves-flt3-inhibitor-therapy-for-acute-myeloid-leukemia
#18
Mark A Gregory, Travis Nemkov, Julie A Reisz, Vadym Zaberezhnyy, Kirk C Hansen, Angelo D'Alessandro, James DeGregori
Acute myeloid leukemia (AML) is a blood cancer that is poorly responsive to conventional cytotoxic chemotherapy and a diagnosis of AML is usually fatal. More effective and better-tolerated therapies for AML are desperately needed. Activating mutations in FMS-like tyrosine kinase 3 (FLT3) are one of the most frequently observed genetic defects in AML. FLT3 tyrosine kinase inhibitors have shown impressive anti-leukemic activity in clinical trials, however, sustained remissions using these inhibitors as monotherapy have not been achieved...
September 22, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28941690/does-l-glutamine-supplemented-diet-extenuate-no-mediated-damage-on-myenteric-plexus-of-walker-256-tumor-bearing-rats
#19
Geraldo Emílio Vicentini, Heber Amilcar Martins, Luciane Fracaro, Sara Raquel Garcia de Souza, Kassio Papi da Silva Zanoni, Thamara Nishida Xavier Silva, Fernanda Paschoal Blegniski, Flávia Alessandra Guarnier, Jacqueline Nelisis Zanoni
This study was designed to appraise the relationship between enteric neuropathy and oxidative stress in cancer cachexia under l-glutamine-supplemented diet. Total and nitrergic neuronal populations were investigated in jejunum and ileum in four experimental groups: control (C); control l-glutamine-supplemented diet (CG); Walker-256 tumor (TW); and Walker-256 tumor supplemented with l-glutamine (TWG). In addition, local oxidative stress, neuronal nitric oxide synthase (nNOS) enzyme and nitric oxide (NO) levels were evaluated...
November 2017: Food Research International
https://www.readbyqxmd.com/read/28934309/increased-plasma-proline-concentrations-are-associated-with-sarcopenia-in-the-elderly
#20
Kenji Toyoshima, Marie Nakamura, Yusuke Adachi, Akira Imaizumi, Tomomi Hakamada, Yasuko Abe, Eiji Kaneko, Soiciro Takahashi, Kentaro Shimokado
BACKGROUND AND PURPOSE: Metabolome analyses have shown that plasma amino acid profiles reflect various pathological conditions, such as cancer and diabetes mellitus. It remains unclear, however, whether plasma amino acid profiles change in patients with sarcopenia. This study therefore aimed to investigate whether sarcopenia-specific changes occur in plasma amino acid profiles. METHODS: A total of 153 community-dwelling and seven institutionalized elderly individuals (56 men, 104 women; mean age, 77...
2017: PloS One
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