glycogen and Neoplasms

Cancer cells possess various biological processes to ensure survival and proliferation even under unfavorable conditions such as hypoxia, nutrient deprivation, and oxidative stress. One of the defining hallmarks of cancer cells is their ability to reprogram their metabolism to suit their needs. Building on over a decade of research in the field of cancer metabolism, numerous unique metabolic capabilities are still being discovered in the present day. One recent discovery in the field of cancer metabolism that was hitherto unexpected is the ability of cancer cells to store vital metabolites in forms that can be readily converted to glucose and glutamine for later use. We called these forms "metabolic reservoirs." While many studies have been conducted on storage molecules such as glycogen, triglyceride, and phosphocreatine (PCr), few have explored the concept of "metabolic reservoirs" for cancer as a whole. In this review, we will provide an overview of this concept, the previously known reservoirs including glycogen, triglyceride, and PCr, and the new discoveries made including the newly discovered reservoirs such as N-acetyl-aspartyl-glutamate (NAAG), lactate, and γ- aminobutyric acid (GABA). We will also discuss whether disrupting these reservoir cycles may be a new avenue for cancer treatment.

Topics: Glutamic Acid; Glutamine; Glycogen; Humans; Lactic Acid; Neoplasms; Triglycerides

Beyond storing and supplying energy in the liver and muscles, glycogen also plays critical roles in cell differentiation, signaling, redox regulation, and stemness under various physiological and pathophysiological conditions. Such versatile functions have been revealed by various forms of glycogen storage diseases. Here, we outline the source of carbon flux in glycogen metabolism and discuss how glycogen metabolism guides CD8

Topics: Animals; Brain; Energy Metabolism; Gluconeogenesis; Glucose; Glycogen; Glycogenolysis; Homeostasis; Humans; Hypoxia; Immunologic Memory; Liver; Macrophages; Muscle, Skeletal; Neoplasms; Pentose Phosphate Pathway; T-Lymphocytes

Glycogen phosphorylase (PG) is a key enzyme taking part in the first step of glycogenolysis. Muscle glycogen phosphorylase (PYGM) differs from other PG isoforms in expression pattern and biochemical properties. The main role of PYGM is providing sufficient energy for muscle contraction. However, it is expressed in tissues other than muscle, such as the brain, lymphoid tissues, and blood. PYGM is important not only in glycogen metabolism, but also in such diverse processes as the insulin and glucagon signaling pathway, insulin resistance, necroptosis, immune response, and phototransduction. PYGM is implicated in several pathological states, such as muscle glycogen phosphorylase deficiency (McArdle disease), schizophrenia, and cancer. Here we attempt to analyze the available data regarding the protein partners of PYGM to shed light on its possible interactions and functions. We also underline the potential for zebrafish to become a convenient and applicable model to study PYGM functions, especially because of its unique features that can complement data obtained from other approaches.

Topics: Animals; Disease Models, Animal; Gene Expression Regulation; Glycogen; Glycogen Phosphorylase; Glycogen Storage Disease Type V; Humans; Insulin Resistance; Light Signal Transduction; Muscle Contraction; Muscle, Skeletal; Necroptosis; Neoplasms; Protein Interaction Mapping; Retinal Pigment Epithelium; Schizophrenia; Zebrafish

Previously we suggested that the early Warburg effect can be explained by the use by cancer cells the glycogen shunt during a rapid increase in glucose concentration. In analogy to the Crabtree effect in yeast, the shunt plays a critical role in maintaining homeostasis of glycolytic intermediate levels during these transitions. We extend this analysis here, and propose that the recently appreciated flexibility of cancer cell glucose and glycogen metabolism involves 4 metabolic states that we recently identified in metabolic control analysis studies of yeast. Under stable conditions of low glucose and normal O

Topics: Carcinogenesis; Gene Expression Regulation, Neoplastic; Glycogen; Homeostasis; Humans; Neoplasms; Warburg Effect, Oncologic

Metabolism consists of a series of reactions that occur within cells of living organisms to sustain life. The process of metabolism involves many interconnected cellular pathways to ultimately provide cells with the energy required to carry out their function. The importance and the evolutionary advantage of these pathways can be seen as many remain unchanged by animals, plants, fungi, and bacteria. In eukaryotes, the metabolic pathways occur within the cytosol and mitochondria of cells with the utilisation of glucose or fatty acids providing the majority of cellular energy in animals. Metabolism is organised into distinct metabolic pathways to either maximise the capture of energy or minimise its use. Metabolism can be split into a series of chemical reactions that comprise both the synthesis and degradation of complex macromolecules known as anabolism or catabolism, respectively. The basic principles of energy consumption and production are discussed, alongside the biochemical pathways that make up fundamental metabolic processes for life.

Topics: Adenosine Triphosphate; Amino Acids; Animals; Bacteria; Citric Acid Cycle; Energy Metabolism; Fatty Acids; Gluconeogenesis; Glycogen; Glycolysis; Humans; Metabolic Diseases; Metabolic Networks and Pathways; Mitochondria; Neoplasms; Plants

Cancer cells use multiple strategies to fuel their unchecked growth. In a recent paper, Curtis et al. (Cell Metab. 2019;29:141-155) delineate a novel strategy whereby cancer-associated fibroblasts (CAFs) secrete cytokines that stimulate glycogen breakdown in ovarian cancer cells. CAF-induced glycogen breakdown increases glycolysis and ATP generation, and facilitates proliferation and metastasis.

Topics: Adenosine Triphosphate; Animals; Cancer-Associated Fibroblasts; Cell Proliferation; Glycogen; Humans; Neoplasms

Glycogen is a high-density glucose polymer, which provides organisms with an immediate source of glucose to support the cell's energy requirements. Epithelial cells primarily store energy as glycogen, but until recently it has not been reported as a major fuel source for cancer growth. Hypoxia, which occurs in many cancers, results in glycogen synthesis and increased survival under stressed conditions. Recently, glycogen mobilization has been shown to play a role in the maturation and immune activity of dendritic cells (DCs) and in the proliferation and metastatic efficiency of cancer cells aided by the tumor microenvironment (TME). These studies indicate that glycogen plays an important role in glucose homeostasis and contributes to key functions related to tumor aggressiveness and the survival of cancer cells.

Topics: Disease Progression; Energy Metabolism; Glucose; Glycogen; Glycolysis; Humans; Metabolic Networks and Pathways; Neoplasms

Cancer cells are characterized by high metabolic demand. The substrates in demand include oxygen, glucose, glutamine and lipids. Oxygen serves as a key substrate in cellular metabolism and bioenergetics. Hypoxia or low oxygen abundance is a common feature of the tumor microenvironment that occurs due to an imbalance in supply and demand. Many of the metabolic responses to hypoxia in both cancer cells and stromal cells are orchestrated by hypoxia-inducible factors (HIFs). In this review we summarize our current understanding of how HIFs modulate the metabolism of hypoxic cancer cells and immune cells, and how altered metabolism plays a role in cancer progression.

Topics: Adenosine; Amino Acids; Aryl Hydrocarbon Receptor Nuclear Translocator; Basic Helix-Loop-Helix Transcription Factors; Cell Hypoxia; Fatty Acids; Glucose; Glycogen; Humans; Lipids; Neoplasms; T-Lymphocytes

Despite many decades of study there is a lack of a quantitative explanation for the Warburg effect in cancer. We propose that the glycogen shunt, a pathway recently shown to be critical for cancer cell survival, may explain the excess lactate generation under aerobic conditions characteristic of the Warburg effect. The proposal is based on research on yeast and mammalian muscle and brain that demonstrates that the glycogen shunt functions to maintain homeostasis of glycolytic intermediates and ATP during large shifts in glucose supply or demand. Loss of the glycogen shunt leads to cell death under substrate stress. Similarities between the glycogen shunt in yeast and cancer cells lead us here to propose a parallel explanation of the lactate produced by cancer cells in the Warburg effect. The model also explains the need for the active tetramer and inactive dimer forms of pyruvate kinase (PKM2) in cancer cells, similar to the two forms of Pyk2p in yeast, as critical for regulating the glycogen shunt flux. The novel role proposed for the glycogen shunt implicates the high activities of glycogen synthase and fructose bisphosphatase in tumors as potential targets for therapy.

Topics: Animals; Carrier Proteins; Glucose; Glycogen; Glycolysis; Homeostasis; Humans; Lactic Acid; Membrane Proteins; Mice; Neoplasms; Thyroid Hormone-Binding Proteins; Thyroid Hormones; Yeasts

Metabolic reprogramming is a hallmark of cancer cells and contributes to their adaption within the tumour microenvironment and resistance to anticancer therapies. Recently, glycogen metabolism has become a recognised feature of cancer cells since it is upregulated in many tumour types, suggesting that it is an important aspect of cancer cell pathophysiology. Here, we provide an overview of glycogen metabolism and its regulation, with a focus on its role in metabolic reprogramming of cancer cells under stress conditions such as hypoxia, glucose deprivation and anticancer treatment. The various methods to detect glycogen in tumours in vivo as well as pharmacological modulators of glycogen metabolism are also reviewed. Finally, we discuss the therapeutic value of targeting glycogen metabolism as a strategy for combinational approaches in cancer treatment.

Topics: Animals; Antineoplastic Agents; Disease Progression; Energy Metabolism; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Glycogen; Humans; Hypoxia; Molecular Targeted Therapy; Neoplasms; Organ Specificity; Tumor Microenvironment

Since its identification more than 150 years ago, there has been an extensive characterisation of glycogen metabolism and its regulatory pathways in the two main glycogen storage organs of the body, i.e. liver and muscle. In recent years, glycogen metabolism has also been demonstrated to be upregulated in many tumour types, suggesting it is an important aspect of cancer cell pathophysiology. Here, we provide an overview of glycogen metabolism and its regulation, with a focus on its role in metabolic reprogramming of cancer cells. The various methods to detect glycogen in tumours in vivo are also reviewed. Finally, we discuss the targeting of glycogen metabolism as a strategy for cancer treatment.

Topics: Gene Expression Regulation, Neoplastic; Glycogen; Glycogen Storage Disease; Humans; Neoplasms; Up-Regulation

Glycogen phosphorylase (GP) is the enzyme responsible for the synthesis of glucose-1-phosphate, the source of energy for muscles and the rest of the body. The binding of different ligands in catalytic or allosteric sites assures activation and deactivation of the enzyme. A description of the regulation mechanism and the implications in glycogen metabolism are given.. Deregulation of GP has been observed in diseases such as diabetes mellitus or cancers. Therefore, it appears as an attractive therapeutic target for the treatment of such pathologies. Numbers of inhibitors have been published in academic literature or patented in the last two decades. This review presents the main patent claims published between 2008 and 2012.. Good inhibitors with interesting IC50 and in vivo results are presented. However, such therapeutic strategy raises questions and some answers are proposed to bring new insights in the field.

Topics: Animals; Diabetes Mellitus; Drug Design; Enzyme Inhibitors; Glucosephosphates; Glycogen; Glycogen Phosphorylase; Humans; Inhibitory Concentration 50; Molecular Targeted Therapy; Neoplasms; Patents as Topic

Interleukin 6 (IL-6) has received significant attention for its regulatory role in muscle wasting during cachexia. This review examines the role of circulating IL-6 for decreasing muscle mass during cancer and emphasizes some of the indirect actions of IL-6 that may cause muscle wasting.

Topics: Cachexia; Exercise; Glycogen; Humans; Hypertrophy; Inflammation; Interleukin-6; Muscle, Skeletal; Neoplasms; Risk Factors; Signal Transduction

Recently, diets low in carbohydrate content have become a matter of international attention because of the WHO recommendations to reduce the overall consumption of sugars and rapidly digestible starches. One of the common metabolic changes assumed to take place when a person follows a low-carbohydrate diet is ketosis. Low-carbohydrate intakes result in a reduction of the circulating insulin level, which promotes high level of circulating fatty acids, used for oxidation and production of ketone bodies. It is assumed that when carbohydrate availability is reduced in short term to a significant amount, the body will be stimulated to maximize fat oxidation for energy needs. The currently available scientific literature shows that low-carbohydrate diets acutely induce a number of favourable effects, such as a rapid weight loss, decrease of fasting glucose and insulin levels, reduction of circulating triglyceride levels and improvement of blood pressure. On the other hand some less desirable immediate effects such as enhanced lean body mass loss, increased urinary calcium loss, increased plasma homocysteine levels, increased low-density lipoprotein-cholesterol have been reported. The long-term effect of the combination of these changes is at present not known. The role of prolonged elevated fat consumption along with low-carbohydrate diets should be addressed. However, these undesirable effects may be counteracted with consumption of a low-carbohydrate, high-protein, low-fat diet, because this type of diet has been shown to induce favourable effects on feelings of satiety and hunger, help preserve lean body mass, effectively reduce fat mass and beneficially impact on insulin sensitivity and on blood lipid status while supplying sufficient calcium for bone mass maintenance. The latter findings support the need to do more research on this type of hypocaloric low-carbohydrate diet.

Topics: Animals; Blood Glucose; Blood Pressure; Body Weight; Cardiovascular Diseases; Diet, Carbohydrate-Restricted; Diet, Reducing; Dietary Carbohydrates; Energy Metabolism; Glycogen; Humans; Insulin; Insulin Resistance; Insulin Secretion; Lipids; Neoplasms; Osteoporosis, Postmenopausal; Risk Factors

Glycogen synthase kinase-3 is an unusual protein serine/threonine kinase that, unlike most of its 500-odd relatives in the genome, is active under resting conditions and is inactivated upon cell stimulation. The two mammalian isoforms, GSK-3alpha and beta, play largely overlapping roles and have been implicated in a variety of human pathologies, including Type II diabetes, Alzheimer's disease, bipolar disorder and cancer. Recently, the modes of regulation of this enzyme have been elucidated through a combination of structural and cell biological studies. A series of relatively selective small molecules have facilitated chemical manipulation of the enzyme in intact cells and tissues, and new roles for the protein kinase in embryonic stem cell differentiation and motility have emerged. Despite these advances, the therapeutic value of this enzyme as a drug target remains clouded by uncertainty over the potential of antagonists to promote tumorigenesis. This article describes the state of understanding of this intriguing enzyme, and weighs current evidence regarding whether there is a therapeutic window for amelioration of diseases in which it is implicated, in the absence of inducing new pathologies.

Topics: Animals; Cell Differentiation; Cell Movement; Enzyme Activation; Glycogen; Glycogen Synthase Kinase 3; Humans; Insulin; Intercellular Signaling Peptides and Proteins; Models, Biological; Mutation; Neoplasms; Phosphorylation; Protein Binding; Protein Isoforms; Signal Transduction; Wnt Proteins

Topics: 2',3'-Cyclic-Nucleotide Phosphodiesterases; Animals; Calcium; Chemotaxis; Cyclic AMP; Cyclic GMP; Diabetes Insipidus; Glycogen; Humans; Hypersensitivity; Intestinal Mucosa; Lipid Metabolism; Lymphocytes; Methods; Mice; Neoplasms; Nucleotides, Cyclic; Parathyroid Diseases; Phagocytosis; Rats

Topics: Acetamides; Azo Compounds; Biological Transport, Active; Carcinogens; Carcinoma, Hepatocellular; Cells, Cultured; Chondroitin; Ethionine; Glucose; Glycogen; Glycosaminoglycans; Heparin; Histocytochemistry; Hyaluronic Acid; Liver; Liver Glycogen; Liver Neoplasms; Microscopy, Electron; Neoplasm Transplantation; Neoplasms; Neoplasms, Experimental; Nitrosamines; Polysaccharides; Radiation Effects

Topics: Acid Phosphatase; Adenocarcinoma; Alkaline Phosphatase; Aminopeptidases; Bone Neoplasms; Breast Neoplasms; Cervix Uteri; Clinical Enzyme Tests; Diagnosis, Differential; Esterases; Female; Glucosephosphate Dehydrogenase; Glycogen; Glycosaminoglycans; Histocytochemistry; Humans; Hyperplasia; Microscopy, Fluorescence; Neoplasms; Nucleic Acids; Sex Chromatin; Uterine Cervical Neoplasms

Topics: Alkaline Phosphatase; Animals; Brain Edema; Cerebrovascular Disorders; Epilepsy; Glycogen; Guinea Pigs; Hematologic Diseases; Humans; Leukocytes; Neoplasms; Rabbits; Tuberculosis; Wounds and Injuries

Topics: Adenoma, Islet Cell; Adrenal Insufficiency; Blood Glucose; Fasting; Female; Gluconeogenesis; Glycogen; Homeostasis; Humans; Hypoglycemia; Hypopituitarism; Lactation; Liver; Neoplasms; Physical Exertion; Pregnancy; Radioimmunoassay

Topics: Adenosine Triphosphate; Animals; Biological Transport, Active; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Cholesterol; Diethylstilbestrol; DNA; Enzyme Induction; Enzyme Repression; Feedback; Glycogen; Glycolysis; Hexokinase; Isocitrate Dehydrogenase; L-Lactate Dehydrogenase; Liver; Liver Neoplasms; Malate Dehydrogenase; NAD; NADP; Neoplasms; Oxygen; Phosphates; Phosphofructokinase-1

Strategies which are used to address the low levels of intracellular hydrogen peroxide and the development of biocompatible catalysts still need to be fulfilled in tumor chemodynamic therapy. Therefore, a novel tumor-targeted glycogen-based nanoparticle system (GN/He/GOx/HA) was developed to co-deliver hemin (He) and GOx, which can self-supply glucose formed upon degradation of glycogen by α-glycosidase in the lysosome environment, in order to achieve synergistic antitumor therapy. Hyaluronic acid (HA) was selected as the outer shell to protect the activity of GOx, and to increase the uptake by tumor cells via CD44 receptor-mediated endocytosis. GN/He/GOx/HA NPs had a good stability in the blood circulation, but fast release of the therapeutic cargos upon intracellular uptake. Hemin had a cascade catalytic reaction with GOx. Furthermore, GN/He/GOx/HA NPs had the strongest cytotoxicity in Hela cells in a glucose concentration dependent manner. The NPs could efficiently produce reactive oxygen species in tumor cells, resulting in a decrease in the mitochondrial membrane potential and apoptosis of tumor cells. The in vivo results showed that the drug-loaded nanoparticles had good safety, biocompatibility, and efficacious antitumor effect. Therefore, the glycogen-based nanoparticle delivery system provides potential application for self-enhancing CDT, which can be used for effective antitumor therapy.

Topics: Antineoplastic Agents; Cell Line, Tumor; Glucose; Glucose Oxidase; Glycogen; HeLa Cells; Hemin; Humans; Hydrogen Peroxide; Nanoparticles; Neoplasms

O-GlcNAcylation is a post-translational modification that links metabolism with signal transduction. High O-GlcNAcylation appears to be a general characteristic of cancer cells. It promotes the invasion, metastasis, proliferation and survival of tumor cells, and alters many metabolic pathways. Glycogen metabolism increases in a wide variety of tumors, suggesting that it is an important aspect of cancer pathophysiology. Herein we focused on the O-GlcNAcylation of liver glycogen phosphorylase (PYGL)-an important catabolism enzyme in the glycogen metabolism pathway. PYGL expressed in both HEK 293T and HCT116 was modified by O-GlcNAc. And both PYGL O-GlcNAcylation and phosphorylation of Ser15 (pSer15) were decreased under glucose and insulin, whereas increased under glucagon and Na2S2O4 (hypoxia) conditions. Then, we identified the major O-GlcNAcylation site to be Ser430, and demonstrated that pSer15 and Ser430 O-GlcNAcylation were mutually reinforced. Lastly, we found that Ser430 O-GlcNAcylation was fundamental for PYGL activity. Thus, O-GlcNAcylation of PYGL positively regulated pSer15 and therefore its enzymatic activity. Our results provided another molecular insight into the intricate post-translational regulation network of PYGL.

Topics: Acetylglucosamine; Glucose; Glycogen; Humans; N-Acetylglucosaminyltransferases; Neoplasms; Phosphorylation; Protein Processing, Post-Translational

Cellular lactate is a key cellular metabolite and marker of anaerobic glycolysis. Cellular lactate uptake, release, production from glucose and glycogen, and interconversion with pyruvate are important determinants of cellular energy. It is known that lactate is present in the spectrum of neoplasms and low malignancy (without necrotic lesions). Also, the appearance of lactate signals is associated with anaerobic glucose, mitochondrial dysfunction, and other inflammatory responses. The aim of this study was the detection of lactate in cell cultures with the use of proton magnetic resonance (

Topics: Glucose; Glycogen; Humans; Lactic Acid; Magnetic Resonance Spectroscopy; Neoplasms; Protons; Pyruvic Acid

Autophagy can selectively target protein aggregates, pathogens, and dysfunctional organelles for the lysosomal degradation. Aberrant regulation of autophagy promotes tumorigenesis, while it is far less clear whether and how tumor-specific alterations result in autophagic aberrance. To form a link between aberrant autophagy selectivity and human cancer, we establish a computational pipeline and prioritize 222 potential LIR (LC3-interacting region) motif-associated mutations (LAMs) in 148 proteins. We validate LAMs in multiple proteins including ATG4B, STBD1, EHMT2 and BRAF that impair their interactions with LC3 and autophagy activities. Using a combination of transcriptomic, metabolomic and additional experimental assays, we show that STBD1, a poorly-characterized protein, inhibits tumor growth via modulating glycogen autophagy, while a patient-derived W203C mutation on LIR abolishes its cancer inhibitory function. This work suggests that altered autophagy selectivity is a frequently-used mechanism by cancer cells to survive during various stresses, and provides a framework to discover additional autophagy-related pathways that influence carcinogenesis.

Topics: Algorithms; Animals; Carcinogenesis; Cell Line, Tumor; Computer Simulation; Datasets as Topic; DNA Mutational Analysis; Gene Knockdown Techniques; Glycogen; Humans; Kaplan-Meier Estimate; Macroautophagy; Membrane Proteins; Mice; Microtubule-Associated Proteins; Models, Genetic; Muscle Proteins; Mutation; Neoplasms; Pentose Phosphate Pathway; Protein Interaction Domains and Motifs; Proteome; RNA-Seq; Tissue Array Analysis; Warburg Effect, Oncologic; Xenograft Model Antitumor Assays

As a natural polysaccharide polymer, glycogen possesses suitable properties for use as a nanoparticle carrier in cancer theranostics. Not only it is inherently biocompatible, it can also be easily chemically modified with various moieties. Synthetic glycogen conjugates can passively accumulate in tumours due to enhanced permeability of tumour vessels and limited lymphatic drainage (the EPR effect). For this study, we developed and examined a glycogen-based carrier containing a gadolinium chelate and near-infrared fluorescent dye. Our aim was to monitor biodistribution and accumulation in tumour-bearing rats using magnetic resonance and fluorescence imaging. Our data clearly show that these conjugates possess suitable imaging and tumour-targeting properties, and are safe under both in vitro and in vivo conditions. Additional modification of glycogen polymers with poly(2-alkyl-2-oxazolines) led to a reduction in the elimination rate and lower uptake in internal organs (lower whole-body background: 45% and 27% lower MRI signals of oxazoline-based conjugates in the liver and kidneys, respectively compared to the unmodified version). Our results highlight the potential of multimodal glycogen-based nanopolymers as a carrier for drug delivery systems in tumour diagnosis and treatment.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Drug Delivery Systems; Glycogen; Neoplasms; Rats; Theranostic Nanomedicine

Cystatin SN (CST1), a known inhibitor of cathepsin B (CatB), has important roles in tumor development. Paradoxically, CatB is a member of the cysteine cathepsin family that acts in cellular processes, such as tumor development and invasion. However, the relationship between CST1 and CatB, and their roles in tumor development are poorly understood. In this study, we observed that the knockdown of CST1 induced the activity of senescence-associated β-galactosidase, a marker of cellular senescence, and expression of senescence-associated secretory phenotype genes, including interleukin-6 and chemokine (C-C motif) ligand 20, in MDA-MB-231 and SW480 cancer cells. Furthermore, CST1 knockdown decreased extracellular CatB activity, and direct CatB inhibition, using specific inhibitors or shCatB, induced cellular senescence. Reconstitution of CST1 restored CatB activity and inhibited cellular senescence in CST1 knockdown cells. CST1 knockdown or CatB inhibition increased glycogen synthase (GS) kinase 3β phosphorylation at serine 9, resulting in the activation of GS and the induction of glycogen accumulation associated with cellular senescence. Importantly, CST1 knockdown suppressed cancer cell proliferation, soft agar colony growth and tumor growth in a xenograft model. These results indicate that CST1-mediated extracellular CatB activity enhances tumor development by preventing cellular senescence. Our findings suggest that antagonists of CST1 or inhibitors of CatB are potential anticancer agents.

Topics: Animals; Cathepsin B; Cell Proliferation; Cellular Senescence; Gene Knockdown Techniques; Glycogen; Glycogen Synthase; HEK293 Cells; Heterografts; Humans; MCF-7 Cells; Mice; Neoplasm Proteins; Neoplasm Transplantation; Neoplasms; Salivary Cystatins

A particle-rich cytoplasmic structure (PaCS) concentrating ubiquitin-proteasome system (UPS) components and barrel-like particles in clear, cytoskeleton- and organelle-free areas has recently been described in some neoplasms and in genetic or infectious diseases at risk of neoplasia. Ultrastructurally similar particulate cytoplasmic structures, interpreted as glycogen deposits, have previously been reported in clear-cell neoplasms and some fetal tissues. It remains to be investigated whether the two structures are the same, colocalize UPS components and polysaccharides, and have a role in highly proliferative cells such as fetal and neoplastic cells. We used immunogold electron microscopy and confocal immunofluorescence microscopy to examine human and mouse fetal tissues and human neoplasms. Fetal and neoplastic cells both showed colocalization of polyubiquitinated proteins, 19S and 20S proteasomes, and polysaccharides, both glycogen and chondroitin sulfate, inside cytoplasmic structures showing all distinctive features of PaCSs. Poorly demarcated and/or hybrid (ribosomes admixed) UPS- and glycogen-enriched areas, likely stages in PaCS development, were also seen in some fetal cells, with special reference to those, like primary alveolar pulmonary cells or pancreatic centroacinar cells, having a crucial role in organogenesis. UPS- and glycogen-rich PaCSs developed extensively in clear-cell neoplasms of the kidney, ovary, pancreas, and other organs, as well as, in infantile, development-related tumors replicating fetal patterns, such as choroid plexus papilloma. UPS-mediated, ATP-dependent proteolysis and its potential energy source, glycogen metabolism, may have a crucial, synergic role in embryo-/organogenesis and carcinogenesis.

Topics: Cytoplasm; Fetus; Glycogen; Humans; Immunohistochemistry; Microscopy, Confocal; Microscopy, Electron, Transmission; Neoplasms; Proteasome Endopeptidase Complex; Ubiquitinated Proteins

The high rate of glucose uptake to fuel the bioenergetic and anabolic demands of proliferating cancer cells is well recognized and is exploited with (18)F-2-fluoro-2-deoxy-d-glucose positron emission tomography ((18)F-FDG-PET) to image tumors clinically. In contrast, enhanced glucose storage as glycogen (glycogenesis) in cancer is less well understood and the availability of a noninvasive method to image glycogen in vivo could provide important biologic insights. Here, we demonstrate that (18)F-N-(methyl-(2-fluoroethyl)-1H-[1,2,3]triazole-4-yl)glucosamine ((18)F-NFTG) annotates glycogenesis in cancer cells and tumors in vivo, measured by PET. Specificity of glycogen labeling was demonstrated by isolating (18)F-NFTG-associated glycogen and with stable knockdown of glycogen synthase 1, which inhibited (18)F-NFTG uptake, whereas oncogene (Rab25) activation-associated glycogen synthesis led to increased uptake. We further show that the rate of glycogenesis is cell-cycle regulated, enhanced during the nonproliferative state of cancer cells. We demonstrate that glycogen levels, (18)F-NFTG, but not (18)F-FDG uptake, increase proportionally with cell density and G1-G0 arrest, with potential application in the assessment of activation of oncogenic pathways related to glycogenesis and the detection of posttreatment tumor quiescence.

Topics: Cell Cycle Checkpoints; Cell Line, Tumor; Fluorodeoxyglucose F18; G1 Phase; Glycogen; Humans; Neoplasms; Positron-Emission Tomography; rab GTP-Binding Proteins; Radiopharmaceuticals; Resting Phase, Cell Cycle

Topics: Antineoplastic Agents; Cell Proliferation; Glycogen; Glycogen Phosphorylase; Glycogenolysis; Humans; Neoplasms

Natural killer (NK) cells, innate immune effectors that mediate rapid responses to various antigens, play an important role in potentiating host defenses through the clearance of tumor cells and virally infected cells. By using enzymatically synthesized glycogen (ESG) with the same characteristics as natural glycogen, we examined whether orally administered glycogen enhances the innate defense of tumor-implanted mice and the cytotoxicity of NK cells. Oral administration of ESG led to the suppression of tumor proliferation and the prolongation of survival times of tumor-bearing mice. Splenic NK activities of BALB/c mice treated orally with ESG were significantly higher than those of water-treated mice, which were used as a negative control. In addition, intraduodenal injections of ESG gradually and markedly lowered splenic sympathetic nerve activity, which has an inverse correlation with NK activity. Furthermore, ESG activated Peyer's patch cells to induce the production of macrophage inflammatory protein-2 (MIP-2), interleukin-6 (IL-6), and immunoglobulin A (IgA) from these cells. These results demonstrated that orally administrated glycogen significantly enhanced the cytotoxicity of NK cells by acting on Peyer's patch cells and autonomic nerves, and eventually induced the potentiation of host defenses. We propose that glycogen functions not only as an energy source for life support but also as an oral adjuvant for immunopotentiation.

Topics: Adjuvants, Immunologic; Animals; Antineoplastic Agents; Cell Line, Tumor; Chemokine CXCL2; Glycogen; Interleukin-6; Killer Cells, Natural; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Neoplasms; Peyer's Patches; Rats; Splanchnic Nerves; Spleen; Tumor Burden

Cancer cells are metabolically stressed during tumour progression due to limited tumour vascularity and resultant nutrient, growth factor and oxygen deficiency that can induce cell death and inhibit tumour growth. We demonstrate that Rab25, a small GTPase involved in endosomal recycling, that is genomically amplified in multiple tumour lineages, is a key regulator of cellular bioenergetics and autophagy. RAB25 enhanced survival during nutrient stress by preventing apoptosis and autophagy via binding and activating AKT leading to increased glucose uptake and improved cellular bioenergetics. Unexpectedly, Rab25 induced the accumulation of glycogen in epithelial cancer cells, a process not previously identified. Strikingly, an increase in basal ATP levels combined with AKT-dependent increases in glucose uptake and glycogen storage allowed maintenance of ATP levels during bioenergetic stress. The clinical relevance of these findings was validated by the ability of a Rab25-dependent expression profile enriched for bioenergetics targets to identify patients with a poor prognosis. Thus, Rab25 is an unexpected regulator of cellular bioenergetics implicated as a useful biomarker and potential therapeutic target.

Topics: Adenosine Triphosphate; Apoptosis; Autophagy; Cell Death; Energy Metabolism; Glycogen; Humans; Neoplasms; rab GTP-Binding Proteins; Tumor Cells, Cultured

Glycogen is demonstrated in a number of lesions and is diagnostically significant, particularly in certain tumors. To stain glycogen accurately, it is essential to choose a suitable fixative, temperature and staining method. We used rabbit liver to assess these variables. Specimens were fixed in three fixatives at two temperatures: 10% formalin, neutral buffered formalin (NBF) and Bouin's solution at 37 and 4 degrees C. Seventy-two paraffin sections were prepared and stained with periodic acid-Schiff (PAS), hexamine (methenamine) silver and Best's carmine methods. Negative control sections using diastase digestion were used for all methods to confirm the presence of glycogen. For the PAS reaction, Bouin's fixative gave better results at both temperatures compared to the other fixatives. For hexamine (methenamine) silver, the quality of staining was improved for tissues fixed in both 10% formalin and NBF at 37 degrees C compared to Bouin's solution. Both 10% formalin and NBF at 4 degrees C gave better results than Bouin's solution. For Best's carmine, Bouin's solution gave the best results for tissues fixed at 4 degrees C. Fixation of tissues with NBF at 37 degrees C gave the best quality staining. We concluded that the quality of glycogen staining in paraffin sections is greatly affected by both the fixative and the temperature of fixation.

Topics: Acetic Acid; Animals; Carmine; Fixatives; Formaldehyde; Glycogen; Liver; Methenamine; Neoplasms; Paraffin Embedding; Periodic Acid-Schiff Reaction; Picrates; Rabbits; Temperature; Tissue Fixation

Insulin-like growth factor (IGF) and insulin (INS) proteins regulate key cellular functions through a complex interacting multi-component molecular network, known as the IGF/INS axis. We describe how dynamic and multilayer interactions give rise to the multifunctional role of the IGF/INS axis. Furthermore, we summarise the importance of the regulatory IGF/INS network in cancer, and discuss the possibilities and limitations of therapies targeting the IGF/INS axis with reference to ongoing clinical trials concerning the blockage of IGF1R in several types of cancer.

Topics: Amino Acids; Disease Progression; Fatty Acids; Glucose; Glycogen; Homeostasis; Humans; Insulin; Insulin-Like Growth Factor Binding Proteins; Neoplasms; Receptor, IGF Type 2; Signal Transduction; Somatomedins

When cellular glucose concentrations fall below normal levels, in general the extent of protein O-GlcNAc modification (O-GlcNAcylation) decreases. However, recent reports demonstrated increased O-GlcNAcylation by glucose deprivation in HepG2 and Neuro-2a cells. Here, we report increased O-GlcNAcylation in non-small cell lung carcinoma A549 cells and various other cells in response to glucose deprivation. Although the level of O-GlcNAc transferase was unchanged, the enzyme contained less O-GlcNAc, and its activity was increased. Moreover, O-GlcNAcase activity was reduced. The studied cells contain glycogen, and we show that its degradation in response to glucose deprivation provides a source for UDP-GlcNAc required for increased O-GlcNAcylation under this condition. This required active glycogen phosphorylase and resulted in increased glutamine:fructose-6-phosphate amidotransferase, the first and rate-limiting enzyme in the hexosamine biosynthetic pathway. Interestingly, glucose deprivation reduced the amount of phosphofructokinase 1, a regulatory glycolytic enzyme, and blocked ATP synthesis. These findings suggest that glycogen is the source for increased O-GlcNAcylation but not for generating ATP in response to glucose deprivation and that this may be useful for cancer cells to survive.

Topics: Acetylglucosamine; AMP-Activated Protein Kinases; Animals; Cell Line; Glucose; Glycogen; Humans; N-Acetylglucosaminyltransferases; Neoplasms; Protein Processing, Post-Translational

Topics: Animals; Biochemistry; Blood Glucose; Glucose; Glycogen; History, 20th Century; Muscles; Neoplasms; Nobel Prize; Phosphoprotein Phosphatases; Phosphorylase a; Phosphorylase b; Phosphorylase Kinase; Phosphorylases; Phosphorylation; Protein Kinases; Proteins; Rabbits

The glycogen content of human megakaryocytes was studied using a quantitative method. Smears of bone marrow from 13 individuals were stained with the modified PAS reaction with and without prior treatment with alpha-amylase. The intensity of the reaction was determined by microspectrophotometry in 50 megakaryocytes from each individual. It was found that megakaryocytes are rich in glycogen which is not only confined to the intensely PAS-positive granules and inclusion bodies, but also makes up a good part of the diffuse cytoplasmic staining. In the diffusely stained megakaryocytes, glycogen makes up 32% of the intensity of the PAS reaction, while it reaches 47% in those with granules and up to 60% in those with inclusion bodies. The total extinction of the PAS-stained megakaryocytes is not only dependent on the morphological appearances of the cells, but is also positively correlated with their size.

Topics: alpha-Amylases; Bone Marrow Examination; Cytoplasmic Granules; Glycogen; Humans; Megakaryocytes; Neoplasms; Periodic Acid-Schiff Reaction

The activities of glycogen synthase and phosphorylase were measured and compared to the growth-related variations of glycogen accumulation in three cultured human tumor cell lines: HT-29 (colon carcinoma); MeWo (malignant melanoma); and RT-4 (carcinoma of the urinary bladder). A similar pattern of variations in the enzyme activities was found in the three cell lines. The activities of the a + b forms of glycogen phosphorylase increased throughout the culture period. Maximal activity of phosphorylase a coincided with low intracellular concentrations of glycogen during the period of exponential growth. When the rate of cell division decreased, phosphorylase a activity also decreased while the glycogen levels increased. Glycogen synthase was almost entirely in b form during the entire culture period, i.e., in both the exponential and the stationary phases. In vitro incubation of the cellular extracts without NaF showed, however, that the enzyme could be partially converted to the a form by the endogenous phosphatases. The A0.5 values of the enzyme for glucose-6-phosphate (Glc-6-P) were of the same order of magnitude as the intracellular Glc-6-P concentrations which ranged from 2.2 to 5.4 mM (almost 10 times those reported in normal cells). Similar Glc-6-P values were obtained by two different extraction methods controlled by the intracellular ATP and ADP concentrations. The Km values for uridine-5'-diphosphoglucose were always 2 to 3 times lower than the intracellular uridine-5'-diphosphoglucose concentrations. These results suggest that: (a) in these tumor cells, glycogen is essentially synthesized by glycogen synthase b via an allosteric activation by intracellular Glc-6-P; (b) there is no obvious growth-related control of glycogen synthase activity; and (c) the activity of glycogen phosphorylase seems to be growth dependent with maximal phosphorylase a activities associated with the period of high division rate.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Cell Line; Colonic Neoplasms; Glucose-6-Phosphate; Glucosephosphates; Glycogen; Glycogen Synthase; Humans; Kinetics; Melanoma; Neoplasms; Uridine Diphosphate Glucose; Urinary Bladder Neoplasms

1. Acid lysosomal and neutral alpha-glucosidase activities are measured during the culture of five human malignant epithelial cell lines, as a function of the growth-related glycogen accumulation. 2. Neutral alpha-glucosidase is found to be active mainly during the exponential phase of cell culture, which could be related to an enhancement of glycosylated compound synthesis. 3. The latent activity of the acid lysosomal alpha-glucosidase increases during the course of cell culture and especially when glycogen accumulates, suggesting that this enzyme could be involved in the control of the polysaccharide storage within the cell.

Topics: alpha-Glucosidases; Cell Division; Cell Line; Glucan 1,4-alpha-Glucosidase; Glucosidases; Glycogen; Humans; Hydrogen-Ion Concentration; Lysosomes; Neoplasms; Time Factors

In the analysis of weight loss in cancer patients, consideration must be given to decreased caloric intake, increased caloric expenditure and abnormal losses of calories. When these factors do not adequately explain the degree of weight loss, this may be due to a specific loss of lean body mass, as the caloric density of muscle is much less than that of fat. The key enzyme for the protection of lean body mass in hypocaloric states is pyruvate dehydrogenase (PDH). During fasting, fast oxidation in host tissues leads to inactivation of PDH, preventing irreversible loss of pyruvate precursors which would have to be replaced by protein breakdown. A tumor in which PDH activity remains high in the fasting state would cause loss of lean body mass in the host. This report suggests that this phenomenon may be important in certain patients with cancer cachexia.

Topics: Amino Acids; Body Weight; Cachexia; Carbohydrate Metabolism; Energy Intake; Energy Metabolism; Glycogen; Humans; Lipid Metabolism; Neoplasms; Proteins; Pyruvate Dehydrogenase Complex

Topics: Cell Division; Cell Line; Glycogen; Humans; Intestinal Neoplasms; Neoplasms

Glucose metabolism and skeletal muscle enzyme activities were studied in nineteen cancer patients and twelve matched controls. The fasting insulin values were normal but the fasting glucose values and the sum of glucose were increased and the sum of insulin was decreased during intravenous glucose tolerance test in the cancer patients. The elimination rate of glucose (k-value) during glucose challenge was, however, not significantly different in cancer patients as compared with that of appropriate controls. The activities of enzymes representative for glycogen turnover, glycolysis, citric acid cycle and respiratory chain were significantly lower in the muscle tissue of cancer patients, while the activity of 3-hydroxyacyl-CoA dehydrogenase, an enzyme in the beta-oxidation of fatty acids, was unchanged and the activity of glucose-6-phosphate dehydrogenase was significantly higher. Rate limiting enzyme activities in muscle tissue, phosphofructokinase and cytochrome c oxidase correlated signficantly with plasma insulin and glucose during glucose challenge. The results point at the possibility of covariating debilitation of pancreatic beta-cells and skeletal muscle enzymes caused by the malignant tumour.

Topics: Aged; Blood Glucose; Citric Acid Cycle; Female; Glucose Tolerance Test; Glycogen; Glycolysis; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Mitochondria, Muscle; Muscles; Neoplasms

In human tumors (cancer of the liver, stomach, lymphogranulomatosis of lymphnodes, metastases in lymphnodes, ascites ovarian tumor cells) the authors studied the content of enzymes participating in glycogen biosynthesis through uridine diphosphateglucose mechanism--UDPG-glycogensynthetase, UDPG-pyrophosphroylase, phosphoglucomutase. As a rule, in human tumor cells the amount of glycogen and the activity of enzymes of its biosynthesis is decreased, the more the higher proliferative activity and autonomization of tumor cells.

Topics: Enzyme Activation; Glycogen; Glycogen Synthase; Humans; Liver Neoplasms; Lymphoma; Neoplasms; Nucleotidyltransferases; Phosphoglucomutase; Stomach Neoplasms; Uridine Diphosphate Glucose; Uridine Diphosphate Sugars; UTP-Glucose-1-Phosphate Uridylyltransferase

Topics: Acid Phosphatase; Alkaline Phosphatase; Glycogen; Histocytochemistry; Humans; Leukocytes; Lipids; Neoplasms; Neutrophils; RNA

In exsudate cells separated from serous body cavities of 29 tumour patients and 30 patients with inflammatory and congestive effusion in cardiac failure or liver cirrhosis respectively the activities of acid and alkaline phosphatase were determined. In addition to sudanophilia the cell content of glycogen and that of ribonucleinic acid were evaluated. By means of cytochemical findings it could be found that an increase of unspecific esterase, acid phosphatase and ribonucleic acid in atypical cells points to a malignous ethiology of the exudate.

Topics: Acid Phosphatase; Alkaline Phosphatase; Ascitic Fluid; Esterases; Exudates and Transudates; Glycogen; Heart Failure; Histocytochemistry; Hodgkin Disease; Humans; Leukemia; Liver Cirrhosis; Lymphoma, Large B-Cell, Diffuse; Neoplasms; Peritonitis; Pleural Effusion; Pleurisy; RNA

Ultrastructural features of neoplastic cells can provide clues for correct diagnosis when light microscopy fails. Secretory granules are characteristic in the following tumors: mucin granules in poorly differentiated adenocarcinomas, zymogen granules in acinic cell carcinomas, lysosomal granules in prostatic carcinomas, melanin granules in malignant melanoma, carcinoid, islet cell tumors, pheochromocytoma, and neuroblastoma granules in the corresponding neoplasms. Among cytoplasmic organelles, rough surfaced endoplasmic reticulum characterizes adrenocortical, ovarian, and hepatocellular carcinomas and plasmacytomas. Tonofibrils are characteristic of squamous cell carcinomas. Glycogen deposits distinguish Ewing's sarcoma from lymphoreticular neoplasms. Intercellular relationships and membrane specialization are important features in the differential diagnosis of various undifferentiated tumors. The frequent resolution of difficult diagnostic problems by electron microscopy outweighs the disadvantages of this technique, such as the expense and time required.

Topics: Cytoplasmic Granules; Desmosomes; Diagnosis, Differential; Endoplasmic Reticulum; Enzyme Precursors; Glycogen; Humans; Lipids; Melanins; Microscopy, Electron; Mucins; Neoplasm Metastasis; Neoplasms; Vacuoles

Topics: Animals; Dog Diseases; Dogs; Endoplasmic Reticulum; Female; Glycogen; Golgi Apparatus; Mammary Glands, Animal; Microscopy, Electron; Myofibrils; Neoplasms; Phyllodes Tumor

Topics: Adenylyl Cyclases; Cyclic AMP; Glycogen; Humans; Melanocytes; Neoplasms; Psoriasis; Skin

Topics: Adenoma; Adenoma, Acidophil; Adenoma, Basophil; Adenoma, Chromophobe; Administration, Oral; Animals; Cell Transformation, Neoplastic; Cystadenoma; Female; Glycogen; Histocytochemistry; Kidney; Kidney Neoplasms; Male; Morpholines; Neoplasms; Neoplasms, Experimental; Nitrosamines; Rats

Topics: Brain Neoplasms; Bromodeoxyuridine; Dactinomycin; DNA; Fluorouracil; Glycogen; Humans; Neoplasms; Oxygen; Radiation-Sensitizing Agents; RNA; Vitamin K

Topics: Adenosine Triphosphatases; Central Nervous System Diseases; Glucosyltransferases; Glycogen; Hexosaminidases; Histocytochemistry; Humans; Hydrolases; L-Lactate Dehydrogenase; Lipids; Lysosomes; Mast Cells; Meningioma; Neoplasms; Oxidoreductases; Succinate Dehydrogenase

Topics: Acyltransferases; Adolescent; Adult; Alkaline Phosphatase; Anemia, Hemolytic; Biliary Tract Diseases; Child; Child, Preschool; Cystic Fibrosis; Erythroblastosis, Fetal; Female; gamma-Glutamyltransferase; Glutamate Dehydrogenase; Glycogen; Hematologic Diseases; Hepatitis A; Humans; Hyperthyroidism; Hypothyroidism; Infant; Infant, Newborn; Kidney Diseases; Leucyl Aminopeptidase; Neoplasms; Oxidoreductases; Pregnancy

Topics: Animals; Culture Techniques; DNA, Neoplasm; Fibroblasts; Glycogen; Glycosaminoglycans; Histocytochemistry; Histones; Lipids; Mice; Mitosis; Neoplasm Proteins; Neoplasms; Ribonucleases; RNA, Neoplasm; Time Factors; Trypsin

Topics: Diagnosis, Differential; Glycogen; Histocytochemistry; Hodgkin Disease; Humans; Neoplasms

Topics: Aged; Biopsy; Bone Marrow; Carcinoma, Squamous Cell; Fats; Female; Glycogen; Glycosaminoglycans; Histocytochemistry; Humans; Inhalation; Kidney Neoplasms; Lymphadenitis; Lymphoma, Non-Hodgkin; Male; Methods; Neoplasms; Pancreatic Neoplasms

Topics: Adult; Anemia, Hemolytic; Cardiovascular Diseases; Chronic Disease; Diabetes Mellitus; Female; Gastrointestinal Diseases; Gestational Age; Glycogen; Humans; Hyperthyroidism; Infant, Newborn; Liver Diseases; Neoplasms; Nephritis, Interstitial; Postpartum Period; Pregnancy; Respiratory Tract Diseases

Topics: Alkaline Phosphatase; Cobalt Isotopes; Glycogen; Humans; L-Lactate Dehydrogenase; Leukocytes; Neoplasms; Neutrophils; Peroxidases; Radioisotope Teletherapy

Topics: Adenoma, Sweat Gland; Adult; Aged; Cytoplasmic Granules; Dermatitis, Seborrheic; Female; Glycogen; Humans; Lipid Metabolism; Male; Melanins; Methods; Middle Aged; Neoplasms; Skin; Sweat Gland Neoplasms; Warts

Topics: Adult; Age Factors; Aged; Carbohydrate Metabolism; Diabetes Complications; Female; Glycogen; Humans; Male; Middle Aged; Neoplasms; Pancreatic Neoplasms; Sex Factors

Topics: Antigens; Autoimmune Diseases; Glycogen; Humans; Leukocyte Count; Leukocytes; Myocardium; Neoplasms; Skin; Tissue Extracts; Transplantation, Homologous

Topics: Animals; Ascites; Carcinoma, Ehrlich Tumor; Exudates and Transudates; Glycogen; Injections, Intraperitoneal; Mice; Neoplasm Transplantation; Neoplasms; Neoplasms, Experimental; Peritoneum; Pharmacology; Radiation Effects; Research; Transplantation, Homologous

Topics: Ascites; Carcinoma, Hepatocellular; Glycogen; Glycolysis; Liver; Liver Glycogen; Liver Neoplasms; Neoplasms; Neoplasms, Experimental; Research

Topics: Animals; Cobalt Isotopes; Glycogen; Neoplasms; Rabbits; Radiation Effects; Radiotherapy Dosage; Ureter

Topics: Animals; Glycogen; In Vitro Techniques; Neoplasms; Rats

Topics: Alkaline Phosphatase; Cell Nucleus; Cytoplasm; DNA; DNA, Neoplasm; Female; Glycogen; Glycosaminoglycans; Histocytochemistry; Humans; Neoplasms; RNA; RNA, Neoplasm; Uterine Cervical Neoplasms

Topics: Asbestosis; Beryllium; Carcinogens; Cholesterol; Glycogen; Lipoproteins; Macromolecular Substances; Methylcellulose; Neoplasms; Neoplasms, Experimental; Polyvinyls; Pyrrolidinones; Research; Resins, Plant; Resins, Synthetic; Silicon Dioxide

Topics: Alkaline Phosphatase; Alkylating Agents; Animals; Antineoplastic Agents; Aziridines; Busulfan; Carcinoma, Ehrlich Tumor; Dihydrolipoamide Dehydrogenase; DNA; DNA, Neoplasm; Electron Transport Complex IV; Glycogen; Histocytochemistry; Lipids; Lymphoma, Non-Hodgkin; Mammary Neoplasms, Animal; Mammary Neoplasms, Experimental; Melanoma; Mice; Neoplasms; Neoplasms, Experimental; Nitrogen Mustard Compounds; Pharmacology; Research; RNA; RNA, Neoplasm; Sarcoma; Sarcoma, Experimental; Succinate Dehydrogenase; Tissue Culture Techniques

Topics: Breast Neoplasms; Carcinoma, Ductal; Clinical Enzyme Tests; Female; Glycogen; Histocytochemistry; Humans; Mammary Glands, Human; Neoplasms; Phosphorylases; Phosphotransferases; Uterine Cervical Neoplasms

Topics: Alkaline Phosphatase; Biopsy; DNA; DNA, Neoplasm; Female; Glycogen; Glycosaminoglycans; Histocytochemistry; Humans; Lymphatic System; Neoplasms; Pathology; Radiation Effects; Ribonucleases; RNA; RNA, Neoplasm; Uterine Cervical Neoplasms

Topics: Alkaline Phosphatase; Cadmium; Electron Transport Complex IV; Fibrosarcoma; Glycogen; Humans; Lactates; Male; Methylcholanthrene; Neoplasm Transplantation; Neoplasms; Nitrogen; Pharmacology; Rats; Research; RNA; RNA, Neoplasm; Testicular Neoplasms; Toxicology

Topics: Central Nervous System Diseases; Central Nervous System Neoplasms; Glycogen; Humans; Neoplasms; Neoplasms, Nerve Tissue

Topics: Coloring Agents; Glycogen; Glycosaminoglycans; Histocytochemistry; Humans; Lipids; Mucins; Neoplasms; Research; Staining and Labeling

Topics: Coloring Agents; Glycogen; Histocytochemistry; Humans; Lipids; Mucins; Neoplasms; Staining and Labeling

Cells which contain glycogen, and which may arise from the connective tissue matrix, can be demonstrated in the estrogen-induced renal tumor of the hamster when the tumor tissue used has either been lyophilized or frozen and then substituted in absolute alcohol containing mercuric chloride. Glycogen has not been found previously in this type of tumor. Studies of the role of glycogen in this type of neoplasm nmay elucidate mechanisms of tumorigenesis.

Topics: Animals; Biochemical Phenomena; Biochemistry; Cricetinae; Estrogens; Glycogen; Kidney Neoplasms; Neoplasms; Research; Toxicology

Topics: Carbohydrate Metabolism; Glycogen; Hyperplasia; Hypertrophy; Neoplasms; Palate

Topics: Adenocarcinoma; Adenoma, Islet Cell; Bile Duct Neoplasms; Biological Assay; Black People; Carbohydrate Metabolism; Carboxy-Lyases; Glucose; Glycogen; Hypoglycemia; Insulin; Neoplasms; Pancreatic Neoplasms; Paraganglioma; Pelvic Neoplasms; Peritoneal Neoplasms; Rats; Research; Sodium Chloride; Stomach Neoplasms

Topics: Enzymes; Glycogen; Humans; Neoplasms

Topics: Breast; Breast Neoplasms; Glycogen; Humans; Neoplasms

Topics: Animals; Antineoplastic Agents; Glycogen; Glycogenolysis; Neoplasms; Sarcoma; Sarcoma, Yoshida

Topics: Female; Glycogen; Glycogenolysis; Humans; Neoplasms; Uterine Cervical Neoplasms

Topics: Glycogen; Humans; Neoplasms; Neoplasms, Glandular and Epithelial

Topics: Bone and Bones; Diagnosis, Differential; Glycogen; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Neoplasms; Sarcoma; Sarcoma, Ewing

Topics: Diabetes Mellitus; Gastrointestinal Tract; Glycogen; Glycogenolysis; Humans; Liver; Liver Glycogen; Neoplasms

Topics: Aged; Encephalomyelitis; Glycogen; Humans; Neoplasms; Neoplasms, Glandular and Epithelial

Topics: Bone and Bones; Bone Neoplasms; Glycogen; Humans; Neoplasms; Sarcoma

Topics: Carbohydrate Metabolism; Glycogen; Humans; Neoplasms; Polysaccharides

Topics: Glycogen; Liver; Neoplasms; Phosphoric Monoester Hydrolases

Topics: Carcinoma; Carcinoma, Squamous Cell; Cervix Uteri; Female; Glycogen; Humans; Neoplasms; Pentylenetetrazole; Uterine Cervical Neoplasms

Topics: Carcinoma; Carcinoma, Squamous Cell; Cervix Uteri; Coloring Agents; Female; Glycogen; Humans; Neoplasms; Staining and Labeling

Topics: Animals; Barbital; Barbiturates; Glycine; Glycine Agents; Glycogen; Glycogenolysis; Liver; Liver Glycogen; Mice; Neoplasms

Topics: Glucose; Glycogen; Insulin; Melanoma; Melanoma, Experimental; Neoplasms

Topics: Carcinoma in Situ; Cervix Uteri; Female; Glycogen; Humans; Hysterectomy; Neoplasms; Uterus

Topics: Adrenal Glands; Fats; Glycogen; Glycogenolysis; Liver; Liver Glycogen; Neoplasms; Urine

Topics: Glycogen; Humans; Kidney Neoplasms; Male; Neoplasms; Testicular Neoplasms; Testis; Urinary Bladder Neoplasms

Topics: Animals; Glycogen; Glycogenolysis; Liver; Liver Glycogen; Mice; Neoplasms; Sarcoma

Topics: Carcinoma; Carcinoma, Squamous Cell; Cervix Uteri; Female; Glycogen; Glycogenolysis; Humans; Neoplasms

Topics: Citric Acid Cycle; Glycogen; Glycolysis; Humans; Neoplasms

Topics: Animals; Ascites; Carcinoma, Ehrlich Tumor; Glycogen; Neoplasms; Sarcoma; Sarcoma, Experimental; Sarcoma, Yoshida

Topics: Carcinoma; Carcinoma, Basal Cell; Cervix Uteri; Diagnosis, Differential; Female; Glycogen; Humans; Neoplasms; Uncertainty; Uterine Cervical Neoplasms

Topics: Glycogen; Glycogenolysis; Humans; Neoplasms

Topics: Carcinoma; Cervix Uteri; Female; Glycogen; Humans; Neoplasms; Neoplasms, Glandular and Epithelial

Topics: Cervix Uteri; Early Diagnosis; Female; Glycogen; Humans; Neoplasms; Nucleic Acids; Uterine Cervical Neoplasms; Uterine Neoplasms

Topics: Glycogen; Heart; Humans; Neoplasms

Topics: Glycogen; Heart; Humans; Neoplasms

Topics: Carcinoma in Situ; Cervix Uteri; Female; Glycogen; Humans; Neoplasms; Uterine Cervical Neoplasms