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https://www.readbyqxmd.com/read/28107631/overcoming-the-heat-endurance-of-tumor-cells-by-interfering-the-anaerobic-glycolysis-metabolism-for-improved-photothermal-therapy
#1
Wei-Hai Chen, Guo-Feng Luo, Qi Lei, Sheng Hong, Wen-Xiu Qiu, Li-Han Liu, Si-Xue Cheng, Xian-Zheng Zhang
In this study, we developed a general method to decorate plasmonic gold nanorods (GNRs) with a CD44-targeting functional polymer, containing hyaluronic acid (HA) targeting moiety and a small molecule Glut1 inhibitor of diclofenac (DC), to obtain GNR/HA-DC. This nanosystem exhibited the superiority of selectively sensitizing tumor cells for photothermal therapy (PTT) by inhibiting the unique anaerobic glycolysis. Upon specifically targeting CD44, sequentially time-dependent DC release could be achieved by the trigger of hyaluronidase (HAase), which abundantly existed in tumor tissue...
January 20, 2017: ACS Nano
https://www.readbyqxmd.com/read/28107588/mitochondrial-uncoupler-exerts-a-synthetic-lethal-effect-against-%C3%AE-catenin-mutant-tumor-cells
#2
Yuki Shikata, Masaki Kiga, Yushi Futamura, Harumi Aono, Hiroyuki Inoue, Manabu Kawada, Hiroyuki Osada, Masaya Imoto
The wingless/int-1 (Wnt) signal transduction pathway plays a central role in cell proliferation, survival, differentiation and apoptosis. When β-catenin: a component of the Wnt pathway, is mutated into an active form, cell growth signaling is hyperactive and drives oncogenesis. As β-catenin is mutated in a wide variety of tumors, including up to 10% of all sporadic colon carcinomas and 20% of hepatocellular carcinomas, it has been considered a promising target for therapeutic interventions. Therefore, we screened an in-house natural product library for compounds that exhibited synthetic lethality towards β-catenin mutations and isolated nonactin, an antibiotic mitochondrial uncoupler, as a hit compound...
January 20, 2017: Cancer Science
https://www.readbyqxmd.com/read/28106780/integrins-and-cell-metabolism-an-intimate-relationship-impacting-cancer
#3
REVIEW
Rehman Ata, Costin N Antonescu
Integrins are important regulators of cell survival, proliferation, adhesion and migration. Once activated, integrins establish a regulated link between the extracellular matrix and the cytoskeleton. Integrins have well-established functions in cancer, such as in controlling cell survival by engagement of many specific intracellular signaling pathways and in facilitating metastasis. Integrins and associated proteins are regulated by control of transcription, membrane traffic, and degradation, as well as by a number of post-translational modifications including glycosylation, allowing integrin function to be modulated to conform to various cellular needs and environmental conditions...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106778/methylglyoxal-glyoxalase-1-balance-the-root-of-vascular-damage
#4
REVIEW
Cecilia Nigro, Alessia Leone, Gregory Alexander Raciti, Michele Longo, Paola Mirra, Pietro Formisano, Francesco Beguinot, Claudia Miele
The highly reactive dicarbonyl methylglyoxal (MGO) is mainly formed as byproduct of glycolysis. Therefore, high blood glucose levels determine increased MGO accumulation. Nonetheless, MGO levels are also increased as consequence of the ineffective action of its main detoxification pathway, the glyoxalase system, of which glyoxalase 1 (Glo1) is the rate-limiting enzyme. Indeed, a physiological decrease of Glo1 transcription and activity occurs not only in chronic hyperglycaemia but also with ageing, during which MGO accumulation occurs...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106765/quantitative-proteomic-profiling-of-tachyplesin-i-targets-in-u251-gliomaspheres
#5
Xuan Li, Jianguo Dai, Yongjun Tang, Lulu Li, Gang Jin
Tachyplesin I is a cationic peptide isolated from hemocytes of the horseshoe crab and its anti-tumor activity has been demonstrated in several tumor cells. However, there is limited information providing the global effects and mechanisms of tachyplesin I on glioblastoma multiforme (GBM). Here, by using two complementary proteomic strategies (2D-DIGE and dimethyl isotope labeling-based shotgun proteomics), we explored the effect of tachyplesin I on the proteome of gliomaspheres, a three-dimensional growth model formed by a GBM cell line U251...
January 18, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28106122/comparative-genomics-and-transcriptome-analysis-of-aspergillus-niger-and-metabolic-engineering-for-citrate-production
#6
Xian Yin, Hyun-Dong Shin, Jianghua Li, Guocheng Du, Long Liu, Jian Chen
Despite a long and successful history of citrate production in Aspergillus niger, the molecular mechanism of citrate accumulation is only partially understood. In this study, we used comparative genomics and transcriptome analysis of citrate-producing strains-namely, A. niger H915-1 (citrate titer: 157 g L(-1)), A1 (117 g L(-1)), and L2 (76 g L(-1))-to gain a genome-wide view of the mechanism of citrate accumulation. Compared with A. niger A1 and L2, A. niger H915-1 contained 92 mutated genes, including a succinate-semialdehyde dehydrogenase in the γ-aminobutyric acid shunt pathway and an aconitase family protein involved in citrate synthesis...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28105938/the-influence-of-pro-longevity-gene-gclc-overexpression-on-the-age-dependent-changes-in-drosophila-transcriptome-and-biological-functions
#7
Alexey Moskalev, Mikhail Shaposhnikov, Ekaterina Proshkina, Alexey Belyi, Alexander Fedintsev, Svetlana Zhikrivetskaya, Zulfiya Guvatova, Asiya Sadritdinova, Anastasia Snezhkina, George Krasnov, Anna Kudryavtseva
BACKGROUND: Transcriptional changes that contribute to the organism's longevity and prevent the age-dependent decline of biological functions are not well understood. Here, we overexpressed pro-longevity gene encoding glutamate-cysteine ligase catalytic subunit (Gclc) and analyzed age-dependent changes in transcriptome that associated with the longevity, stress resistance, locomotor activity, circadian rhythmicity, and fertility. RESULTS: Here we reproduced the life extension effect of neuronal overexpression of the Gclc gene and investigated its influence on the age-depended dynamics of transcriptome and biological functions such as fecundity, spontaneous locomotor activity and circadian rhythmicity, as well as on the resistance to oxidative, proteotoxic and osmotic stresses...
December 28, 2016: BMC Genomics
https://www.readbyqxmd.com/read/28105937/effect-of-lentivirus-mediated-shrna-inactivation-of-hk1-hk2-and-hk3-genes-in-colorectal-cancer-and-melanoma-cells
#8
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/28105855/analysis-of-a549-cell-proteome-alteration-in-response-to-recombinant-influenza-a-virus-nucleoprotein-and-its-interaction-with-cellular-proteins-a-preliminary-study
#9
D Kumar, K Tiwari, M S Rajala
 Influenza A virus undergoes frequent changes of antigenicity and contributes to seasonal epidemics or unpredictable pandemics. Nucleoprotein, encoded by gene segment 5, is an internal protein of the virus and is conserved among strains of different host origins. In the current study, we analyzed the differentially expressed proteins in A549 cells transiently transfected with the recombinant nucleoprotein of influenza A virus by 2D gel electrophoresis. The resolved protein spots on gel were identified by MALDI-TOF/Mass spectrometry analysis...
January 19, 2017: Acta Virologica
https://www.readbyqxmd.com/read/28104912/paclitaxel-resistant-cancer-cell-derived-secretomes-elicit-abcb1-associated-docetaxel-cross-resistance-and-escape-from-apoptosis-through-foxo3a-driven-glycolytic-regulation
#10
Mark Borris D Aldonza, Ji-Young Hong, Sang Kook Lee
Chemotherapy-induced cancer cell secretomes promote resistance due, in part, to a predominant glycolytic energy metabolism, which drives aggressive cancer cell proliferation. However, the characterization of these secretomes and the molecular events that associate them with acquired drug resistance remain poorly understood. In this study, we show that secretomes of cancer cells with high-level paclitaxel resistance stimulated cell proliferation and suppressed drug-induced apoptosis of drug-sensitive cells. We also found that drug (docetaxel)-stimulated induction of interferon-α (IFN-α), IFN-λ and tumor necrosis factor-α (TNF-α) release in drug-sensitive cells was lowered by these secretomes...
January 20, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28104391/na-h-exchanger-mediated-hydrogen-ion-extrusion-as-a-carcinogenic-signal-in-triple-negative-breast-cancer-etiopathogenesis-and-prospects-for-its-inhibition-in-therapeutics
#11
REVIEW
Schammim Ray Amith, Larry Fliegel
Breast cancer is the leading cause of cancer-related death in women in Europe and North America, and metastasis is the primary cause of fatality in patients with breast cancer. While some breast cancers are quite treatable, the triple-negative breast cancers are more metastatic and resistant to chemotherapy. There is clearly an urgent need for better treatments for this form of the disease. Breast cancer is characterized by genetically complex intra-tumour heterogeneity, particularly within the triple-negative clinical subtype...
January 16, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28103744/strategies-to-enhance-implantation-and-survival-of-stem-cells-after-their-injection-in-ischemic-neural-tissue
#12
Ioanna Sandvig, Ivana Gadjanski, Marija Vlaski, Leonora Buzanska, Darija Loncaric, Anna Sarnowska, Laura Rodriguez, Axel Sandvig, Zoran Ivanovic
High post-transplantation cell mortality is the main limitation of various approaches aimed to improve regeneration of injured neural tissue by injection of neural stem cells (NSCs) and mesenchymal stromal cells (MStroCs) in and/or around the lesion. Therefore, it is of paramount importance to identify efficient ways to increase cell transplant viability. We have previously proposed the "evolutionary stem cell paradigm", which explains the association between stem cell anaerobic/microaerophilic metabolic set-up and stem cell self-renewal and inhibition of differentiation...
January 19, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28103301/differences-in-beef-quality-between-angus-bos-taurus-taurus-and-nellore-bos-taurus-indicus-cattle-through-a-proteomic-and-phosphoproteomic-approach
#13
Rafael Torres de Souza Rodrigues, Mario Luiz Chizzotti, Camilo Elber Vital, Maria Cristina Baracat-Pereira, Edvaldo Barros, Karina Costa Busato, Rafael Aparecido Gomes, Márcio Machado Ladeira, Taiane da Silva Martins
Proteins are the major constituents of muscle and are key molecules regulating the metabolic changes during conversion of muscle to meat. Brazil is one of the largest exporters of beef and most Brazilian cattle are composed by zebu (Nellore) genotype. Bos indicus beef is generally leaner and tougher than Bos taurus such as Angus. The aim of this study was to compare the muscle proteomic and phosphoproteomic profile of Angus and Nellore. Seven animals of each breed previously subjected the same growth management were confined for 84 days...
2017: PloS One
https://www.readbyqxmd.com/read/28102676/novel-antitumor-platinum-ii-conjugates-containing-the-nonsteroidal-anti-inflammatory-agent-diclofenac-synthesis-and-dual-mechanisms-of-antiproliferative-effects
#14
Francesco Paolo Intini, Juraj Zajac, Vojtech Novohradsky, Teresa Saltarella, Concetta Pacifico, Viktor Brabec, Giovanni Natile, Jana Kasparkova
One concept how to improve anticancer effects of conventional metallodrugs consists in conjugation of these compounds with other biologically (antitumor) active agents, acting by a different mechanism. Here, we present synthesis, biological effects, and mechanisms of action of new Pt(II) derivatives containing one or two nonsteroidal anti-inflammatory diclofenac (DCF) ligands also known for their antitumor effects. The antiproliferative properties of these metallic conjugates show that these compounds are potent and cancer cell selective cytotoxic agents exhibiting activity in cisplatin resistant and the COX-2 positive tumor cell lines...
January 19, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28102299/systemic-regulation-of-l-carnitine-in-nutritional-metabolism-in-zebrafish-danio-rerio
#15
Jia-Min Li, Ling-Yu Li, Xun Qin, Li-Jun Ning, Dong-Liang Lu, Dong-Liang Li, Mei-Ling Zhang, Xin Wang, Zhen-Yu Du
Excess fat accumulation has been observed widely in farmed fish; therefore, efficient lipid-lowering factors have obtained high attention in the current fish nutrition studies. Dietary L-carnitine can increase fatty acid β-oxidation in mammals, but has produced contradictory results in different fish species. To date, the mechanisms of metabolic regulation of L-carnitine in fish have not been fully determined. The present study used zebrafish to investigate the systemic regulation of nutrient metabolism by dietary L-carnitine supplementation...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28101249/3-bromopyruvate-inhibits-human-gastric-cancer-tumor-growth-in-nude-mice-via-the-inhibition-of-glycolysis
#16
Shu-Lin Xian, Wei Cao, Xiao-Dong Zhang, Yun-Fei Lu
[This retracts the article DOI: 10.3892/ol.2014.2779.].
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28100843/pathophysiology-and-molecular-basis-of-selected-metabolic-abnormalities-in-huntington-s-disease
#17
Jolanta Krzysztoń-Russjan
Huntington's disease (HD) is an incurable, devastating neurodegenerative disease with a known genetic background and autosomally dominant inheritance pattern. HTT gene mutation (mHTT) is associated with polymorphic fragment elongation above 35 repeats of the CAG triplet. The mHTT product is an altered protein with a poly-Q elongated fragment, with the highest expression determined in the central nervous system (CNS) and with differentiated expression outside the CNS. A drastic loss of striatal and deeper layers of the cerebral cortex neurons was determined in the CNS, but muscle and body weight mass loss with dysfunction of many organs was also observed...
December 30, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28100784/mitochondrial-o-glcnac-transferase-mogt-regulates-mitochondrial-structure-function-and-survival-in-hela-cells
#18
Juliana L Sacoman, Raul Y Dagda, Amanda R Burnham-Marusich, Ruben K Dagda, Patricia M Berninsone
O-linked N-acetylglucosamine transferase (OGT) catalyzes O-GlcNAcylation of target proteins and regulates numerous biological processes. OGT is encoded by a single gene that yields nucleocytosolic and mitochondrial isoforms. To date, the role of the mitochondrial isoform of OGT (mOGT) remains largely unknown. Using high-throughput proteomics, we identified 84 candidate mitochondrial glycoproteins, of which 44 are novel. Notably, two of the candidate glycoproteins identified (cytochrome oxidase 2 (COX2) and NADH: ubiquinone oxidoreductase core subunit 4 (MT-ND4)) are encoded by mitochondrial DNA...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28099989/effects-of-a-dietary-ketone-ester-on-hippocampal-glycolytic-and-tca-cycle-intermediates-and-amino-acids-in-a-3xtgad-mouse-model-of-alzheimer-s-disease
#19
Robert J Pawlosky, Martin F Kemper, Yoshihero Kashiwaya, M Todd King, Mark P Mattson, Richard L Veech
In patients with Alzheimer's disease (AD) and in a triple transgenic (3xTgAD) mouse model of AD low glucose metabolism in the brain precedes loss of memory and cognitive decline. The metabolism of ketones in the brain by-passes glycolysis and therefore may correct several deficiencies that are associated with glucose hypometabolism. A dietary supplement composed of an ester of D-β-hydroxybutyrate and R-1,3 butane diol referred to as ketone ester (KE) was incorporated into a rodent diet and fed to 3xTgAD mice for 8 months...
January 18, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28099845/absence-of-neurofibromin-induces-an-oncogenic-metabolic-switch-via-mitochondrial-erk-mediated-phosphorylation-of-the-chaperone-trap1
#20
Ionica Masgras, Francesco Ciscato, Anna Maria Brunati, Elena Tibaldi, Stefano Indraccolo, Matteo Curtarello, Federica Chiara, Giuseppe Cannino, Elena Papaleo, Matteo Lambrughi, Giulia Guzzo, Alberto Gambalunga, Marco Pizzi, Vincenza Guzzardo, Massimo Rugge, Stefania Edith Vuljan, Fiorella Calabrese, Paolo Bernardi, Andrea Rasola
Mutations in neurofibromin, a Ras GTPase-activating protein, lead to the tumor predisposition syndrome neurofibromatosis type 1. Here, we report that cells lacking neurofibromin exhibit enhanced glycolysis and decreased respiration in a Ras/ERK-dependent way. In the mitochondrial matrix of neurofibromin-deficient cells, a fraction of active ERK1/2 associates with succinate dehydrogenase (SDH) and TRAP1, a chaperone that promotes the accumulation of the oncometabolite succinate by inhibiting SDH. ERK1/2 enhances both formation of this multimeric complex and SDH inhibition...
January 17, 2017: Cell Reports
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