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SLC2A1

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https://www.readbyqxmd.com/read/28423551/metabolic-reprogramming-of-the-premalignant-colonic-mucosa-is-an-early-event-in-carcinogenesis
#1
Mart Dela Cruz, Sarah Ledbetter, Sanjib Chowdhury, Ashish K Tiwari, Navneet Momi, Ramesh K Wali, Charles Bliss, Christopher Huang, David Lichtenstein, Swati Bhattacharya, Anisha Varma-Wilson, Vadim Backman, Hemant K Roy
BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States. There is an increasing need for the identification of biomarkers of pre-malignant and early stage CRC to improve risk-stratification and screening recommendations. In this study, we investigated the possibility of metabolic and mitochondrial reprogramming early in the pre-malignant colorectal field. METHODS: Rectal biopsies were taken from 81 patients undergoing screening colonoscopy, and gene expression of metabolic and mitochondrial markers were assessed using real time quantitative PCR...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423529/pif-promotes-brain-re-myelination-locally-while-regulating-systemic-inflammation-clinically-relevant-multiple-sclerosis-m-smegmatis-model
#2
Giuseppe Migliara, Martin Mueller, Alessia Piermattei, Chaya Brodie, Michael J Paidas, Eytan R Barnea, Francesco Ria
Neurologic disease diagnosis and treatment is challenging. Multiple Sclerosis (MS) is a demyelinating autoimmune disease with few clinical forms and uncertain etiology. Current studies suggest that it is likely caused by infection(s) triggering a systemic immune response resulting in antigen/non-antigen-related autoimmune response in central nervous system (CNS). New therapeutic approaches are needed. Secreted by viable embryos, PreImplantation Factor (PIF) possesses a local and systemic immunity regulatory role...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28419980/evaluation-of-glut1-variation-in-non-acquired-focal-epilepsy
#3
Alexander Peeraer, John A Damiano, Susannah T Bellows, Ingrid E Scheffer, Samuel F Berkovic, Saul A Mullen, Michael S Hildebrand
Brain glucose transport is dependent on glucose transporter 1 (GLUT1), encoded by the solute carrier family 2 member 1 (SLC2A1) gene. Mutations in SLC2A1 cause GLUT1 deficiency which is characterized by a broad spectrum of neurological phenotypes including generalized epilepsy, motor disorders, developmental delay and microcephaly. Recent case reports suggest SLC2A1 mutations can contribute to non-acquired focal epilepsy (NAFE) but interrogation of a large patient cohort has not been reported. We studied 200 patients with NAFE (126 with temporal lobe epilepsy) comprising 104 females and 96 males with a mean age of onset of 18 years...
April 10, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28412205/slc2a1-glut1-expression-in-mural-nodules-of-intraductal-papillary-mucinous-neoplasm-of-the-pancreas
#4
Yasunori Oda, Shinichi Aishima, Koji Shindo, Minoru Fujino, Yusuke Mizuuchi, Masami Hattori, Tetsuyuki Miyazaki, Masao Tanaka, Yoshinao Oda
In intraductal papillary mucinous neoplasms (IPMNs), the presence of a mural nodule showing a papillary or nodular proliferation of tumor cells in the dilated pancreatic duct is an indication for resection of the IPMN. Solute carrier family 2, facilitated glucose transporter member 1, known as Glucose transporter type 1 (SLC2A1/GLUT1) mediates cellular glucose uptake in many carcinomas and is correlated with increased 18F-fluorodeoxyglucose ((18)F-FDG) uptake. We examined SLC2A1/GLUT1 expression in the mural nodules of 180 IPMN specimens to distinguish malignant/benign tumors...
April 12, 2017: Human Pathology
https://www.readbyqxmd.com/read/28407523/glut1-deficiency-syndrome-report-of-a-four-generation-norwegian-family-with-a-mild-phenotype
#5
Anette Ramm-Pettersen, Karl O Nakken, Kathrine C Haavardsholm, Kaja Kristine Selmer
INTRODUCTION: Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is a rare metabolic encephalopathy with a wide variation of clinical phenotypes. Familial variants are often milder than de novo cases, and may therefore remain undiagnosed. The aim of this study was to characterize the clinical course of GLUT1-DS in a four-generation Norwegian family where the oldest generations had never received any treatment. METHOD: Through interviews and clinical investigations, we characterized a family of 26 members, where 11 members had symptoms strongly suggesting GLUT1-DS...
April 10, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28401064/helicobacter-pylori-induced-phosphatidylinositol-3-oh-kinase-mtor-activation-increases-hypoxia-inducible-factor-1%C3%AE-to-promote-loss-of-cyclin-d1-and-g0-g1-cell-cycle-arrest-in-human-gastric-cells
#6
Jimena Canales, Manuel Valenzuela, Jimena Bravo, Paulina Cerda-Opazo, Carla Jorquera, Héctor Toledo, Denisse Bravo, Andrew F G Quest
Helicobacter pylori (H. pylori) is a human gastric pathogen that has been linked to the development of several gastric pathologies, such as gastritis, peptic ulcer, and gastric cancer. In the gastric epithelium, the bacterium modifies many signaling pathways, resulting in contradictory responses that favor both proliferation and apoptosis. Consistent with such observations, H. pylori activates routes associated with cell cycle progression and cell cycle arrest. H. pylori infection also induces the hypoxia-induced factor HIF-1α, a transcription factor known to promote expression of genes that permit metabolic adaptation to the hypoxic environment in tumors and angiogenesis...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28381250/transcriptional-signatures-of-steroid-hormones-in-the-striatal-neurons-and-astrocytes
#7
Marcin Piechota, Michał Korostynski, Slawomir Golda, Joanna Ficek, Danuta Jantas, Ziolkowska Barbara, Ryszard Przewlocki
BACKGROUND: The mechanisms of steroids actions in the brain mainly involve the binding and nuclear translocation of specific cytoplasmic receptors. These receptors can act as transcription factors and regulate gene expression. However, steroid-dependent transcriptional regulation in different types of neural cells is not yet fully understood. The aim of this study was to evaluate and compare transcriptional alterations induced by various steroid receptor agonists in primary cultures of astrocytes and neurons from mouse brain...
April 5, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28378819/upstream-slc2a1-translation-initiation-causes-glut1-deficiency-syndrome
#8
Michèl A Willemsen, Lisenka Elm Vissers, Marcel M Verbeek, Bregje W van Bon, Sinje Geuer, Christian Gilissen, Joerg Klepper, Michael P Kwint, Wilhelmina G Leen, Maartje Pennings, Ron A Wevers, Joris A Veltman, Erik-Jan Kamsteeg
Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a neurometabolic disorder with a complex phenotypic spectrum but simple biomarkers in cerebrospinal fluid. The disorder is caused by impaired glucose transport into the brain resulting from variants in SCL2A1. In 10% of GLUT1DS patients, a genetic diagnosis can not be made. Using whole-genome sequencing, we identified a de novo 5'-UTR variant in SLC2A1, generating a novel translation initiation codon, severely compromising SLC2A1 function. This finding expands our understanding of the disease mechanisms underlying GLUT1DS and encourages further in-depth analysis of SLC2A1 non-coding regions in patients without variants in the coding region...
April 5, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28319810/inhibitors-of-glut-slc2a-enhance-the-action-of-bcnu-and-temozolomide-against-high-grade-gliomas
#9
Alberto Azzalin, Giulia Nato, Elena Parmigiani, Francesca Garello, Annalisa Buffo, Lorenzo Magrassi
Glucose transport across glioblastoma membranes plays a crucial role in maintaining the enhanced glycolysis typical of high-grade gliomas and glioblastoma. We tested the ability of two inhibitors of the glucose transporters GLUT/SLC2A superfamily, indinavir (IDV) and ritonavir (RTV), and of one inhibitor of the Na/glucose antiporter type 2 (SGLT2/SLC5A2) superfamily, phlorizin (PHZ), in decreasing glucose consumption and cell proliferation of human and murine glioblastoma cells. We found in vitro that RTV, active on at least three different GLUT/SLC2A transporters, was more effective than IDV, a specific inhibitor of GLUT4/SLC2A4, both in decreasing glucose consumption and lactate production and in inhibiting growth of U87MG and Hu197 human glioblastoma cell lines and primary cultures of human glioblastoma...
April 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28318025/maternal-chronic-hypoxia-increases-expression-of-genes-regulating-lung-liquid-movement-and-surfactant-maturation-in-male-fetuses-in-late-gestation
#10
Erin V McGillick, Sandra Orgeig, Beth J Allison, Kirsty L Brain, Youguo Niu, Nozomi Itani, Katie L Skeffington, Andrew D Kane, Emilio A Herrera, Dino A Giussani, Janna L Morrison
Chronic fetal hypoxaemia is a common pregnancy complication that may arise from maternal, placental and/or fetal factors. Respiratory outcome of the infant at birth likely depends on the duration, timing and severity of the hypoxaemic insult. We have isolated the effect of maternal chronic hypoxia (MCH) for a month in late gestation on fetal lung development. Pregnant ewes were exposed to normoxia (21% O2 ) or hypoxia (10% O2 ) from 105-138 d gestation (term ∼145 d). At 138 d, gene expression in fetal lung tissue was determined by qRT-PCR...
March 20, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28281552/reaching-the-limits-of-prognostication-in-non-small-cell-lung-cancer-an-optimized-biomarker-panel-fails-to-outperform-clinical-parameters
#11
Marianna Grinberg, Dijana Djureinovic, Hans Rr Brunnström, Johanna Sm Mattsson, Karolina Edlund, Jan G Hengstler, Linnea La Fleur, Simon Ekman, Hirsh Koyi, Eva Branden, Elisabeth Ståhle, Karin Jirström, Derek K Tracy, Fredrik Pontén, Johan Botling, Jörg Rahnenführer, Patrick Micke
Numerous protein biomarkers have been analyzed to improve prognostication in non-small cell lung cancer, but have not yet demonstrated sufficient value to be introduced into clinical practice. Here, we aimed to develop and validate a prognostic model for surgically resected non-small cell lung cancer. A biomarker panel was selected based on (1) prognostic association in published literature, (2) prognostic association in gene expression data sets, (3) availability of reliable antibodies, and (4) representation of diverse biological processes...
March 10, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28266149/iodne-an-integrated-optimization-method-for-identifying-the-deregulated-subnetwork-for-precision-medicine-in-cancer
#12
S Mounika Inavolu, J Renbarger, M Radovich, V Vasudevaraja, G H Kinnebrew, S Zhang, L Cheng
Subnetwork analysis can explore complex patterns of entire molecular pathways for the purpose of drug target identification. In this article, the gene expression profiles of a cohort of patients with breast cancer are integrated with protein-protein interaction (PPI) networks using, simultaneously, both edge scoring and node scoring. A novel optimization algorithm, integrated optimization method to identify deregulated subnetwork (IODNE), is developed to search for the optimal dysregulated subnetwork of the merged gene and protein network...
March 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28190498/classification-of-involuntary-movements-in-dogs-paroxysmal-dyskinesias
#13
REVIEW
Mark Lowrie, Laurent Garosi
Paroxysmal dyskinesias (PDs) are a group of hyperkinetic movement disorders characterised by circumscribed episodes of disturbed movement, superimposed on a background state in which such abnormality is absent. There is no loss of consciousness. Episodes can last seconds, minutes or hours, and the beginning and end of the movement disturbance are abrupt. Neurological examination is typically normal between episodes. PDs are associated with a broad spectrum of clinical presentations, encompassing various aetiologies...
February 2017: Veterinary Journal
https://www.readbyqxmd.com/read/28187435/glucose-transporter-glut1-expression-and-clinical-outcome-in-solid-tumors-a-systematic-review-and-meta-analysis
#14
Ji Wang, Chenyang Ye, Cong Chen, Hanchu Xiong, Binbin Xie, Jichun Zhou, Yongxia Chen, Shu Zheng, Linbo Wang
Glucose transporter 1 (GLUT1), the uniporter protein encoded by the SLC2A1 gene, is a key rate-limiting factor in the transport of glucose in cancer cells, and frequently expressed in a significant proportion of human cancers. Numerous studies have reported paradoxical evidence of the relationship between GLUT1 expression and prognosis in solid human tumors. To address this discrepancy, we conducted a thorough search of Pubmed and Web of Science for studies evaluating the expression of GLUT1 and overall survival (OS) and disease-free survival (DFS) in patients with solid cancer from 1993 to April 2016...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28184927/downregulation-of-ocln-and-gas1-in-clear-cell-renal-cell-carcinoma
#15
André Luis Giacometti Conceição, Camila Tainah Da Silva, Rodolfo Miglioli Badial, Marina Curado Valsechi, Bruna Stuqui, Jéssica Domingues Gonçalves, Miriam Galvonas Jasiulionis, Marilia De Freitas Calmon, Paula Rahal
Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of kidney cancer. This carcinoma is histologically characterized by the presence of clear and abundant cytoplasm. In the present study, we sought to identify genes differentially expressed in ccRCC and build a molecular profile of this cancer. We selected genes described in the literature related to cellular differentiation and proliferation. We analyzed the gene and protein expression by quantitative PCR (qPCR) and immunohistochemistry, respectively, and examined possible epigenetic mechanisms that regulate their expression in ccRCC samples and cell lines...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28119822/gene-therapy-for-a-mouse-model-of-glucose-transporter-1-deficiency-syndrome
#16
Sachie Nakamura, Hitoshi Osaka, Shin-Ichi Muramatsu, Naomi Takino, Mika Ito, Shiho Aoki, Eriko F Jimbo, Kuniko Shimazaki, Tatsushi Onaka, Sumio Ohtsuki, Tetsuya Terasaki, Takanori Yamagata
OBJECTIVE: We generated an adeno-associated virus (AAV) vector in which the human SLC2A1 gene was expressed under the synapsin I promoter (AAV-hSLC2A1) and examined if AAV-hSLC2A1 administration can lead to functional improvement in GLUT1-deficient mice. METHODS: AAV-hSLC2A1 was injected into heterozygous knock-out murine Glut1 (GLUT1(+/-)) mice intraperitoneally (systemic; 1.85 × 10(11) vg/mouse) or intra-cerebroventricularly (local; 1.85 × 10(10) vg/mouse)...
March 2017: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/28117388/identification-of-key-residues-for-urate-specific-transport-in-human-glucose-transporter-9-hslc2a9
#17
Wentong Long, Rashmi Panigrahi, Pankaj Panwar, Kenneth Wong, Debbie O Neill, Xing-Zhen Chen, M Joanne Lemieux, Chris I Cheeseman
Human glucose transporter 9 (hSLC2A9) is critical in human urate homeostasis, for which very small deviations can lead to chronic or acute metabolic disorders. Human SLC2A9 is unique in that it transports hexoses as well as the organic anion, urate. This ability is in contrast to other homologous sugar transporters such as glucose transporters 1 and 5 (SLC2A1 &SLC2A5) and the xylose transporter (XylE), despite the fact that these transporters have similar protein structures. Our in silico substrate docking study has revealed that urate and fructose bind within the same binding pocket in hSLC2A9, yet with distinct orientations, and allowed us to identify novel residues for urate binding...
January 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28116237/brain-correlates-of-spike-and-wave-discharges-in-glut1-deficiency-syndrome
#18
Anna Elisabetta Vaudano, Sara Olivotto, Andrea Ruggieri, Giuliana Gessaroli, Valentina De Giorgis, Antonia Parmeggiani, Pierangelo Veggiotti, Stefano Meletti
PURPOSE: To provide imaging biomarkers of generalized spike-and-wave discharges (GSWD) in patients with GLUT1 deficiency syndrome (GLUT1DS). METHODS: Eighteen GLUT1DS patients with pathogenetic mutation in SLC2A1 gene were studied by means of Video-EEG simultaneously recorded with functional MRI (VideoEEG-fMRI). A control group of sex and age-matched patients affected by Genetic Generalized Epilepsy (GGE) with GSWD were investigated with the same protocol. Within and between groups comparison was performed as appropriated...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28106060/brain-microvasculature-defects-and-glut1-deficiency-syndrome-averted-by-early-repletion-of-the-glucose-transporter-1-protein
#19
Maoxue Tang, Guangping Gao, Carlos B Rueda, Hang Yu, David N Thibodeaux, Tomoyuki Awano, Kristin M Engelstad, Maria-Jose Sanchez-Quintero, Hong Yang, Fanghua Li, Huapeng Li, Qin Su, Kara E Shetler, Lynne Jones, Ryan Seo, Jonathan McConathy, Elizabeth M Hillman, Jeffrey L Noebels, Darryl C De Vivo, Umrao R Monani
Haploinsufficiency of the SLC2A1 gene and paucity of its translated product, the glucose transporter-1 (Glut1) protein, disrupt brain function and cause the neurodevelopmental disorder, Glut1 deficiency syndrome (Glut1 DS). There is little to suggest how reduced Glut1 causes cognitive dysfunction and no optimal treatment for Glut1 DS. We used model mice to demonstrate that low Glut1 protein arrests cerebral angiogenesis, resulting in a profound diminution of the brain microvasculature without compromising the blood-brain barrier...
January 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28045438/d11-mediated-inhibition-of-protein-kinase-ck2-impairs-hif-1%C3%AE-mediated-signaling-in-human-glioblastoma-cells
#20
Susanne Schaefer, Tina H Svenstrup, Mette Fischer, Barbara Guerra
Compelling evidence indicates that protein kinase CK2 plays an important role in many steps of cancer initiation and progression, therefore, the development of effective and cell-permeable inhibitors targeting this kinase has become an important objective for the treatment of a variety of cancer types including glioblastoma. We have recently identified 1,3-dichloro-6-[(E)-((4-methoxyphenyl)imino)methyl]dibenzo(b,d)furan-2,7-diol (D11) as a potent and selective inhibitor of protein kinase CK2. In this study, we have further characterized this compound and demonstrated that it suppresses CK2 kinase activity by mixed type inhibition (KI 7...
January 1, 2017: Pharmaceuticals
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