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Cancer AND glutamine

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https://www.readbyqxmd.com/read/29790697/the-inhibition-of-c-myc-transcription-factor-modulates-the-expression-of-glycolytic-and-glutaminolytic-enzymes-in-fadu-hypopharyngeal-carcinoma-cells
#1
Robert Kleszcz, Jarosław Paluszczak, Violetta Krajka-Kuźniak, Wanda Baer-Dubowska
BACKGROUND: Cancer cells are dependent on aerobic glycolysis for energy production and increased glutamine consumption. HIF-1α and c-MYC transcription factors regulate the expression of glycolytic and glutaminolytic genes. Their activity may be repressed by SIRT6. Head and neck carcinomas show frequent activation of c-MYC function and SIRT6 down-regulation, which contributes to a strong dependence on glucose and glutamine availability. OBJECTIVES: The aim of this study was to compare the influence of HIF-1α and c-MYC inhibitors (KG-548 and 10058-F4, respectively) and potential SIRT6 inducers - resveratrol and its synthetic derivative DMU-212 with the effect of glycolysis and glutaminolysis inhibitors (2-deoxyglucose and aminooxyacetic acid, respectively) on the metabolism and expression of metabolic enzymes in FaDu hypopharyngeal carcinoma cells...
May 17, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29789716/xct-slc7a11-mediated-metabolic-reprogramming-promotes-non-small-cell-lung-cancer-progression
#2
Xiangming Ji, Jun Qian, S M Jamshedur Rahman, Peter J Siska, Yong Zou, Bradford K Harris, Megan D Hoeksema, Irina A Trenary, Chen Heidi, Rosana Eisenberg, Jeffrey C Rathmell, Jamey D Young, Pierre P Massion
Many tumors increase uptake and dependence on glucose, cystine or glutamine. These basic observations on cancer cell metabolism have opened multiple new diagnostic and therapeutic avenues in cancer research. Recent studies demonstrated that smoking could induce the expression of xCT (SLC7A11) in oral cancer cells, suggesting that overexpression of xCT may support lung tumor progression. We hypothesized that overexpression of xCT occurs in lung cancer cells to satisfy the metabolic requirements for growth and survival...
May 23, 2018: Oncogene
https://www.readbyqxmd.com/read/29788890/inhibition-of-pyruvate-dehydrogenase-kinase-as-a-therapeutic-strategy-against-cancer
#3
Swatishree Sradhanjali, Mamatha M Reddy
Cancer cells alter their metabolism to support the uninterrupted supply of biosynthetic molecules required for continuous proliferation. Glucose metabolism is frequently reprogrammed in several tumors in addition to fatty acid, amino acid and glutamine metabolism. Pyruvate dehydrogenase kinase (PDK) is a gatekeeper enzyme involved in altered glucose metabolism in tumors. There are four isoforms of PDK (1 to 4) in humans. PDK phosphorylates E1α subunit of pyruvate dehydrogenase complex (PDC) and inactivates it...
May 22, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29777783/accelerated-lipid-catabolism-and-autophagy-are-cancer-survival-mechanisms-under-inhibited-glutaminolysis
#4
Anna Halama, Michal Kulinski, Shaima S Dib, Shaza B Zaghlool, Kodappully S Siveen, Ahmad Iskandarani, Jonas Zierer, Kirti S Prabhu, Noothan J Satheesh, Aditya M Bhagwat, Shahab Uddin, Gabi Kastenmüller, Olivier Elemento, Steven S Gross, Karsten Suhre
Suppressing glutaminolysis does not always induce cancer cell death in glutamine dependent tumors because cells may switch to alternative energy sources. To reveal compensatory metabolic pathways, we investigated the metabolome-wide cellular response to inhibited glutaminolysis in cancer cells. Glutaminolysis inhibition with C.968 suppressed cell proliferation but was insufficient to induce cancer cell death. We found that lipid catabolism was activated as a compensation for glutaminolysis inhibition. Accelerated lipid catabolism, together with oxidative stress induced by glutaminolysis inhibition, triggered autophagy...
May 16, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29773061/development-of-novel-therapeutics-targeting-isocitrate-dehydrogenase-mutations-in-cancer
#5
Horrick Sharma
Isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (αKG). IDH 1 and IDH2 regulate several cellular processes, including oxidative respiration, glutamine metabolism, lipogenesis, and cellular defense against oxidative damage. Mutations in IDH1 and IDH2 have recently been observed in multiple tumor types, including gliomas, acute myeloid leukemia, myelodysplastic syndromes, and chondrosarcoma. IDH1 and IDH2 mutations involve a gain in neomorphic activity that catalyze αKG conversion to (R)-2-hydroxyglutarate ((R)-2HG)...
May 17, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29769291/key-transport-and-ammonia-recycling-genes-involved-in-aphid-symbiosis-respond-to-host-plant-specialization
#6
Dohyup Kim, Bushra F Minhas, Hongmei Li-Byarlay, Allison K Hansen
Microbes are known to influence insect-plant interactions; however, it is unclear if host-plant diet influences the regulation of nutritional insect symbioses. The pea aphid, Acyrthosiphon pisum , requires its nutritional endosymbiont, Buchnera , for the production of essential amino acids. We hypothesize that key aphid genes that regulate the nutritional symbioses respond to host-plant diet when aphids feed on a specialized (alfalfa) compared to a universal host-plant diet (fava), which vary in amino acid profiles...
May 16, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29764521/amino-acid-transporter-slc7a11-xct-at-the-crossroads-of-regulating-redox-homeostasis-and-nutrient-dependency-of-cancer
#7
REVIEW
Pranavi Koppula, Yilei Zhang, Li Zhuang, Boyi Gan
Cancer cells often upregulate nutrient transporters to fulfill their increased biosynthetic and bioenergetic needs, and to maintain redox homeostasis. One nutrient transporter frequently overexpressed in human cancers is the cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11; also known as xCT). SLC7A11 promotes cystine uptake and glutathione biosynthesis, resulting in protection from oxidative stress and ferroptotic cell death. Recent studies have unexpectedly revealed that SLC7A11 also plays critical roles in glutamine metabolism and regulates the glucose and glutamine dependency of cancer cells...
April 25, 2018: Cancer communications
https://www.readbyqxmd.com/read/29763624/the-gsk3-signaling-axis-regulates-adaptive-glutamine-metabolism-in-lung-squamous-cell-carcinoma
#8
Milica Momcilovic, Sean T Bailey, Jason T Lee, Michael C Fishbein, Daniel Braas, James Go, Thomas G Graeber, Francesco Parlati, Susan Demo, Rui Li, Tonya C Walser, Michael Gricowski, Robert Shuman, Julio Ibarra, Deborah Fridman, Michael E Phelps, Karam Badran, Maie St John, Nicholas M Bernthal, Noah Federman, Jane Yanagawa, Steven M Dubinett, Saman Sadeghi, Heather R Christofk, David B Shackelford
Altered metabolism is a hallmark of cancer growth, forming the conceptual basis for development of metabolic therapies as cancer treatments. We performed in vivo metabolic profiling and molecular analysis of lung squamous cell carcinoma (SCC) to identify metabolic nodes for therapeutic targeting. Lung SCCs adapt to chronic mTOR inhibition and suppression of glycolysis through the GSK3α/β signaling pathway, which upregulates glutaminolysis. Phospho-GSK3α/β protein levels are predictive of response to single-therapy mTOR inhibition while combinatorial treatment with the glutaminase inhibitor CB-839 effectively overcomes therapy resistance...
May 14, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29763620/targeting-therapy-resistance-when-glutamine-catabolism-becomes-essential
#9
Michael J Lukey, William P Katt, Richard A Cerione
Identifying contexts in which cancer cells become addicted to specific nutrients is critical for developing targeted metabolic therapies. In this issue of Cancer Cell, Momcilovic et al. report that suppressed glycolysis following mTOR inhibition is countered by adaptive glutamine catabolism in lung squamous cell carcinoma, sensitizing tumors to glutaminase inhibition.
May 14, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29760796/b-cell-lymphoma-with-different-metabolic-characteristics-show-distinct-sensitivities-to-metabolic-inhibitors
#10
Xiaoxia Liu, Li Wang, Weiye Jiang, Wenhua Lu, Jing Yang, Wenbiao Yang
Purpose: Cancer cells exhibit profound alterations in their metabolism (abnormal glucose and glutamine metabolism). Targeting cancer metabolism is a promising therapeutic strategy. Lymphoma can be classified into many different types and it is very complicated. Therefore, in this paper, we want to know whether the B cell lymphoma cells with different metabolic characteristics have distinct sensitivities to metabolic inhibitors. Methods: We classified 9 B cell lymphoma cell lines into different metabolic subtypes according to the dependency on glutamine and glucose...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29760045/gfpt2-expressing-cancer-associated-fibroblasts-mediate-metabolic-reprogramming-in-human-lung-adenocarcinoma
#11
Weiruo Zhang, Gina Bouchard, Alice Yu, Majid Shafiq, Mehran Jamali, Joseph B Shrager, Kelsey Ayers, Shaimaa Bakr, Andrew J Gentles, Maximilian Diehn, Andrew Quon, Robert B West, Viswam Nair, Matt van de Rijn, Sandy Napel, Sylvia K Plevritis
Metabolic reprogramming of the tumor microenvironment is recognized as a cancer hallmark. To identify new molecular processes associated with tumor metabolism, we analyzed the transcriptome of bulk and flow-sorted human primary non-small cell lung cancer (NSCLC) together with 18FDG-positron emission tomography scans, which provide a clinical measure of glucose uptake. Tumors with higher glucose uptake were functionally enriched for molecular processes associated with invasion in adenocarcinoma (AD) and cell growth in squamous cell carcinoma (SCC)...
May 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/29759594/liquid-chromatography-mass-spectrometry-based-metabolomics-and-lipidomics-reveal-toxicological-mechanisms-of-bisphenol-f-in-breast-cancer-xenografts
#12
Chao Zhao, Peisi Xie, Hailin Wang, Zongwei Cai
Bisphenol F (BPF) is a major alternative to bisphenol (BPA) and has been widely used. Although BPA exposure is known to generate various toxic effects, toxicity of BPF remains under-explored. A comprehensive method involving mass spectrometry (MS)-based global lipidomics and metabolomics, and matrix-assisted laser desorption/ionization-mass spectrometry (MALDI)- MS imaging (MSI) was used to study toxic effects of BPF and the underlying mechanisms on tumor metastasis-related tissues (liver and kidney) in breast cancer xenografts...
May 5, 2018: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/29756979/prevention-of-oral-mucositis-secondary-to-antineoplastic-treatments-in-head-and-neck-cancer-by-supplementation-with-oral-glutamine
#13
Jerónimo Pachón Ibáñez, José Luis Pereira Cunill, Guiovana Fernanda Osorio Gómez, Jose Antonio Irles Rocamora, Pilar Serrano Aguayo, Begoña Quintana Ángel, José Fuentes Pradera, Manuel Chaves Conde, María José Ortiz Gordillo, Pedro Pablo García Luna
OBJECTIVES: to evaluate the efficacy of glutamine in the prevention of the incidence of oral mucositis secondary to cancer therapies in patients with head and neck cancer (HNC). Secondary objectives were to know the incidence of odynophagia, interruptions of treatment and the requirements of analgesia and nasogastric tube. MATERIAL AND METHODS: prospective cohort study of patients with squamous cell carcinoma of HNC treated with radiotherapy ± concomitant chemotherapy...
February 27, 2018: Nutrición Hospitalaria: Organo Oficial de la Sociedad Española de Nutrición Parenteral y Enteral
https://www.readbyqxmd.com/read/29755574/branched-chain-amino-acids-in-health-and-disease-metabolism-alterations-in-blood-plasma-and-as-supplements
#14
REVIEW
Milan Holeček
Branched-chain amino acids (BCAAs; valine, leucine, and isoleucine) are essential amino acids with protein anabolic properties, which have been studied in a number of muscle wasting disorders for more than 50 years. However, until today, there is no consensus regarding their therapeutic effectiveness. In the article is demonstrated that the crucial roles in BCAA metabolism play: (i) skeletal muscle as the initial site of BCAA catabolism accompanied with the release of alanine and glutamine to the blood; (ii) activity of branched-chain keto acid dehydrogenase (BCKD); and (iii) amination of branched-chain keto acids (BCKAs) to BCAAs...
2018: Nutrition & Metabolism
https://www.readbyqxmd.com/read/29753740/2-deoxy-d-glucose-increases-gfat1-phosphorylation-resulting-in-endoplasmic-reticulum-related-apoptosis-via-disruption-of-protein-n-glycosylation-in-pancreatic-cancer-cells
#15
Kousuke Ishino, Mitsuhiro Kudo, Wei-Xia Peng, Shoko Kure, Kiyoko Kawahara, Kiyoshi Teduka, Yoko Kawamoto, Taeko Kitamura, Takenori Fujii, Tetsushi Yamamoto, Ryuichi Wada, Zenya Naito
The glycolytic inhibitor 2-deoxy-d-glucose (2DG) causes energy starvation, affecting cell viability in a wide range of cancer cell lines. To determine the action of 2DG in pancreatic cancer, we performed proteomic analysis of pancreatic cancer cell line after 2DG treatment. Eighty proteins showed differential expression and among these, proteins involved in phosphohexose metabolism were upregulated. Up-regulation of glutamine: fructose 6-phosphate aminotransferase 1 (GFAT1), which belongs to the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein, was validated by evaluation of mRNA and protein levels...
May 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29752600/pancreatic-cancer-metabolism-molecular-mechanisms-and-clinical-applications
#16
REVIEW
Abdel Nasser Hosein, Muhammad Shaalan Beg
PURPOSE OF REVIEW: Pancreatic adenocarcinoma is a leading cause of cancer mortality in western countries with a uniformly poor prognosis. Unfortunately, there has been little in the way of novel therapeutics for this malignancy over the last several decades. Derangements in metabolic circuitry favoring excess glycolysis are increasingly recognized as a key hallmark of cancer. RECENT FINDINGS: The role of alterations in glutamine metabolism in pancreatic tumor progression has been elucidated in animal models and human cells lines, and there has been considerable interest in exploiting these aberrations for the treatment of pancreatic cancer...
May 11, 2018: Current Oncology Reports
https://www.readbyqxmd.com/read/29750943/metabolomics-analysis-of-the-potential-anticancer-mechanism-of-annonaceous-acetogenins-on-a-multidrug-resistant-mammary-adenocarcinoma-cell
#17
Chengyao Ma, Yue Li, Hanqing Wu, Junyang Ji, Qianqian Sun, Yilin Song, Shen Wang, Xiang Li, Yong Chen, Jianwei Chen
Although annonaceous acetogenins (ACGs) have been reported to have antitumor activity for over three decades, and many of the underlying mechanism of ACGs on cancer have been clarified, there are still outstanding issues. In particular, the changes of small metabolite in cancer cells, caused by ACGs intake, have been reported rarely. Recent research has showed that cellular metabolic profiling coupled with ultra-flow liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UFLC-Q-TOF-MS) and multivariable statistical analysis enables a good understanding of ACGs' effects on multidrug resistant human mammary adenocarcinoma (MCF-7/Adr) cells...
May 8, 2018: Analytical Biochemistry
https://www.readbyqxmd.com/read/29750207/mechanistic-insights-into-the-differential-catalysis-by-rheb-and-its-mutants-y35a-and-y35a-d65a
#18
Chaithanya Kotyada, Aditi Maulik, Anand Srivastava, Mahavir Singh
RheB GTPase is a Ras-related molecular switch, which regulates the mTOR signaling pathway by cycling between the active [guanosine triphosphate (GTP)] state and inactive [guanine diphosphate (GDP)] state. Impairment of GTPase activity because of mutations in several small GTPases is known to be associated with several cancers. The conventional GTPase mechanism such as in H-Ras requires a conserved glutamine (Q64) in the switch-II region of RheB to align the catalytic water molecule for efficient GTP hydrolysis...
October 31, 2017: ACS Omega
https://www.readbyqxmd.com/read/29733372/cnf1-like-deamidase-domains-common-lego-bricks-among-cancer-promoting-immunomodulatory-bacterial-virulence-factors
#19
Mengfei Ho, Amel Mettouchi, Brenda A Wilson, Emmanuel Lemichez
Alterations of the cellular proteome over time due to spontaneous or toxin-mediated enzymatic deamidation of glutamine (Gln) and asparagine (Asn) residues contribute to bacterial infection and might represent a source of aging-related diseases. Here, we put into perspective what is known about the mode of action of the CNF1 toxin from pathogenic E. coli, a paradigm of bacterial deamidases that activate Rho GTPases, to illustrate the importance of determining whether exposure to these factors are risk factors in the etiology age-related diseases, such as cancer...
May 3, 2018: Pathogens and Disease
https://www.readbyqxmd.com/read/29730197/heat-shock-factor-1-epigenetically-stimulates-glutaminase-1-dependent-mtor-activation-to-promote-colorectal-carcinogenesis
#20
Jiaqiu Li, Ping Song, Tingting Jiang, Dongjun Dai, Hanying Wang, Jie Sun, Liyuan Zhu, Wenxia Xu, Lifeng Feng, Vivian Y Shin, Helen Morrison, Xian Wang, Hongchuan Jin
Heat shock factor 1 (HSF1) generally exhibits its properties under stress conditions. In tumors, HSF1 has a pleiotropic feature in regulating growth, survival, and aggressiveness of cancer cells. In this study, we found HSF1 was increased in colorectal cancer (CRC) and had a positive correlation with shorter disease-free survival (DFS). Knockdown of HSF1 in CRC cells attenuated their growth while inhibiting mTOR activation and glutamine metabolism. HSF1 inhibited the expression of microRNA137 (MIR137), which targeted GLS1 (glutaminase 1), thus stimulating GLS1 protein expression to promote glutaminolysis and mTOR activation...
April 14, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
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