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Cancer AND glutamine

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https://www.readbyqxmd.com/read/28087332/exo-mfa-a-13c-metabolic-flux-analysis-to-dissect-tumor-microenvironment-secreted-exosome-contributions-towards-cancer-cell-metabolism
#1
Abhinav Achreja, Hongyun Zhao, Lifeng Yang, Tae Hyun Yun, Juan Marini, Deepak Nagrath
Dissecting the pleiotropic roles of tumor micro-environment (TME) on cancer progression has been brought to the foreground of research on cancer pathology. Extracellular vesicles such as exosomes, transport proteins, lipids, and nucleic acids, to mediate intercellular communication between TME components and have emerged as candidates for anti-cancer therapy. We previously reported that cancer-associated fibroblast (CAF) derived exosomes (CDEs) contain metabolites in their cargo that are utilized by cancer cells for central carbon metabolism and promote cancer growth...
January 10, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28074323/changes-in-cerebral-metabolism-during-ketogenic-diet-in-patients-with-primary-brain-tumors-1-h-mrs-study
#2
Moran Artzi, Gilad Liberman, Nachum Vaisman, Felix Bokstein, Faina Vitinshtein, Orna Aizenstein, Dafna Ben Bashat
Normal brain cells depend on glucose metabolism, yet they have the flexibility to switch to the usage of ketone bodies during caloric restriction. In contrast, tumor cells lack genomic and metabolic flexibility and are largely dependent on glucose. Ketogenic-diet (KD) was suggested as a therapeutic option for malignant brain cancer. This study aimed to detect metabolic brain changes in patients with malignant brain gliomas on KD using proton magnetic-resonance-spectroscopy ((1)H-MRS). Fifty MR scans were performed longitudinally in nine patients: four patients with recurrent glioblastoma (GB) treated with KD in addition to bevacizumab; one patient with gliomatosis-cerebri treated with KD only; and four patients with recurrent GB who did not receive KD...
January 10, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28065856/hypoxia-promotes-mitochondrial-glutamine-metabolism-through-hif1%C3%AE-gdh-pathway-in-human-lung-cancer-cells
#3
Zi-Feng Jiang, Min Wang, Jian-Lin Xu, Ya-Jing Ning
Drug-resistance is common in human lung cancer therapy. Hypoxia remarkably contributes to drug-resistance in lung cancer but the underlying mechanism remains elusive. Here we demonstrate that hypoxia-induced glutamine metabolism is involved in drug resistance in lung cancer cells. Hypoxia increases glutamine up-take, glutamate to α-ketoglutarate flux and the generation of ATP in lung cancer cells by up-regulating the expression of glutamate dehydrogenase (GDH). Hypoxia-induced expression of GDH relies on the up-regulation of HIF1α but not HIF2α...
January 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28060739/a-novel-micrornas-expression-signature-for-hepatocellular-carcinoma-diagnosis-and-prognosis
#4
Mengxuan Lu, Xia Kong, Huaigao Wang, Guoliang Huang, Caiguo Ye, Zhiwei He
This study aims to identify prognostic microRNAs (miRNAs) biomarkers for diagnosis and survival of hepatocellular carcinoma (HCC) based on large patients cohort analysis. HCC patient cohort data were downloaded from The Cancer Genome Atlas, including paired HCC and adjacent non-cancer tissues. Receiver operating characteristic curve method was used to classify cancer and non-cancer tissues according to microRNAs expression levels. The aberrant microRNAs expression level were ranked and risked for building a prognostic miRNAs signature model...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28059703/glycolysis-and-glutaminolysis-cooperatively-control-t-cell-function-by-limiting-metabolite-supply-to-n-glycosylation
#5
Lindsey Araujo, Phillip Khim, Haik Mkhikian, Christie-Lynn Mortales, Michael Demetriou
Rapidly proliferating cells switch from oxidative phosphorylation to aerobic glycolysis plus glutaminolysis, markedly increasing glucose and glutamine catabolism. Although Otto Warburg first described aerobic glycolysis in cancer cells >90 years ago, the primary purpose of this metabolic switch remains controversial. The hexosamine biosynthetic pathway requires glucose and glutamine for de novo synthesis of UDP-GlcNAc, a sugar-nucleotide that inhibits receptor endocytosis and signaling by promoting N-acetylglucosamine branching of Asn (N)-linked glycans...
January 6, 2017: ELife
https://www.readbyqxmd.com/read/28057420/structure-activity-relationships-of-benzylproline-derived-inhibitors-of-the-glutamine-transporter-asct2
#6
Kurnvir Singh, Rose Tanui, Armanda Gameiro, Gilad Eisenberg, Claire Colas, Avner Schlessinger, Christof Grewer
The glutamine transporter ASCT2 has been identified as a promising target to inhibit rapid growth of cancer cells. However, ASCT2 pharmacology is not well established. In this report, we performed a systematic structure activity analysis of a series of substituted benzylproline derivatives. Substitutions on the phenyl ring resulted in compounds with characteristics of ASCT2 inhibitors. Apparent binding affinity increased with increasing hydrophobicity of the side chain. In contrast, interaction of the ASCT2 binding site with specific positions on the phenyl ring was not observed...
December 27, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28034771/lkb1-promotes-metabolic-flexibility-in-response-to-energy-stress
#7
Seth J Parker, Robert U Svensson, Ajit S Divakaruni, Austin E Lefebvre, Anne N Murphy, Reuben J Shaw, Christian M Metallo
The Liver Kinase B1 (LKB1) tumor suppressor acts as a metabolic energy sensor to regulate AMP-activated protein kinase (AMPK) signaling and is commonly mutated in various cancers, including non-small cell lung cancer (NSCLC). Tumor cells deficient in LKB1 may be uniquely sensitized to metabolic stresses, which may offer a therapeutic window in oncology. To address this question we have explored how functional LKB1 impacts the metabolism of NSCLC cells using (13)C metabolic flux analysis. Isogenic NSCLC cells expressing functional LKB1 exhibited higher flux through oxidative mitochondrial pathways compared to those deficient in LKB1...
December 26, 2016: Metabolic Engineering
https://www.readbyqxmd.com/read/28030790/nutrient-deprivation-in-neuroblastoma-cells-alters-4-hydroxynonenal-induced-stress-response
#8
Lars Zimmermann, Rudolf Moldzio, Katarina Vazdar, Christopher Krewenka, Elena E Pohl
4-hydroxy-2-nonenal (HNE), a toxic lipid peroxidation product, is associated with oxidative damage in cells and involved in various diseases including the initiation and progression of cancer. Cancer cells have a high, adaptable metabolism with a shift from oxidative phosphorylation to glycolysis and rely on high levels of glucose and glutamine as essential nutrients for cell growth. Here we investigated whether the toxic effects of HNE on the mitochondrial membrane potential (MMP) of cancer cells depends on their metabolic state by deprivation of glucose and/or glutamine...
December 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/28011713/germline-compound-heterozygous-poly-glutamine-deletion-in-usf3-may-be-involved-in-predisposition-to-heritable-and-sporadic-epithelial-thyroid-carcinoma
#9
Ying Ni, Spencer Seballos, Benjamin Fletcher, Todd Romigh, Lamis Yehia, Jessica Mester, Leigha Senter, Farshad Niazi, Motoyasu Saji, Matthew D Ringel, Thomas LaFramboise, Charis Eng
Cowden syndrome (CS) is an autosomal dominant disorder that predisposes to breast, thyroid, and other epithelial cancers. Differentiated thyroid carcinoma (DTC), as one of the major component cancers of CS, is the fastest rising incident cancer in the USA, and the most familial of all solid tumors. To identify additional candidate genes of CS and potentially DTC, we analyzed a multi-generation CS-like family with papillary thyroid cancer (PTC), applying a combined linkage-based and whole-genome sequencing strategy and identified an in-frame germline compound heterozygous deletion, p...
December 22, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27996048/high-expression-of-gfat1-predicts-poor-prognosis-in-patients-with-pancreatic-cancer
#10
Caiting Yang, Peike Peng, Lili Li, Miaomiao Shao, Junjie Zhao, Lan Wang, Fangfang Duan, Shushu Song, Hao Wu, Jie Zhang, Ran Zhao, Dongwei Jia, Mingming Zhang, Weicheng Wu, Can Li, Yefei Rong, Lei Zhang, Yuanyuan Ruan, Jianxin Gu
Pancreatic cancer is one of the most lethal of all types of cancer, with the 5-year survival rate ranging only at 6-7%. The aberrant glucose metabolism is one of the hallmarks of cancer cells, and as a branch of glucose metabolism, hexosamine biosynthesis pathway (HBP) has been reported to play a critical role in the insulin resistance and progression of cancer. Glutamine:fructose-6-phosphate amidotransferase (GFAT1) is the rate-limiting enzyme of the HBP; nevertheless, the prognostic value of GFAT1 in pancreatic cancer remains elusive...
December 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27993669/contrasting-effects-of-glutamine-deprivation-on-apoptosis-induced-by-conventionally-used-anticancer-drugs
#11
Kadri Valter, Lian Chen, Björn Kruspig, Polina Maximchik, Hengmin Cui, Boris Zhivotovsky, Vladimir Gogvadze
Tumor cells dependence on glutamine offers a rationale for their elimination via targeting of glutamine metabolism. The aim of this work was to investigate how glutamine deprivation affects the cellular response to conventionally used anticancer drugs. To answer this question, neuroblastoma cells were pre-incubated in a glutamine-free medium and treated with cisplatin or etoposide. Obtained results revealed that glutamine withdrawal affected cellular response to therapeutic drugs in a different manner. Glutamine deprivation suppressed etoposide-induced, but markedly stimulated cisplatin-induced apoptosis...
December 18, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27989748/nox4-supports-glycolysis-and-promotes-glutamine-metabolism-in-non-small-cell-lung-cancer-cells
#12
Cheng Zeng, Qipeng Wu, Jing Wang, Bei Yao, Lei Ma, Zhicheng Yang, Juan Li, Bing Liu
Our previous studies have confirmed that NADPH oxidase 4 (NOX4) is abundantly expressed in non-small cell lung cancer (NSCLC) and contributes to cancer progression. Nevertheless, the comprehensive mechanisms for NOX4-mediated malignant progression and oxidative resistance of cancer cells remain largely unknown. This study found that NOX4 directed glucose metabolism not only to the glycolysis but also to pentose phosphate pathway (PPP) pathway for production of NADPH in non-small cell lung cancer (NSCLC) cell lines...
October 27, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27989504/morin-and-esculetin-supplementation-modulates-c-myc-induced-energy-metabolism-and-attenuates-neoplastic-changes-in-rats-challenged-with-the-procarcinogen-1-2-dimethylhydrazine
#13
Sharada H Sharma, Senthilkumar Thulasingam, David Raj Chellappan, Prabu Chinnaswamy, Sangeetha Nagarajan
Targeting tumor metabolism by natural products is a novel approach and provides rationale for anti-cancer drug discovery. The present study aims to explore the impact of morin and/or esculetin on c-myc induced energy metabolism in 1,2-dimethylhydrazine (DMH) induced colon cancer in rats. In order to achieve this aim we analyzed the expression of glucose and glutamine transporters and the key enzymes of glycolytic pathway besides the markers of neoplastic changes viz., mucin depleted foci (MDF), beta catenin accumulated crypts (BCAC), and markers of cell proliferation viz...
December 15, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27981621/targeting-%C3%AE-catenin-in-hepatocellular-cancers-induced-by-co-expression-of-mutant-%C3%AE-catenin-and-k-ras-in-mice
#14
Junyan Tao, Rong Zhang, Sucha Singh, Minakshi Poddar, Emily Xu, Michael Oertel, Xin Chen, Shanthi Ganesh, Marc Abrams, Satdarshan P Monga
Recently we have shown that co-expression of hMet and mutant-β-catenin using sleeping beauty transposon/transposase leads to HCC in mice that represents around 10% of human HCC. In the current study, we investigate if Ras activation, which can occur downstream of Met signaling, is sufficient to cause HCC in association with mutant-β-catenin. We also tested therapeutic efficacy of targeting β-catenin in HCC model. We show that mutant-K-Ras (G12D), which leads to Ras activation, cooperates with β-catenin mutants (S33Y, S45Y) to yield HCC in mice...
December 16, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27973397/p53-as-a-regulator-of-lipid-metabolism-in-cancer
#15
REVIEW
Alejandro Parrales, Tomoo Iwakuma
Enhanced proliferation and survival are common features of cancer cells. Cancer cells are metabolically reprogrammed which aids in their survival in nutrient-poor environments. Indeed, changes in metabolism of glucose and glutamine are essential for tumor progression. Thus, metabolic reprogramming is now well accepted as a hallmark of cancer. Recent findings suggest that reprogramming of lipid metabolism also occurs in cancer cells, since lipids are used for biosynthesis of membranes, post-translational modifications, second messengers for signal transduction, and as a source of energy during nutrient deprivation...
December 10, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27913195/breast-cancer-derived-extracellular-vesicles-stimulate-myofibroblast-differentiation-and-pro-angiogenic-behavior-of-adipose-stem-cells
#16
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
#17
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
#18
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...
25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27898344/may-glutamine-addiction-drive-the-delivery-of-antitumor-cisplatin-based-pt-iv-prodrugs
#19
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...
February 2017: 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
#20
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
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