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https://www.readbyqxmd.com/read/28644842/investigation-of-discriminant-metabolites-in-tamoxifen-resistant-and-choline-kinase-alpha-downregulated-breast-cancer-cells-using-1h-nuclear-magnetic-resonance-spectroscopy
#1
Hoe Suk Kim, Lianji Tian, Hyeonjin Kim, Woo Kyung Moon
Metabolites linked to changes in choline kinase-α (CK-α) expression and drug resistance, which contribute to survival and autophagy mechanisms, are attractive targets for breast cancer therapies. We previously reported that autophagy played a causative role in driving tamoxifen (TAM) resistance of breast cancer cells (BCCs) and was also promoted by CK-α knockdown, resulting in the survival of TAM-resistant BCCs. There is no comparative study yet about the metabolites resulting from BCCs with TAM-resistance and CK-α knockdown...
2017: PloS One
https://www.readbyqxmd.com/read/28641927/from-prokaryotes-to-cancer-glutamine-flux-in-multicellular-units
#2
REVIEW
Ayelet Erez, Ilana Kolodkin-Gal
Bacteria in nature reside in organized communities, termed biofilms, which are composed of multiple individual cells adhering to each other. Similarly, tumors are a multicellular mass with distinct cellular phenotypes. Both tumors and biofilms are considered to be an active interphase between unicellular and multicellular life states. Because both of these units depend on glutamine for growth and survival, we review here glutamine flux within them as a readout for intra- and inter-commensal metabolism. We suggest that the difference between glutamine fluxes in these cellular communities lies mainly in their global multicellular metabolic organization...
June 19, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28637353/hallmarks-of-pulmonary-hypertension-mesenchymal-and-inflammatory-cell-metabolic-reprogramming
#3
Angelo D'Alessandro, Karim El Kasmi, Lydie Plecita-Hlavata, Petr Jezek, Min Li, Hui Zhang, Sachin A Gupte, Kurt Randall Stenmark
The molecular events that promote the development of pulmonary hypertension (PH) are complex and incompletely understood. The complex interplay between the pulmonary vasculature and its immediate microenvironment involving cells of immune system (i.e. macrophages) promotes a persistent inflammatory state, pathological angiogenesis and fibrosis that is driven by metabolic reprogramming of mesenchymal and immune cells. Consistent with previous findings in the field of cancer metabolism, increased glycolytic rates, incomplete glucose and glutamine oxidation to support anabolism and anaplerosis, altered lipid synthesis/oxidation ratios, increased one-carbon metabolism and activation of the pentose phosphate pathway to support nucleoside synthesis are but some of the key metabolic signatures of vascular cells in PH...
June 22, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28630436/a-novel-gd-dtpa-conjugated-poly-l-%C3%AE-glutamyl-glutamine-paclitaxel-polymeric-delivery-system-for-tumor-theranostics
#4
Lipeng Gao, Jinge Zhou, Jing Yu, Qilong Li, Xueying Liu, Lei Sun, Ting Peng, Jing Wang, Jianzhong Zhu, Jihong Sun, Weiyue Lu, Lei Yu, Zhiqiang Yan, Yiting Wang
The conventional chemotherapeutics could not be traced in vivo and provide timely feedback on the clinical effectiveness of drugs. In this study, poly(L-γ-glutamyl-glutamine)-paclitaxel (PGG-PTX), as a model polymer, was chemically conjugated with Gd-DTPA (Gd-diethylenetriaminepentaacetic acid), a T1-contrast agent of MRI, to prepare a Gd-DTPA-conjugated PGG-PTX (PGG-PTX-DTPA-Gd) delivery system used for tumor theranostics. PGG-PTX-DTPA-Gd can be self-assembled to NPs in water with a z-average hydrodynamic diameter about 35...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28623324/rapid-discrimination-of-human-oesophageal-squamous-cell-carcinoma-by-mass-spectrometry-based-on-differences-in-amino-acid-metabolism
#5
Zhang Jianyong, Xu Jianjun, Ouyang Yongzhong, Liu Junwen, Lu Haiyan, Yu Dongliang, Peng Jinhua, Xiong Junwen, Chen Huanwen, Wei Yiping
Oesophageal cancer (OC) is associated with high morbidity and mortality, and surgery is the most effective approach to treat it. In order to reduce surgical risks and duration of surgery, we explored a new strategy to determine tumour margins in surgery. In this study, we included 128 cancerous and 128 noncancerous database entries obtained from 32 human patients. Using internal extractive electrospray ionization-MS, in positive ion detection mode, the relative abundances of m/z 104.13, m/z 116.10, m/z 132...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28616574/therapeutic-arginine-starvation-in-ass1-deficient-cancers-inhibits-the-warburg-effect
#6
Jeff C Kremer, Brian A Van Tine
Argininosuccinate Synthetase 1 deficiency induces dependence on extracellular arginine for continued cellular growth and survival. Arginine starvation inhibits the Warburg effect and diverts glucose into serine biosynthesis, while simultaneously increasing glutamine metabolism via the tricarboxylic acid cycle. Simultaneous arginine deprivation and inhibition of the subsequent metabolic adaptations induce synthetic lethality.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28614770/transcription-factor-gata3-expression-is-induced-by-gls2-overexpression-in-a-glioblastoma-cell-line-but-is-gls2-independent-in-patient-derived-glioblastoma
#7
E Majewska, R Rola, M Barczewska, J Marquez, J Albrecht, M Szeliga
Phosphate-activated glutaminase (GA), a ubiquitous glutamine-metabolizing enzyme, is encoded by two genes, GLS and GLS2. In mammalian cancers, GLS isoforms are perceived as molecules promoting cell proliferation and invasion, whereas the role of GLS2 isoforms seems to be more complex and cell type-specific. Previous studies have shown abundance of GLS and lack of GLS2 transcripts in T98G human glioblastoma (GBM) cell line and patient-derived GBM. Transfection with GAB sequence, the whole GLS2 cDNA transcript, suppressed malignant phenotype of T98G cells...
April 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28611296/does-the-1h-nmr-plasma-metabolome-reflect-the-host-tumor-interactions-in-human-breast-cancer
#8
Vincent Richard, Raphaël Conotte, David Mayne, Jean-Marie Colet
Breast cancer (BC) is the most common diagnosed cancer and the leading cause of cancer death in women worldwide. There is an obvious need for a better understanding of BC biology. Alterations in the serum metabolome of BC patients have been identified but their clinical significance remains elusive. We evaluated by 1H-Nuclear Magnetic Resonance (1H-NMR) spectroscopy, filtered plasma metabolome of 50 early (EBC) and 15 metastatic BC (MBC) patients. Using Principal Component Analysis, Partial Least-Squares Discriminant Analysis and Hierarchical Clustering we show that plasma levels of glucose, lactate, pyruvate, alanine, leucine, isoleucine, glutamate, glutamine, valine, lysine, glycine, threonine, tyrosine, phenylalanine, acetate, acetoacetate, β-hydroxy-butyrate, urea, creatine and creatinine are modulated across patients clusters...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28599655/canine-reic-dkk-3-interacts-with-sgta-and-restores-androgen-receptor-signalling-in-androgen-independent-prostate-cancer-cell-lines
#9
Yuiko Kato, Kazuhiko Ochiai, Shota Kawakami, Nobuhiro Nakao, Daigo Azakami, Makoto Bonkobara, Masaki Michishita, Masami Morimatsu, Masami Watanabe, Toshinori Omi
BACKGROUND: The pathological condition of canine prostate cancer resembles that of human androgen-independent prostate cancer. Both canine and human androgen receptor (AR) signalling are inhibited by overexpression of the dimerized co-chaperone small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA), which is considered to cause the development of androgen-independency. Reduced expression in immortalised cells (REIC/Dkk-3) interferes with SGTA dimerization and rescues AR signalling...
June 9, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28597996/sensitization-of-melanoma-cells-to-temozolomide-by-overexpression-of-microrna-203-through-direct-targeting-of-glutaminase-mediated-glutamine-metabolism
#10
X Chang, W Zhu, H Zhang, S Lian
BACKGROUND: Malignant melanoma (MM) is an aggressive malignancy, which accounts for 80% of skin cancer-related deaths and is notably resistant to conventional chemotherapeutic agents. One of the most common treatments for melanoma is surgery, followed by various combinations of chemotherapy drugs. AIM: To investigate the role of microRNA (miR)-203 in sensitivity of MM cells to the chemotherapy drug temozolomide (TMZ). METHODS: Using quantitative reverse transcription PCR, we measured the expression of miR-203 in an MM cell line...
June 9, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28588793/double-blind-randomized-study-of-oral-glutamine-on-the-management-of-radio-chemotherapy-induced-mucositis-and-dermatitis-in-head-and-neck-cancer
#11
David Lopez-Vaquero, Lucia Gutierrez-Bayard, Juan-Andres Rodriguez-Ruiz, Monica Saldaña-Valderas, Pedro Infante-Cossio
This randomized clinical trial was designed to determine whether glutamine administration was effective in reducing the incidence and severity of mucositis and dermatitis induced by radiotherapy (RT) or chemoradiotherapy (CHRT) in patients with head and neck cancer (HNC). Fifty patients were randomized to receive orally either L-Glutamine or placebo (25 patients in each arm). In the glutamine-treated group, 10 g of oral glutamine was administered three times daily. The primary endpoint was to compare the appearance of clinical mucositis between groups at the 6th week, according to the Common Terminology Criteria for Adverse Events...
June 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28582843/acute-lymphoblastic-leukemia-and-genetic-variations-in-bhmt-gene-case-control-study-and-computational-characterization
#12
Ravishankara Bellampalli, Manik Vohra, Kashish Sharma, Nalini Bhaskaranand, Kamalakshi G Bhat, Krishna Prasad, Anu R Sharma, Kapaettu Satyamoorthy, Padmalatha S Rai
BACKGROUND: Remethylation of homocysteine is catalyzed by B12 dependent methionine synthase (MTR) in all types of cells and by B12 non-dependent betaine homocysteine methyltransferase (BHMT) in liver and kidney cells. Of many etiologies of cancer, an unexplored area is the variations of genes implicated in methylation reaction. OBJECTIVE: The study evaluated the association of BHMT (rs3733890) with acute lymphoblastic leukemia (ALL), followed by in-silico characterization of variations in BHMT gene...
May 19, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28574837/6-mercaptopurine-promotes-energetic-failure-in-proliferating-t-cells
#13
Ana A Fernández-Ramos, Catherine Marchetti-Laurent, Virginie Poindessous, Samantha Antonio, Pierre Laurent-Puig, Sylvie Bortoli, Marie-Anne Loriot, Nicolas Pallet
The anticancer drug 6-mercaptopurine (6-MP) inhibits de novo purine synthesis and acts as an antiproliferative agent by interfering with protein, DNA and RNA synthesis and promoting apoptosis. Metabolic reprogramming is crucial for tumor progression to foster cancer cells growth and proliferation, and is regulated by mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) as well as the oncogenes Myc and hypoxia inducible factor 1α (HIF-1α). We hypothesized that 6-MP impacts metabolic remodeling through its action on nucleotide synthesis...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28571744/kr-pok-zbtb7c-regulates-cancer-cell-proliferation-through-glutamine-metabolism
#14
Man-Wook Hur, Jae-Hyeon Yoon, Min-Young Kim, Hyeonseok Ko, Bu-Nam Jeon
Kr-POK (ZBTB7c) is a kidney cancer-related POK transcription factor that not only represses transcription of CDKN1A but also increases expression of FASN. However, precisely how Kr-POK affects cell metabolism by controlling gene expression in response to an energy source in rapidly proliferating cells remains unknown. In this study, we characterized the molecular and functional features of Kr-POK in the context of tumor growth and glutamine metabolism. We found that cells expressing Kr-POK shRNA exhibited more severe cell death than control cells in glucose-deprived medium, and that knockdown of Kr-POK decreased glutamine uptake...
May 30, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28566705/nitrogen-isotopes-provide-clues-to-amino-acid-metabolism-in-human-colorectal-cancer-cells
#15
R V Krishnamurthy, Yogesh R Suryawanshi, Karim Essani
Glutamic acid and alanine make up more than 60 per cent of the total amino acids in the human body. Glutamine is a significant source of energy for cells and also a prime donor of nitrogen in the biosynthesis of many amino acids. Several studies have advocated the role of glutamic acid in cancer therapy. Identification of metabolic signatures in cancer cells will be crucial for advancement of cancer therapies based on the cell's metabolic state. Stable nitrogen isotope ratios ((15)N/(14)N, δ(15)N) are of particular advantage to understand the metabolic state of cancer cells, since most biochemical reactions involve transfer of nitrogen...
May 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28553292/asct2-slc1a5-deficient-mice-have-normal-b-cell-development-proliferation-and-antibody-production
#16
Etienne Masle-Farquhar, Angelika Bröer, Mehmet Yabas, Anselm Enders, Stefan Bröer
SLC1A5 (solute carrier family 1, member 5) is a small neutral amino acid exchanger that is upregulated in rapidly proliferating lymphocytes but also in many primary human cancers. Furthermore, cancer cell lines have been shown to require SLC1A5 for their survival in vitro. One of SLC1A5's primary substrates is the immunomodulatory amino acid glutamine, which plays an important role in multiple key processes, such as energy supply, macromolecular synthesis, nucleotide biosynthesis, redox homeostasis, and resistance against oxidative stress...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28544376/hif-2%C3%AE-regulates-non-canonical-glutamine-metabolism-via-activation-of-pi3k-mtorc2-pathway-in-human-pancreatic-ductal-adenocarcinoma
#17
Wenzhu Li, Changhao Chen, Xiaohui Zhao, Huilin Ye, Yue Zhao, Zhiqiang Fu, Wenwei Pan, Shangyou Zheng, Lusheng Wei, Tianwen Nong, Zhihua Li, Rufu Chen
Hypoxia-inducible factor-2α (HIF-2α) plays an important role in increasing cancer progression and distant metastasis in a variety of tumour types. We aimed to investigate its biological function and clinical significance in human pancreatic ductal adenocarcinoma (PDAC). A total of 283 paired PDAC tissues and adjacent normal tissues were collected from patients who underwent surgery or biopsy at Sun Yat-sen Memorial Hospital between February 2004 and October 2016. In this study, we noted that HIF-2α expression was significantly up-regulated in PDAC, positively associated with disease stage, lymph-node metastasis and patient survival, and identified as an independent prognostic factor of PDAC patients...
May 24, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28541810/effects-of-a-carbohydrate-glutamine-and-antioxidant-enriched-oral-nutrition-supplement-on-major-surgery-induced-insulin-resistance-a-randomized-pilot-study
#18
Mireille F M van Stijn, Maarten R Soeters, Paul A M van Leeuwen, W H Schreurs, Margreet G Schoorl, Jos W R Twisk, Jean-Pascal De Bandt, Dominique Bonnefont-Rousselot, Luc Cynober, Mariette T Ackermans, Mireille J Serlie, Alexander P J Houdijk
BACKGROUND: Insulin resistance after surgery hampers recovery. Oxidative stress is shown to be involved in the occurrence of postoperative insulin resistance. Preoperative carbohydrate-rich oral nutrition supplements reduce but do not prevent insulin resistance. The aim of the present study was to investigate the effect of a carbohydrate-, glutamine-, and antioxidant-enriched preoperative oral nutrition supplement on postoperative insulin resistance. METHODS: A double-blind randomized controlled pilot study in 18 patients with rectal cancer, who received either the supplement (S) or the placebo (P) 15, 11, and 4 hours preoperatively, was conducted...
May 1, 2017: JPEN. Journal of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28537472/a-novel-role-for-a-glycolytic-pathway-kinase-in-regulating-autophagy-has-implications-in-cancer-therapy
#19
Aileen R Ariosa, Daniel J Klionsky
When it comes to cancer initiation and progression, macroautophagy/autophagy seemingly acts in a contradictory fashion, serving either as a suppressive factor that functions to protect against tumor formation or as a support mechanism that sustains the disease itself through its cytoprotective functions. In tumor suppression, autophagy assists by restricting oxidative stress and curbing genomic instability that could possibly cause oncogenic mutations. However, in certain circumstances, autophagy can also promote cancer by providing nourishment and by limiting stress-response pathways, leading to cancer cell survival and rapid proliferation...
May 24, 2017: Autophagy
https://www.readbyqxmd.com/read/28536931/guanosine-promotes-cytotoxicity-via-adenosine-receptors-and-induces-apoptosis-in-temozolomide-treated-a172-glioma-cells
#20
Karen A Oliveira, Tharine A Dal-Cim, Flávia G Lopes, Cláudia B Nedel, Carla Inês Tasca
Gliomas are a malignant tumor group whose patients have survival rates around 12 months. Among the treatments are the alkylating agents as temozolomide (TMZ), although gliomas have shown multiple resistance mechanisms for chemotherapy. Guanosine (GUO) is an endogenous nucleoside involved in extracellular signaling that presents neuroprotective effects and also shows the effect of inducing differentiation in cancer cells. The chemotherapy allied to adjuvant drugs are being suggested as a novel approach in gliomas treatment...
May 23, 2017: Purinergic Signalling
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