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Terezinha M Souza, Linda Rieswijk, Twan van den Beucken, Jos Kleinjans, Danyel Jennen
Chemical carcinogenesis, albeit complex, often relies on modulation of transcription through activation or repression of key transcription factors. While analyzing extensive networks may hinder the biological interpretation, one may focus on dynamic network motifs, among which persistent feed-forward loops (FFLs) are known to chronically influence transcriptional programming. Here, to investigate the relevance a FFL-oriented approach in depth, we have focused on aflatoxin B1-induced transcriptomic alterations during distinct states of exposure (daily administration during 5 days followed by a non-exposed period) of human hepatocytes, by exploring known interactions in human transcription...
October 17, 2016: Toxicology
Kaijun Di, Naomi Lomeli, Spencer D Wood, Christopher D Vanderwal, Daniela A Bota
Mitochondrial dysfunction is a hallmark of cancer biology. Tumor mitochondrial metabolism is characterized by an abnormal ability to function in scarce oxygen conditions through glycolysis (the Warburg effect), and accumulation of mitochondrial DNA defects are present in both hereditary neoplasia and sporadic cancers. Mitochondrial Lon is a major regulator of mitochondrial metabolism and the mitochondrial response to free radical damage, and plays an essential role in the maintenance and repair of mitochondrial DNA...
October 15, 2016: Oncotarget
D Kabzińska, H Mierzewska, J Senderek, A Kochański
The Warburg micro syndrome (WARBM) is a genetically heterogeneous syndrome linked to at least 4 loci. At the clinical level, WARBM is characterized by microcephaly, microphthalmia, microcornea, congenital cataracts, corpus callosum hypoplasia, severe mental retardation, and hypogonadism. In some families additional clinical features have been reported. The presence of uncommon clinical features (peripheral neuropathy, cardiomyopathy) may result in misdirected molecular diagnostics. Using the next generation sequencing approach (NGS), we were able to diagnose WARBM1 syndrome by detection of a new mutation within the RAB3GAP1 gene...
2016: Folia Neuropathologica
Fangzhou Shen, Jian Li, Ying Zhu, Zhuo Wang
Cancer cells have different metabolism in contrast to normal cells. The advancement in omics measurement technology enables the genome-wide characterization of altered cellular processes in cancers, but the metabolic flux landscape of cancer is still far from understood. In this study, we compared the well-reconstructed tissue-specific models of five cancers, including breast, liver, lung, renal, and urothelial cancer, and their corresponding normal cells. There are similar patterns in majority of significantly regulated pathways and enriched pathways in correlated reaction sets...
August 29, 2016: Journal of Bioinformatics and Computational Biology
Mª Del Mar Blanquer-Rosselló, Reyniel Hernández-López, Pilar Roca, Jordi Oliver, Adamo Valle
BACKGROUND: The polyphenol resveratrol (RSV) is found in the skin of red grapes and has been reported to exhibit anticancer properties. The antitumor effects of RSV in the gastrointestinal tract have gained considerable interest due to the high exposure of this tissue to this dietary compound. One of the hallmarks of cancer cells is their particular metabolism mainly relying on glycolysis for ATP production rather than mitochondrial oxidative phosphorylation. Although RSV has been described to act as a calorie-restriction mimetic, modulating energy metabolism in normal tissues, little efforts have been done to study the effects of this polyphenol in the metabolism of cancer cells...
October 17, 2016: Biochimica et Biophysica Acta
Perparim Limani, Michael Linecker, Philipp Kron, Panagiotis Samaras, Bernhard Pestalozzi, Roger Stupp, Alexander Jetter, Philipp Dutkowski, Beat Müllhaupt, Andrea Schlegel, Claude Nicolau, Jean-Marie Lehn, Henrik Petrowsky, Bostjan Humar, Rolf Graf, Pierre-Alain Clavien
BACKGROUND: Solid tumors, such as hepato-pancreato-biliary cancer, develop tumor hypoxia with tumor growth. Despite advances in surgery, a majority of these patients are in an unresectable condition. At this stage standard cytotoxic chemotherapy regimens are applied with limited success. Novel biological treatment options based on an antiangiogenic mechanism of action neglect other hypoxia mediated mechanisms (e.g. epithelial-mesenchymal transition, Warburg effect, and immunological response) leading to an increased invasiveness with a poor outcome...
October 19, 2016: BMC Cancer
Raquel Guimarães Coelho, Juliana de Menezes Cazarin, João Paulo Albuquerque Cavalcanti de Albuquerque, Bruno Moulin de Andrade, Denise P Carvalho
Acceleration of glycolysis is a characteristic of neoplasia. Previous studies have shown that a metabolic shift occurs in many tumors and correlates with a negative prognosis. The present study aimed to investigate the glycolytic profile of thyroid carcinoma cell lines. We investigated glycolytic and oxidative parameters of two thyroid carcinoma papillary cell lines (BCPAP and TPC1) and the non-tumor cell line NTHY-ori. All carcinoma cell lines showed higher rates of glycolysis efficiency, when compared to NTHY-ori, as assessed by a higher rate of glucose consumption and lactate production...
October 4, 2016: Oncology Reports
Tatjana Harting, Mandy Stubbendorff, Saskia Willenbrock, Siegfried Wagner, Patrik Schadzek, Anaclet Ngezahayo, Hugo Murua Escobar, Ingo Nolte
The Warburg effect describes the ability of cancer cells to produce energy via aerobic glycolysis instead of oxidative phosphorylation of pyruvate. This deviation in mitochondrial metabolism inhibits apoptosis, allowing increased proliferation under conditions of reduced oxygen levels. Dichloroacetate (DCA) was successfully used in several human cancer cell lines to reactivate oxidative phosphorylation in mitochondria. The aim of this study was the characterization and response of canine cancer cell lines after DCA exposure...
October 5, 2016: International Journal of Oncology
G Barbero
The derivation of Warburg's impedance presented in several books and scientific papers is reconsidered. In the past it was obtained by assuming that the total electric current across the sample is just due to the diffusion, and that the external potential applied to the electrode is responsible for an increase of the bulk density of charge described by Nernst's model. We show that these assumptions are not correct, and hence the proposed derivations are questionable. When the electrochemical impedance of a cell of an insulating material where external charges are injected of a given sign is correctly determined, in the high frequency region the real and imaginary parts do not follow the trends predicted by Warburg's impedance...
October 17, 2016: Physical Chemistry Chemical Physics: PCCP
Juan Yang, Cun Wang, Fengbo Zhao, Xiaoying Luo, Meilin Qin, Einthavy Arunachalam, Zhouhong Ge, Ning Wang, Xuan Deng, Guangzhi Jin, Wenming Cong, Wenxin Qin
Reprogrammed metabolism has been identified as an emerging hallmark in cancer cells. It has been demonstrated that fructose-1, 6-bisphosphatase 1 (FBP1) as a rate-limiting enzyme in gluconeogenesis plays critical roles in tumor initiation and progression in several cancer types. However, function of FBP1 in hepatocelluar carcinoma (HCC) is still not clear. In this study, we observed that the expression of FBP1 was obviously downregulated in the cell lines and tissues of HCC. Downregulation of FBP1 in HCC tissues was correlated with a lower overall survival rate and had a relatively higher tendency of tumor recurrence (n = 224)...
October 14, 2016: Carcinogenesis
Jingtao Luo, Yun Hong, Xiaoan Tao, Xi Wei, Lun Zhang, Qiang Li
Unlike normal cells, cancer cells are recently identified to rely on aerobic glycolysis for energy production called the Warburg effect. Several attempts are being made to target this metabolic reprogramming pathway in treating cancers; however, the successful rate is very limited. In this study, we investigated the functional roles of fatty acid oxidation key enzyme carnitine palmitoyl transferase 1a (CPT-1a), during the metabolic programming of pancreatic ductal adenocarcinoma (PDAC) cells induced by glucose deprivation...
October 13, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Siroon Bekkering, Bastiaan A Blok, Leo A B Joosten, Niels P Riksen, Reinout van Crevel, Mihai G Netea
BACKGROUND: Innate immune memory or 'trained immunity' has recently been described as an important property of cells of the innate immune system. Due to the increased interest in this important new field of immunological investigation we sought to determine the optimal conditions for an in-vitro experimental protocol of monocyte training using three of the most commonly used training stimuli from the literature: β-glucan, the Bacille Calmette-Guérin (BCG) vaccine, and oxidized LDL (oxLDL)...
October 12, 2016: Clinical and Vaccine Immunology: CVI
Bradley Smith, Xenia L Schafer, Aslihan Ambeskovic, Cody M Spencer, Hartmut Land, Joshua Munger
Metabolic reprogramming is critical to oncogenesis, but the emergence and function of this profound reorganization remain poorly understood. Here we find that cooperating oncogenic mutations drive large-scale metabolic reprogramming, which is both intrinsic to cancer cells and obligatory for the transition to malignancy. This involves synergistic regulation of several genes encoding metabolic enzymes, including the lactate dehydrogenases LDHA and LDHB and mitochondrial glutamic pyruvate transaminase 2 (GPT2)...
October 11, 2016: Cell Reports
Stephanie Sprowl-Tanio, Amber N Habowski, Kira T Pate, Miriam M McQuade, Kehui Wang, Robert A Edwards, Felix Grun, Yung Lyou, Marian L Waterman
BACKGROUND: There is increasing evidence that oncogenic Wnt signaling directs metabolic reprogramming of cancer cells to favor aerobic glycolysis or Warburg metabolism. In colon cancer, this reprogramming is due to direct regulation of pyruvate dehydrogenase kinase 1 (PDK1) gene transcription. Additional metabolism genes are sensitive to Wnt signaling and exhibit correlative expression with PDK1. Whether these genes are also regulated at the transcriptional level, and therefore a part of a core metabolic gene program targeted by oncogenic WNT signaling, is not known...
2016: Cancer & Metabolism
Yaqing Li, Ruixia Huang, Xiaoli Li, Xiaoran Li, Dandan Yu, Mingzhi Zhang, Jianguo Wen, Mariusz Adam Goscinski, Claes G Trope, Jahn M Nesland, Zhenhe Suo
Pyruvate dehydrogenase A1 (PDHA1) serves as a gate-keeper enzyme link between glycolysis and the mitochondrial citric acid cycle. The inhibition of PDHA1 in cancer cells can result in an increased Warburg effect and a more aggressive phenotype in cancer cells. This study was conducted to investigate the expression of PDHA1 in ovarian cancer and the correlation between PDHA1 expression and the prognosis of patients. The PDHA1 protein expression in 3 ovarian cancer cell lines (OVCAR-3, SKOV-3 and ES-2) and 248 surgically removed ovarian carcinoma samples was immunocytochemically examined...
2016: American Journal of Cancer Research
Shubha Gururaja Rao
Mitochondrial structural and functional integrity defines the health of a cell by regulating cellular metabolism. Thus, mitochondria play an important role in both cell proliferation and cell death. Cancer cells are metabolically altered compared to normal cells for their ability to survive better and proliferate faster. Resistance to apoptosis is an important characteristic of cancer cells and given the contribution of mitochondria to apoptosis, it is imperative that mitochondria could behave differently in a tumor situation...
October 8, 2016: Handbook of Experimental Pharmacology
Min Peng, Na Yin, Sagar Chhangawala, Ke Xu, Christina S Leslie, Ming O Li
Aerobic glycolysis (the Warburg effect) is a metabolic hallmark of activated T cells, and has been implicated in augmenting effector T cell responses including expression of the proinflammatory cytokine interferon-γ (IFN-γ) via 3' untranslated region (3'UTR)-mediated mechanisms. Here, we show that lactate dehydrogenase A (LDHA) is induced in activated T cells to support aerobic glycolysis but promotes IFN-γ expression independently of its 3'UTR. Instead, LDHA maintains high levels of acetyl-coenzyme A to enhance histone acetylation and transcription of Ifng Ablation of LDHA in T cells protects mice from immunopathology triggered by excessive IFN-γ expression or deficiency of regulatory T cells...
September 29, 2016: Science
Jorgelindo da Veiga Moreira, Minoo Hamraz, Mohammad Abolhassani, Erwan Bigan, Sabine Pérès, Loïc Paulevé, Marcel Levy Nogueira, Jean-Marc Steyaert, Laurent Schwartz
To better understand the energetic status of proliferating cells, we have measured the intracellular pH (pHi) and concentrations of key metabolites, such as adenosine triphosphate (ATP), nicotinamide adenine dinucleotide (NAD), and nicotinamide adenine dinucleotide phosphate (NADP) in normal and cancer cells, extracted from fresh human colon tissues. Cells were sorted by elutriation and segregated in different phases of the cell cycle (G0/G1/S/G2/M) in order to study their redox (NAD, NADP) and bioenergetic (ATP, pHi) status...
October 3, 2016: Metabolites
Taro Sugiyama, Kohei Taniguchi, Nobuhisa Matsuhashi, Toshihiro Tajirika, Manabu Futamura, Tomoaki Takai, Yukihiro Akao, Kazuhiro Yoshida
The metabolism in tumor cells shifts from oxidative phosphorylation to glycolysis even in an aerobic environment, which phenomenon is known as the Warburg effect. This effect is regulated mainly by polypyrimidine tract-binding protein 1 (PTBP1), which is a splicer of the mRNA for the rate-limiting enzymes of glycolysis, pyruvate kinase muscle 1 and 2 (PKM1 and PKM2). In the present study, we demonstrated that miR-133b reduced PTBP1 expression at translational level and that the expression levels of miR-133b were significantly down-regulated in gastric cancer clinical samples and human cell lines, whereas the protein expression level of PTBP1 was up-regulated in 80% of the 20 clinical samples of gastric cancer examined...
October 3, 2016: Cancer Science
Neeta Pandit-Taskar, Darren R Veach, Josef J Fox, Howard I Scher, Michael J Morris, Steven M Larson
Castration-resistant prostate cancer (CRPC) is the lethal form of prostate cancer, and more than 26,000 men will die from this disease in 2016. The pathophysiology of CRPC is clearly multifactorial, but most often, androgen receptor (AR) upregulation is associated with its earliest beginnings and the AR increase is part of the multimolecular complex including downstream effector proteins linked to AR (AR-axis) responsible for rapid proliferation and malignant features of the malignant cell. In both animal models and patients, glycolysis (Warburg effect) is also an early manifestation of CRPC transformation...
October 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
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