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Lactate AND mTOR

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https://www.readbyqxmd.com/read/28978054/effects-of-soluble-cpe-on-glioma-cell-migration-are-associated-with-mtor-activation-and-enhanced-glucose-flux
#1
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...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28978011/aldose-reductase-interacts-with-akt1-to-augment-hepatic-akt-mtor-signaling-and-promote-hepatocarcinogenesis
#2
Jia-Xing Zhao, Ya-Wei Yuan, Cheng-Fu Cai, Dong-Yan Shen, Mao-Li Chen, Feng Ye, Yan-Jun Mi, Qi-Cong Luo, Wang-Yu Cai, Wei Zhang, Ying Long, Yong Zeng, Guo-Dong Ye, Shu-Yu Yang
Marked up-regulation of aldose reductase (AR) is reportedly associated with the development of hepatocellular carcinoma (HCC). We investigated how aberrantly overexpressed AR might promote oncogenic transformation in liver cells and tissues. We found that overexpressed AR interacted with the kinase domain of AKT1 to increase AKT/mTOR signaling. In both cultured liver cancer cells and liver tissues in DEN-induced transgenic HCC model mice, we observed that AR overexpression-induced AKT/mTOR signaling tended to enhance lactate formation and hepatic inflammation to enhance hepatocarcinogenesis...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28969664/perspective-on-the-dynamics-of-cancer
#3
REVIEW
Youcef Derbal
BACKGROUND: The genetic diversity of cancer and the dynamic interactions between heterogeneous tumor cells, the stroma and immune cells present daunting challenges to the development of effective cancer therapies. Although cancer biology is more understood than ever, this has not translated into therapies that overcome drug resistance, cancer recurrence and metastasis. The future development of effective therapies will require more understanding of the dynamics of homeostatic dysregulation that drives cancer growth and progression...
October 3, 2017: Theoretical Biology & Medical Modelling
https://www.readbyqxmd.com/read/28952842/clinical-significance-of-chemokine-receptor-cxcr4-and-mammalian-target-of-rapamycin-mtor-expression-in-patients-with-diffuse-large-b-cell-lymphoma
#4
Zi-Zhen Xu, Jian-Kang Shen, Shu-Qing Zhao, Jun-Min Li
To assess the relevance of C-X-C chemokine receptor type 4 (CXCR4) and mammalian target of rapamycin (mTOR) to large-B-cell lymphoma (DLBCL), levels of protein expression were measured in 56 DLBCL patients who had received rituximab-based therapy. Of these, 34 were positive for CXCR4 expression (60.7%) and 31 for mTOR (55.4%). CXCR4 expression was positively correlated with mTOR expression (r = 0.602; p = .000). CXCR4 expression was significantly associated with high lactate dehydrogenase (LDH) level (p = ...
September 27, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28933986/the-antiangiogenesis-effect-of-pirfenidone-in-wound-healing-in-vitro
#5
Xiao'an Liu, Yangfan Yang, Xiujuan Guo, Liling Liu, Kaili Wu, Minbin Yu
Abstracts Background: Pirfenidone is mostly used in antifibrotic and anti-inflammatory therapies. We have previously demonstrated that pirfenidone had antifibrotic and anti-inflammatory effects on the wound healing process after glaucoma filtration surgery in vitro and in vivo. Since the wound healing and reactive scarring process simultaneously involves inflammation, fibrosis, and angiogenesis, and angiogenesis plays a more important role in chronic or prolonged wound healing, we tried to explore the antiangiogenesis effect in pirfenidone and its potential multitarget function in regulating excessive scarring...
September 21, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28905500/salidroside-suppressing-lps-induced-myocardial-injury-by-inhibiting-ros-mediated-pi3k-akt-mtor-pathway-in-vitro-and-in-vivo
#6
Lvyi Chen, Peng Liu, Xin Feng, Chunhua Ma
The purpose of the present study was to investigate the effect of salidroside (Sal) on myocardial injury in lipopolysaccharide (LPS)-induced endotoxemic in vitro and in vivo. SD rats were randomly divided into five groups: control group, LPS group (15 mg/kg), LPS plus dexamethasone (2 mg/kg), LPS plus Sal groups with different Sal doses (20, 40 mg/kg). Hemodynamic measurement and haematoxylin and eosin staining were performed. Serum levels of creatine kinase (CK), lactate dehydrogenase, the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-px), glutathione, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were measured after the rats were killed...
September 14, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28886081/orexin-a-affects-hepg2-human-hepatocellular-carcinoma-cells-glucose-metabolism-via-hif-1%C3%AE-dependent-and-independent-mechanism
#7
Xing Wan, Yuanyuan Liu, Yuyan Zhao, Xiaoqi Sun, Dongxiao Fan, Lei Guo
Orexins are hypothalamic neuropeptides that regulate feeding, reward, wakefulness and energy homeostasis. The present study sought to characterize the involvement of orexin A in glucose metabolism in HepG2 human hepatocellular carcinoma cells, and investigated the role of hypoxia-inducible factor-1α (HIF-1α) in the response. HepG2 cells were exposed to different concentrations of orexin A (10-9 to 10-7 M) in vitro, without or with the orexin receptor 1 (OX1R) inhibitor (SB334867), HIF-1α inhibitor (YC-1) or a combination of both inhibitors...
2017: PloS One
https://www.readbyqxmd.com/read/28881606/gsk1059615-kills-head-and-neck-squamous-cell-carcinoma-cells-possibly-via-activating-mitochondrial-programmed-necrosis-pathway
#8
Jing Xie, Quan Li, Xi Ding, Yunyun Gao
This study tested the anti-head and neck squamous cell carcinoma (HNSCC) cell activity by GSK1059615, a novel PI3K and mTOR dual inhibitor. GSK1059615 inhibited survival and proliferation of established (SCC-9, SQ20B and A253 lines) and primary human HNSCC cells. GSK1059615 blocked PI3K-AKT-mTOR activation in HNSCC cells. Intriguingly, GSK1059615 treatment in HNSCC cells failed to provoke apoptosis, but induced programmed necrosis. The latter was tested by mitochondria depolarization, ANT-1-cyclophilin-D mitochondrial association and lactate dehydrogenase (LDH) release...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28866373/ros-activates-autophagy-in-follicular-granulosa-cells-via-mtor-pathway-to-regulate-broodiness-in-goose
#9
Yaping Lou, Wensai Yu, Lu Han, Songbai Yang, Yali Wang, Ting Ren, Jing Yu, Ayong Zhao
Broodiness causes reduced reproductive ability in poultry, but its regulatory mechanism remains poorly understood. ROS (reactive oxygen species) and autophagy are important for follicular development, and the interaction between the two may play a role in regulating broodiness. We examined goose follicles for ROS and oxidation scavenger activities during the egg-laying and broody stages. The follicular granulosa cells were exposed to media containing H2O2, and the interactions between ROS and autophagy in follicular granulosa cells in vitro were analyzed using a Western blot method...
October 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/28857857/isoflurane-preconditioning-alleviated-murine-liver-ischemia-and-reperfusion-injury-by-restoring-ampk-mtor-mediated-autophagy
#10
Zhuqing Rao, Xiongxiong Pan, Hui Zhang, Jie Sun, Jingjin Li, Ting Lu, Mei Gao, Siying Liu, Dan Yu, Zhengnian Ding
BACKGROUND: Isoflurane has a pharmacological preconditioning effect against ischemia injury in the heart, kidney, and brain, but whether and how isoflurane preconditioning protects livers against ischemia and reperfusion (IR) injury is unclear. METHODS: Mice were randomly divided into an isoflurane preconditioning (ISO) group and control group, receiving 1.5% isoflurane or carrier gas for 40 minutes, respectively (n = 8/group). A partial warm liver IR model was used, and liver injury was evaluated...
October 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28842848/dead-box-helicase-6-ddx6-is-a-new-negative-regulator-for-milk-synthesis-and-proliferation-of-bovine-mammary-epithelial-cells
#11
Zhen Zhen, Minghui Zhang, Xiaohan Yuan, Bo Qu, Yanbo Yu, Xuejun Gao, Youwen Qiu
Milk synthesis of bovine mammary gland is a complex biological process that is regulated by hormones and nutrients, but the mechanism of these regulations still needs further research. DEAD-box helicase 6 (DDX6) is an important member of the RNA helicase family, involved in the regulation of mRNA storage and translation in different systems, but its physiological role and mechanism are largely unclear. In this study, we describe DDX6 as a potentially novel negative regulator for milk synthesis and proliferation of bovine mammary epithelial cells (BMECs)...
August 25, 2017: In Vitro Cellular & Developmental Biology. Animal
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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