Project description:RNA-sequencing of megakaryocyte-erythroid progenitors of CALRdel52/+ MxCre mice treated with either vehicle or 2-deoxy-D-glucose for 21 days.
Project description:The gene expression patterns of macrophages were analyzed to understand how glycolysis inhibitor affects macrophage differentiation. Human monocytes derived from peripheral blood were cultured in vitro in the presence of macrophage colony-stimulating factor (M-CSF) to yield regulatory macrophages (M-Mφs), or M-CSF plus interferon-gamma to yield inflammatory macrophages (Mγ-Mφs). 2-deoxy-D-glucose (2-DG), a glycolysis inhibitor, was added during macrophage differentiation. Gene expression patterns of monocytes, M-Mφs and Mγ-Mφs diffrentiated with or without 2-DG were analyzed by microarray analysis.
Project description:The Warburg effect, consisting of increased glucose uptake and glycolysis, provides metabolic energy as well as cellular building blocks for tumor growth. Inhibition of the Warburg effect with 2-deoxyglucose (2DG) has been explored in clinical trials with limited efficacy. Blockage of glycolysis can induce autopahgy resulting in alternative energy generation through oxidative phosphorylation providing a potential bypass of the effects of inhibition of glycolysis. Here in we demonstrate that activation of AMPK, as a consequence of energetic stress, induces mitochondrial energy production potentially bypassing the effects of glycolysis inhibition. We thus combined blockage of glycolysis by 2DG with inhibition of the electron transfer complex I (ETC1) in the mitochondria with the clinically applicable antidiabetic drug metformin. The combination resulted in activation of AMPK and autopahgy that however rendered eventual depletion of ATP and cell death. Furthermore, combined inhibition of glycolysis and mitochondrial respiration inhibited tumor growth and markedly decreased metastatic capacity in vivo. In order to understand the mechanism of these metabolic inhibitors, we performed whole genome transcriptional analysis. Human SK-4 esophageal cancer cell lines were treated with 5 different treatment groups [2 deoxy glucose (4mM), Metformin (5mM), AICAR (2mM), 2 deoxy glucose (4mM) plus Metformin (5mM) and 2 deoxy glucose (4mM) plus AICAR (2mM)] with non treated control groups for 12 hrs. Each groups was quadruplicated. Microarray experiments and data analysis were done at Dept. of Systems Biology, MDACC (Houston, USA)
Project description:The purpose of this study is to evaluate the effect of primary tumor resection on the metabolic activity of metastases in patients with a colorectal primary tumor and synchronous liver metastases by positron emission tomography (PET) with 2-deoxy-2-fluoro[18F]-D-glucose (FDG-PET) scanning.
Project description:To determine the effect of adherence on the metabolic and functional response of human monocytes. Monocytes were stimulated with lipopolysaccharide (LPS) under non-adherent and adherent conditions. To determine the role of glycolysis in LPS-induced immune responses, this pathway was inhibited by glucose deprivation or the glucose analog 2-deoxy-D-glucose (2DG).
Project description:The goal of this study was to identify the role of glycolysis in the activity of immunomodulatory peptides with respect to macrophage function using the glycolytic inhibitor 2-deoxy-d-glucose
Project description:SILAC labelled peptides from control and UV or 2-deoxy glucose treated A549 cells. Control is light labelled and treatment groups are heavy labelled. Fractions are as per below:
UV1: APM-0331-2 to APM-0331-6
UV2: APM-0331-12 to APM-0331-16
2DG1: APM-0331-7 to APM-0331-11
2DG2: APM-0331-17 to APM-0331-21
Project description:In the EORTC 90111, open-label, randomised, multicentre, phase II trial, patients were treated with afatinib for 14 days (day 15 until day 1) before surgery (day 0). Tumour biopsies, 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography (18-FDG PET) and magnetic resonance imaging (MRI) were performed at diagnosis and just before surgery. The main aim of the study was to identify predictive biomarkers among treatment-naive patients in this curative setting.
Project description:Inhibiting the unfolded protein response (UPR) can be a therapeutic approach, especially for targeting the tumor microenvironment. We found that compound C (also known as dorsomorphin) prevented the UPR and exerted enhanced cytotoxicity during glucose deprivation. The UPR-inhibiting activity of compound C was not associated with either AMPK or BMP signaling inhibition. To induce the UPR, we treated HT1080 cells for 18 hours under ER stress conditions by adding 10 mM 2-Deoxy-D-glucose (2DG) to culture medium. UPR inhibitors (compound C, versipelostatin and phenformin) were added just before 2DG was added in medium. Total 8 samples were prepared for RNA extraction and hybridization on Affymetrix microarrays.
Project description:Background: C. elegans fed with a chemical inhibitor of glucose, namely 2-deoxy-D-glucose (DOG), exhibit considerably extended life span. DOG, in contradiction to D-glucose, cannot be metabolized in the glycolytic pathway. This results in the fact that less glucose is available for ATP production, and thus makes DOG-feeding of the roundworms equivalent to glucose restriction. The RNA-seq data comprises 4 age groups (1, 5, 10 and 20 days after L4) Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de)
