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https://www.readbyqxmd.com/read/28922380/the-warburg-effect-as-an-adaptation-of-cancer-cells-to-rapid-fluctuations-in-energy-demand
#1
Tamir Epstein, Robert A Gatenby, Joel S Brown
To maintain optimal fitness, a cell must balance the risk of inadequate energy reserve for response to a potentially fatal perturbation against the long-term cost of maintaining high concentrations of ATP to meet occasional spikes in demand. Here we apply a game theoretic approach to address the dynamics of energy production and expenditure in eukaryotic cells. Conventionally, glucose metabolism is viewed as a function of oxygen concentrations in which the more efficient oxidation of glucose to CO2 and H2O produces all or nearly all ATP except under hypoxic conditions when less efficient (2 ATP/ glucose vs...
2017: PloS One
https://www.readbyqxmd.com/read/28919675/therapeutic-uses-of-epicatechin-in-diabetes-and-cancer
#2
REVIEW
Layth Abdulmajeed Abdulkhaleq, Mohammed Abdulrazzaq Assi, Mohd Hezmee Mohd Noor, Rasedee Abdullah, Mohd Zamri Saad, Yun Hin Taufiq-Yap
Epicatechin is a natural flavonoid found in green tea. It has been reported to possess an immense antioxidant effect which contributes to its therapeutic effect against a handful of ailments. In this review, we discuss its therapeutic role in the management of two of the most important human diseases; diabetes and cancer. The consumption of epicatechin has been shown to reduce blood glucose levels in diabetic patients, while is anticancer effect was attributed to its antioxidant properties, antiangiogenic and direct cytotoxicity to cancer cells...
August 2017: Veterinary World
https://www.readbyqxmd.com/read/28918937/a-predictive-model-for-selective-targeting-of-the-warburg-effect-through-gapdh-inhibition-with-a-natural-product
#3
Maria V Liberti, Ziwei Dai, Suzanne E Wardell, Joshua A Baccile, Xiaojing Liu, Xia Gao, Robert Baldi, Mahya Mehrmohamadi, Marc O Johnson, Neel S Madhukar, Alexander A Shestov, Iok I Christine Chio, Olivier Elemento, Jeffrey C Rathmell, Frank C Schroeder, Donald P McDonnell, Jason W Locasale
Targeted cancer therapies that use genetics are successful, but principles for selectively targeting tumor metabolism that is also dependent on the environment remain unknown. We now show that differences in rate-controlling enzymes during the Warburg effect (WE), the most prominent hallmark of cancer cell metabolism, can be used to predict a response to targeting glucose metabolism. We establish a natural product, koningic acid (KA), to be a selective inhibitor of GAPDH, an enzyme we characterize to have differential control properties over metabolism during the WE...
September 8, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28918129/where-do-substrates-of-diacylglycerol-kinases-come-from-diacylglycerol-kinases-utilize-diacylglycerol-species-supplied-from-phosphatidylinositol-turnover-independent-pathways
#4
REVIEW
Fumio Sakane, Satoru Mizuno, Daisuke Takahashi, Hiromichi Sakai
Diacylglycerol kinase (DGK) phosphorylates diacylglycerol (DG) to produce phosphatidic acid (PA). Mammalian DGK comprises ten isozymes (α-κ) and regulates a wide variety of physiological and pathological events, such as cancer, type II diabetes, neuronal disorders and immune responses. DG and PA consist of various molecular species that have different acyl chains at the sn-1 and sn-2 positions, and consequently, mammalian cells contain at least 50 structurally distinct DG/PA species. Because DGK is one of the components of phosphatidylinositol (PI) turnover, the generally accepted dogma is that all DGK isozymes utilize 18:0/20:4-DG derived from PI turnover...
September 9, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28917899/polysaccharides-from-brown-algae-sargassum-duplicatum-the-structure-and-anticancer-activity-in-vitro
#5
Roza V Usoltseva, Stanislav D Anastyuk, Natalia M Shevchenko, Valerii V Surits, Artem S Silchenko, Vladimir V Isakov, Tatiana N Zvyagintseva, Pham Duc Thinh, Svetlana P Ermakova
The laminaran SdL and fucoidan SdF were isolated from brown algae Sargassum duplicatum. SdL was 1,3;1,6-β-d-glucan (1,3:1,6=6:1) with a main chain, represented by 1,3-linked glucose residues, due to NMR spectroscopy data. Single glucose residues could form branches at C6. Unusual structure of fucoidan SdF was studied by chemical and enzymatic methods, NMR spectroscopy of desulfated and deacetylated polysaccharide and mass spectrometry of fucoidan fragments labeled with (18)O. Fucoidan was sulfated (31.7%) and acetylated galactofucan (Fuc:Gal∼1:1) with a main chain of 1,4-linked alternating α-l-fucose and β-d-galactose residues...
November 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28917545/effects-of-acarbose-on-cardiovascular-and-diabetes-outcomes-in-patients-with-coronary-heart-disease-and-impaired-glucose-tolerance-ace-a-randomised-double-blind-placebo-controlled-trial
#6
Rury R Holman, Ruth L Coleman, Juliana C N Chan, Jean-Louis Chiasson, Huimei Feng, Junbo Ge, Hertzel C Gerstein, Richard Gray, Yong Huo, Zhihui Lang, John J McMurray, Lars Rydén, Stefan Schröder, Yihong Sun, Michael J Theodorakis, Michal Tendera, Lynne Tucker, Jaakko Tuomilehto, Yidong Wei, Wenying Yang, Duolao Wang, Dayi Hu, Changyu Pan
BACKGROUND: The effect of the α-glucosidase inhibitor acarbose on cardiovascular outcomes in patients with coronary heart disease and impaired glucose tolerance is unknown. We aimed to assess whether acarbose could reduce the frequency of cardiovascular events in Chinese patients with established coronary heart disease and impaired glucose tolerance, and whether the incidence of type 2 diabetes could be reduced. METHODS: The Acarbose Cardiovascular Evaluation (ACE) trial was a randomised, double-blind, placebo-controlled, phase 4 trial, with patients recruited from 176 hospital outpatient clinics in China...
September 12, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28917433/surveillance-imaging-in-patients-with-endometrial-cancer-in-first-remission
#7
Yazan Z Alabed, Su-Chun Cheng, Christopher Mudge, Christopher Sakellis, Annick D Van den Abbeele, Susana M Campos, Heather A Jacene
OBJECTIVE: The clinical benefit of surveillance imaging in endometrial cancer remains undefined. This retrospective study was conducted to evaluate the positive predictive value (PPV) of surveillance imaging in endometrial cancer. METHODS: A total of 128 patients in first remission after treatment for endometrial cancer (uterine papillary serous, clear cell, stage III endometroid) who had surveillance imaging were retrospectively identified. The surveillance period was defined from the time of first-negative scan after treatment to the time when treatment was started for recurrent disease...
August 24, 2017: Current Problems in Diagnostic Radiology
https://www.readbyqxmd.com/read/28916747/hormetic-potential-of-methylglyoxal-a-side-product-of-glycolysis-in-switching-tumours-from-growth-to-death
#8
Marie-Julie Nokin, Florence Durieux, Justine Bellier, Olivier Peulen, Koji Uchida, David A Spiegel, James R Cochrane, Craig A Hutton, Vincent Castronovo, Akeila Bellahcène
Metabolic reprogramming toward aerobic glycolysis unavoidably favours methylglyoxal (MG) and advanced glycation end products (AGEs) formation in cancer cells. MG was initially considered a highly cytotoxic molecule with potential anti-cancer value. However, we have recently demonstrated that MG enhanced tumour growth and metastasis. In an attempt to understand this dual role, we explored MG-mediated dicarbonyl stress status in four breast and glioblastoma cancer cell lines in relation with their glycolytic phenotype and MG detoxifying capacity...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28915924/pdl1-and-ldha-act-as-cernas-in-triple-negative-breast-cancer-by-regulating-mir-34a
#9
Xiaojia Huang, Xinhua Xie, Hua Wang, Xiangsheng Xiao, Lu Yang, Zhi Tian, Xiaofang Guo, Lijuan Zhang, Hailin Tang, Xiaoming Xie
BACKGROUD: The purpose of this study was to elucidate the regulation of programmed death ligand 1 (PDL1), lactate dehydrogenase A (LDHA) and miR-34a in triple negative breast cancer (TNBC) and to explore the function and mechanism of PDL1 and LDHA as competitive endogenous RNAs (ceRNAs) in TNBC via regulation of miR-34a. METHODS: Western blotting, quantitative RT-PCR (qRT-PCR) and immunohistochemistry (IHC) assays were conducted to explore the expression of PDL1, LDHA and miR-34a in TNBC and correlations between them...
September 15, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28915713/the-reverse-warburg-effect-is-likely-to-be-an-achilles-heel-of-cancer-that-can-be-exploited-for-cancer-therapy
#10
REVIEW
Yaojie Fu, Shanshan Liu, Shanghelin Yin, Weihong Niu, Wei Xiong, Ming Tan, Guiyuan Li, Ming Zhou
Although survival outcomes of cancer patients have been improved dramatically via conventional chemotherapy and targeted therapy over the last decades, there are still some tough clinical challenges that badly needs to be overcome, such as anticancer drug resistance, inevitable recurrences, cancer progression and metastasis. Simultaneously, accumulated evidence demonstrates that aberrant glucose metabolism termed 'the Warburg effect' in cancer cell is closely associated with malignant phenotypes. In 2009, a novel 'two-compartment metabolic coupling' model, also named 'the reverse Warburg effect', was proposed and attracted lots of attention...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915636/role-of-glucose-metabolism-related-gene-glut1-in-the-occurrence-and-prognosis-of-colorectal-cancer
#11
Wenming Feng, Ge Cui, Cheng-Wu Tang, Xiao-Lan Zhang, Chuang Dai, Yong-Qiang Xu, Hui Gong, Tao Xue, Hui-Hui Guo, Ying Bao
Colorectal cancer (CRC) ranks the third most commonly diagnosed cancer in males and the second in females worldwide. However, the functional and causal SNPs for CRC remain to be mined. Glucose transporter 1 (GLUT1), a pivotal rate-limiting element in the transport of glucose in malignancy cells, has been identified to be associated with many cancers. Here, we aim to explore the role of GLUT1 in the occurrence and prognosis of colorectal cancer in a Chinese population. We found that GLUT1 expression levels in CRC tumor tissues were significantly higher than those in the corresponding adjacent normal tissues, and Cox multivariate analysis demonstrated that the GLUT1 expression was an independent prognostic factor for CRC (HR = 2...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915583/n-acetylcysteine-breaks-resistance-to-trastuzumab-caused-by-muc4-overexpression-in-human-her2-positive-bc-bearing-nude-mice-monitored-by-89-zr-trastuzumab-and-18-f-fdg-pet-imaging
#12
Zéna Wimana, Geraldine Gebhart, Thomas Guiot, Bruno Vanderlinden, Denis Larsimont, Gilles Doumont, Gaetan Van Simaeys, Serge Goldman, Patrick Flamen, Ghanem Ghanem
Trastuzumab remains an important drug in the management of human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer (BC). Several studies reported resistance mechanisms to trastuzumab, including impaired HER2-accessibility caused by mucin 4 (MUC4). Previously, we demonstrated an increase of Zirconium-89-radiolabeled-trastuzumab ((89)Zr-Trastuzumab) accumulation when MUC4-overexpressing BC-cells were challenged with the mucolytic drug N-Acetylcysteine (NAC). Hereby, using the same approach we investigated whether tumor exposure to NAC would also enhance trastuzumab-efficacy...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915575/hexokinase-2-promotes-tumor-growth-and-metastasis-by-regulating-lactate-production-in-pancreatic-cancer
#13
Marybeth Anderson, Raoud Marayati, Richard Moffitt, Jen Jen Yeh
Pancreatic ductal adenocarcinoma (PDAC) is a KRAS-driven cancer with a high incidence of metastasis and an overall poor prognosis. Previous work in a genetically engineered mouse model of PDAC showed glucose metabolism to be important for maintaining tumor growth. Multiple glycolytic enzymes, including hexokinase 2 (HK2), were upregulated in primary PDAC patient tumors, supporting a role for glycolysis in promoting human disease. HK2 was most highly expressed in PDAC metastases, suggesting a link between HK2 and aggressive tumor biology...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915394/overcoming-the-warburg-effect-is-it-the-key-to-survival-in-sepsis
#14
REVIEW
David Bar-Or, Matthew Carrick, Allen Tanner, Mark J Lieser, Leonard T Rael, Edward Brody
Sepsis is a leading cause of mortality in the U.S. and Europe. Sepsis and septic shock are the results of severe metabolic abnormalities following infection. Aerobic glycolysis (the Warburg Effect) is as much a hallmark of sepsis as it is of cancer. Warburg observed that cancer cells generated energy through glycolysis (generation of ATP through degradation of glucose, usually associated with anaerobic conditions) rather than through oxidative phosphorylation (generation of ATP through the mitochondrial inner membrane via the tricarboxylic acid cycle, usually associated with aerobic conditions)...
September 8, 2017: Journal of Critical Care
https://www.readbyqxmd.com/read/28912919/intravenous-carnitine-administration-in-addition-to-parenteral-nutrition-with-lipid-emulsion-may-decrease-the-inflammatory-reaction-in-postoperative-surgical-patients
#15
Yu Koyama, Kazuki Moro, Masato Nakano, Kohei Miura, Masayuki Nagahashi, Shin-Ichi Kosugi, Junko Tsuchida, Mayuko Ikarashi, Masato Nakajima, Hiroshi Ichikawa, Takaaki Hanyu, Yoshifumi Shimada, Jun Sakata, Hitoshi Kameyama, Takashi Kobayashi, Toshifumi Wakai
BACKGROUND: A prospective randomized study was performed to investigate the validity of intravenous carnitine administration during postoperative parenteral nutrition (PN) with lipid emulsion. METHODS: Patients undergoing surgery for gastric or colorectal cancer were enrolled in the study and were randomly divided into two groups (n = 8 in each group): 1) group L, who received a peripheral PN (PPN) solution of 7.5% glucose, 30% amino acid, and 20% lipid emulsion; and 2) group LC, who received the same PPN solution, as well as carnitine intravenously...
October 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28905672/the-influence-of-ketogenic-therapy-on-the-5-r-s-of-radiobiology
#16
Rainer J Klement
PURPOSE: Radiotherapy (RT) is a mainstay in the treatment of solid tumors and works by inducing free radical stress in tumor cells, leading to loss of reproductive integrity. The optimal treatment strategy has to consider damage to both tumor and normal cells and is determined by five factors known as the 5 R's of radiobiology: Reoxygenation, DNA Repair, Radiosensitivity, Redistribution in the cell cycle and Repopulation. The aim of this review is (i) to present evidence that these 5 R's are strongly influenced by cellular and whole body metabolism that in turn can be modified through ketogenic therapy in form of ketogenic diets and short term fasting, and (ii) to stimulate new research into this field including some research questions deserving further study...
September 14, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28904818/nf-%C3%AE%C2%BAb-pathway-link-with-er-stress-induced-autophagy-and-apoptosis-in-cervical-tumor-cells
#17
Xiaolan Zhu, Li Huang, Jie Gong, Chun Shi, Zhiming Wang, Bingkun Ye, Aiguo Xuan, Xiaosong He, Dahong Long, Xiao Zhu, Ningfang Ma, Shuilong Leng
Targeting endoplasmic reticulum (ER) stress is being investigated for its anticancer effect in various cancers, including cervical cancer. However, the molecular pathways whereby ER stress mediates cell death remain to be fully elucidated. In this study, we confirmed that ER stress triggered by compounds such as brefeldin A (BFA), tunicamycin (TM), and thapsigargin (TG) leads to the induction of the unfolded protein response (UPR) in cervical cancer cell lines, which is characterized by elevated levels of inositol-requiring kinase 1α, glucose-regulated protein-78, and C/EBP homologous protein, and swelling of the ER observed by transmission electron microscope (TEM)...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28904060/early-exposure-to-a-high-fat-high-sugar-diet-increases-the-mammary-stem-cell-compartment-and-mammary-tumor-risk-in-female-mice
#18
Isabel U Lambertz, Linjie Luo, Thomas R Berton, Scott L Schwartz, Stephen D Hursting, Claudio J Conti, Robin Fuchs-Young
Obesity and alterations in metabolic programming from early diet exposures can affect the propensity to disease in later life. Through dietary manipulation, developing mouse pups were exposed to a hyperinsulinemic, hyperglycemic milieu during three developmental phases: gestation, lactation and post-weaning. Analyses showed that a post-weaning high fat/high sugar (HF/HS) diet had the main negative effect on adult body weight, glucose tolerance and insulin resistance. However, dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis revealed that animals born to a mother fed a HF/HS gestation diet, nursed by a mother on a mildly diet-restricted, low fat/low sugar diet (DR) and weaned onto a HF/HS diet (HF/DR/HF) had the highest mammary tumor incidence, while HF/HF/DR had the lowest tumor incidence...
September 13, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28903386/synergistic-inhibition-of-colon-cancer-growth-by-the-combination-of-methylglyoxal-and-silencing-of-glyoxalase-i-mediated-by-the-stat1-pathway
#19
Yuan Chen, Lei Fang, Gefei Li, Jiali Zhang, Changxi Li, Mengni Ma, Chen Guan, Fumao Bai, Jianxin Lyu, Qing H Meng
Methylglyoxal (MG), an extremely reactive glucose metabolite, exhibits antitumor activity. Glyoxalase I (GLOI), which catalyzes MG metabolism, is associated with the progression of human malignancies. While the roles of MG or GLOI have been demonstrated in some types of cancer, their effects in colon cancer and the mechanisms underlying these effects remain largely unknown. For this study, MG and GLOI levels were manipulated in colon cancer cells and the effects on their viability, proliferation, apoptosis, migration, and invasion in vitro were quantified by Cell Counting Kit-8, colony formation assay, flow cytometry, and transwell assays...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903349/the-g-protein-coupled-bile-acid-receptor-gpbar1-tgr5-protects-against-renal-inflammation-and-renal-cancer-cell-proliferation-and-migration-through-antagonizing-nf-%C3%AE%C2%BAb-and-stat3-signaling-pathways
#20
Jia Su, Qiqi Zhang, Hui Qi, Linlin Wu, Yuanqiang Li, Donna Yu, Wendong Huang, Wei-Dong Chen, Yan-Dong Wang
Gpbar1 (TGR5), a G-protein-coupled bile acid membrane receptor, is well known for its roles in regulation of glucose metabolism and energy homeostasis. In the current work, we found that TGR5 activation by its ligand suppressed lipopolysaccharide (LPS)-induced proinflammatory gene expression in wild-type (WT) but not TGR5(-/-) mouse kidney. Furthermore, we found that TGR5 is a suppressor of kidney cancer cell proliferation and migration. We show that TGR5 activation antagonized NF-κB and STAT3 signaling pathways through suppressing the phosphorylation of IκBα, the translocation of p65 and the phosphorylation of STAT3...
August 15, 2017: Oncotarget
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