glycogen and Pancreatic-Neoplasms

Topics: Adenoma, Islet Cell; Adrenal Gland Neoplasms; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Alanine; Animals; Blood Glucose; Ethanol; Fasting; Female; Gluconeogenesis; Glucose; Glycogen; Glycolysis; Humans; Hypoglycemia; Insulin; Kidney; Liver; Male; Middle Aged; Pancreatic Neoplasms; Sulfonylurea Compounds

Topics: Amino Acids; Cyclic AMP; Diabetes Mellitus; Digestive System; Fatty Acids, Nonesterified; Glucagon; Gluconeogenesis; Glucose; Glycogen; Humans; Hyperglycemia; Insulin; Insulin Secretion; Liver Glycogen; Pancreas; Pancreatic Diseases; Pancreatic Neoplasms

UDP-glucose pyrophosphorylase 2 (UGP2), the enzyme that synthesizes uridine diphosphate (UDP)-glucose, rests at the convergence of multiple metabolic pathways, however, the role of UGP2 in tumor maintenance and cancer metabolism remains unclear. Here, we identify an important role for UGP2 in the maintenance of pancreatic ductal adenocarcinoma (PDAC) growth in both in vitro and in vivo tumor models. We found that transcription of UGP2 is directly regulated by the Yes-associated protein 1 (YAP)-TEA domain transcription factor (TEAD) complex, identifying UGP2 as a bona fide YAP target gene. Loss of UGP2 leads to decreased intracellular glycogen levels and defects in N-glycosylation targets that are important for the survival of PDACs, including the epidermal growth factor receptor (EGFR). These critical roles of UGP2 in cancer maintenance, metabolism, and protein glycosylation may offer insights into therapeutic options for otherwise intractable PDACs.

Topics: Animals; Carcinoma, Pancreatic Ductal; Cell Line, Tumor; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Glycogen; Glycosylation; Humans; Mice; Mice, Nude; Neoplasms, Experimental; Pancreatic Neoplasms; TEA Domain Transcription Factors; UTP-Glucose-1-Phosphate Uridylyltransferase; YAP-Signaling Proteins

Cancer cells respond to hypoxia by upregulating the hypoxia-inducible factor 1α (HIF1A) transcription factor, which drives survival mechanisms that include metabolic adaptation and induction of angiogenesis by VEGF. Pancreatic tumors are poorly vascularized and severely hypoxic. To study the angiogenic role of HIF1A, and specifically probe whether tumors are able to use alternative pathways in its absence, we created a xenograft mouse tumor model of pancreatic cancer lacking HIF1A. After an initial delay of about 30 days, the HIF1A-deficient tumors grew as rapidly as the wild-type tumors and had similar vascularization. These changes were maintained in subsequent passages of tumor xenografts

Topics: Animals; Cell Line, Tumor; Cell Proliferation; Glycogen; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Mice; Mice, Inbred NOD; Mice, SCID; Neovascularization, Pathologic; Pancreas; Pancreatic Neoplasms; Signal Transduction

One of the important functions of the liver is glycogen storage. Most processes associated with increased hepatic glycogen, or glycogenoses, are metabolic and affect the entire liver leading to diffuse glycogenosis. We present a case in which the liver contained multiple small pale nodules that on initial assessment were recognized to be composed of glycogenated hepatocytes. Most of the known causes of hepatic glycogenosis were not pertinent to this case. After cutting many deeper levels and obtaining additional sections, small foci of insulinoma were revealed in the center of each of these lesions. The glycogenosis surrounding the foci of insulinoma can be best explained as a local effect of insulin on the hepatocytes, a phenomenon that has been previously described in primate models, but not in human subjects. Here, we report the first case of metastatic insulinoma causing local hepatic glycogenosis.

Topics: Adult; Female; Glycogen; Glycogen Storage Disease; Hepatocytes; Humans; Insulinoma; Liver; Liver Neoplasms; Male; Neoplasm Metastasis; Pancreatic Neoplasms

Novel quantitative proteomic approaches were used to study the effects of inhibition of glycogen phosphorylase on proteome and signaling pathways in MIA PaCa-2 pancreatic cancer cells.. We performed quantitative proteomic analysis in MIA PaCa-2 cancer cells treated with a stratified dose of CP-320626 (5-chloro-1H-indole-2-carboxylic acid [1-(4-fuorobenzyl)-2-(4-hydroxypiperidin-1-yl)-2 oxoethyl] amide) (25, 50, and 100 μM). The effect of metabolic inhibition on cellular protein turnover dynamics was also studied using the modified SILAC (stable isotope labeling with amino acids in cell culture) method.. A total of 22 protein spots and 4 phosphoprotein spots were quantitatively analyzed. We found that dynamic expression of total proteins and phosphoproteins was significantly changed in MIA PaCa-2 cells treated with an incremental dose of CP-320626. Functional analyses suggested that most of the proteins differentially expressed were in the pathways of mitogen-activated protein kinase/extracellular signal-regulated kinase and tumor necrosis factor α/nuclear factor κB.. Signaling pathways and metabolic pathways share many common cofactors and substrates forming an extended metabolic network. The restriction of substrate through 1 pathway such as inhibition of glycogen phosphorylation induces pervasive metabolomic and proteomic changes manifested in protein synthesis, breakdown, and posttranslational modification of signaling molecules. Our results suggest that quantitative proteomic is an important approach to understand the interaction between metabolism and signaling pathways.

Topics: Amides; Apoptosis; Cell Cycle Checkpoints; Cell Line, Tumor; Dose-Response Relationship, Drug; Electrophoresis, Gel, Two-Dimensional; Enzyme Inhibitors; Glycogen; Glycogen Phosphorylase; Humans; Indoles; Neoplasm Proteins; Pancreatic Neoplasms; Peptide Mapping; Phosphorylation; Proteomics; Signal Transduction; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Pancreatic cysts are common, but cystic tumors are uncommon. We report a rare case of serous cystadenoma of the pancreas synchronous with ampullary adenocarcinoma which supports a common etiopathogeny of these tumors. We discuss the differential diagnosis with mucinous cystadenoma which is potentially malignant and recall the microscopic and radiologic features.

Topics: Adenocarcinoma; Aged; Cystadenoma, Serous; Diagnosis, Differential; Female; Glycogen; Humans; Neoplasms, Second Primary; Pancreatic Neoplasms

Serous microcystic adenoma of the pancreas, also known as microcystic adenoma, glycogen-rich cystadenoma or serous cystadenoma, is an uncommon benign tumor. We have studied 11 cases involving eight women and three men. The average age at diagnosis was 61.7 years. Four tumors were discovered incidentally. Tumors varied from 1.2 to 20 cm in maximum diameter and all were multicystic. Within the pancreas, three were located in the pancreas head, one involved the head and body, one was located in the body, five were in the tail, and one occupied the whole pancreas. Central stellate scar was seen in five (45%) cases. Histologically, all tumors were composed of microglandular cysts lined by clear epithelial cells rich in glycogen, which were separated by fibrocollagenous stroma. The expression of keratin in clear epithelial cells resembled that in ductal and/or centroacinar cells, but not acinar cells. alpha-Smooth muscle actin (SMA)-positive myoepithelial cells and stromal amyloid deposits were not detected. Ultrastructurally, fibrocollagenous stroma was composed of alpha-SMA-positive myofibroblasts and endothelial cells embedded in thick collagen bundles. Regardless of female propensity, estrogen and progesterone receptors were not detected. Therefore, female predominance in this tumor remains to be elucidated.

Topics: Aged; Biomarkers, Tumor; Cystadenoma, Serous; Female; Glycogen; Humans; Immunohistochemistry; Male; Middle Aged; Pancreatic Neoplasms; Periodic Acid-Schiff Reaction; Sex Distribution

Serous cystic tumours of the pancreas are uncommon and are usually classified as microcystic adenomas (MCA). As new types of serous cystic tumours of this organ have been reported we reviewed a series of 14 lesions and from macroscopic findings two groups were distinguished: ten tumours revealed the features of MCA, while four were clearly distinct from MCA. Grossly, the latter tumours showed only few cysts which were irregularly assembled in fibrous stroma. On the cut surface, there was neither a central stellate scar nor a circumscribed tumour border, features characterizing MCA. Microscopically, the cysts were lined by cuboidal, non-mucin-producing cells. Immunocytochemical staining for cytokeratins 7, 8, 18 and 19 revealed a ductal phenotype. All non-MCA were found in the head of the pancreas and three of them occurred in men. There were no tumour recurrences or signs or malignant transformation after resection (mean follow-up, 2.9 years). These results suggest that there are serous cystic tumours distinct from MCA which may represent another variant of the category of serous cystic adenomas of the pancreas. We propose the term serous oligocystic and ill-demarcated adenoma (SOIA) for these tumours. It is possible that the recently described macrocystic sybtype of serous cystadenoma and SOIA and variants of the same tumour.

Topics: Adenoma; Aged; Aged, 80 and over; Amylases; Cystadenoma, Serous; Cytoplasm; Female; Glycogen; Humans; Immunohistochemistry; Male; Middle Aged; Pancreatic Neoplasms; Periodic Acid-Schiff Reaction

Diabetes in patients with pancreatic cancer occurs in 70% to 80% of the patients and is characterized by high plasma levels of insulin. In type II diabetes that is not associated with pancreatic cancer, peripheral insulin resistance and impaired muscle glycogen synthesis are major pathogenic factors. We investigated peripheral insulin sensitivity in patients with pancreatic cancer before and after tumor removal. The effects of pancreatic tumor extracts on glycogen synthesis in skeletal muscle in vitro and the tumor content of pancreatic islet hormones were also investigated. Marked peripheral insulin resistance was found in the patients with pancreatic cancer and was more pronounced in the diabetic patients than in the nondiabetic patients. Insulin sensitivity was not correlated with weight loss, tumor size, or bilirubin levels but improved after surgery. Tumor extracts from diabetic patients with pancreatic cancer caused a marked reduction of glycogen synthesis in skeletal muscle in vitro. All tumors contained islet hormones but not in concentrations sufficient to explain the effect on glycogen synthesis. These findings indicate that a diabetogenic factor associated with pancreatic adenocarcinomas could be involved in the development of the profound peripheral insulin resistance and thereby could contribute to the high incidence of diabetes observed in patients with pancreatic cancer.

Topics: Aged; Animals; Carcinoma, Intraductal, Noninfiltrating; Diabetes Complications; Female; Glucose Clamp Technique; Glycogen; Humans; Insulin Resistance; Male; Muscles; Pancreatic Hormones; Pancreatic Neoplasms; Radioimmunoassay; Rats; Rats, Wistar

True cystic neoplasms of the pancreas generally have mucinous, glycogen-rich, or acinar-type-cyst-lining epithelium. A malignant polycystic pancreatic neoplasm in a 74-year-old black woman whose cyst-lining epithelium had none of the above-cited attributes and thus appears to represent an exception is described. The primary tumor was a large, encapsulated mass whose cysts contained watery fluid. Basically, two types of epithelium lined the cysts: a single layered, low-grade malignant-appearing type and a proliferative, overtly malignant-appearing pseudostratified and papillary type. Oncocytic metaplasia, canaliculi, and microvilli were ultrastructural features.

Topics: Aged; Cystadenocarcinoma; Female; Glycogen; Humans; Immunohistochemistry; Mucins; Pancreatic Neoplasms

Acinar, centroacinar, and endocrine cells of the adult rat pancreas each exhibit distinctive cell-surface glycoconjugate patterns as detected by binding of a battery of lectin-ferritin conjugates. Acquisition of these unique glycoconjugate patterns appears to be developmentally regulated, as studies on embryonic rat pancreases at days 15, 17, and 19 of gestation indicate. Further, the three cell types appear to arise from a common stem cell(s) with surface glycoconjugate properties similar to those of the adult centroacinar cell. STudies on the cell-surface properties of a rat acinar cell tumor indicate that the neoplastic acinar cells are likely to be arrested at a developmental stage equivalent to acinar cells of the day 19 embryonic pancreas and are characterized by absence of detectable basal lamina. We hypothesize that pancreatic cancers may arise from the equivalent of the undifferentiated embryonic stem cell(s) and that the morphologic features of the tumor depend on the extent of cell differentiation, including expression of cell-surface glycoproteins and extracellular matrix, prior to neoplastic proliferation.

Topics: Animals; Basement Membrane; Binding Sites; Cell Differentiation; Cell Membrane; Ferritins; Glycogen; Glycoproteins; Guinea Pigs; Islets of Langerhans; Lectins; Neoplasms, Experimental; Pancreas; Pancreatic Neoplasms; Rats; Receptors, Mitogen; Surface Properties

Seven cases of cystadenoma of the pancreas were examined in detail histologically and histochemically and two variants were identified: a microcyst type lined by glycogen-rich cuboidal epithelium which also secretes some neutral mucins; and macrocystic type lined exclusively by mucus-secreting columnar cells which secrete predominantly sulphated acidic mucins with some neutral mucins. Electron microscopy of two cases of the microcystic variant showed neoplastic cells with an ultrastructure comparable to that of centroacinar cells of the normal exocrine pancreas.

Topics: Aged; Connective Tissue; Cystadenoma; Cytoplasm; Epithelium; Female; Glycogen; Humans; Male; Middle Aged; Mucins; Organoids; Pancreatic Neoplasms

This report concerns an 8-year-old girl with fasting hypoglycemia caused by a functional islet cell adenoma. During two separate fasting studies the blood glucose concentrations decreased to abnormally low levels yet the serum concentrations of insulin were consistently within the accepted range of normal. This report illustrates the diagnostic value of three simple functional tests--the inhibitory effect of insulin on ketogenesis and on glycogenolysis and the stimulatory effect of leucine on insulin secretion.

Topics: Adenoma, Islet Cell; Blood Glucose; Child; Fasting; Female; Glucose; Glycogen; Humans; Hypoglycemia; Insulin; Insulin Secretion; Ketone Bodies; Leucine; Pancreatic Neoplasms

Thirty-four cases of microcystic adenoma of the pancreas were studied. These benign tumors have traditionally been classified as cystadenomas, but have not been clearly distinguished from those cystic neoplasms of the pancreas that have a significant malignant potential. Microcystic adenomas are benign, usually large (mean diameter 10.8 cm), and are composed of many tiny cysts lined by small cuboidal cells containing glycogen but little or no mucin. The tumor may be found incidentally at autopsy or, more commonly, may manifest as an abdominal mass with some associated local pain or discomfort. There is no sex predilection. The patients are usually elderly, both mean and median ages being 68. A microcystic pattern is apparent both grossly and microscopically. Electron microscopy confirms the presence of intracytoplasmic glycogen and the epithelial character of the cells. Follow-up data (mean 6.4 years), available in all cases, indicate that when these tumors occur in the head of the pancreas, fatalities may result either from complications of radical surgery or from gastrointestinal or biliary obstruction. When the tumors occur in the body or tail of the pancreas, biopsy alone may be sufficient.

Topics: Adult; Aged; Cystadenoma; Cytoplasmic Granules; Epithelium; Female; Follow-Up Studies; Glycogen; Humans; Male; Middle Aged; Neoplasms, Multiple Primary; Pancreatic Neoplasms

Topics: Amantadine; Carcinoma; Cells, Cultured; DNA, Neoplasm; Embryo, Mammalian; Female; Glycogen; Hemangiosarcoma; Humans; In Vitro Techniques; Mitosis; Ovarian Neoplasms; Pancreatic Neoplasms; RNA, Neoplasm; Stomach 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; Age Factors; Aged; Carbohydrate Metabolism; Diabetes Complications; Female; Glycogen; Humans; Male; Middle Aged; Neoplasms; Pancreatic Neoplasms; Sex Factors

Topics: Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Bile; Bile Duct Neoplasms; Bilirubin; Biomedical Research; Cholelithiasis; Cholestasis, Extrahepatic; Glycogen; Humans; Jaundice; Jaundice, Obstructive; Liver; Liver Function Tests; Liver Glycogen; Pancreatic Neoplasms; Thymol

Topics: Adenoma, Islet Cell; Blood; Diaphragm; Fasting; Glycogen; Injections; Injections, Intraperitoneal; Insulin; Muscles; Pancreatic Neoplasms; Pharmacology; Rats; Research; Sodium Chloride

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