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Cancer AND glutamine

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https://www.readbyqxmd.com/read/28346230/glutaminase-and-poly-adp-ribose-polymerase-inhibitors-suppress-pyrimidine-synthesis-and-vhl-deficient-renal-cancers
#1
Arimichi Okazaki, Paulo A Gameiro, Danos Christodoulou, Laura Laviollette, Meike Schneider, Frances Chaves, Anat Stemmer-Rachamimov, Stephanie A Yazinski, Richard Lee, Gregory Stephanopoulos, Lee Zou, Othon Iliopoulos
Many cancer-associated mutations that deregulate cellular metabolic responses to hypoxia also reprogram carbon metabolism to promote utilization of glutamine. In renal cell carcinoma (RCC), cells deficient in the von Hippel-Lindau (VHL) tumor suppressor gene use glutamine to generate citrate and lipids through reductive carboxylation (RC) of α-ketoglutarate (αKG). Glutamine can also generate aspartate, the carbon source for pyrimidine biosynthesis, and glutathione for redox balance. Here we have shown that VHL-/- RCC cells rely on RC-derived aspartate to maintain de novo pyrimidine biosynthesis...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28345452/l-glutamine-supplementation-promotes-an-improved-energetic-balance-in-walker-256-tumor-bearing-rats
#2
Heber Amilcar Martins, Roberto Barbosa Bazotte, Geraldo Emilio Vicentini, Mariana Machado Lima, Flavia Alessandra Guarnier, Catchia Hermes-Uliana, Flavia Cristina Vieira Frez, Gleison Daion Piovezana Bossolani, Luciane Fracaro, Larissa Dos Santos Fávaro, Mariana Inocêncio Manzano, Jacqueline Nelisis Zanoni
We evaluated the effects of supplementation with oral l-glutamine in Walker-256 tumor-bearing rats. A total of 32 male Wistar rats aged 54 days were randomly divided into four groups: rats without Walker-256 tumor, that is, control rats (C group); control rats supplemented with l-glutamine (CG group); Walker-256 tumor rats without l-glutamine supplementation (WT group); and WT rats supplemented with l-glutamine (WTG group). l-Glutamine was incorporated into standard food at a proportion of 2 g/100 g (2%). After 10 days of the experimental period, the jejunum and duodenum were removed and processed...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28342810/expression-and-putative-role-of-mitochondrial-transport-proteins-in-cancer
#3
REVIEW
Oleksandr Lytovchenko, Edmund R S Kunji
Cancer cells undergo major changes in energy and biosynthetic metabolism. One of them is the Warburg effect, in which pyruvate is used for fermentation rather for oxidative phosphorylation. Another major one is their increased reliance on glutamine, which helps to replenish the pool of Krebs cycle metabolites used for other purposes, such as amino acid or lipid biosynthesis. Mitochondria are central to these alterations, as the biochemical pathways linking these processes run through these organelles. Two membranes, an outer and inner membrane, surround mitochondria, the latter being impermeable to most organic compounds...
March 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28336107/enriched-enteral-nutrition-may-improve-short-term-survival-in-stage-iv-gastric-cancer-patients-a-randomized-controlled-trial
#4
Stanislaw Klek, Lucyna Scislo, Elzbieta Walewska, Ryszard Choruz, Aleksander Galas
OBJECTIVE: The aim of the study was to determine whether the postoperative use of enteral nutrition enriched with arginine, glutamine, and omega-3 fatty acids influences survival in patients diagnosed with stomach cancer. For the purpose of the study, the second wave of the trial performed in 2003 to 2009 was done. METHODS: Ninety-nine patients who underwent surgery for gastric cancer (27 F, 72 M, mean age: 62.9 y) met the inclusion criteria. Of those, 54 were randomized to standard and 45 to enriched enteral nutrition (EEN)...
April 2017: Nutrition
https://www.readbyqxmd.com/read/28319096/hyperglycemia-exacerbates-colon-cancer-malignancy-through-hexosamine-biosynthetic-pathway
#5
A Vasconcelos-Dos-Santos, H F B R Loponte, N R Mantuano, I A Oliveira, I F de Paula, L K Teixeira, J C M de-Freitas-Junior, K C Gondim, N Heise, R Mohana-Borges, J A Morgado-Díaz, W B Dias, A R Todeschini
Hyperglycemia is a common feature of diabetes mellitus, considered as a risk factor for cancer. However, its direct effects in cancer cell behavior are relatively unexplored. Herein we show that high glucose concentration induces aberrant glycosylation, increased cell proliferation, invasion and tumor progression of colon cancer. By modulating the activity of the rate-limiting enzyme, glutamine-fructose-6-phosphate amidotransferase (GFAT), we demonstrate that hexosamine biosynthetic pathway (HBP) is involved in those processes...
March 20, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28314989/inhibition-of-got1-sensitizes-colorectal-cancer-cells-to-5-fluorouracil
#6
Chengyu Hong, Jian Zheng, Xiaoling Li
PURPOSE: Almost all colorectal cancer (CRC) cell lines are known to overexpress aspartate aminotransferase (GOT1), which potentially regulates the intracellular levels of reactive oxygen species (ROS) via the production of NADPH, and supports tumor growth. In our study, the role of GOT1 in the anticancer efficacy of 5-fluorouracil (5-FU) was examined. METHODS: HCT116, SW480, and HT-29 cells were transfected with lentiviral vectors expressing short hairpin RNA (shRNA) against GOT1...
March 17, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28301735/glutaminolysis-a-hallmark-of-cancer-metabolism
#7
Lifeng Yang, Sriram Venneti, Deepak Nagrath
Glutamine is the most abundant circulating amino acid in blood and muscle and is critical for many fundamental cell functions in cancer cells, including synthesis of metabolites that maintain mitochondrial metabolism; generation of antioxidants to remove reactive oxygen species; synthesis of nonessential amino acids (NEAAs), purines and pyrimidines, and fatty acids for cellular replication; and activation of cell signaling. In light of the pleiotropic role of glutamine in cancer cells, a comprehensive understanding of glutamine metabolism is essential for the development of metabolic therapeutic strategies for targeting cancer cells...
March 8, 2017: Annual Review of Biomedical Engineering
https://www.readbyqxmd.com/read/28281102/glutamine-addiction-in-gliomas
#8
Javier Márquez, Francisco J Alonso, José M Matés, Juan A Segura, Mercedes Martín-Rufián, José A Campos-Sandoval
Cancer cells develop and succeed by shifting to different metabolic programs compared with their normal cell counterparts. One of the classical hallmarks of cancer cells is their higher glycolysis rate and lactate production even in the presence of abundant O2 (Warburg effect). Another common metabolic feature of cancer cells is a high rate of glutamine (Gln) consumption normally exceeding their biosynthetic and energetic needs. The term Gln addiction is now widely used to reflect the strong dependence shown by most cancer cells for this essential nitrogen substrate after metabolic reprogramming...
March 9, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28272402/influence-of-enteral-glutamine-on-inflammatory-and-hormonal-response-in-patients-with-rectal-cancer-during-preoperative-radiochemotherapy
#9
N Rotovnik Kozjek, L Kompan, T Žagar, Ž Mrevlje
We conducted a randomized double-blind placebo-controlled study evaluating the influence of 5 weeks' duration of 30 g enteral glutamine supplementation on inflammatory and hormonal responses in 73 patients with rectal cancer undergoing preoperative radiochemotherapy. Plasma levels of inflammatory and hormonal parameters were controlled at the beginning and at the end of supplementation. Enteral glutamine resulted in modulation of inflammatory and hormonal responses as shown by a decreased plasma interleukin 6 and cortisol levels in glutamine compared with placebo group: 5...
March 8, 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28263970/cytosolic-malate-dehydrogenase-activity-helps-support-glycolysis-in-actively-proliferating-cells-and-cancer
#10
E A Hanse, C Ruan, M Kachman, D Wang, X H Lowman, A Kelekar
Increased glucose consumption is a hallmark of cancer cells. The increased consumption and subsequent metabolism of glucose during proliferation creates the need for a constant supply of NAD, a co-factor in glycolysis. Regeneration of the NAD required to support enhanced glycolysis has been attributed to the terminal glycolytic enzyme, lactate dehydrogenase (LDH). However, loss of glucose carbons to biosynthetic pathways early in glycolysis reduces the carbon supply to LDH. Thus, alternative routes for NAD regeneration must exist to support the increased glycolytic rate while allowing for the diversion of glucose to generate biomass and support proliferation...
March 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28261475/the-action-of-%C3%AE-hydroxybutyrate-on-the-growth-metabolism-and-global-histone-h3-acetylation-of-spontaneous-mouse-mammary-tumours-evidence-of-a-%C3%AE-hydroxybutyrate-paradox
#11
Loreta M Rodrigues, Santiago Uribe-Lewis, Basetti Madhu, Davina J Honess, Marion Stubbs, John R Griffiths
BACKGROUND: Ketone bodies have both metabolic and epigenetic roles in cancer. In several studies, they showed an anti-cancer effect via inhibition of histone deacetylases; however, other studies observed faster tumour growth. The related molecule butyrate also inhibits growth of some cancer cells and accelerates it in others. This "butyrate paradox" is thought to be due to butyrate mediating histone acetylation and thus inhibiting cell proliferation in cancers that preferentially utilise glucose (the Warburg effect); whereas in cells that oxidise butyrate as a fuel, it fails to reach inhibitory concentrations and can stimulate growth...
2017: Cancer & Metabolism
https://www.readbyqxmd.com/read/28259988/targeting-glutamine-metabolism-and-the-focal-adhesion-kinase-additively-inhibits-the-mammalian-target-of-the-rapamycin-pathway-in-spheroid-cancer-stem-like-properties-of-ovarian-clear-cell-carcinoma-in%C3%A2-vitro
#12
Masakazu Sato, Kei Kawana, Katsuyuki Adachi, Asaha Fujimoto, Mitsuyo Yoshida, Hiroe Nakamura, Haruka Nishida, Tomoko Inoue, Ayumi Taguchi, Juri Ogishima, Satoko Eguchi, Aki Yamashita, Kensuke Tomio, Osamu Wada-Hiraike, Katsutoshi Oda, Takeshi Nagamatsu, Yutaka Osuga, Tomoyuki Fujii
Ovarian cancer is one of the leading causes of death in the world, which is linked to its resistance to chemotherapy. Strategies to overcome chemoresistance have been keenly investigated. Culturing cancer cells in suspension, which results in formation of spheroids, is a more accurate reflection of clinical cancer behavior in vitro than conventional adherent cultures. By performing RNA-seq analysis, we found that the focal adhesion pathway was essential in spheroids. The phosphorylation of focal adhesion kinase (FAK) was increased in spheroids compared to adherent cells, and inhibition of FAK in spheroids resulted in inhibition of the downstream mammalian target of the rapamycin (mTOR) pathway in ovarian clear cell carcinomas...
February 23, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28259749/metabolic-rewiring-in-cancer-cells-overexpressing-the-glucocorticoid-induced-leucine-zipper-protein-gilz-activation-of-mitochondrial-oxidative-phosphorylation-and-sensitization-to-oxidative-cell-death-induced-by-mitochondrial-targeted-drugs
#13
Fanny André, Anne Trinh, Stéphane Balayssac, Patrice Maboudou, Salim Dekiouk, Myriam Malet-Martino, Bruno Quesnel, Thierry Idziorek, Jérome Kluza, Philippe Marchetti
Cancer cell metabolism is largely controlled by oncogenic signals and nutrient availability. Here, we highlighted that the glucocorticoid-induced leucine zipper (GILZ), an intracellular protein influencing many signaling pathways, reprograms cancer cell metabolism to promote proliferation. We provided evidence that GILZ overexpression induced a significant increase of mitochondrial oxidative phosphorylation as evidenced by the augmentation in basal respiration, ATP-linked respiration as well as respiratory capacity...
March 1, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28255082/pten-regulates-glutamine-flux-to-pyrimidine-synthesis-and-sensitivity-to-dihydroorotate-dehydrogenase-inhibition
#14
Deepti Mathur, Elias Stratikopoulos, Sait Ozturk, Nicole Steinbach, Sarah Pegno, Sarah Schoenfeld, Raymund Yong, Vundavalli V Murty, John M Asara, Lewis C Cantley, Ramon Parsons
Metabolic changes induced by oncogenic drivers of cancer contribute to tumor growth and are attractive targets for cancer treatment. Here, we found that increased growth of PTEN-mutant cells was dependent on glutamine flux through the de novo pyrimidine synthesis pathway, which created sensitivity to the inhibition of dihydroorotate dehydrogenase, a rate-limiting enzyme for pyrimidine ring synthesis. S-phase PTEN-mutant cells showed increased numbers of replication forks, and inhibitors of dihydroorotate dehydrogenase led to chromosome breaks and cell death due to inadequate ATR activation and DNA damage at replication forks...
March 2, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28252650/amino-acid-transporters-in-t-cell-activation-and-differentiation
#15
REVIEW
W Ren, G Liu, J Yin, B Tan, G Wu, F W Bazer, Y Peng, Y Yin
T-cell-mediated immune responses aim to protect mammals against cancers and infections, and are also involved in the pathogenesis of various inflammatory or autoimmune diseases. Cellular uptake and the utilization of nutrients is closely related to the T-cell fate decision and function. Research in this area has yielded surprising findings in the importance of amino-acid transporters for T-cell development, homeostasis, activation, differentiation and memory. In this review, we present current information on amino-acid transporters, such as LAT1 (l-leucine transporter), ASCT2 (l-glutamine transporter) and GAT-1 (γ-aminobutyric acid transporter-1), which are critically important for mediating peripheral naive T-cell homeostasis, activation and differentiation, especially for Th1 and Th17 cells, and even memory T cells...
March 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28250801/press-pulse-a-novel-therapeutic-strategy-for-the-metabolic-management-of-cancer
#16
Thomas N Seyfried, George Yu, Joseph C Maroon, Dominic P D'Agostino
BACKGROUND: A shift from respiration to fermentation is a common metabolic hallmark of cancer cells. As a result, glucose and glutamine become the prime fuels for driving the dysregulated growth of tumors. The simultaneous occurrence of "Press-Pulse" disturbances was considered the mechanism responsible for reduction of organic populations during prior evolutionary epochs. Press disturbances produce chronic stress, while pulse disturbances produce acute stress on populations. It was only when both disturbances coincide that population reduction occurred...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28245869/regulation-of-stem-like-cancer-cells-by-glutamine-through-%C3%AE-catenin-pathway-mediated-by-redox-signaling
#17
Jianwei Liao, Pan-Pan Liu, Guoxin Hou, Jiajia Shao, Jing Yang, Kaiyan Liu, Wenhua Lu, Shijun Wen, Yumin Hu, Peng Huang
BACKGROUND: Cancer stem cells (CSCs) are thought to play an important role in tumor recurrence and drug resistance, and present a major challenge in cancer therapy. The tumor microenvironment such as growth factors, nutrients and oxygen affect CSC generation and proliferation by providing the necessary energy sources and growth signals. The side population (SP) analysis has been used to detect the stem-like cancer cell populations based on their high expression of ABCG2 that exports Hoechst-33342 and certain cytotoxic drugs from the cells...
February 28, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28239030/metabolic-profiling-of-gemcitabine-and-paclitaxel-treated-immortalized-human-pancreatic-cell-lines-with-k-ras-g12d
#18
Akiko Todaka, Rina Umehara, Keiko Sasaki, Masakuni Serizawa, Kenichi Urakami, Masatoshi Kusuhara, Ken Yamaguchi, Hirofumi Yasui
The mechanisms of action of gemcitabine (GEM) and paclitaxel (PTX) have been well investigated, and shown to be the inhibition of DNA polymerase and polymerization of tubulin, respectively. Meanwhile, genomic research has revealed that mutations in the K-RAS oncogene occur in over 90% of pancreatic cancer. Oncogenic alteration rewires alternative metabolic pathways to satisfy the demands of growth. The K-RAS oncogene also has been shown to upregulate glycolysis and glutaminolysis. However, it is still unclear whether K-RAS independently plays a central role in controlling tumor metabolism...
2017: Biomedical Research
https://www.readbyqxmd.com/read/28219903/myc-driven-inhibition-of-the-glutamate-cysteine-ligase-promotes-glutathione-depletion-in-liver-cancer
#19
Brittany Anderton, Roman Camarda, Sanjeev Balakrishnan, Asha Balakrishnan, Rebecca A Kohnz, Lionel Lim, Kimberley J Evason, Olga Momcilovic, Klaus Kruttwig, Qiang Huang, Guowang Xu, Daniel K Nomura, Andrei Goga
How MYC reprograms metabolism in primary tumors remains poorly understood. Using integrated gene expression and metabolite profiling, we identify six pathways that are coordinately deregulated in primary MYC-driven liver tumors: glutathione metabolism; glycine, serine, and threonine metabolism; aminoacyl-tRNA biosynthesis; cysteine and methionine metabolism; ABC transporters; and mineral absorption. We then focus our attention on glutathione (GSH) and glutathione disulfide (GSSG), as they are markedly decreased in MYC-driven tumors...
February 20, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28218035/microrna-153-regulates-glutamine-metabolism-in-glioblastoma-through-targeting-glutaminase
#20
Zhenyang Liu, Junyu Wang, Yunjun Li, Juan Fan, Lihua Chen, Ruxiang Xu
Glioblastoma is the most aggressive manifestation of malignant gliomas and considered to be among the deadliest forms of human cancers. MicroRNAs are found to tightly regulate diverse biological processes and considered to play important roles in cancer etiology. In this study, we found that microRNA-153 was significantly downregulated in glioblastoma tissues compared to matched non-tumor tissues and in glioblastoma cell lines. To investigate the potential function of microRNA-153 in glioblastoma, we transfected glioblastoma cell line U87MG as well as U373MG with synthetic microRNA-153 oligos and observed decreased cell proliferation and increased apoptosis...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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