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https://www.readbyqxmd.com/read/28106737/a-novel-combination-rnai-toward-warburg-effect-by-replacement-with-mir-145-and-silencing-of-ptbp1-induces-apoptotic-cell-death-in-bladder-cancer-cells
#1
Tomoaki Takai, Yuki Yoshikawa, Teruo Inamoto, Koichiro Minami, Kohei Taniguchi, Nobuhiko Sugito, Yuki Kuranaga, Haruka Shinohara, Minami Kumazaki, Takuya Tsujino, Kiyoshi Takahara, Yuko Ito, Yukihiro Akao, Haruhito Azuma
Bladder cancer is one of the most difficult malignancies to control. We explored the use of a novel RNA-interference method for a driver oncogene regulating cancer specific energy metabolism by the combination treatment with a small interfering RNA (siRNA) and a microRNA. After transfection of T24 and 253JB-V cells with miR-145 and/or siR-PTBP1, we examined the effects of cell growth and gene expression by performing the trypan blue dye exclusion test, Western blot, Hoechst 33342 staining, reverse transcription polymerase chain reaction (RT-PCR), and electron microscopy...
January 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28105937/effect-of-lentivirus-mediated-shrna-inactivation-of-hk1-hk2-and-hk3-genes-in-colorectal-cancer-and-melanoma-cells
#2
Anna V Kudryavtseva, Maria S Fedorova, Alex Zhavoronkov, Alexey A Moskalev, Alexander S Zasedatelev, Alexey A Dmitriev, Asiya F Sadritdinova, Irina Y Karpova, Kirill M Nyushko, Dmitry V Kalinin, Nadezhda N Volchenko, Nataliya V Melnikova, Kseniya M Klimina, Dmitry V Sidorov, Anatoly Y Popov, Tatiana V Nasedkina, Andrey D Kaprin, Boris Y Alekseev, George S Krasnov, Anastasiya V Snezhkina
BACKGROUND: The switch from oxidative phosphorylation to glycolysis in proliferating cancer cells, even under aerobic conditions, has been shown first in 1926 by Otto Warburg. Today this phenomenon is known as the "Warburg effect" and recognized as a hallmark of cancer. The metabolic shift to glycolysis is associated with the alterations in signaling pathways involved in energy metabolism, including glucose uptake and fermentation, and regulation of mitochondrial functions. Hexokinases (HKs), which catalyze the first step of glycolysis, have been identified to play a role in tumorigenesis of human colorectal cancer (CRC) and melanoma...
December 22, 2016: BMC Genetics
https://www.readbyqxmd.com/read/28098871/lectin-pcl-inhibits-the-warburg-effect-of-pc3-cells-by-combining-with-egfr-and-inhibiting-hk2
#3
Hong Zhang, Xia Du, Ting-Ting Sun, Chun-Liu Wang, Ye Li, Shou-Zhen Wu
Prostatic carcinoma is the most aggressive tumor in adult men. Warburg effect is an important characteristic of tumor cell metabolism including prostate cancer cells, in which hexokinase 2 (HK2), a major rate-limiting enzyme involved in Warburg effect, is selectively upregulated. The lectin PCL is a mannose binding lectin which induces tumor cell apoptosis and autophagy. In the present study, we report that PCL could lower glucose consumption and lactate production, shift the Warburg effect by inhibiting the expression of HK2 in PC3 cells and the suppression of HK2 by siRNA reversed the effect of PCL on glucose consumption and lactate production...
January 16, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28094552/glucose-metabolism-in-cancer-and-ischemia-possible-therapeutic-consequences-of-the-warburg-effect
#4
Spela Salamon, Eva Podbregar, Peter Kubatka, Dietrich Büsselberg, Martin Caprnda, Radka Opatrilova, Vanda Valentova, Mariusz Adamek, Peter Kruzliak, Matej Podbregar
The Warburg effect states that the main source of energy for cancer cells is not aerobic respiration, but glycolysis-even in normoxia. The shift from one to the other is governed by mutually counteracting enzymes: pyruvate dehydrogenase and pyruvate dehydrogenase kinase (PDK). Anaerobic metabolism of cancer cells promotes cell proliferation, local tissue immunosuppression, resistance to hypoxic conditions, and metastatic processes. By switching glucose back to oxidative metabolism, these effects might be reversed...
January 17, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28093985/ketogenic-diet-and-other-dietary-intervention-strategies-in-the-treatment-of-cancer
#5
Matteo Vergati, Eriseld Krasniqi, Girolamo Del Monte, Silvia Riondino, Doriana Vallone, Fiorella Guadagni, Patrizia Ferroni, Mario Roselli
Pre-clinical and clinical studies have investigated the role of a dysregulated metabolism in the sustainability of tumor initiation and progression. One of the most familiar metabolic alterations encountered in several types of cancers is the upregulation of glycolysis, which is also maintained in conditions of normal oxygen tension (aerobic glycolysis, Warburg effect) while oxidative phosphorylation is apparently reduced. As a result, cancer cells convert most incoming glucose to lactate. Although more rapid, adenosine triphosphate (ATP) production by glycolysis is less efficient in terms of ATP generated per unit of glucose consumed than oxidative phosphorylation...
January 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28093201/molecular-targets-of-the-warburg-effect-and-inflammatory-cytokines-in-the-pathogenesis-of-pulmonary-artery-hypertension
#6
REVIEW
Na Liu, Stephanie Parry, Yunbin Xiao, Shenghua Zhou, Qiming Liu
Pulmonary arterial hypertension (PAH) is a progressive vascular disease characterized by increased pulmonary arterial pressure and vasoconstriction and structural remolding of pulmonary arterioles. Recent clinical and experimental studies have discovered the relationship between metabolic alterations and the pathogenesis of PAH. The primary metabolic alteration, previously demonstrated in various cancers, is a gradual change in energy generated from complete aerobic cellular respiration to from solely "aerobic glycolysis," termed the "Warburg effect...
January 13, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28088584/proton-pump-inhibition-and-cancer-therapeutics-a-specific-tumor-targeting-or-it-is-a-phenomenon-secondary-to-a-systemic-buffering
#7
REVIEW
Enrico Spugnini, Stefano Fais
One of the unsolved mysteries in oncology includes the strategies that cancer cells adopt to cope with an adverse microenvironment. However, we knew, from the Warburg's discovery that through their metabolism based on sugar fermentation, cancer cells acidify their microenvironment and this progressive acidification induces a selective pressure, leading to the development of very malignant cells entirely armed to survive in the hostile microenvironment generated by their own metabolism. In the last decades a primordial role for proton exchangers has been supported as a key tumor advantage in facing off the acidic milieu...
January 11, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28088583/environmental-carcinogenesis-and-ph-homeostasis-not-only-a-matter-of-dysregulated-metabolism
#8
REVIEW
Kévin Hardonnière, Laurence Huc, Odile Sergent, Jørn A Holme, Dominique Lagadic-Gossmann
According to the World Health Organization, around 20% of all cancers would be due to environmental factors. Among these factors, several chemicals are indeed well recognized carcinogens. The widespread contaminant benzo[a]pyrene (B[a]P), an often used model carcinogen of the polycyclic aromatic hydrocarbons' family, has been suggested to target most, if not all, cancer hallmarks described by Hanahan and Weinberg. It is classified as a group I carcinogen by the International Agency for Research on Cancer; however, the precise intracellular mechanisms underlying its carcinogenic properties remain yet to be thoroughly defined...
January 11, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28078877/congenital-muscular-dystrophy-and-epilepsy-a-prospective-case-series-of-pediatric-patients
#9
G Vitaliti, P Pavone, C Romano, M Barbagallo, M Vecchio, C Ledda, R Lubrano, R Falsaperla
Congenital Muscular Dystrophies (CMDs) can be considered as a heterogeneous group of diseases characterized by marked weakness, generalized hypotonia and joint contractures. They are divided into pure and classical forms, without ocular and cerebral involvement, and complex forms, which are associated with cerebral abnormalities. Seizures have rarely been described in the pure forms while they seem to occur more frequently in complex forms. The aim of our study was to evaluate the incidence of seizure in CMD...
October 2016: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28077309/physical-and-biological-characteristics-of-multi-drug-resistance-mdr-an-integral-approach-considering-ph-and-drug-resistance-in-cancer
#10
REVIEW
Ziad Omran, Paula Scaife, Simon Stewart, Cyril Rauch
The role of the Warburg effect in cancer remains to be elucidated with a resurgence in research efforts over the past decade. Why a cancer cell would prefer to use energy inefficient glycolysis, leading to an alteration of pH both inside and outside of the cell, remains to be uncovered. The development of MDR represents a major challenge in the treatment of cancer and it is explained, so far, by the over expression of drug transporters such as the well-known and archetypal P-glycoprotein (Pgp). However, controversies exist regarding the function of Pgp in multi-drug resistance...
January 8, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28076853/pyruvate-dehydrogenase-expression-is-negatively-associated-with-cell-stemness-and-worse-clinical-outcome-in-prostate-cancers
#11
Yali Zhong, Xiaoli Li, Yasai Ji, Xiaoran Li, Yaqing Li, Dandan Yu, Yuan Yuan, Jian Liu, Huixiang Li, Mingzhi Zhang, Zhenyu Ji, Dandan Fan, Jianguo Wen, Mariusz Adam Goscinski, Long Yuan, Bin Hao, Jahn M Nesland, Zhenhe Suo
Cells generate adenosine-5'-triphosphate (ATP), the major currency for energy-consuming reactions, through mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis. One of the remarkable features of cancer cells is aerobic glycolysis, also known as the "Warburg Effect", in which cancer cells rely preferentially on glycolysis instead of mitochondrial OXPHOS as the main energy source even in the presence of high oxygen tension. One of the main players in controlling OXPHOS is the mitochondrial gatekeeperpyruvate dehydrogenase complex (PDHc) and its major subunit is E1α (PDHA1)...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28076790/the-anti-warburg-effect-elicited-by-the-camp-pgc1%C3%AE-pathway-drives-differentiation-of-glioblastoma-cells-into-astrocytes
#12
Fan Xing, Yizhao Luan, Jing Cai, Sihan Wu, Jialuo Mai, Jiayu Gu, Haipeng Zhang, Kai Li, Yuan Lin, Xiao Xiao, Jiankai Liang, Yuan Li, Wenli Chen, Yaqian Tan, Longxiang Sheng, Bingzheng Lu, Wanjun Lu, Mingshi Gao, Pengxin Qiu, Xingwen Su, Wei Yin, Jun Hu, Zhongping Chen, Ke Sai, Jing Wang, Furong Chen, Yinsheng Chen, Shida Zhu, Dongbing Liu, Shiyuan Cheng, Zhi Xie, Wenbo Zhu, Guangmei Yan
Glioblastoma multiforme (GBM) is among the most aggressive of human cancers. Although differentiation therapy has been proposed as a potential approach to treat GBM, the mechanisms of induced differentiation remain poorly defined. Here, we established an induced differentiation model of GBM using cAMP activators that specifically directed GBM differentiation into astroglia. Transcriptomic and proteomic analyses revealed that oxidative phosphorylation and mitochondrial biogenesis are involved in induced differentiation of GBM...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28069585/expression-of-hmgb2-indicates-worse-survival-of-patients-and-is-required-for-the-maintenance-of-warburg-effect-in-pancreatic-cancer
#13
Xin Cai, Hongjian Ding, Yanxia Liu, Gaofeng Pan, Qingguo Li, Zhen Yang, Weiyan Liu
High mobility group proteins (HMGs) are the second most abundant chromatin proteins and exert global genomic functions in the establishment of active or inactive chromatin domains. Through interaction with nucleosomes, transcription factors, nucleosome-remodeling machines and histones, the HMGs family proteins contribute to the fine tuning of transcription in response to rapid environmental changes. Mammalian high mobility group Bs (HMGBs) are characterized by two tandem HMG box domains followed by a long acidic tail...
January 9, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28068289/cancer-metabolism-the-volatile-signature-of-glycolysis-in-vitro-model-in-lung-cancer-cells
#14
Tali Feinberg, Jens Herbig, Ingrid Kohl, Guy Las, John C Cancilla, Jose S Torrecilla, Maya Ilouze, Hossam Haick, Nir Peled
Discovering the volatile signature of cancer cells is an emerging approach in cancer research, as it may contribute to a fast and simple diagnosis of tumors in vivo and in vitro. One of the main contributors to such a volatile signature is hyperglycolysis, which characterizes the cancerous cell. The metabolic perturbation in cancer cells is known as the Warburg effect; glycolysis is preferred over oxidative phosphorylation (OXPHOS), even in the presence of oxygen. The precise mitochondrial alterations that underlie the increased dependence of cancer cells on aerobic glycolysis for energy generation have remained a mystery...
January 9, 2017: Journal of Breath Research
https://www.readbyqxmd.com/read/28059703/glycolysis-and-glutaminolysis-cooperatively-control-t-cell-function-by-limiting-metabolite-supply-to-n-glycosylation
#15
Lindsey Araujo, Phillip Khim, Haik Mkhikian, Christie-Lynn Mortales, Michael Demetriou
Rapidly proliferating cells switch from oxidative phosphorylation to aerobic glycolysis plus glutaminolysis, markedly increasing glucose and glutamine catabolism. Although Otto Warburg first described aerobic glycolysis in cancer cells >90 years ago, the primary purpose of this metabolic switch remains controversial. The hexosamine biosynthetic pathway requires glucose and glutamine for de novo synthesis of UDP-GlcNAc, a sugar-nucleotide that inhibits receptor endocytosis and signaling by promoting N-acetylglucosamine branching of Asn (N)-linked glycans...
January 6, 2017: ELife
https://www.readbyqxmd.com/read/28051182/nesting-of-colon-and-ovarian-cancer-cells-in-the-endothelial-niche-is-associated-with-alterations-in-glycan-and-lipid-metabolism
#16
Anna Halama, Bella S Guerrouahen, Jennifer Pasquier, Noothan J Satheesh, Karsten Suhre, Arash Rafii
The metabolic phenotype of a cancer cell is determined by its genetic makeup and microenvironment, which dynamically modulates the tumor landscape. The endothelial cells provide both a promoting and protective microenvironment - a niche for cancer cells. Although metabolic alterations associated with cancer and its progression have been fairly defined, there is a significant gap in our understanding of cancer metabolism in context of its microenvironment. We deployed an in vitro co-culture system based on direct contact of cancer cells with endothelial cells (E4(+)EC), mimicking the tumor microenvironment...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28049773/crosstalk-between-alternatively-spliced-ugt1a-isoforms-and-colon-cancer-cell-metabolism
#17
Yannick Audet-Delage, Michele Rouleau, Melanie Rouleau, Joannie Roberge, Stephanie Miard, Frederic Picard, Bernard Tetu, Chantal Guillemette
Alternative splicing at the human glucuronosyltransferase 1 gene locus (UGT1) produces alternate isoforms UGT1A_i2s that control glucuronidation activity through protein-protein interactions. Here, we hypothesized that UGT1A_i2s function into a complex protein network connecting other metabolic pathways with influence on cancer cell metabolism. This is based on a pathway enrichment analysis of proteomic data that identified several high-confidence candidate interaction proteins of UGT1A_i2 proteins in human tissues, namely the rate-limiting enzyme of glycolysis pyruvate kinase (PKM), which plays a critical role in cancer cell metabolism and tumor growth...
January 3, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28048289/su-f-t-678-clotrimazole-sensitizes-mcf-7-breast-cancer-cell-line-to-radiation
#18
L Garcia, M Tambasco
PURPOSE: To study the effects of Clotrimazole (CLT) on radiosensitivity of MCF-7 Cells in correlation to detachment of Hexokinase II from the Voltage Dependent Anion Channel on the outer membrane of the mitochondria. Apoptotic fractions were also analyzed in relation to the detachment of Hexokinase. METHODS: This study focused on the mammary adenocarcinoma cell line, MCF-7. Colony forming assays were used to analyze radiosensitization by CLT. Flow cytometry methods were used to analyze apoptotic vs necrotic fractions after treatment with CLT...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28040923/the-determination-of-ionic-transport-properties-at-high-pressures-in-a-diamond-anvil-cell
#19
Qinglin Wang, Cailong Liu, Yonghao Han, Chunxiao Gao, Yanzhang Ma
A two-electrode configuration was adopted in an in situ impedance measurement system to determine the ionic conductivity at high pressures in a diamond anvil cell. In the experimental measurements, Mo thin-films were specifically coated on tops of the diamond anvils to serve as a pair of capacitance-like electrodes for impedance spectrum measurements. In the spectrum analysis, a Warburg impedance element was introduced into the equivalent circuit to reveal the ionic transport property among other physical properties of a material at high pressures...
December 2016: Review of Scientific Instruments
https://www.readbyqxmd.com/read/28030896/cancer-metabolism-fueling-more-than-just-growth
#20
REVIEW
Namgyu Lee, Dohoon Kim
The early landmark discoveries in cancer metabolism research have uncovered metabolic processes that support rapid proliferation, such as aerobic glycolysis (Warburg effect), glutaminolysis, and increased nucleotide biosynthesis. However, there are limitations to the effectiveness of specifically targeting the metabolic processes which support rapid proliferation. First, as other normal proliferative tissues also share similar metabolic features, they may also be affected by such treatments. Secondly, targeting proliferative metabolism may only target the highly proliferating "bulk tumor" cells and not the slower-growing, clinically relevant cancer stem cell subpopulations which may be required for an effective cure...
December 2016: Molecules and Cells
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