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Glutamine cancer

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https://www.readbyqxmd.com/read/29662176/cancer-cell-secreted-exosomal-mir-105-promotes-tumour-growth-through-the-myc-dependent-metabolic-reprogramming-of-stromal-cells
#1
Wei Yan, Xiwei Wu, Weiying Zhou, Miranda Y Fong, Minghui Cao, Juan Liu, Xiaojing Liu, Chih-Hong Chen, Oluwole Fadare, Donald P Pizzo, Jiawen Wu, Liang Liu, Xuxiang Liu, Andrew R Chin, Xiubao Ren, Yuan Chen, Jason W Locasale, Shizhen Emily Wang
Cancer and other cells residing in the same niche engage various modes of interactions to synchronize and buffer the negative effects of environmental changes. Extracellular microRNAs (miRNAs) have recently been implicated in the intercellular crosstalk. Here we show a mechanistic model involving breast-cancer-secreted, extracellular-vesicle-encapsulated miR-105, which is induced by the oncoprotein MYC in cancer cells and, in turn, activates MYC signalling in cancer-associated fibroblasts (CAFs) to induce a metabolic program...
April 16, 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29662010/metabolic-features-of-multiple-myeloma
#2
REVIEW
Chaima El Arfani, Kim De Veirman, Ken Maes, Elke De Bruyne, Eline Menu
Cancer is known for its cellular changes contributing to tumour growth and cell proliferation. As part of these changes, metabolic rearrangements are identified in several cancers, including multiple myeloma (MM), which is a condition whereby malignant plasma cells accumulate in the bone marrow (BM). These metabolic changes consist of generation, inhibition and accumulation of metabolites and metabolic shifts in MM cells. Changes in the BM micro-environment could be the reason for such adjustments. Enhancement of glycolysis and glutaminolysis is found in MM cells compared to healthy cells...
April 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29661856/glutamine-utilizing-transaminases-are-a-metabolic-vulnerability-of-taz-yap-activated-cancer-cells
#3
Chih-Sheng Yang, Eleni Stampouloglou, Nathan M Kingston, Liye Zhang, Stefano Monti, Xaralabos Varelas
The transcriptional regulators TAZ and YAP (TAZ/YAP) have emerged as pro-tumorigenic factors that drive many oncogenic traits, including induction of cell growth, resistance to cell death, and activation of processes that promote migration and invasion. Here, we report that TAZ/YAP reprogram cellular energetics to promote the dependence of breast cancer cell growth on exogenous glutamine. Rescue experiments with glutamine-derived metabolites suggest an essential role for glutamate and α-ketoglutarate (AKG) in TAZ/YAP-driven cell growth in the absence of glutamine...
April 16, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29642388/oligodendroglioma-cells-lack-glutamine-synthetase-and-are-auxotrophic-for-glutamine-but-do-not-depend-on-glutamine-anaplerosis-for-growth
#4
Martina Chiu, Giuseppe Taurino, Massimiliano G Bianchi, Laura Ottaviani, Roberta Andreoli, Tecla Ciociola, Costanza A M Lagrasta, Saverio Tardito, Ovidio Bussolati
In cells derived from several types of cancer, a transcriptional program drives high consumption of glutamine (Gln), which is used for anaplerosis, leading to a metabolic addiction for the amino acid. Low or absent expression of Glutamine Synthetase (GS), the only enzyme that catalyzes de novo Gln synthesis, has been considered a marker of Gln-addicted cancers. In this study, two human cell lines derived from brain tumors with oligodendroglioma features, HOG and Hs683, have been shown to be GS-negative. Viability of both lines depends from extracellular Gln with EC50 of 0...
April 6, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29628997/cancer-metabolism-new-insights-into-classic-characteristics
#5
REVIEW
Yasumasa Kato, Toyonobu Maeda, Atsuko Suzuki, Yuh Baba
Initial studies of cancer metabolism in the early 1920s found that cancer cells were phenotypically characterized by aerobic glycolysis, in that these cells favor glucose uptake and lactate production, even in the presence of oxygen. This property, called the Warburg effect, is considered a hallmark of cancer. The mechanism by which these cells acquire aerobic glycolysis has been uncovered. Acidic extracellular fluid, secreted by cancer cells, induces a malignant phenotype, including invasion and metastasis...
February 2018: Japanese Dental Science Review
https://www.readbyqxmd.com/read/29627862/a-phase-ii-study-of-hmb-arg-gln-against-oral-mucositis-induced-by-chemoradiotherapy-for-patients-with-head-and-neck-cancer
#6
Tomoya Yokota, Satoshi Hamauchi, Yukio Yoshida, Takashi Yurikusa, Miho Suzuki, Aiko Yamashita, Hirofumi Ogawa, Tsuyoshi Onoe, Keita Mori, Tetsuro Onitsuka
PURPOSE: This phase II trial assessed the clinical benefit of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine (HMB/Arg/Gln) for preventing chemoradiotherapy (CRT)-induced oral mucositis (OM) in patients with head and neck cancer (HNC). METHODS: Patients with HNC receiving definitive or postoperative cisplatin-based CRT were enrolled. HMB/Arg/Gln was administered orally or per percutaneous endoscopic gastrostomy from the first day of CRT up to its completion...
April 7, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/29626382/discriminating-gastric-cancer-and-gastric-ulcer-using-human-plasma-amino-acid-metabolic-profile
#7
Fangyu Jing, Xin Hu, Yunfeng Cao, Minghao Xu, Yuanyuan Wang, Yu Jing, Xiaodan Hu, Yu Gao, Zhitu Zhu
Patients with gastric ulcer (GU) have a significantly higher risk of developing gastric cancer (GC), especially within 2 years after diagnosis. The main way to improve the prognosis of GC is to predict the tumorigenesis and metastasis in the early stage. The objective of this study was to demonstrate the ability of human plasma amino acid metabolic profile for discriminating GC and GU. In this study, we first used liquid chromatography-tandem mass spectrometry technique to characterize the plasma amino acid metabolism in GC and GU patients...
April 6, 2018: IUBMB Life
https://www.readbyqxmd.com/read/29620160/metabolome-analysis-of-esophageal-cancer-tissues-using-capillary-electrophoresis-time-of-flight-mass-spectrometry
#8
Masanori Tokunaga, Kenjiro Kami, Soji Ozawa, Junya Oguma, Akihito Kazuno, Hayato Miyachi, Yoshiaki Ohashi, Masatoshi Kusuhara, Masanori Terashima
Reports of the metabolomic characteristics of esophageal cancer are limited. In the present study, we thus conducted metabolome analysis of paired tumor tissues (Ts) and non-tumor esophageal tissues (NTs) using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). The Ts and surrounding NTs were surgically excised pair-wise from 35 patients with esophageal cancer. Following tissue homogenization and metabolite extraction, a total of 110 compounds were absolutely quantified by CE-TOFMS. We compared the concentrations of the metabolites between Ts and NTs, between pT1 or pT2 (pT1-2) and pT3 or pT4 (pT3-4) stage, and between node-negative (pN-) and node-positive (pN+) samples...
March 28, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29617730/ovarian-cancer-therapeutic-potential-of-glutamine-depletion-based-on-gs-expression
#9
Akiko Furusawa, Morikazu Miyamoto, Masashi Takano, Hitoshi Tsuda, Yong Sang Song, Daisuke Aoki, Naoyuki Miyasaka, Johji Inazawa, Jun Inoue
Amino acids (AAs) are biologically important nutrient compounds necessary for the survival of any cell. Of the 20 AAs, cancer cells depend on the uptake of several extracellular AAs for survival. However, which extracellular AA is indispensable for the survival of cancer cells and the molecular mechanism involved have not been fully defined. In this study, we found that the reduction of cell survival caused by glutamine (Gln) depletion is inversely correlated with the expression level of glutamine synthetase (GS) in ovarian cancer (OVC) cells...
April 2, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29605436/the-role-of-za-channel-water-mediated-interactions-in-the-design-of-bromodomain-selective-bet-inhibitors
#10
Nagakumar Bharatham, Peter J Slavish, Brandon M Young, Anang A Shelat
The Bromodomain and Extra-Terminal domain (BET) family of proteins are involved in the regulation of gene transcription, and their dysregulation is implicated in several diseases including cancer. BET proteins contain two tandem bromodomains (BD1 and BD2) that independently recognize acetylated-lysine residues and appear to have distinct biological roles. We compared several published co-crystal structures and found five positions near the substrate binding pocket that vary between BET bromodomains. One position located in the ZA loop has unique properties...
March 22, 2018: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29601126/expression-of-cytosolic-malic-enzyme-me1-is-associated-with-disease-progression-in-human-oral-squamous-cell-carcinoma
#11
Chie Nakashima, Kazuhiko Yamamoto, Rina Fujiwara-Tani, Yi Luo, Sayako Matsushima, Kiyomu Fujii, Hitoshi Ohmori, Tomonori Sasahira, Takamitsu Sasaki, Yasuhiko Kitadai, Tadaaki Kirita, Hiroki Kuniyasu
Malic enzyme 1 (ME1) is a multifunctional protein involved in glycolysis, the citric acid cycle, NADPH production, glutamine metabolism, and lipogenesis. It is overexpressed in various cancers. We examined the expression of ME1 in 119 oral squamous cell carcinomas (OSCCs) via immunohistochemistry. ME1 expression was moderate to strong expression in 57 (48%) OSCCs and correlated with pT, pN, clinical stage, and histological grade. In 37 cases with prognostic evaluation, moderate to strong ME1 expression indicated a worse prognosis than did weak ME1 expression...
March 30, 2018: Cancer Science
https://www.readbyqxmd.com/read/29599338/trap1-inhibition-increases-glutamine-synthetase-activity-in-glutamine-auxotrophic-non-small-cell-lung-cancer-cells
#12
Vu T A Vo, Jong-Whan Choi, Ai N H Phan, Tuyen N M Hua, Min-Kyu Kim, Byoung Heon Kang, Soon-Hee Jung, Suk-Joong Yong, Yangsik Jeong
BACKGROUND/AIM: Cancer cells are distinct in terms of glutamine dependence. Here we investigated the different susceptibility of glutamine-independent and glutamine-dependent non-small cell lung cancer (NSCLC) to treatment with tumor necrosis factor receptor-associated protein 1 (TRAP1) inhibitor gamitrinib-triphenylphosphonium (G-TPP). MATERIALS AND METHODS: Cell viability and proliferation under glutamine deprivation and G-TPP treatment were determined by the MTT and colony-formation assays...
April 2018: Anticancer Research
https://www.readbyqxmd.com/read/29594839/o-glcnac-in-cancer-an-oncometabolism-fueled-vicious-cycle
#13
REVIEW
John A Hanover, Weiping Chen, Michelle R Bond
Cancer cells exhibit unregulated growth, altered metabolism, enhanced metastatic potential and altered cell surface glycans. Fueled by oncometabolism and elevated uptake of glucose and glutamine, the hexosamine biosynthetic pathway (HBP) sustains glycosylation in the endomembrane system. In addition, the elevated pools of UDP-GlcNAc drives the O-GlcNAc modification of key targets in the cytoplasm, nucleus and mitochondrion. These targets include transcription factors, kinases, key cytoplasmic enzymes of intermediary metabolism, and electron transport chain complexes...
March 29, 2018: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/29575012/high-expression-of-glutamate-ammonia-ligase-is-associated-with-unfavorable-prognosis-in-patients-with-ovarian-cancer
#14
Shaohua Fan, Yanyan Wang, Zifeng Zhang, Jun Lu, Zhiyong Wu, Qun Shan, Chunhui Sun, Dongmei Wu, Mengqiu Li, Ning Sheng, Ying Xie, Yuanlin Zheng
Glutamate-ammonia ligase (GLUL), which is also called GS (glutamine synthetase), is the enzyme that catalyzes the synthesis of glutamine from glutamate and ammonia in an ATP-dependent reaction. Here, we found higher expression of GLUL in the ovarian cancer patients was associated with worse disease-free survival (DFS) and overall survival (OS). In addition, GLUL was heterogeneously expressed in various ovarian cancer cells. The mRNA and protein expression levels of GLUL in NIH:OVCAR-3 and ES-2 cells were obviously higher than that in the other types of ovarian cancer cells...
March 25, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29569872/concomitant-use-of-heat-shock-protein-70-glutamine-synthetase-and-glypican-3-is-useful-in-diagnosis-of-hbv-related-hepatocellular-carcinoma-with-higher-specificity-and-sensitivity
#15
Bita Moudi, Zahra Heidari, Hamidreza Mahmoudzadeh-Sagheb, Seyed-Moayed Alavian, Kamran B Lankarani, Parisa Farrokh, Jens Randel Nyengaard
Hepatocellular carcinoma is the third leading cause of cancer-related death worldwide and late diagnosis is the main cause of death in HCC patients. In this study expression patterns of HSP70, GPC3 and GS and their relationships with pathogenesis of HCC in Iranian patients were investigated. The expression of HSP70, GPC3 and GS were determined by immunohistochemistry and quantitative real-time PCR (q-PCR) methods, using 121 cases from patients with HBV alone, HCC without HBV, HBV+HCC and 30 normal tissues as control group...
January 29, 2018: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/29569717/the-effect-of-fasn-inhibition-on-the-growth-and-metabolism-of-a-cisplatin-resistant-ovarian-carcinoma-model
#16
Efthymia Papaevangelou, Gilberto S Almeida, Carol Box, Nandita M deSouza, Yuen-Li Chung
Overexpression of fatty acid synthase (FASN), a key regulator of the de novo synthesis of fatty acids, has been demonstrated in a variety of cancers and is associated with poor prognosis and increased multidrug resistance. Inhibition of FASN with the anti-obesity drug orlistat has been shown to have significant anti-tumorigenic effects in many cancers, notably breast and prostate. In this study, we investigated whether FASN inhibition using orlistat is an effective adjunctive treatment for ovarian cancers that have become platinum resistant using a cisplatin-resistant ovarian tumour xenograft model in mice...
March 23, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29563155/sorting-nexin-27-snx27-regulates-the-trafficking-and-activity-of-the-glutamine-transporter-asct2
#17
Zhe Yang, Jordan Follett, Markus C Kerr, Thomas Clairfeuille, Mintu Chandra, Brett M Collins, Rohan D Teasdale
The Alanine, Serine, Cysteine-preferring Transporter 2 (ASCT2; SLC1A5) is responsible for the uptake of glutamine into cells, a major source of cellular energy and a key regulator of mammalian Target of Rapamycin (mTOR) activation. Furthermore, ASCT2 expression has reported in several human cancers making it a potential target for both diagnostic and therapeutic purposes. Here we identify ASCT2 as a membrane trafficked cargo molecule, sorted through a direct interaction with the PDZ domain of Sorting Nexin 27 (SNX27)...
March 21, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29562706/amino-acid-transporters-and-glutamine-metabolism-in-breast-cancer
#18
REVIEW
Yoon Jin Cha, Eun-Sol Kim, Ja Seung Koo
Amino acid transporters are membrane transport proteins, most of which are members of the solute carrier families. Amino acids are essential for the survival of all types of cells, including tumor cells, which have an increased demand for nutrients to facilitate proliferation and cancer progression. Breast cancer is the most common malignancy in women worldwide and is still associated with high mortality rates, despite improved treatment strategies. Recent studies have demonstrated that the amino acid metabolic pathway is altered in breast cancer and that amino acid transporters affect tumor growth and progression...
March 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29555211/inhibition-of-mtor-complexes-protects-cancer-cells-from-glutamine-starvation-induced-cell-death-by-restoring-akt-stability
#19
Wasim Khan, Brian T Layden, Partha Chakrabarti
Glutamine, a well-established oncometabolite, anaplerotically fuels mitochondrial energy metabolism and modulates activity of mammalian/mechanistic target of rapamycin complexes (mTOR). Currently, mTOR inhibitors are in clinical use for certain types of cancer but with limited success. Since glutamine is essential for growth of many cancers, we reasoned that glutamine deprivation under conditions of mTOR inhibition should be more detrimental to cancer cell survival. However, our results show that when cells are deprived of glutamine concomitant with mTOR inhibition, hepatocarcinoma cells elicit an adaptive response which aids in their survival due to enhanced autophagic flux...
March 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29545929/metabolic-profiles-of-triple-negative-and-luminal-a-breast-cancer-subtypes-in-african-american-identify-key-metabolic-differences
#20
Fariba Tayyari, G A Nagana Gowda, Olufunmilayo F Olopade, Richard Berg, Howard H Yang, Maxwell P Lee, Wilfred F Ngwa, Suresh K Mittal, Daniel Raftery, Sulma I Mohammed
Breast cancer, a heterogeneous disease with variable pathophysiology and biology, is classified into four major subtypes. While hormonal- and antibody-targeted therapies are effective in the patients with luminal and HER-2 subtypes, the patients with triple-negative breast cancer (TNBC) subtype do not benefit from these therapies. The incidence rates of TNBC subtype are higher in African-American women, and the evidence indicates that these women have worse prognosis compared to women of European descent. The reasons for this disparity remain unclear but are often attributed to TNBC biology...
February 20, 2018: Oncotarget
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