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SLC2A1

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https://www.readbyqxmd.com/read/28319810/inhibitors-of-glut-slc2a-enhance-the-action-of-bcnu-and-temozolomide-against-high-grade-gliomas
#1
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...
March 17, 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
#2
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
#3
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
#4
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
#5
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
#6
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...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28184927/downregulation-of-ocln-and-gas1-in-clear-cell-renal-cell-carcinoma
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28043370/assessment-of-the-effect-of-adding-l-carnitine-and-or-resveratrol-to-maturation-medium-before-vitrification-on-in%C3%A2-vitro-matured-calf-oocytes
#13
José Felipe Sprícigo, Roser Morató, Núria Arcarons, Marc Yeste, Margot Alves Dode, Manuel López-Bejar, Teresa Mogas
Cryopreservation may lead bovine oocytes to undergo morphological changes and functional damage due to the high-lipid content in the cytoplasm and the formation of reactive oxygen species. Against this background, the present study aimed to improve the cryotolerance and developmental competence of prepubertal calf oocytes by adding L-carnitine (LC) and/or resveratrol (R) to the IVM medium, as the former is involved in lipid metabolism and both are able to scavenge reactive oxygen species. With this purpose, different quality and functional oocyte parameters, such as spindle and chromosome configuration, DNA integrity, caspase activity, and the profile of genes involved in lipid metabolism and oxidative stress were evaluated in IVM bovine oocytes before or after vitrification/warming...
February 2017: Theriogenology
https://www.readbyqxmd.com/read/28042592/paroxysmal-nonepileptic-events-in-glut1-deficiency
#14
Joerg Klepper, Baerbel Leiendecker, Christin Eltze, Nicole Heussinger
View Supplementary Video Movement disorders are a major feature of Glut1 deficiency. As recently identified in adults with paroxysmal exercise-induced dystonia, similar events were reported in pediatric Glut1 deficiency. In a case series, parent videos of regular motor state and paroxysmal events were requested from children with Glut1 deficiency on clinical follow-up. A questionnaire was sent out to 60 families. Videos of nonparoxysmal/paroxysmal states in 3 children illustrated the ataxic-dystonic, choreatiform, and dyskinetic-dystonic nature of paroxysmal events...
November 2016: Movement Disorders Clinical Practice
https://www.readbyqxmd.com/read/28018440/glucose-transport-1-deficiency-presenting-as-infantile-spasms-with-a-mutation-identified-in-exon-9-of-slc2a1
#15
Hyun Hee Lee, Yun Jung Hur
Glucose transport 1 (GLUT-1) deficiency is a rare syndrome caused by mutations in the glucose transporter 1 gene (SLC2A1) and is characterized by early-onset intractable epilepsy, delayed development, and movement disorder. De novo mutations and several hot spots in N34, G91, R126, R153, and R333 of exons 2, 3, 4, and 8 of SLC2A1 are associated with this condition. Seizures, one of the main clinical features of GLUT-1 deficiency, usually develop during infancy. Most patients experience brief and subtle myoclonic jerk and focal seizures that evolve into a mixture of different types of seizures, such as generalized tonic-clonic, absence, myoclonic, and complex partial seizures...
November 2016: Korean Journal of Pediatrics
https://www.readbyqxmd.com/read/27998284/the-glucose-transporter-glut1-is-required-for-erbb2-induced-mammary-tumorigenesis
#16
Elizabeth A Wellberg, Stevi Johnson, Jessica Finlay-Schultz, Andrew S Lewis, Kristina L Terrell, Carol A Sartorius, E Dale Abel, William J Muller, Steven M Anderson
BACKGROUND: Altered tumor cell metabolism is an emerging hallmark of cancer; however, the precise role for glucose in tumor initiation is not known. GLUT1 (SLC2A1) is expressed in breast cancer cells and is likely responsible for avid glucose uptake observed in established tumors. We have shown that GLUT1 was necessary for xenograft tumor formation from primary mammary cells transformed with the polyomavirus middle-T antigen but that it was not necessary for growth after tumors had formed in vivo, suggesting a differential requirement for glucose depending on the stage of tumorigenesis...
December 20, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27935189/epigenetic-regulation-of-the-glucose-transporter-gene-slc2a1-by-%C3%AE-hydroxybutyrate-underlies-preferential-glucose-supply-to-the-brain-of-fasted-mice
#17
Kosuke Tanegashima, Yukiko Sato-Miyata, Masabumi Funakoshi, Yasumasa Nishito, Toshiro Aigaki, Takahiko Hara
We carried out liquid chromatography-tandem mass spectrometry analysis of metabolites in mice. Those metabolome data showed that hepatic glucose content is reduced, but that brain glucose content is unaffected, during fasting, consistent with the priority given to brain glucose consumption during fasting. The molecular mechanisms for this preferential glucose supply to the brain are not fully understood. We also showed that the fasting-induced production of the ketone body β-hydroxybutyrate (β-OHB) enhances expression of the glucose transporter gene Slc2a1 (Glut1) via histone modification...
January 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/27927575/novel-mutation-in-a-patient-with-late-onset-glut1-deficiency-syndrome
#18
Sandra Juozapaite, Ruta Praninskiene, Birute Burnyte, Laima Ambrozaityte, Birute Skerliene
Glucose transporter 1 deficiency syndrome (GLUT1-DS) is an inborn error of metabolism caused by impaired glucose transport through blood brain barrier due to mutation in SLC2A1 gene, encoding transporter protein. Clinical spectrum includes various signs and symptoms, ranging from severe epileptic encephalopathy to movement disorders. The diagnosis of GLUT1-DS requires hypoglycorrhachia in the presence of normoglycaemia with a reduced cerebrospinal fluid (CSF):plasma glucose ratio. The absence of pathogenic mutation in SLC2A1 gene does not exclude the diagnosis...
December 5, 2016: Brain & Development
https://www.readbyqxmd.com/read/27884183/rna-sequencing-for-profiling-goat-milk-transcriptome-in-colostrum-and-mature-milk
#19
Alessandra Crisà, Fabrizio Ferrè, Giovanni Chillemi, Bianca Moioli
BACKGROUND: In this work we aimed at sequencing and assembling the goat milk transcriptome corresponding at colostrum and 120 days of lactation. To reconstruct transcripts we used both the genome as reference, and a de novo assembly approach. Additionally, we aimed at identifying the differentially expressed genes (DEGs) between the two lactation stages and at analyzing the expression of genes involved in oligosaccharides metabolism. RESULTS: A total of 44,635 different transcripts, organized in 33,757 tentative genes, were obtained using the goat genome as reference...
November 25, 2016: BMC Veterinary Research
https://www.readbyqxmd.com/read/27863474/hypoxic-resistance-of-kras-mutant-tumor-cells-to-3-bromopyruvate-is-counteracted-by-prima-1-and-reversed-by-n-acetylcysteine
#20
Andrea Orue, Valery Chavez, Mary Strasberg-Rieber, Manuel Rieber
BACKGROUND: The metabolic inhibitor 3-bromopyruvate (3-BrPA) is a promising anti-cancer alkylating agent, shown to inhibit growth of some colorectal carcinoma with KRAS mutation. Recently, we demonstrated increased resistance to 3-BrPA in wt p53 tumor cells compared to those with p53 silencing or mutation. Since hypoxic microenvironments select for tumor cells with diminished therapeutic response, we investigated whether hypoxia unequally increases resistance to 3-BrPA in wt p53 MelJuso melanoma harbouring (Q61L)-mutant NRAS and wt BRAF, C8161 melanoma with (G12D)-mutant KRAS (G464E)-mutant BRAF, and A549 lung carcinoma with a KRAS (G12S)-mutation...
November 18, 2016: BMC Cancer
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