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https://www.readbyqxmd.com/read/28454342/feasibility-and-antitumor-efficacy-in-vivo-of-simultaneously-targeting-glycolysis-glutaminolysis-and-fatty-acid-synthesis-using-lonidamine-6-diazo-5-oxo-l-norleucine-and-orlistat-in-colon-cancer
#1
Diana Cervantes-Madrid, Guadalupe Dominguez-Gomez, Aurora Gonzalez-Fierro, Enrique Perez-Cardenas, Lucia Taja-Chayeb, Catalina Trejo-Becerril, Alfonso Duenas-Gonzalez
The aim of the present study was to investigate in vivo the feasibility and efficacy of the combination of lonidamine (LND), 6-diazo-5-oxo-L-norleucine (DON) and orlistat to simultaneously target glycolysis, glutaminolysis and de novo synthesis of fatty acids, respectively. The doses of LND and DON used in humans were translated to mouse doses (77.7 mg/kg and 145.5 mg/kg, respectively) and orlistat was used at 240 mg/kg. Three schedules of LND, DON and orlistat at different doses were administered by intraperitoneal injection to BALB/c mice in a 21-day cycle (schedule 1: LND, 0...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28449083/proteomic-response-to-linoleic-acid-hydroperoxide-in-saccharomyces-cerevisiae
#2
Patrick J O'Doherty, Alamgir Khan, Adam J Johnson, Peter J Rogers, Trevor D Bailey, Ming J Wu
Yeast AP-1 transcription factor (Yap1p) and the enigmatic oxidoreductases Oye2p and Oye3p are involved in counteracting lipid oxidants and their unsaturated breakdown products. In order to uncover the response to linoleic acid hydroperoxide (LoaOOH) and the roles of Oye2p, Oye3p, and Yap1p, we carried out proteomic analysis of the homozygous deletion mutants oye3Δ, oye2Δ, and yap1Δ alongside the diploid parent strain BY4743. The findings demonstrate that deletion of YAP1 narrowed the response to LoaOOH, as the number of proteins differentially expressed in yap1Δ was 70% of that observed in BY4743...
April 25, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28448945/teaching-the-basics-of-cancer-metabolism-developing-antitumor-strategies-by-exploiting-the-differences-between-normal-and-cancer-cell-metabolism
#3
REVIEW
Balaraman Kalyanaraman
This review of the basics of cancer metabolism focuses on exploiting the metabolic differences between normal and cancer cells. The first part of the review covers the different metabolic pathways utilized in normal cells to generate cellular energy, or ATP, and the glycolytic intermediates required to build the cellular machinery. The second part of the review discusses aerobic glycolysis, or the Warburg effect, and the metabolic reprogramming involving glycolysis, tricarboxylic acid cycle, and glutaminolysis in the context of developing targeted inhibitors in cancer cells...
April 13, 2017: Redox Biology
https://www.readbyqxmd.com/read/28448552/transcriptomic-analysis-of-the-hepatic-response-to-stress-in-the-red-cusk-eel-genypterus-chilensis-insights-into-lipid-metabolism-oxidative-stress-and-liver-steatosis
#4
Sebastian Naour, Brisa M Espinoza, Jorge E Aedo, Rodrigo Zuloaga, Jonathan Maldonado, Macarena Bastias-Molina, Herman Silva, Claudio Meneses, Cristian Gallardo-Escarate, Alfredo Molina, Juan Antonio Valdés
Teleosts exhibit a broad divergence in their adaptive response to stress, depending on the magnitude, duration, and frequency of stressors and the species receiving the stimulus. We have previously reported that the red cusk-eel (Genypterus chilensis), an important marine farmed fish, shows a physiological response to stress that results in increased skeletal muscle atrophy mediated by over-expression of components of the ubiquitin proteasome and autophagy-lysosomal systems. To better understand the systemic effects of stress on the red cusk-eel metabolism, the present study assessed the transcriptomic hepatic response to repetitive handling-stress...
2017: PloS One
https://www.readbyqxmd.com/read/28448534/intense-light-elicited-upregulation-of-mir-21-facilitates-glycolysis-and-cardioprotection-through-per2-dependent-mechanisms
#5
Colleen Marie Bartman, Yoshimasa Oyama, Kelley Brodsky, Ludmila Khailova, Lori Walker, Michael Koeppen, Tobias Eckle
A wide search for ischemic preconditioning (IPC) mechanisms of cardioprotection identified the light elicited circadian rhythm protein Period 2 (Per2) to be cardioprotective. Studies on cardiac metabolism found a key role for light elicited Per2 in mediating metabolic dependence on carbohydrate metabolism. To profile Per2 mediated pathways following IPC of the mouse heart, we performed a genome array and identified 352 abundantly expressed and well-characterized Per2 dependent micro RNAs. One prominent result of our in silico analysis for cardiac Per2 dependent micro RNAs revealed a selective role for miR-21 in the regulation of hypoxia and metabolic pathways...
2017: PloS One
https://www.readbyqxmd.com/read/28447727/advanced-glycation-end-products%C3%A2-induced-mitochondrial-energy-metabolism-dysfunction-alters-proliferation-of-human-umbilical-vein-endothelial-cells
#6
Yuan Li, Ye Chang, Ning Ye, Yintao Chen, Naijin Zhang, Yingxian Sun
Advanced glycation end products (AGEs) restrain the proliferation of endothelial cells, which is an important determinant of diabetic vasculopathy. Mitochondrial biogenesis serves an essential role in cellular adaptation and repair. The current study aimed to investigate alterations in mitochondrial energy metabolism in human umbilical vein endothelial cells (HUVECs) and the latent mechanism regulated by AGEs. The proliferation of cultured HUVECs stimulated with AGEs was detected using an MTT assay and a real‑time cell analyzer (RTCA)...
March 10, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28447204/comparative-transcriptome-profiling-of-freezing-stress-responses-in-loquat-eriobotrya-japonica-fruitlets
#7
Hong-Xia Xu, Xiao-Ying Li, Jun-Wei Chen
Loquat (Eriobotrya japonica Lindl.) is an important subtropical, commercial fruit in China. It blossoms during autumn and winter in most areas of China and its fruitlets usually suffer from freezing stress. However, studies about the mechanisms underlying freezing stress in loquat are very limited. The gene expression profiles of loquat fruitlets subjected to freezing (G2 library) versus non-treated ones (G1 library) were investigated using Illumina sequencing technology to elucidate the molecular mechanisms and identify the genes that play vital roles in the freezing stress response...
April 26, 2017: Journal of Plant Research
https://www.readbyqxmd.com/read/28446878/computational-model-predicts-the-effects-of-targeting-cellular-metabolism-in-pancreatic-cancer
#8
Mahua Roy, Stacey D Finley
Reprogramming of energy metabolism is a hallmark of cancer that enables the cancer cells to meet the increased energetic requirements due to uncontrolled proliferation. One prominent example is pancreatic ductal adenocarcinoma, an aggressive form of cancer with an overall 5-year survival rate of 5%. The reprogramming mechanism in pancreatic cancer involves deregulated uptake of glucose and glutamine and other opportunistic modes of satisfying energetic demands in a hypoxic and nutrient-poor environment. In the current study, we apply systems biology approaches to enable a better understanding of the dynamics of the distinct metabolic alterations in KRAS-mediated pancreatic cancer, with the goal of impeding early cell proliferation by identifying the optimal metabolic enzymes to target...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28446816/sirt2-and-glycolytic-enzyme-acetylation-in-pluripotent-stem-cells
#9
Tong Ming Liu, Ng Shyh-Chang
The metabolic transition from mitochondrial oxidative phosphorylation (OXPHOS) to glycolysis is critical for somatic reprogramming of induced pluripotent stem cells (iPSCs). SIRT2 has now been established as a previously unknown regulator of this metabolic transition during somatic reprogramming by controlling the acetylation status of glycolytic enzymes.
April 27, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28446224/immunosuppressive-capacity-of-mesenchymal-stem-cells-correlates-with-metabolic-activity-and-can-be-enhanced-by-valproic-acid
#10
Madeleine C Killer, Philipp Nold, Katharina Henkenius, Lea Fritz, Tabea Riedlinger, Christina Barckhausen, Miriam Frech, Holger Hackstein, Andreas Neubauer, Cornelia Brendel
BACKGROUND: Mesenchymal stem cells (MSCs) have entered the clinic as an Advanced Therapy Medicinal Product and are currently evaluated in a wide range of studies for tissue regeneration or in autoimmune disorders. Various efforts have been made to standardize and optimize expansion and manufacturing processes, but until now reliable potency assays for the final MSC product are lacking. Because recent findings suggest superior therapeutic efficacy of freshly administered MSCs in comparison with frozen cells, we sought to correlate the T-cell suppressive capacity of MSCs with their metabolic activity...
April 26, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28445985/interleukin-22-promotes-aerobic-glycolysis-associated-with-tumor-progression-via-targeting-hexokinase-2-in-human-colon-cancer-cells
#11
Yulin Liu, Fan Xiang, Yongming Huang, Liang Shi, Chaojie Hu, Yiming Yang, Di Wang, Nan He, Kaixiong Tao, Ke Wu, Guobin Wang
Interleukin-22 has been explored extensively in human cancer, but its functions and underlying mechanisms are incompletely understood. Here, we show that aberrant interleukin-22 expression facilitates aerobic glycolysis in colon cancer cells. Elevated interleukin-22 mRNA expression was observed and positively correlated with hexokinase-2 in colon cancer tissues. In vitro, interleukin-22 enhanced glucose consumption and lactate production via targeting hexokinase-2 in colon cancer cells. Moreover, the transcriptional factor c-Myc and signal transducer and activator of transcription 3 were involved in interleukin-22-induced up-regulation of hexokinase-2...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445971/stat3-regulates-glycolysis-via-targeting-hexokinase-2-in-hepatocellular-carcinoma-cells
#12
Man Li, Rui Jin, Weihua Wang, Tieying Zhang, Jiao Sang, Na Li, Qunying Han, Wenxuan Zhao, Chunyan Li, Zhengwen Liu
Signal transducer and activator of transcription 3 (STAT3) and hexokinase 2 (HK2) are involved in hepatocellular carcinoma (HCC). Deregulation of cellular energetics involving an increase in glycolysis is a characteristic of HCC. This study examined whether STAT3 regulates HCC glycolysis through the HK2 pathway in HCC cells. Human HCC cell lines HepG2 and Hep3B cells were transfected with pcDNA3.1(+)-EGFP-STAT3, STAT3 siRNA and HK2 siRNA, respectively, or treated with rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), and the effects on STAT3 and HK2 expression and cell glycolysis were determined...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445958/repressing-cd147-is-a-novel-therapeutic-strategy-for-malignant-melanoma
#13
REVIEW
Xing Hu, Juan Su, Youyou Zhou, Xiaoyun Xie, Cong Peng, Zhimin Yuan, Xiang Chen
CD147/basigin, a transmembrane protein, is a member of the immunoglobulin super family. Accumulating evidence has revealed the role of CD147 in the development and progression of various cancers, including malignant melanoma (MM). MM is a malignancy of pigment-producing cells that causes the greatest number of skin cancer-related deaths worldwide. CD147 is overexpressed in MM and plays an important role in cell viability, apoptosis, proliferation, invasion, and metastasis, probably by mediating vascular endothelial growth factor (VEGF) production, glycolysis, and multi-drug resistance (MDR)...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445868/suppressionof-pyruvate-dehydrogenase-kinase-2-re-sensitizes-paclitaxel-resistant-human-lung-cancer-cells-to-paclitaxel
#14
Hong Sun, Anyou Zhu, Xiang Zhou, Fengchao Wang
Despite impressive initial clinical responses, the majority of lung cancer patients treated with paclitaxel eventually develop resistance to the drug. Pyruvate dehydrogenase kinase-2 (PDK2) is a key regulator of glycolysis and oxidative phosphorylation, and its expression is increased in a variety of tumors. In this study, the role of PDK2 in mediating paclitaxel resistance in lung cancer cells was investigated using biochemical and isotopic tracing methods. Increased expression of PDK2 was observed in paclitaxel-resistant cells ascompared totheir parental cells...
April 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445287/prognostic-value-of-pretreatment-18f-fdg-pet-ct-for-nasopharyngeal-carcinoma-patients
#15
Yecai Huang, Mei Feng, Qiao He, Jun Yin, Peng Xu, Qinghua Jiang, Jinyi Lang
BACKGROUND: Nasopharyngeal carcinoma (NPC) is a special subtype of head and neck cancer (HNC). At present, there are no highly specific prognostic markers to aid in tumor grading and guide patient treatment modalities for NPC. The prognostic value of pretreatment F-fluorodeoxyglucose positron emission tomography-computed tomography (F-PET-CT) in NPC patients is controversial and no consensus exists as to its predictive capability. METHODS: To analyze the predictive efficacy of F-PET-CT imaging in NPC patients, data from MEDLINE, EMBASE, the Cochrane library, CBM, CNKI, and VIP (inception to July 2016) were accessed...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28445144/stroma-derived-hgf-drives-metabolic-adaptation-of-colorectal-cancer-to-angiogenesis-inhibitors
#16
Alessia Mira, Virginia Morello, Maria Virtudes Céspedes, Timothy Perera, Paolo M Comoglio, Ramon Mangues, Paolo Michieli
The role of paracrine Hepatocyte Growth Factor (HGF) in the resistance to angiogenesis inhibitors (AIs) is hidden in xenograft models because mouse HGF fails to fully activate human MET. To uncover it, we compared the efficacy of AIs in wild-type and human HGF knock-in SCID mice bearing orthotopic human colorectal tumors. Species-specific HGF/MET signaling dramatically impaired the response to anti-angiogenic agents and boosted metastatic dissemination. In cell-based assays mimicking the consequences of anti-angiogenic therapy, colorectal cancer cells were completely resistant to hypoxia but extremely sensitive to nutrient deprivation...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444544/methylglyoxal-detoxification-by-a-dj-1-family-protein-provides-dual-abiotic-and-biotic-stress-tolerance-in-transgenic-plants
#17
Prasad Melvin, Kondalarao Bankapalli, Patrick D'Silva, P V Shivaprasad
Methylglyoxal (MG) is a key signaling molecule resulting from glycolysis and other metabolic pathways. During abiotic stress, MG levels accumulate to toxic levels in affected cells. However, MG is routinely detoxified through the action of DJ1/PARK7/Hsp31 proteins that are highly conserved across kingdoms and mutations in such genes are associated with neurodegenerative diseases. Here, we report for the first time that, similar to abiotic stresses, MG levels increase during biotic stresses in plants, likely contributing to enhanced susceptibility to a wide range of stresses...
April 25, 2017: Plant Molecular Biology
https://www.readbyqxmd.com/read/28443474/atp-citrate-lyase-is-increased-in-human-breast-cancer-depletion-of-which-promotes-apoptosis
#18
Diyu Wang, Lei Yin, Jinrong Wei, Zhixue Yang, Guoqin Jiang
Breast cancer is a malignant tumor that is harmful to women's health around the world. Investigating the biological mechanism is, therefore, of pivotal importance to improve patients' prognoses. Compared to non-neoplastic tissues, enhanced glucose and lipid metabolism is one of the most common properties of malignant breast cancer. Adenosine triphosphate (ATP) citrate lyase is a key enzyme linking aerobic glycolysis and fatty acid synthesis and is of high biological and prognostic significance in breast cancer...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28443245/overexpression-of-the-atpase-inhibitory-factor-1-favors-a-non-metastatic-phenotype-in-breast-cancer
#19
Lucía García-Ledo, Cristina Nuevo-Tapioles, Carmen Cuevas-Martín, Inmaculada Martínez-Reyes, Beatriz Soldevilla, Lucía González-Llorente, José M Cuezva
Partial suppression of mitochondrial oxidative phosphorylation and the concurrent activation of aerobic glycolysis is a hallmark of proliferating cancer cells. Overexpression of the ATPase inhibitory factor 1 (IF1), an in vivo inhibitor of the mitochondrial ATP synthase, is observed in most prevalent human carcinomas favoring metabolic rewiring to an enhanced glycolysis and cancer progression. Consistently, a high expression of IF1 in hepatocarcinomas and in carcinomas of the lung, bladder, and stomach and in gliomas is a biomarker of bad patient prognosis...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28443115/cytosolic-glyceraldehyde-3-phosphate-dehydrogenase-is-phosphorylated-during-seed-development
#20
Claudia V Piattoni, Danisa M L Ferrero, Ignacio Dellaferrera, Abelardo Vegetti, Alberto Á Iglesias
Cytosolic glyceraldehyde-3-phosphate dehydrogenase (NAD-GAPDH) is involved in a critical energetic step of glycolysis and also has many important functions besides its enzymatic activity. The recombinant wheat NAD-GAPDH was phosphorylated in vitro at Ser205 by a SNF1-Related protein kinase 1 (SnRK1) from wheat heterotrophic (but not from photosynthetic) tissues. The S205D mutant enzyme (mimicking the phosphorylated form) exhibited a significant decrease in activity but similar affinity toward substrates. Immunodetection and activity assays showed that NAD-GAPDH is phosphorylated in vivo, the enzyme depicting different activity, abundance and phosphorylation profiles during development of seeds that mainly accumulate starch (wheat) or lipids (castor oil seed)...
2017: Frontiers in Plant Science
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