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Cancer AND glutamine

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https://www.readbyqxmd.com/read/27913195/breast-cancer-derived-extracellular-vesicles-stimulate-myofibroblast-differentiation-and-pro-angiogenic-behavior-of-adipose-stem-cells
#1
REVIEW
Young Hye Song, Christine Warncke, Sung Jin Choi, Siyoung Choi, Aaron E Chiou, Lu Ling, Han-Yuan Liu, Susan Daniel, Marc A Antonyak, Richard A Cerione, Claudia Fischbach
Adipose-derived stem cells (ASCs) are abundantly present in the mammary microenvironment and can promote breast cancer malignancy by differentiating into myofibroblasts. However, it remains largely unclear which role tumor-derived extracellular vesicles (TEVs) play in this process. Here, we used microfabricated, type I collagen-based 3-D tissue culture platforms to investigate the effect of breast cancer cell-derived TEVs on ASCs myofibroblast differentiation and consequential changes in extracellular matrix remodeling and vascular sprouting...
November 29, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27908619/correlation-of-dna-repair-gene-polymorphisms-with-clinical-outcome-in-patients-with-locally-advanced-non-small-cell-lung-cancer-receiving-induction-chemotherapy-followed-by-surgery
#2
Mariacarmela Santarpia, Jose Luis Ramirez, Itziar de Aguirre, Pilar Garrido, Maria Pérez Cano, Cristina Queralt, Jose Luis Gonzalez-Larriba, Amelia Insa, Mariano Provencio, Dolores Isla, Carlos Camps, Remei Blanco, Teresa Moran, Rafael Rosell
OBJECTIVE: The aim of this study was to evaluate whether xeroderma pigmentosum group D (XPD) and ribonucleotide reductase subunit M1 (RRM1) polymorphisms influenced clinical outcome in patients with stage IIIA-B non-small-cell lung cancer (NSCLC) treated with neoadjuvant gemcitabine/cisplatin/docetaxel followed by surgery. MATERIALS AND METHODS: A total of 109 patients with stage IIIA and IIIB NSCLC were prospectively genotyped to examine a potential association between XPD 312 (aspartic acid [Asp]/asparagine [Asn]), XPD 751 (lysine [Lys]/glutamine [Gln]), and RRM1 (-37 C/A) polymorphisms with response and survival...
November 9, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27902968/selenite-inhibits-glutamine-metabolism-and-induces-apoptosis-by-regulating-gls1-protein-degradation-via-apc-c-cdh1-pathway-in-colorectal-cancer-cells
#3
Junzhang Zhao, Rui Zhou, Kaiyuan Hui, Yang Yang, QiuYue Zhang, Yali Ci, Lei Shi, Caimin Xu, Fang Huang, Yu Hu
Glutaminolysis is important for metabolism and biosynthesis of cancer cells, and GLS is essential in the process. Selenite is widely regarded as a chemopreventive agent against cancer risk. Emerging evidence suggests that it also has chemotherapeutic potential in various cancer types, but the mechanism remains elusive. We demonstrate for the first time that supranutritional dose of selenite suppresses glutaminolysis by promoting GLS1 protein degradation and apoptosis. Mechanistically, selenite promotes association of APC/C-CDH1 with GLS1 and leads to GLS1 degradation by ubiquitination, this process is related to induction of PTEN expression...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27898344/may-glutamine-addiction-drive-the-delivery-of-antitumor-cisplatin-based-pt-iv-prodrugs
#4
Mauro Ravera, Elisabetta Gabano, Stefano Tinello, Ilaria Zanellato, Domenico Osella
A small series of Pt(IV) prodrugs containing Gln-like (Gln=glutamine) axial ligands has been designed with the aim to take advantage of the increased demand of Gln showed by some cancer cells (glutamine addiction). In complex 4 the Gln, linked through the α-carboxylic group is recognized by the Gln transporters, in particular by the solute carrier transporter SLC1A5. All compounds showed cellular accumulation, as well as antiproliferative activity, related to their lipophilicity, as already demonstrated for the majority of Pt(IV) prodrugs, that enter cells mainly by passive diffusion...
November 17, 2016: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/27897391/a-systematic-review-on-the-role-of-vitamins-minerals-proteins-and-other-supplements-for-the-treatment-of-cachexia-in-cancer-a-european-palliative-care-research-centre-cachexia-project
#5
REVIEW
Mochamat, Henning Cuhls, Milka Marinova, Stein Kaasa, Christiane Stieber, Rupert Conrad, Lukas Radbruch, Martin Mücke
We provide a systematic review to support the European Palliative Care Research Collaboration development of clinical guidelines for cancer patients suffering from cachexia. CENTRAL, MEDLINE, PsycINFO, ClinicalTrials.gov, and a selection of cancer journals have been searched up until 15 April 2016. The systematic literature research yielded 4214 publications with 21 of these included in the final evaluation. Regarding minerals, our search identified only one study examining the use of magnesium with no effect on weight loss...
July 20, 2016: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/27894844/the-tricarboxylic-acid-cycle-activity-in-cultured-primary-astrocytes-is-strongly-accelerated-by-the-protein-tyrosine-kinase-inhibitor-tyrphostin-23
#6
Michaela C Hohnholt, Eva-Maria Blumrich, Helle S Waagepetersen, Ralf Dringen
Tyrphostin 23 (T23) is a well-known inhibitor of protein tyrosine kinases and has been considered as potential anti-cancer drug. T23 was recently reported to acutely stimulate the glycolytic flux in primary cultured astrocytes. To investigate whether T23 also affects the tricarboxylic acid (TCA) cycle, we incubated primary rat astrocyte cultures with [U-(13)C]glucose in the absence or the presence of 100 μM T23 for 2 h and analyzed the (13)C metabolite pattern. These incubation conditions did not compromise cell viability and confirmed that the presence of T23 doubled glycolytic lactate production...
November 25, 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27892481/autophagy-is-required-for-pdac-glutamine-metabolism
#7
Ju-Won Seo, Jungwon Choi, So-Yeon Lee, Suhyun Sung, Hyun Ju Yoo, Min-Ji Kang, Heesun Cheong, Jaekyoung Son
Macroautophagy (autophagy) is believed to maintain energy homeostasis by degrading unnecessary cellular components and molecules. Its implication in regulating cancer metabolism recently started to be uncovered. However, the precise roles of autophagy in cancer metabolism are still unclear. Here, we show that autophagy plays a critical role in glutamine metabolism, which is required for tumor survival. Pancreatic ductal adenocarcinoma (PDAC) cells require both autophagy and typical glutamine transporters to maintain intracellular glutamine levels...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27890529/mass-spectrometry-analysis-shows-the-biosynthetic-pathways-supported-by-pyruvate-carboxylase-in-highly-invasive-breast-cancer-cells
#8
Phatchariya Phannasil, Israr-Ul H Ansari, Mahmoud El Azzouny, Melissa J Longacre, Khanti Rattanapornsompong, Charles F Burant, Sarawut Jitrapakdee, Michael J MacDonald
We recently showed that the anaplerotic enzyme pyruvate carboxylase (PC) is up-regulated in human breast cancer tissue and its expression is correlated with the late stages of breast cancer and tumor size [Phannasil et al., PloS One 10, e0129848, 2015]. In the current study we showed that PC enzyme activity is much higher in the highly invasive breast cancer cell line MDA-MB-231 than in less invasive breast cancer cell lines. We generated multiple stable PC knockdown cell lines from the MDA-MB-231 cell line and used mass spectrometry with (13)C6-glucose and (13)C5-glutamine to discern the pathways that use PC in support of cell growth...
November 23, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27882349/the-airway-epithelium-undergoes-metabolic-reprogramming-in-individuals-at-high-risk-for-lung-cancer
#9
S M Jamshedur Rahman, Xiangming Ji, Lisa J Zimmerman, Ming Li, Bradford K Harris, Megan D Hoeksema, Irina A Trenary, Yong Zou, Jun Qian, Robbert J C Slebos, Jennifer Beane, Avrum Spira, Yu Shyr, Rosana Eisenberg, Daniel C Liebler, Jamey D Young, Pierre P Massion
The molecular determinants of lung cancer risk remain largely unknown. Airway epithelial cells are prone to assault by risk factors and are considered to be the primary cell type involved in the field of cancerization. To investigate risk-associated changes in the bronchial epithelium proteome that may offer new insights into the molecular pathogenesis of lung cancer, proteins were identified in the airway epithelial cells of bronchial brushing specimens from risk-stratified individuals by shotgun proteomics...
November 17, 2016: JCI Insight
https://www.readbyqxmd.com/read/27872968/new-functions-and-potential-applications-of-amino-acids
#10
Hisayuki Uneyama, Hisamine Kobayashi, Naoto Tonouchi
Currently, several types of amino acids are being produced and used worldwide. Nevertheless, several new functions of amino acids have been recently discovered that could result in other applications. For example, oral stimulation by glutamate triggers the cephalic phase response to prepare for food digestion. Further, the stomach and intestines have specific glutamate-recognizing systems in their epithelial mucosa. Regarding clinical applications, addition of monosodium glutamate to the medicinal diet has been shown to markedly enhance gastric secretion in a vagus-dependent manner...
November 22, 2016: Advances in Biochemical Engineering/biotechnology
https://www.readbyqxmd.com/read/27865832/establishment-of-monoclonal-antibodies-against-cell-surface-domains-of-asct2-slc1a5-and-their-inhibition-of-glutamine-dependent-tumor-cell-growth
#11
Masayo Suzuki, Hiroe Toki, Akiko Furuya, Hiroshi Ando
Human alanine-serine-cysteine transporter 2 (ASCT2; SLC1A5) is a major transporter of the amino acid glutamine that is known to be overexpressed in certain malignant tumors. In this study, we generated specific monoclonal antibodies (MAbs) against ASCT2 by establishing an ASCT2-expressing Chinese hamster ovary cell line that was used to immunize mice and rats. The MAbs KM4008, KM4012, and KM4018 against ASCT2 were isolated through a cell-based screen; these specifically bound to ASCT2-positive cells, as determined by flow cytometry and immunoprecipitation...
November 16, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27863447/hepatitis-c-virus-infection-triggers-a-tumor-like-glutamine-metabolism
#12
Pierre L Lévy, Sarah Duponchel, Hannah Eischeid, Jennifer Molle, Maud Michelet, Gaëlle Diserens, Martina Vermathen, Peter Vermathen, Jean-Francois Dufour, Hans-Peter Dienes, Hans-Michael Steffen, Margarete Odenthal, Fabien Zoulim, Birke Bartosch
Chronic infection with hepatitis C virus (HCV) is one of the main causes of hepatocellular carcinoma. However, the molecular mechanisms linking the infection to cancer development remain poorly understood. Here we used HCV-infected cells and liver biopsies to study how HCV modulates the glutaminolysis pathway, which is known to play an important role in cellular energetics, stress defense and neoplastic transformation. Transcript levels of glutaminolytic factors were quantified in Huh7.5 cells or primary human hepatocytes infected with the JFH1 HCV strain as well as in biopsies of chronic HCV patients...
November 18, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27860485/an-update-on-the-use-of-benzoate-phenylacetate-and-phenylbutyrate-ammonia-scavengers-for-interrogating-and-modifying-liver-nitrogen-metabolism-and-its-implications-in-urea-cycle-disorders-and-liver-disease
#13
Javier de Las Heras, Luis Aldámiz-Echevarría, María-Luz Martínez-Chantar, Teresa C Delgado
Ammonia-scavenging drugs, benzoate and phenylacetate (PA)/phenylbutyrate (PB), modulate hepatic nitrogen metabolism mainly by providing alternative pathways for nitrogen disposal. Areas Covered: We review the major findings and potential novel applications of ammonia-scavenging drugs, focusing on urea cycle disorders and liver disease. Expert Opinion: For over 40 years, ammonia-scavenging drugs have been used in the treatment of urea cycle disorders. Recently, the use of these compounds has been advocated in acute liver failure and cirrhosis for reducing hyperammonemic-induced hepatic encephalopathy...
November 18, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27856334/quantitative-metabolic-flux-analysis-reveals-an-unconventional-pathway-of-fatty-acid-synthesis-in-cancer-cells-deficient-for-the-mitochondrial-citrate-transport-protein
#14
Lei Jiang, Adam Boufersaoui, Chendong Yang, Bookyung Ko, Dinesh Rakheja, Gerardo Guevara, Zeping Hu, Ralph J DeBerardinis
The mitochondrial citrate transport protein (CTP), encoded by SLC25A1, accommodates bidirectional trafficking of citrate between the mitochondria and cytosol, supporting lipid biosynthesis and redox homeostasis. Genetic CTP deficiency causes a fatal neurodevelopmental syndrome associated with the accumulation of L- and D-2-hydroxyglutaric acid, and elevated CTP expression is associated with poor prognosis in several types of cancer, emphasizing the importance of this transporter in multiple human pathologies...
November 14, 2016: Metabolic Engineering
https://www.readbyqxmd.com/read/27847310/dual-loss-of-succinate-dehydrogenase-sdh-and-complex-i-activity-is-necessary-to-recapitulate-the-metabolic-phenotype-of-sdh-mutant-tumors
#15
Doriane Lorendeau, Gianmarco Rinaldi, Ruben Boon, Pieter Spincemaille, Kristine Metzger, Christian Jäger, Stefan Christen, Xiangyi Dong, Sabine Kuenen, Karin Voordeckers, Patrik Verstreken, David Cassiman, Pieter Vermeersch, Catherine Verfaillie, Karsten Hiller, Sarah-Maria Fendt
Mutations in succinate dehydrogenase (SDH) are associated with tumor development and neurodegenerative diseases. Only in tumors, loss of SDH activity is accompanied with the loss of complex I activity. Yet, it remains unknown whether the metabolic phenotype of SDH mutant tumors is driven by loss of complex I function, and whether this contributes to the peculiarity of tumor development versus neurodegeneration. We addressed this question by decoupling loss of SDH and complex I activity in cancer cells and neurons...
November 12, 2016: Metabolic Engineering
https://www.readbyqxmd.com/read/27835669/the-glutaminase-1-inhibitor-968-enhances-dihydroartemisinin-mediated-antitumor-efficacy-in-hepatocellular-carcinoma-cells
#16
Diancheng Wang, Gang Meng, Meihong Zheng, Yonghui Zhang, Aiping Chen, Junhua Wu, Jiwu Wei
Reprogrammed metabolism and redox homeostasis are potential targets of cancer therapy. Our previous study demonstrated that the kidney form of glutaminase (GLS1) is highly expressed in hepatocellular carcinoma (HCC) cells and can be used as a target for effective anticancer therapy. Dihydroartemisinin (DHA) increases intracellular reactive oxygen species (ROS) levels leading to cytotoxicity in cancer cells. However, the heterogeneity of cancer cells often leads to differing responses to oxidative lesions. For instance, cancer cells with high ratio of GSH/GSSG, a critical ROS scavenger, are resistant to ROS-induced cytotoxicity...
2016: PloS One
https://www.readbyqxmd.com/read/27833036/metabolic-reprogramming-of-carcinoma-associated-fibroblasts-and-its-impact-on-metabolic-heterogeneity-of-tumors
#17
REVIEW
Duojiao Wu, Leying Zhuo, Xiangdong Wang
Tumor metabolism is characterized with up-regulated glucose uptake and glycolytic rate of tumor cells as the source of ATP and tumors growth, and regulated by a poorly defined combination of cell-intrinsic and extrinsic factors.Metabolic heterogeneity of human tumors is dependent upon the mutational status of specific oncogenes and influenced by tumor microenvironment.Carcinoma-associated fibroblasts (CAFs) adapt in a dynamic manner to the metabolic needs of cancer cells, associated with tumorigenesis and resistance to treatments...
November 7, 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27830395/glutamine-for-the-treatment-of-vincristine-induced-neuropathy-in-children-and-adolescents-with-cancer
#18
Stephen Sands, Elena J Ladas, Kara M Kelly, Michael Weiner, Meiko Lin, Deborah Hughes Ndao, Amie Dave, Linda T Vahdat, Julia Glade Bender
BACKGROUND: Vincristine is an integral treatment component of many childhood tumors with potentially dose-limiting sensory and/or motor neuropathy. Results from a pilot study on the incidence of vincristine-induced peripheral neuropathy (VIPN) as well as the efficacy and safety of glutamine in reducing signs and symptoms of VIPN in children with cancer are presented. METHODS: Fifty-six patients between the ages of 5-21 with newly diagnosed leukemia, lymphoma, extracranial solid tumor or medulloblastoma and expected to receive a minimum cumulative dose of 6 mg/m(2) of vincristine over a 30-week period were eligible...
November 9, 2016: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/27830380/recovery-of-pan-genotypic-and-genotype-specific-amino-acid-alterations-in-chronic-hepatitis-c-after-viral-clearance-transition-at-the-crossroad-of-metabolism-and-immunity
#19
Ming-Ling Chang, Mei-Ling Cheng, Su-Wei Chang, Hsiang-Yu Tang, Cheng-Tang Chiu, Chau-Ting Yeh, Ming-Shi Shiao
Recovery of amino acid (AA) metabolism and the associated clinical implications in chronic hepatitis C (CHC) patients with sustained virological response (SVR) following anti-hepatitis C virus (HCV) therapy remains elusive. A prospective cohort study was conducted on 222 CHC patients with SVR. Eighty-two age-matched male genotype 1 (G1) and G2 patients underwent paired serum metabolomics analyses with liquid chromatography-tandem mass spectrometry to examine AAs before and 24 weeks after anti-HCV therapy. Before anti-HCV therapy, G1 patients had a higher HCV RNA level than G2 patients...
November 10, 2016: Amino Acids
https://www.readbyqxmd.com/read/27830010/glutaminase-inhibitor-compound-968-inhibits-cell-proliferation-and-sensitizes-paclitaxel-in-ovarian-cancer
#20
Lingqin Yuan, Xiugui Sheng, Leslie H Clark, Lu Zhang, Hui Guo, Hannah M Jones, Adam K Willson, Paola A Gehrig, Chunxiao Zhou, Victoria L Bae-Jump
Our overall goal was to investigate the anti-tumor activity of the glutaminase 1 (GLS1) Inhibitor compound 968 in ovarian cancer cells. The human ovarian cancer cell lines, HEY, SKOV3 and IGROV-1 were used. Cell proliferation was assessed by MTT assay after treatment with compound 968. Cell cycle progression and Annexin V expression were evaluated using Cellometer. Western blotting was performed to determine changes in GLS1, cellular stress and cell cycle checkpoints. Reactive oxygen species (ROS) and glutamate dehydrogenase (GDH) activity were assessed by ELISA assay...
2016: American Journal of Translational Research
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