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https://www.readbyqxmd.com/read/28918508/metabolic-engineering-of-schizosaccharomyces-pombe-to-produce-punicic-acid-a-conjugated-fatty-acid-with-nutraceutic-properties
#1
Martina Garaiova, Elzbieta Mietkiewska, Randall J Weselake, Roman Holic
Punicic acid (PuA) is a conjugated linolenic acid (C18:3Δ(9c,11t,13c)) with a wide range of nutraceutic effects with the potential to reduce the incidence of a number of health disorders including diabetes, obesity, and cancer. It is the main component of seed oil from Punica granatum and Trichosanthes kirilowii. Previously, production of relatively high levels of this unusual fatty acid in the seed oil of transgenic Arabidopsis thaliana plant was accomplished by the use of A. thaliana fad3/fae1 mutant high in linoleic acid (18:2∆(9c,12c)) and by co-expression of P...
September 16, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28917600/atp-alters-protein-folding-and-function-of-escherichia-coli-uridine-phosphorylase
#2
Yi-Kai Liu, Tzu-Hsuan Lin, Pei-Fen Liu
Uridine phosphorylase is one of the critical enzymes in the pyrimidine salvage pathway. Cells regenerate uridine for nucleotide metabolism by incorporating uracil with ribose-1-phosphate with this enzyme. Recent studies indicate that Escherichia coli uridine phosphorylase is destabilized in the presence of ATP. However, the mechanism underlying the destabilization process and its influence on uridine phosphorylase function remain to be established. Here, we comprehensively investigated the effects of ATP on protein folding and function of Escherichia coli uridine phosphorylase...
September 13, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28917054/association-of-single-nucleotide-polymorphisms-in-selenoprotein-genes-with-cancer-risk
#3
Catherine Méplan
Genetic association studies have linked genetic variants in the Selenium (Se) metabolism with the development of complex diseases such as cancer and helped unravel novel mechanisms underlying cancer development. The chapter describes the specificity of genetic variants in the Se metabolism, the approaches used in association studies, and the limitations of such approaches.
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28916931/physical-exercise-prescription-in-metabolic-chronic-disease
#4
Laura Stefani, Giorgio Galanti
Metabolic syndrome as a consequence of the association to overweight, hypertension, and diabetes is at high risk of coronary events. Regular physical training has been recently promoted to reduce cardiovascular risks factors, by the improved lifestyle and also by the "anti-inflammatory effectiveness." A positive impact has been shown in case of cancer survived patients either with or without comorbidities and especially in those subjects where the inflammatory process is globally represented. The American College of Sports Medicine (ACSM) guidelines and more recently a new Italian model both support the role of "exercise as therapy" at moderate level of energy expenditure...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28916747/hormetic-potential-of-methylglyoxal-a-side-product-of-glycolysis-in-switching-tumours-from-growth-to-death
#5
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/28916726/the-nqo1-bioactivatable-drug-%C3%AE-lapachone-alters-the-redox-state-of-nqo1-pancreatic-cancer-cells-causing-perturbation-in-central-carbon-metabolism
#6
Molly A Silvers, Stanislaw Deja, Naveen Singh, Robert A Egnatchik, Jessica Sudderth, Xiuquan Luo, Muhammad S Beg, Shawn C Burgess, Ralph J DeBerardinis, David A Boothman, Matthew E Merritt
Many cancer treatments, such as those for managing recalcitrant tumors like pancreatic ductal adenocarcinoma, cause off-target toxicities in normal, healthy tissue, highlighting the need for more tumor-selective chemotherapies. β-Lapachone is bioactivated by NAD(P)H:quinone oxidoreductase 1 (NQO1). This enzyme exhibits elevated expression in most solid cancers and therefore is a potential cancer-specific target. β-Lapachone's therapeutic efficacy partially stems from the drug's induction of a futile NQO1-mediated redox cycle that causes high levels of superoxide, then peroxide formation, which damages DNA and causes hyperactivation of poly (ADP-ribose) polymerase (PARP), resulting in extensive NAD+/ATP depletion...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28916476/pharmacologic-ascorbate-induces-neuroblastoma-cell-death-by-hydrogen-peroxide-mediated-dna-damage-and-reduction-in-cancer-cell-glycolysis
#7
Enlong Ma, Ping Chen, Heather M Wilkins, Tao Wang, Russell H Swerdlow, Qi Chen
An ascorbate-mediated production of oxidative stress has been shown to retard tumor growth. Subsequent glycolysis inhibition has been suggested. Here, we further define the mechanisms relevant to this observation. Ascorbate was cytotoxic to human neuroblastoma cells through the production of H2O2, which led to ATP depletion, inhibited GAPDH, and non-apoptotic and non-autophagic cell death. The mechanism of cytotoxicity is different when PARP-dependent DNA repair machinery is active or inhibited. Ascorbate-generated H2O2 damaged DNA, activated PARP, depleted NAD+, and reduced glycolysis flux...
September 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28916189/phosphoinositide-5-phosphatase-activities-control-cell-motility-in-glioblastoma-two-phosphoinositides-pi-4-5-p2-and-pi-3-4-p2-are-involved
#8
REVIEW
Ana Raquel Ramos, William's Elong Edimo, Christophe Erneux
Inositol polyphosphate 5-phosphatases or phosphoinositide 5-phosphatases (PI 5-phosphatases) are enzymes that can act on soluble inositol phosphates and/or phosphoinositides (PIs). Several PI 5-phosphatases have been linked to human genetic diseases, in particular the Lowe protein or OCRL which is mutated in the Lowe syndrome. There are 10 different members of this family and 9 of them can use PIs as substrate. One of these substrates, PI(3,4,5)P3 binds to specific PH domains and recruits as effectors specific proteins to signaling complexes...
September 5, 2017: Advances in Biological Regulation
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/28915708/targeting-metabolism-and-amp-activated-kinase-with-metformin-to-sensitize-non-small-cell-lung-cancer-nsclc-to-cytotoxic-therapy-translational-biology-and-rationale-for-current-clinical-trials
#11
REVIEW
Michael Troncone, Stephanie M Cargnelli, Linda A Villani, Naghmeh Isfahanian, Lindsay A Broadfield, Laura Zychla, Jim Wright, Gregory Pond, Gregory R Steinberg, Theodoros Tsakiridis
Lung cancer is the most fatal malignancy worldwide, in part, due to high resistance to cytotoxic therapy. There is need for effective chemo-radio-sensitizers in lung cancer. In recent years, we began to understand the modulation of metabolism in cancer and its importance in tumor progression and survival after cytotoxic therapy. The activity of biosynthetic pathways, driven by the Growth Factor Receptor/Ras/PI3k/Akt/mTOR pathway, is balanced by the energy stress sensor pathway of LKB1/AMPK/p53. AMPK responds both to metabolic and genotoxic stress...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915652/pld1-overexpression-promotes-invasion-and-migration-and-function-as-a-risk-factor-for-chinese-glioma-patients
#12
Wenjun Tang, Richu Liang, Yonghong Duan, Qiaoling Shi, Xiaofei Liu, Yongshi Liao
Glioma is a lethal disease with few effective therapeutic options. Recently, insights into cancer biology had suggested that abnormal lipid metabolism was a risk factor for various human malignancies, including glioma. As a key enzyme implicated in lipid metabolism, PLD1 was overexpression in multiple human cancers, and it was stated to be responsible for aggressive phenotypes, such as angiogenesis and chemoresistance. However, there was still much to know about its expression and function in glioma. In the present study, we showed that PLD1 was overexpression in clinical samples of glioma...
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
#13
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
#14
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/28915578/targeting-hypoxic-cancer-stem-cells-cscs-with-doxycycline-implications-for-optimizing-anti-angiogenic-therapy
#15
Ernestina Marianna De Francesco, Marcello Maggiolini, Herbert B Tanowitz, Federica Sotgia, Michael P Lisanti
Here, we report new mechanistic insight into how chronic hypoxia increases 'stemness' in cancer cells. Using chemical inhibitors, we provide direct experimental evidence that ROS production and mitochondrial biogenesis are both required for the hypoxia-induced propagation of CSCs. More specifically, we show that hypoxic CSCs can be effectively targeted with i) simple mitochondrial anti-oxidants (Mito-TEMPO) and/or ii) inhibitors of mitochondrial biogenesis (Doxycycline). In this context, we discuss the idea that mitochondrial biogenesis itself may be a primary driver of "stemness" in hypoxic cancer cells, with metabolic links to fatty acid oxidation (FAO)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915575/hexokinase-2-promotes-tumor-growth-and-metastasis-by-regulating-lactate-production-in-pancreatic-cancer
#16
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/28915495/impact-of-chemotherapy-on-metabolic-reprogramming-characterization-of-the-metabolic-profile-of-breast-cancer-mda-mb-231-cells-using-1-h-hr-mas-nmr-spectroscopy
#17
Roberta M Maria, Wanessa F Altei, Heloisa S Selistre-de-Araujo, Luiz A Colnago
Doxorubicin, cisplatin, and tamoxifen are part of many chemotherapeutic regimens. However, studies investigating the effect of chemotherapy on the metabolism of breast cancer cells are still limited. We used (1)H high-resolution magic angle spinning (HR-MAS) NMR spectroscopy to study the metabolic profile of human breast cancer MDA-MB-231 cells either untreated (control) or treated with tamoxifen, cisplatin, and doxorubicin. (1)H HR-MAS NMR single pulse spectra evidenced signals from all mobile cell compounds, including fatty acids (membranes), water-soluble proteins, and metabolites...
September 12, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28915394/overcoming-the-warburg-effect-is-it-the-key-to-survival-in-sepsis
#18
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/28915052/mass-spectrometric-analysis-of-sox11-binding-proteins-in-head-and-neck-cancer-cells-demonstrates-the-interaction-of-sox11-and-hsp90%C3%AE
#19
Naseim Elzakra, Li Cui, Tong Liu, Hong Li, Junwei Huang, Shen Hu
Deregulated expression of SOX11 has been shown to involve in the progression of various types of cancer. However, the role of SOX11 in head and neck cancer remains largely unknown. In this study, co-immunoprecipitation (Co-IP) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were performed to identify the proteins that binds to SOX11 at significant higher levels in head and neck cancer cells compared to the normal human oral keratinocytes. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that many potential SOX11-binding partners were associated with protein synthesis, cell metabolism and cell-cell adhesion...
September 15, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28914765/statin-and-bisphosphonate-induce-starvation-in-fast-growing-cancer-cell-lines
#20
Heidrun Karlic, Florian Haider, Roman Thaler, Silvia Spitzer, Klaus Klaushofer, Franz Varga
Statins and bisphosphonates are increasingly recognized as anti-cancer drugs, especially because of their cholesterol-lowering properties. However, these drugs act differently on various types of cancers. Thus, the aim of this study was to compare the effects of statins and bisphosphonates on the metabolism (NADP⁺/NADPH-relation) of highly proliferative tumor cell lines from different origins (PC-3 prostate carcinoma, MDA-MB-231 breast cancer, U-2 OS osteosarcoma) versus cells with a slower proliferation rate like MG-63 osteosarcoma cells...
September 15, 2017: International Journal of Molecular Sciences
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