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Lactate AND mTOR

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https://www.readbyqxmd.com/read/28753560/enhancement-of-the-anti-tumor-activity-of-fgfr1-inhibition-in-squamous-cell-lung-cancer-by-targeting-downstream-signaling-involved-in-glucose-metabolism
#1
Claudia Fumarola, Daniele Cretella, Silvia La Monica, Mara A Bonelli, Roberta Alfieri, Cristina Caffarra, Federico Quaini, Denise Madeddu, Angela Falco, Andrea Cavazzoni, Graziana Digiacomo, Giulia Mazzaschi, Valentina Vivo, Elisabetta Barocelli, Marcello Tiseo, Pier Giorgio Petronini, Andrea Ardizzoni
Fibroblast Growth Factor Receptor (FGFR) signaling is a complex pathway which controls several processes, including cell proliferation, survival, migration, and metabolism. FGFR1 signaling is frequently deregulated via amplification/over-expression in NSCLC of squamous histotype (SQCLC), however its inhibition has not been successfully translated in clinical setting. We determined whether targeting downstream signaling implicated in FGFR1 effects on glucose metabolism potentiates the anti-tumor activity of FGFR1 inhibition in SQCLC...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28743867/using-rna-sequencing-to-identify-putative-competing-endogenous-rnas-cernas-potentially-regulating-fat-metabolism-in-bovine-liver
#2
Ruobing Liang, Bo Han, Qian Li, Yuwei Yuan, Jianguo Li, Dongxiao Sun
RNA sequencing has been extensively used to study specific gene expression patterns to discover potential key genes related to complex traits of interest in animals. Of note, a new regulatory mechanism builds a large-scale regulatory network among transcriptome, where lncRNAs act as competing endogenous RNAs (ceRNAs) to sponge miRNAs to regulate the expression of miRNA target genes post-transcriptionally. In this study, we sequenced the cDNA and sRNA libraries of nine liver samples from three Holstein cows during dry period, early lactation, and peak of lactation with HiSeq platform...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733523/preclinical-efficacy-of-the-novel-competitive-nampt-inhibitor-stf-118804-in-pancreatic-cancer
#3
Jair Machado Espindola-Netto, Claudia C S Chini, Mariana Tarragó, Enfeng Wang, Shamit Dutta, Krishnendu Pal, Debabrata Mukhopadhyay, Mauro Sola-Penna, Eduardo N Chini
NAD salvage is one of the pathways used to generate NAD in mammals. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in this pathway, uses nicotinamide (NAM) to generate nicotinamide mononucleotide (NMN). NMN is one of the main precursors of NAD synthesis in cells. Our previous study showed the importance of NAMPT in maintaining NAD levels in pancreatic ductal adenocarcinoma cells (PDAC), and that the NAMPT inhibitor FK866 decreased pancreatic cancer growth. We now tested the effect of STF-118804, a new highly specific NAMPT inhibitor, in models of pancreatic ductal adenocarcinoma...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28731193/promotion-of-glycolysis-by-hotair-through-glut1-upregulation-via-mtor-signaling
#4
Shibo Wei, Qing Fan, Liang Yang, Xiaodong Zhang, Yingbo Ma, Zhihong Zong, Xiangdong Hua, Dongming Su, Hongzhi Sun, Hangyu Li, Zhen Liu
The long non-coding RNA HOX transcript antisense RNA (HOTAIR) plays a key role in the progression of various carcinomas. However, whether or not HOTAIR influences glucose metabolism and the specific underlying mechanism in hepatocellular carcinoma (HCC) cells remain unclear. In the present study, we found markedly increased HOTAIR expression in 84 HCC tissues and demonstrated that HOTAIR overexpression promoted cell proliferation using Cell Counting Kit-8. The effect on glucose metabolism regulated by HOTAIR in HCC cells was determined by detecting lactate and glucose levels: HOTAIR promoted glycolysis by upregulating glucose transporter isoform 1 (GLUT1) and activating mammalian target of rapamycin (mTOR) signaling, whereas knockdown of HOTAIR suppressed this effect...
July 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28724379/regulation-of-glucose-uptake-in-lymphoma-cell-lines-by-c-myc-and-pi3k-dependent-signaling-pathways-and-impact-of-glycolytic-pathways-on-cell-viability
#5
Martina Broecker-Preuss, Nina Becher-Boveleth, Andreas Bockisch, Ulrich Dührsen, Stefan Müller
BACKGROUND: Changes in glucose and energy metabolism contribute to the altered phenotype of cancer cells and are the basis for positron emission tomography with (18)F-fluoro-2-deoxy-D-glucose (FDG) to visualize tumors in vivo. The molecular background of the enhanced glucose uptake and its regulation in lymphoma cells is not fully clarified and may provide new possibilities to reverse the altered metabolism. Thus in this study we investigated regulation of glucose uptake by different signaling pathways...
July 19, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28721162/the-influence-of-rapamycin-on-the-early-cardioprotective-effect-of-hypoxic-preconditioning-on-cardiomyocytes
#6
Jiang Wang, YiLiyaer Maimaitili, Hong Zheng, Jin Yu, Hai Guo, Hai-Ping Ma, Chun-Ling Chen
INTRODUCTION: The purpose of this study was to examine the effects of rapamycin on the cardioprotective effect of hypoxic preconditioning (HPC) and on the mammalian target of rapamycin (mTOR)-mediated hypoxia-inducible factor 1 (HIF-1) signaling pathway. MATERIAL AND METHODS: Primary cardiomyocytes were isolated from rat pups and underwent rapamycin and/or HPC, followed by hypoxia/re-oxygenation (H/R) injury. Cell viability and cell injury were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, and qRT-PCR was used to measure HIF-1α and mTOR mRNA expression...
June 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28713934/upregulation-of-connexin-43-and-apoptosis%C3%A2-associated-protein-expression-by-high-glucose-in-h9c2-cells-was-improved-by-resveratrol-via-the-autophagy-signaling-pathway
#7
Guang-Yu Wang, Ya-Guang Bi, Xiang-Dong Liu, Jun-Feng Han, Meng Wei, Qing-Yong Zhang
The expression of connexin43 (Cx43) protein and the apoptotic rate of cardiomyocytes may be regulated by autophagy and associated with diabetic cardiomyopathy. It is possible that the beneficial effect of resveratrol on diabetic cardiomyocytes occurs via the autophagy pathway. However, it remains to be elucidated whether resveratrol treatment may attenuate the hyperglycemia‑induced remodeling of Cx43 and apoptosis through the regulation of autophagy. H9c2 cardiac cells were incubated with 5.5 and 25 mM glucose, 25 mM glucose with chloroquine (50 µM), and 25 mM glucose with or without resveratrol (10, 25 µM) for 24 h...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28710500/men1-menin-regulates-milk-protein-synthesis-through-mtor-signaling-in-mammary-epithelial-cells
#8
Honghui Li, Xue Liu, Zhonghua Wang, Xueyan Lin, Zhengui Yan, Qiaoqiao Cao, Meng Zhao, Kerong Shi
The MEN1 gene, which encodes the protein Menin, was investigated for its regulatory role in milk protein synthesis in mammary glands. Menin responds to nutrient and hormone levels via the PI3K/Akt/mTOR pathway. Bovine mammary epithelial cells and tissues were used as experimental models in this study. The results revealed that the milk protein synthesis capacity of mammary epithelial cells could be regulated by MEN1/Menin. The overexpression of Menin caused significant suppression of factors involved in the mTOR pathway, as well as milk protein κ-casein (CSNK)...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28705212/moringa-isothiocyanate-complexed-with-%C3%AE-cyclodextrin-a-new-perspective-in-neuroblastoma-treatment
#9
Sabrina Giacoppo, Renato Iori, Patrick Rollin, Placido Bramanti, Emanuela Mazzon
BACKGROUND: Several lines of evidence suggest the consume of natural products for cancer prevention or treatment. In particular, isothiocyanates (ITCs) exerting anti-cancer properties, have received great interest as potential chemotherapeutic agents. This study was designed to assess the anti-proliferative activities of a new preparation of Moringa oleifera-derived 4-(α-L-rhamnopyranosyloxy)benzyl ITC (moringin) complexed with alpha-cyclodextrin (moringin + α-CD; MAC) on SH-SY5Y human neuroblastoma cells...
July 14, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28704425/in-vitro-nuclear-magnetic-resonance-spectroscopy-metabolic-biomarkers-for-the-combination-of-temozolomide-with-pi3k-inhibition-in-paediatric-glioblastoma-cells
#10
Nada M S Al-Saffar, Alice Agliano, Lynley V Marshall, L Elizabeth Jackson, Geetha Balarajah, Jasmin Sidhu, Paul A Clarke, Chris Jones, Paul Workman, Andrew D J Pearson, Martin O Leach
Recent experimental data showed that the PI3K pathway contributes to resistance to temozolomide (TMZ) in paediatric glioblastoma and that this effect is reversed by combination treatment of TMZ with a PI3K inhibitor. Our aim is to assess whether this combination results in metabolic changes that are detectable by nuclear magnetic resonance (NMR) spectroscopy, potentially providing metabolic biomarkers for PI3K inhibition and TMZ combination treatment. Using two genetically distinct paediatric glioblastoma cell lines, SF188 and KNS42, in vitro 1H-NMR analysis following treatment with the dual pan-Class I PI3K/mTOR inhibitor PI-103 resulted in a decrease in lactate and phosphocholine (PC) levels (P<0...
2017: PloS One
https://www.readbyqxmd.com/read/28680592/hif-prolyl-hydroxylase-phd3-regulates-translational-machinery-and-glucose-metabolism-in-clear-cell-renal-cell-carcinoma
#11
Petra Miikkulainen, Heidi Högel, Krista Rantanen, Tomi Suomi, Petri Kouvonen, Laura L Elo, Panu M Jaakkola
BACKGROUND: A key feature of clear cell renal cell carcinoma (ccRCC) is the inactivation of the von Hippel-Lindau tumour suppressor protein (pVHL) that leads to the activation of hypoxia-inducible factor (HIF) pathway also in well-oxygenated conditions. Important regulator of HIF-α, prolyl hydroxylase PHD3, is expressed in high amounts in ccRCC. Although several functions and downstream targets for PHD3 in cancer have been suggested, the role of elevated PHD3 expression in ccRCC is not clear...
2017: Cancer & Metabolism
https://www.readbyqxmd.com/read/28674211/effects-of-soluble-cpe-on-glioma-cell-migration-are-associated-with-mtor-activation-and-enhanced-glucose-flux
#12
Elena I Ilina, Angela Armento, Leticia Garea Sanchez, Marina Reichlmeir, Yannick Braun, Cornelia Penski, David Capper, Felix Sahm, Lukas Jennewein, Patrick N Harter, Sven Zukunft, Ingrid Fleming, Dorothea Schulte, Francois Le Guerroué, Christian Behrends, Michael W Ronellenfitsch, Ulrike Naumann, Michel Mittelbronn
Carboxypeptidase E (CPE) has recently been described as a multifunctional protein that regulates proliferation, migration and survival in several tumor entities. In glioblastoma (GBM), the most malignant primary brain tumor, secreted CPE (sCPE) was shown to modulate tumor cell migration. In our current study, we aimed at clarifying the underlying molecular mechanisms regulating anti-migratory as well as novel metabolic effects of sCPE in GBM. Here we show that sCPE activates mTORC1 signaling in glioma cells detectable by phosphorylation of its downstream target RPS6...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28643224/establishment-of-a-3d-cell-culture-model-of-primary-bovine-mammary-epithelial-cells-extracted-from-fresh-milk
#13
Maria Hillreiner, Nadine I Müller, Heiner M Koch, Christiane Schmautz, Bernhard Küster, Michael W Pfaffl, Heike Kliem
For the investigation of molecular processes underlying diseases of the bovine mammary gland, primary bovine mammary epithelial cells (pbMEC) are used. They are known to contribute to the innate immune system of the bovine mammary gland. The functionality of pbMEC depends on the maintenance of in vivo characteristics. So far, the optimization of pbMEC culture conditions was intended in a variety of experiments. For this purpose, most of the studies used stable cell lines or primary cells obtained from udder biopsies of slaughtered animals...
June 22, 2017: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/28624789/pediatric-and-adult-glioblastoma-radiosensitization-induced-by-pi3k-mtor-inhibition-causes-early-metabolic-alterations-detected-by-nuclear-magnetic-resonance-spectroscopy
#14
Alice Agliano, Geetha Balarajah, Daniela M Ciobota, Jasmin Sidhu, Paul A Clarke, Chris Jones, Paul Workman, Martin O Leach, Nada M S Al-Saffar
Poor outcome for patients with glioblastomas is often associated with radioresistance. PI3K/mTOR pathway deregulation has been correlated with radioresistance; therefore, PI3K/mTOR inhibition could render tumors radiosensitive. In this study, we show that NVP-BEZ235, a dual PI3K/mTOR inhibitor, potentiates the effects of irradiation in both adult and pediatric glioblastoma cell lines, resulting in early metabolic changes detected by nuclear magnetic resonance (NMR) spectroscopy. NVP-BEZ235 radiosensitises cells to X ray exposure, inducing cell death through the inhibition of CDC25A and the activation of p21cip1(CDKN1A)...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28609310/blockade-of-glut1-by-wzb117-resensitizes-breast-cancer-cells-to-adriamycin
#15
Qing Chen, Ya-Qiu Meng, Xiao-Fan Xu, Jun Gu
The tolerance to adriamycin of cancer as a common and stubborn obstacle occurred during curing breast cancer patients needs to be overcome. In the present study, we explored whether inhibiting the glucose transporter 1 (GLUT1) could restore the activity of adriamycin in breast cancer cell line MCF-7 resistant to adriamycin and the possible underlying mechanisms. Adriamycin-resistant cell line MCF-7/ADR was selected stepwise from the parental MCF-7 cells and the level of GLUT1 was measured. Then, the MCF-7/ADR cells were incubated with adriamycin, WZB117 (a specific GLUT1 inhibitor), or both...
September 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28591574/mtor-inhibition-subdues-milk-disorder-caused-by-maternal-vldlr-loss
#16
HoangDinh Huynh, Wei Wei, Yihong Wan
It is unknown whether and how very-low density lipoprotein receptors (VLDLRs) impact skeletal homeostasis. Here, we report that maternal and offspring VLDLRs play opposite roles in osteoclastogenesis and bone resorption. VLDLR deletion in the offspring augments osteoclast differentiation by enhancing RANKL signaling, leading to osteoporosis. In contrast, VLDLR deletion in the mother alters milk metabolism, which inhibits osteoclast differentiation and causes osteopetrosis in the offspring. The maternal effects are dominant...
June 6, 2017: Cell Reports
https://www.readbyqxmd.com/read/28586051/overexpression-of-microrna-133b-is-associated-with-the-increased-survival-of-patients-with-hepatocellular-carcinoma-after-curative-hepatectomy-involvement-of-the-egfr-pi3k-akt-mtor-signaling-pathway
#17
Xuedong Wang, Jianping Zeng, Liang Wang, Xinjing Zhang, Zhiqian Liu, Hongyi Zhang, Jiahong Dong
The aim of the present study was carried out to investigate the association of microRNA-133b (miRNA-133b) expression with the prognosis of patients with hepatocellular carcinoma (HCC) after curative hepatectomy. In the present study, the expression of miRNA-133b in HCC tissues was determined to be lower than that noted in the adjacent normal tissues. Overall and disease-free survival of the HCC patients with high miRNA-133b expression was observably extended, compared with the HCC patients with low miRNA‑133b expression...
June 6, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28581641/clk1-regulated-aerobic-glycolysis-is-involved-in-glioma-chemoresistance
#18
Li Zhang, Huicui Yang, Wenbin Zhang, Zhongqin Liang, Qiang Huang, Guoqiang Xu, Xuechu Zhen, Long Tai Zheng
Chemoresistance remains a major challenge for the treatment of glioma. In this study, we investigated the role of Clock 1 (Clk1), which encodes an enzyme that is necessary for ubiquinone biosynthesis in glioma chemoresistance in vitro. The results showed that Clk1 was highly expressed in GL261 mouse glioma cells which were most sensitive to 1,3Bis (2-chloroethyl) 1 nitrosourea (BCNU) while was low expressed in BCNU resistant cells such as glioma cancer stem cells, T98G, U87MG and U251 glioma cells. Knockdown of Clk1 in GL261 glioma cells significantly reduced BCNU- or cisplatin-induced cell apoptosis, whereas the proliferative activity and the expression of multidrug resistance-related genes including MDR1, O6-methylguanine-DNA methyltransferase, and GSTP1 were not changed...
June 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28581448/trimetazidine-protects-cardiomyocytes-against-hypoxia-reoxygenation-injury-by-promoting-amp-activated-protein-kinase-dependent-autophagic-flux
#19
Yongkang Zhong, Peiyao Zhong, Shangfei He, Ya Zhang, Lu Tang, Yuanna Ling, Shanshan Fu, Ying Tang, Pingzhen Yang, Tao Luo, Baihe Chen, Aihua Chen, Xianbao Wang
Trimetazidine (TMZ), a metabolic agent, may protect against myocardial ischemia/reperfusion injury. Because of the critical role of autophagy in cardioprotection, we aimed to evaluate whether autophagy was involved in TMZ-induced protection during hypoxia/reoxygenation (H/R). Neonatal rat cardiomyocytes were subjected to H/R injury, and they were divided into 7 groups: control, control+TMZ, control+chloroquine (Cq)/compound C (com C), H/R, H/R+TMZ, H/R+Cq/com C, and H/R+TMZ+Cq/com C. Autophagic flux was primarily assessed by Western blot and tandem fluorescent mRFP-GFP-LC3...
June 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28578659/rapamycin-mtorc1-inhibitor-reduces-the-production-of-lactate-and-2-hydroxyglutarate-oncometabolites-in-idh1-mutant-fibrosarcoma-cells
#20
Zoltán Hujber, Gábor Petővári, Norbert Szoboszlai, Titanilla Dankó, Noémi Nagy, Csilla Kriston, Ildikó Krencz, Sándor Paku, Olivér Ozohanics, László Drahos, András Jeney, Anna Sebestyén
BACKGROUND: Multiple studies concluded that oncometabolites (e.g. D-2-hydroxyglutarate (2-HG) related to mutant isocitrate dehydrogenase 1/2 (IDH1/2) and lactate) have tumour promoting potential. Regulatory mechanisms implicated in the maintenance of oncometabolite production have great interest. mTOR (mammalian target of rapamycin) orchestrates different pathways, influences cellular growth and metabolism. Considering hyperactivation of mTOR in several malignancies, the question has been addressed whether mTOR operates through controlling of oncometabolite accumulation in metabolic reprogramming...
June 2, 2017: Journal of Experimental & Clinical Cancer Research: CR
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