Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN.
A benign tumor of the pancreatic ISLET CELLS. Usually it involves the INSULIN-producing PANCREATIC BETA CELLS, as in INSULINOMA, resulting in HYPERINSULINISM.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm but is often wrongly used as a synonym for "cancer." (From Dorland, 27th ed)
The transference of pancreatic islets within an individual, between individuals of the same species, or between individuals of different species.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
A primary malignant neoplasm of the pancreatic ISLET CELLS. Usually it involves the non-INSULIN-producing cell types, the PANCREATIC ALPHA CELLS and the pancreatic delta cells (SOMATOSTATIN-SECRETING CELLS) in GLUCAGONOMA and SOMATOSTATINOMA, respectively.
A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)
A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A lesion with cytological characteristics associated with invasive carcinoma but the tumor cells are confined to the epithelium of origin, without invasion of the basement membrane.
A type of pancreatic cell representing about 50-80% of the islet cells. Beta cells secrete INSULIN.
Promoter-specific RNA polymerase II transcription factor that binds to the GC box, one of the upstream promoter elements, in mammalian cells. The binding of Sp1 is necessary for the initiation of transcription in the promoters of a variety of cellular and viral GENES.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Established cell cultures that have the potential to propagate indefinitely.
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
A malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells. (Stedman, 25th ed)
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
A pancreatic beta-cell hormone that is co-secreted with INSULIN. It displays an anorectic effect on nutrient metabolism by inhibiting gastric acid secretion, gastric emptying and postprandial GLUCAGON secretion. Islet amyloid polypeptide can fold into AMYLOID FIBRILS that have been found as a major constituent of pancreatic AMYLOID DEPOSITS.
A benign tumor of the PANCREATIC BETA CELLS. Insulinoma secretes excess INSULIN resulting in HYPOGLYCEMIA.
A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence.
Tumors or cancer of the LIVER.
Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
A cell line derived from cultured tumor cells.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A nodular organ in the ABDOMEN that contains a mixture of ENDOCRINE GLANDS and EXOCRINE GLANDS. The small endocrine portion consists of the ISLETS OF LANGERHANS secreting a number of hormones into the blood stream. The large exocrine portion (EXOCRINE PANCREAS) is a compound acinar gland that secretes several digestive enzymes into the pancreatic ductal system that empties into the DUODENUM.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.
A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal GLUCAGON-LIKE PEPTIDES. Glucagon is secreted by PANCREATIC ALPHA CELLS and plays an important role in regulation of BLOOD GLUCOSE concentration, ketone metabolism, and several other biochemical and physiological processes. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1511)
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).
Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).
A type of pancreatic cell representing about 5-20% of the islet cells. Alpha cells secrete GLUCAGON.
An invasive (infiltrating) CARCINOMA of the mammary ductal system (MAMMARY GLANDS) in the human BREAST.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
A malignant skin neoplasm that seldom metastasizes but has potentialities for local invasion and destruction. Clinically it is divided into types: nodular, cicatricial, morphaic, and erythematoid (pagetoid). They develop on hair-bearing skin, most commonly on sun-exposed areas. Approximately 85% are found on the head and neck area and the remaining 15% on the trunk and limbs. (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1471)
The first nucleotide of a transcribed DNA sequence where RNA polymerase (DNA-DIRECTED RNA POLYMERASE) begins synthesizing the RNA transcript.
A family of DNA-binding transcription factors that contain a basic HELIX-LOOP-HELIX MOTIF.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-6 family members. STAT3 is constitutively activated in a variety of TUMORS and is a major downstream transducer for the CYTOKINE RECEPTOR GP130.
An almost always malignant GLUCAGON-secreting tumor derived from the PANCREATIC ALPHA CELLS. It is characterized by a distinctive migratory ERYTHEMA; WEIGHT LOSS; STOMATITIS; GLOSSITIS; DIABETES MELLITUS; hypoaminoacidemia; and normochromic normocytic ANEMIA.
A multiprotein complex composed of the products of c-jun and c-fos proto-oncogenes. These proteins must dimerize in order to bind to the AP-1 recognition site, also known as the TPA-responsive element (TRE). AP-1 controls both basal and inducible transcription of several genes.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
A DNA-dependent RNA polymerase present in bacterial, plant, and animal cells. It functions in the nucleoplasmic structure and transcribes DNA into RNA. It has different requirements for cations and salt than RNA polymerase I and is strongly inhibited by alpha-amanitin. EC
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
A malignant neoplasm derived from TRANSITIONAL EPITHELIAL CELLS, occurring chiefly in the URINARY BLADDER; URETERS; or RENAL PELVIS.
A 14-amino acid peptide named for its ability to inhibit pituitary GROWTH HORMONE release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of THYROID-STIMULATING HORMONE; PROLACTIN; INSULIN; and GLUCAGON besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, SRIF-28 with a 14-amino acid extension at the N-terminal.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Elements of limited time intervals, contributing to particular results or situations.
Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or body fluids. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including hormones, antigens, amino and nucleic acids, enzymes, polyamines, and specific cell membrane proteins and lipids.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
The so-called general transcription factors that bind to RNA POLYMERASE II and that are required to initiate transcription. They include TFIIA; TFIIB; TFIID; TFIIE; TFIIF; TFIIH; TFII-I; and TFIIJ. In vivo they apparently bind in an ordered multi-step process and/or may form a large preinitiation complex called RNA polymerase II holoenzyme.
The major sequence-specific DNA-binding component involved in the activation of transcription of RNA POLYMERASE II. It was originally described as a complex of TATA-BOX BINDING PROTEIN and TATA-BINDING PROTEIN ASSOCIATED FACTORS. It is now know that TATA BOX BINDING PROTEIN-LIKE PROTEINS may take the place of TATA-box binding protein in the complex.
A malignant epithelial tumor with a glandular organization.
Malignant neoplasm arising from the epithelium of the BRONCHI. It represents a large group of epithelial lung malignancies which can be divided into two clinical groups: SMALL CELL LUNG CANCER and NON-SMALL-CELL LUNG CARCINOMA.
Ducts that collect PANCREATIC JUICE from the PANCREAS and supply it to the DUODENUM.
A noninvasive (noninfiltrating) carcinoma of the breast characterized by a proliferation of malignant epithelial cells confined to the mammary ducts or lobules, without light-microscopy evidence of invasion through the basement membrane into the surrounding stroma.
Tumors or cancer of the human BREAST.
Enzymes that catalyze DNA template-directed extension of the 3'-end of an RNA strand one nucleotide at a time. They can initiate a chain de novo. In eukaryotes, three forms of the enzyme have been distinguished on the basis of sensitivity to alpha-amanitin, and the type of RNA synthesized. (From Enzyme Nomenclature, 1992).
Carcinoma characterized by bands or cylinders of hyalinized or mucinous stroma separating or surrounded by nests or cords of small epithelial cells. When the cylinders occur within masses of epithelial cells, they give the tissue a perforated, sievelike, or cribriform appearance. Such tumors occur in the mammary glands, the mucous glands of the upper and lower respiratory tract, and the salivary glands. They are malignant but slow-growing, and tend to spread locally via the nerves. (Dorland, 27th ed)
An anaplastic, highly malignant, and usually bronchogenic carcinoma composed of small ovoid cells with scanty neoplasm. It is characterized by a dominant, deeply basophilic nucleus, and absent or indistinct nucleoli. (From Stedman, 25th ed; Holland et al., Cancer Medicine, 3d ed, p1286-7)
Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter.
Nucleic acid sequences involved in regulating the expression of genes.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
A subclass of winged helix DNA-binding proteins that share homology with their founding member fork head protein, Drosophila.
Ability of neoplasms to infiltrate and actively destroy surrounding tissue.
The biosynthesis of DNA carried out on a template of RNA.
A carcinoma composed mainly of epithelial elements with little or no stroma. Medullary carcinomas of the breast constitute 5%-7% of all mammary carcinomas; medullary carcinomas of the thyroid comprise 3%-10% of all thyroid malignancies. (From Dorland, 27th ed; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1141; Segen, Dictionary of Modern Medicine, 1992)
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A 36-amino acid pancreatic hormone that is secreted mainly by endocrine cells found at the periphery of the ISLETS OF LANGERHANS and adjacent to cells containing SOMATOSTATIN and GLUCAGON. Pancreatic polypeptide (PP), when administered peripherally, can suppress gastric secretion, gastric emptying, pancreatic enzyme secretion, and appetite. A lack of pancreatic polypeptide (PP) has been associated with OBESITY in rats and mice.
A technique for identifying specific DNA sequences that are bound, in vivo, to proteins of interest. It involves formaldehyde fixation of CHROMATIN to crosslink the DNA-BINDING PROTEINS to the DNA. After shearing the DNA into small fragments, specific DNA-protein complexes are isolated by immunoprecipitation with protein-specific ANTIBODIES. Then, the DNA isolated from the complex can be identified by PCR amplification and sequencing.
An antibiotic that is produced by Stretomyces achromogenes. It is used as an antineoplastic agent and to induce diabetes in experimental animals.
A infiltrating (invasive) breast cancer, relatively uncommon, accounting for only 5%-10% of breast tumors in most series. It is often an area of ill-defined thickening in the breast, in contrast to the dominant lump characteristic of ductal carcinoma. It is typically composed of small cells in a linear arrangement with a tendency to grow around ducts and lobules. There is likelihood of axillary nodal involvement with metastasis to meningeal and serosal surfaces. (DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1205)
A large superfamily of transcription factors that contain a region rich in BASIC AMINO ACID residues followed by a LEUCINE ZIPPER domain.
Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.
Any of the processes by which cytoplasmic or intercellular factors influence the differential control of gene action in bacteria.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Tumors or cancer of the NASOPHARYNX.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Tumors or cancer of the THYROID GLAND.
A group of carcinomas which share a characteristic morphology, often being composed of clusters and trabecular sheets of round "blue cells", granular chromatin, and an attenuated rim of poorly demarcated cytoplasm. Neuroendocrine tumors include carcinoids, small ("oat") cell carcinomas, medullary carcinoma of the thyroid, Merkel cell tumor, cutaneous neuroendocrine carcinoma, pancreatic islet cell tumors, and pheochromocytoma. Neurosecretory granules are found within the tumor cells. (Segen, Dictionary of Modern Medicine, 1992)
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
A pyridoxal-phosphate protein that catalyzes the alpha-decarboxylation of L-glutamic acid to form gamma-aminobutyric acid and carbon dioxide. The enzyme is found in bacteria and in invertebrate and vertebrate nervous systems. It is the rate-limiting enzyme in determining GAMMA-AMINOBUTYRIC ACID levels in normal nervous tissues. The brain enzyme also acts on L-cysteate, L-cysteine sulfinate, and L-aspartate. EC
Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked.
Tumors or cancer of the LUNG.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
An RNA POLYMERASE II specific transcription factor. It plays a role in assembly of the pol II transcriptional preinitiation complex and has been implicated as a target of gene-specific transcriptional activators.
A family of transcription factors that control EMBRYONIC DEVELOPMENT within a variety of cell lineages. They are characterized by a highly conserved paired DNA-binding domain that was first identified in DROSOPHILA segmentation genes.
Antibodies specific to INSULIN.
Enzymes that oxidize certain LUMINESCENT AGENTS to emit light (PHYSICAL LUMINESCENCE). The luciferases from different organisms have evolved differently so have different structures and substrates.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Methods which attempt to express in replicable terms the extent of the neoplasm in the patient.
Surgical removal of the pancreas. (Dorland, 28th ed)
A family of DNA binding proteins that regulate expression of a variety of GENES during CELL DIFFERENTIATION and APOPTOSIS. Family members contain a highly conserved carboxy-terminal basic HELIX-TURN-HELIX MOTIF involved in dimerization and sequence-specific DNA binding.
Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Proteins prepared by recombinant DNA technology.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
A signal transducer and activator of transcription that mediates cellular responses to INTERFERONS. Stat1 interacts with P53 TUMOR SUPPRESSOR PROTEIN and regulates expression of GENES involved in growth control and APOPTOSIS.
An electrophoretic technique for assaying the binding of one compound to another. Typically one compound is labeled to follow its mobility during electrophoresis. If the labeled compound is bound by the other compound, then the mobility of the labeled compound through the electrophoretic medium will be retarded.
A family of zinc finger transcription factors that share homology with Kruppel protein, Drosophila. They contain a highly conserved seven amino acid spacer sequence in between their ZINC FINGER MOTIFS.
Endocrine cells found throughout the GASTROINTESTINAL TRACT and in islets of the PANCREAS. D cells secrete SOMATOSTATIN that acts in both an endocrine and paracrine manner. Somatostatin acts on a variety of tissues including the PITUITARY GLAND; gastrointestinal tract; pancreas; and KIDNEY by inhibiting the release of hormones, such as GROWTH HORMONE; GASTRIN; INSULIN; and RENIN.
A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in fungi.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.
A ubiquitously expressed zinc finger-containing protein that acts both as a repressor and activator of transcription. It interacts with key regulatory proteins such as TATA-BINDING PROTEIN; TFIIB; and ADENOVIRUS E1A PROTEINS.
Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.
A specificity protein transcription factor that regulates expression of a variety of genes including VASCULAR ENDOTHELIAL GROWTH FACTOR and CYCLIN-DEPENDENT KINASE INHIBITOR P27.
A pancreatic polypeptide of about 110 amino acids, depending on the species, that is the precursor of insulin. Proinsulin, produced by the PANCREATIC BETA CELLS, is comprised sequentially of the N-terminal B-chain, the proteolytically removable connecting C-peptide, and the C-terminal A-chain. It also contains three disulfide bonds, two between A-chain and B-chain. After cleavage at two locations, insulin and C-peptide are the secreted products. Intact proinsulin with low bioactivity also is secreted in small amounts.
Glucose in blood.
A conserved A-T rich sequence which is contained in promoters for RNA polymerase II. The segment is seven base pairs long and the nucleotides most commonly found are TATAAAA.
A highly malignant, primitive form of carcinoma, probably of germinal cell or teratomatous derivation, usually arising in a gonad and rarely in other sites. It is rare in the female ovary, but in the male it accounts for 20% of all testicular tumors. (From Dorland, 27th ed & Holland et al., Cancer Medicine, 3d ed, p1595)
Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
A tumor of both low- and high-grade malignancy. The low-grade grow slowly, appear in any age group, and are readily cured by excision. The high-grade behave aggressively, widely infiltrate the salivary gland and produce lymph node and distant metastases. Mucoepidermoid carcinomas account for about 21% of the malignant tumors of the parotid gland and 10% of the sublingual gland. They are the most common malignant tumor of the parotid. (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p575; Holland et al., Cancer Medicine, 3d ed, p1240)
A mixed adenocarcinoma and squamous cell or epidermoid carcinoma.
Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
Proteins found in any species of bacterium.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
A subclass of receptor-like protein tryosine phosphatases that contain an extracellular RDGS-adhesion recognition motif and a single cytosolic protein tyrosine phosphate domain.
Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651)
A family of transcription factors characterized by the presence of highly conserved calcineurin- and DNA-binding domains. NFAT proteins are activated in the CYTOPLASM by the calcium-dependent phosphatase CALCINEURIN. They transduce calcium signals to the nucleus where they can interact with TRANSCRIPTION FACTOR AP-1 or NF-KAPPA B and initiate GENETIC TRANSCRIPTION of GENES involved in CELL DIFFERENTIATION and development. NFAT proteins stimulate T-CELL activation through the induction of IMMEDIATE-EARLY GENES such as INTERLEUKIN-2.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Transport proteins that carry specific substances in the blood or across cell membranes.
Tumors or cancer of the COLON.
An activating transcription factor that regulates expression of a variety of GENES including C-JUN GENES; CYCLIN A; CYCLIN D1; and ACTIVATING TRANSCRIPTION FACTOR 3.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
An adenocarcinoma characterized by the presence of cells resembling the glandular cells of the ENDOMETRIUM. It is a common histological type of ovarian CARCINOMA and ENDOMETRIAL CARCINOMA. There is a high frequency of co-occurrence of this form of adenocarcinoma in both tissues.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
Transplantation between animals of different species.
Tumors or cancer of the MOUTH.
Motifs in DNA- and RNA-binding proteins whose amino acids are folded into a single structural unit around a zinc atom. In the classic zinc finger, one zinc atom is bound to two cysteines and two histidines. In between the cysteines and histidines are 12 residues which form a DNA binding fingertip. By variations in the composition of the sequences in the fingertip and the number and spacing of tandem repeats of the motif, zinc fingers can form a large number of different sequence specific binding sites.
A family of transcription factors that contain regions rich in basic residues, LEUCINE ZIPPER domains, and HELIX-LOOP-HELIX MOTIFS.
In bacteria, a group of metabolically related genes, with a common promoter, whose transcription into a single polycistronic MESSENGER RNA is under the control of an OPERATOR REGION.
A GATA transcription factor that is expressed in the MYOCARDIUM of developing heart and has been implicated in the differentiation of CARDIAC MYOCYTES. GATA4 is activated by PHOSPHORYLATION and regulates transcription of cardiac-specific genes.
Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.
A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.
Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.
Tumors or cancer of the ESOPHAGUS.
An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A and activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F1 is involved in DNA REPAIR and APOPTOSIS.
Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.
An activating transcription factor that plays a key role in cellular responses to GENOTOXIC STRESS and OXIDATIVE STRESS.
A protein that has been shown to function as a calcium-regulated transcription factor as well as a substrate for depolarization-activated CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASES. This protein functions to integrate both calcium and cAMP signals.
A carcinoma arising from MERKEL CELLS located in the basal layer of the epidermis and occurring most commonly as a primary neuroendocrine carcinoma of the skin. Merkel cells are tactile cells of neuroectodermal origin and histologically show neurosecretory granules. The skin of the head and neck are a common site of Merkel cell carcinoma, occurring generally in elderly patients. (Holland et al., Cancer Medicine, 3d ed, p1245)
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
The rate dynamics in chemical or physical systems.
Any of the processes by which cytoplasmic factors influence the differential control of gene action in viruses.
A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.
Malignant neoplasms involving the ductal systems of any of a number of organs, such as the MAMMARY GLANDS, the PANCREAS, the PROSTATE, or the LACRIMAL GLAND.
The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
A subunit of NF-kappa B that is primarily responsible for its transactivation function. It contains a C-terminal transactivation domain and an N-terminal domain with homology to PROTO-ONCOGENE PROTEINS C-REL.
DNA present in neoplastic tissue.
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
Transfer of a neoplasm from its primary site to lymph nodes or to distant parts of the body by way of the lymphatic system.
A family of DNA-binding proteins that are primarily expressed in T-LYMPHOCYTES. They interact with BETA CATENIN and serve as transcriptional activators and repressors in a variety of developmental processes.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
A signal transducer and activator of transcription that mediates cellular responses to a variety of CYTOKINES. Stat5 activation is associated with transcription of CELL CYCLE regulators such as CYCLIN KINASE INHIBITOR P21 and anti-apoptotic genes such as BCL-2 GENES. Stat5 is constitutively activated in many patients with acute MYELOID LEUKEMIA.
A malignant neoplasm of the ADRENAL CORTEX. Adrenocortical carcinomas are unencapsulated anaplastic (ANAPLASIA) masses sometimes exceeding 20 cm or 200 g. They are more likely to be functional than nonfunctional, and produce ADRENAL CORTEX HORMONES that may result in hypercortisolism (CUSHING SYNDROME); HYPERALDOSTERONISM; and/or VIRILISM.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
Tumors or cancer of the SKIN.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
Genes which regulate or circumscribe the activity of other genes; specifically, genes which code for PROTEINS or RNAs which have GENE EXPRESSION REGULATION functions.
Iwafuchi-Doi M, Zaret KS (June 2016). "Cell fate control by pioneer transcription factors". Development. 143 (11): 1833-7. doi: ... knockout studies show that Foxa2 is important for the formation of pancreatic islets and maturation of alpha and beta cells, ... Single nucleotide polymorphisms in the FOXA2 gene are associated with hepatocellular carcinoma, especially in males. This ... December 2012). "Foxa2 and H2A.Z mediate nucleosome depletion during embryonic stem cell differentiation". Cell. 151 (7): 1608- ...
TTC39B is expressed in a multitude of tissues: testis, lung, islets of langerhans, pancreas, kidney, pooled germ cell tumors, ... cell-cycle, transcription, and protein transport complexes. Two more TPR domains are found in the TTC39B protein: TPR1 which ... breast carcinoma, etc. There are five different transcript variants for the TTC39B gene. Isoform 1 is the longest transcript ... The transcription start site for TTC39B protein isoform 1 is located from base pairs 15,307,340 to 15,307,389 and has a length ...
Several forms of cancer (see below) including elevation of miR-184 levels in squamous cell carcinoma of the tongue. All-trans- ... showed miR-184 reduced Argonaute 2 levels in the MIN6 mouse pancreatic beta islet cell line. Furthermore, miR-184 has multiple ... MicroRNA Cullen BR (December 2004). "Transcription and processing of human microRNA precursors". Mol. Cell. 16 (6): 861-5. doi: ... Wong TS, Ho WK, Chan JY, Ng RW, Wei WI (2009). "Mature miR-184 and squamous cell carcinoma of the tongue". ...
"Hepatocyte Nuclear Factor 1A Is a Cell-Intrinsic Transcription Factor Required for B Cell Differentiation and Development in ... HNF-1 protein is present in clear cell carcinoma of ovary In humans, mutations in HNF1A cause diabetes that responds to low ... and GLUT2 transporter expression in pancreatic β-cells and angiotensin-converting enzyme 2 gene expression in pancreatic islets ... It is ubiquitously expressed in many tissues and cell types. The protein encoded by this gene is a transcription factor that is ...
The islet cell autoantibodies are absent in MODY in at least some populations (Japanese, Britons). Persistence of a low insulin ... March 2005). "Role of transcription factor KLF11 and its diabetes-associated gene variants in pancreatic beta cell function". ... Liver adenoma or hepatocellular carcinoma in MODY type 3 Renal cysts, rudimentary or bicornuate uterus, vaginal aplasia, ... found that about one quarter of Central European MODY patients are positive for islet cell autoantibodies (GABA and IA2A). ...
... pancreatic islet cells and lymphoid cells. PAX8 and other transcription factors play a role in binding to DNA and regulating ... almost all subtypes of renal cell carcinoma, nephrogenic adenomas, ovarian cancer cells, bladder, prostate, and endometrial ... of oncocytic carcinomas (aka Hurthle-Cell Neoplasms). Expression of PAX8 is increased in neoplastic renal tissues, Wilms tumors ... cell motility and adhesion. Mutations in this gene have been associated with thyroid dysgenesis, thyroid follicular carcinomas ...
... has been used in miR fluorescence in situ hybridization to distinguish Merkel cell polyomavirus-positive Merkel cell carcinoma ... "Up-regulated pancreatic tissue microRNA-375 associates with human type 2 diabetes through beta-cell deficit and islet amyloid ... the involvement of miR-375 in pancreas development includes the fact that its expression is regulated by several transcription ... "MicroRNA-375 is downregulated in gastric carcinomas and regulates cell survival by targeting PDK1 and 14-3-3zeta". Cancer Res. ...
Immunohistochemically, prostatic small cell carcinoma are positive for thyroid transcription factor 1 (TTF-1), CD56, ... of neuroendocrine cell islets that are spread throughout the tumor and account for the majority of its constituent cells. The ... Prostatic neuroendocrine cells, also known as endocrine-paracrine cells, are part of a larger regulatory cell population ... small cell carcinoma of the prostate, in turn, exhibit a universal type in that virtually all the constituent tumor cells ...
The glial cells missing homolog 1 and the oligodendrocyte lineage transcription factors are notable because KIAA1211L is highly ... breast carcinoma, the islets of Langerhans, the pancreas, the kidney, and 38 other tissues. Additionally, it is expressed an ... "Cell atlas - KIAA1211L - The Human Protein Atlas". Retrieved 2017-04-23. "GenScript Protein Subcellular ... Furthermore, it is associated with bipolar disease and is active in breast cancer cells. As such, the predicted interaction ...
P27 transcription has also been linked to another tumor suppressor gene, MEN1, in pancreatic islet cells where it promotes ... In hepatocellular carcinoma cells p27 co-localizes with actin fibers to act on GTPase Rac and induce cell migration. In breast ... Studies of various cell lines including glioblastoma cell lines, three prostate cancer cell lines, and a breast tumor cell line ... Lack of CDKN1B expression appears to release the hair cells from natural cell-cycle arrest. Because hair cell death in the ...
They infiltrate islets and may even co-operate with αβ T cells to induce T1D. RA is a chronic autoimmune disease caused by ... γδ T cells have regulatory and suppressive role in the tumor microenvironment through expression of transcription factors ( ... Trials in numerous cancers (renal carcinoma, leukemia, lung cancer) showed that they are tolerated and safe, but on the other ... Gamma delta T cells (γδ T cells) are T cells that have a distinctive T-cell receptor (TCR) on their surface. Most T cells are ...
In this approach, transcription factors from progenitor cells of the target cell type are transfected into a somatic cell to ... "Virgin Beta Cells Persist throughout Life at a Neogenic Niche within Pancreatic Islets" (PDF). Cell Metabolism. 25 (4): 911-926 ... No standard of care exists for these patients, and those diagnosed with treatment induced neruoendocrine carcinoma are ... by inducing a shift in the developmental fate of cells in the liver and converting them into 'pancreatic beta-cell-like' cells ...
... pancreatic islet cells and lymphoid cells.[8] PAX8 and other transcription factors play a role in binding to DNA and regulating ... almost all subtypes of renal cell carcinoma, nephrogenic adenomas, ovarian cancer cells, bladder, prostate, and endometrial ... "Seminars in Cell & Developmental Biology. Paramutation & Pax Transcription Factors. 44: 97-106. doi:10.1016/j.semcdb.2015.09. ... regulation of transcription, DNA-templated. • positive regulation of metanephric DCT cell differentiation. • negative ...
B-cell receptor-associated protein 29 BCC6: encoding protein basal cell carcinoma, susceptibility to, 6 BRAT1: BRCA1-associated ... Cell division cycle-associated 7-like protein CNOT4: CCR4-NOT transcription complex, subunit 4 CPED1: cadherin like and PC- ... islet cell autoantigen 1 ING3: inhibitor of growth protein 3 INTS1: encoding protein Integrator complex subunit 1 IQCE: IQ ... These changes include an extra copy of part of chromosome 7 in each cell (partial trisomy 7) or a missing segment of the ...
"Regulation of p63 isoforms by snail and slug transcription factors in human squamous cell carcinoma". Am J Pathol. 176 (4): ... and the mesenchymal cells derived from pancreatic islets can undergo the reverse of EMT - MET - to generate islet-like cell ... Initiation of metastasis requires invasion, which is enabled by EMT.[36][37] Carcinoma cells in a primary tumor lose cell-cell ... The epithelial-mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell-cell ...
"Master transcription factors and mediator establish super-enhancers at key cell identity genes". Cell. 153 (2): 307-19. doi: ... March 2016). "An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma". Nature Genetics. 48 (3 ... February 2014). "Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants". Nature Genetics. 46 ... "Super-enhancers in the control of cell identity and disease". Cell. 155 (4): 934-47. doi:10.1016/j.cell.2013.09.053. PMC ...
Hui H, Perfetti R (Feb 2002). "Pancreas duodenum homeobox-1 regulates pancreas development during embryogenesis and islet cell ... "Enhancement of serum-response factor-dependent transcription and DNA binding by the architectural transcription factor HMG-I(Y ... expression represents a potential diagnostic indicator of carcinoma". Cancer Research. 58 (18): 4193-8. PMID 9751634. Vogel B, ... John S, Reeves RB, Lin JX, Child R, Leiden JM, Thompson CB, Leonard WJ (Mar 1995). "Regulation of cell-type-specific ...
... receptor-gamma stimulates the growth arrest and DNA-damage inducible 153 gene in non-small cell lung carcinoma cells". Oncogene ... "Expression and transactivating functions of the bZIP transcription factor GADD153 in mammary epithelial cells". Oncogene. 21 ( ... January 2011). "UPR induces transient burst of apoptosis in islets of early lactating rats through reduced AKT phosphorylation ... The overexpression of CHOP can lead to cell cycle arrest and result in cell apoptosis. At the same time, CHOP-induced apoptosis ...
"PKM2 phosphorylates histone H3 and promotes gene transcription and tumorigenesis". Cell. 150 (4): 685-96. doi:10.1016/j.cell. ... Brinck U, Eigenbrodt E, Oehmke M, Mazurek S, Fischer G (1994). "L- and M2-pyruvate kinase expression in renal cell carcinomas ... PKM2 is expressed in some differentiated tissues, such as lung, fat tissue, retina, and pancreatic islets, as well as in all ... such as normal proliferating cells, embryonic cells, and especially tumor cells. Two isozymes are encoded by the PKM gene: PKM1 ...
Transcription factor 7-like 2 (T-cell specific, HMG-box), also known as TCF7L2 or TCF4, is a protein acting as a transcription ... TCF7L2 modulates pancreatic islet β-cell function strongly implicating its significant association with GDM risk. T alleles of ... colon carcinoma". Science. 275 (5307): 1784-7. doi:10.1126/science.275.5307.1784. hdl:20.500.11755/27e2349d-dfbe-4458-9a4e- ... Duval A, Rolland S, Tubacher E, Bui H, Thomas G, Hamelin R (July 2000). "The human T-cell transcription factor-4 gene: ...
"Estrogen receptor alpha polymorphisms and renal cell carcinoma--a possible risk". Mol. Cell. Endocrinol. 202 (1-2): 109-16. doi ... Hu YC, Shyr CR, Che W, Mu XM, Kim E, Chang C (Sep 2002). "Suppression of estrogen receptor-mediated transcription and cell ... Gay F, Anglade I, Gong Z, Salbert G (Oct 2000). "The LIM/homeodomain protein islet-1 modulates estrogen receptor functions". ... Studies in cell extracts and intact cells and their implications for hormone-dependent transcriptional activation". J. Biol. ...
Transcription factors (TFs) bind to the promoter region of SLC46A3 and modulate the transcription of the gene. The table below ... The protein functions independent of the cell surface target or cell line, thus is most likely to recognize maytansine or a ... Microarray data from NCBI GEO present high expression in pancreatic islets, pituitary gland, lymph nodes, peripheral blood, and ... June 2019). "Increased expression of SLC46A3 to oppose the progression of hepatocellular carcinoma and its effect on sorafenib ...
This leads to activation of the Drosophila STAT, Stat92E, a transcription factor which effects GSC adhesion to the hub cells, ... "Localization of Islet-1-Positive Cells in the Healthy and Infarcted Adult Murine Heart". Circulation Research. 110 (10): 1303- ... "Activation of beta-catenin by hypoxia in hepatocellular carcinoma contributes to enhanced metastatic potential and poor ... The GSC niche consists of necessary somatic cells-terminal filament cells, cap cells, escort cells, and other stem cells which ...
Another factor that will support the activation of MMP-2 is cell-cell clustering. A wild-type activated leukocyte cell adhesion ... For instance, when studying carcinogenesis of pancreatic islets in transgenic mice, Bergers et al. showed that MMP-2 and MMP-9 ... Furthermore, changes in MMP-2 activity can come from alterations in levels of transcription, MMP secretion, MMP activation, or ... Furthermore, increased expression and activity of MMP-2 has been tied to increased vascularization of lung carcinoma metastases ...
... bone marrow cells, islet cells and endothelial cells. However, the derivation of such cell types from ESCs is not without ... Retinoblastoma proteins that inhibit the transcription factor E2F until the cell is ready to enter S phase are ... Kleinsmith LJ, Pierce GB Jr (1964). "Multipotentiality of Single Embryoncal Carcinoma Cells". Cancer Res. 24: 1544-51. PMID ... The resulting inner cell mass cells are plated onto cells that will supply support. The inner cell mass cells attach and expand ...
... in the angiogenic blood vessels and invasive fronts of carcinoma in the RIP-Tag2 transgenic mouse model of pancreatic islet ... Activated c-kit is then able to recruit hematopoietic, endothelial and mast cell progenitor cells, these cells are then ... MMP activity is regulated at the level of transcription, post-translationally by proteolytic cleavage, and by endogenous ... Cathepsins also can be secreted by cells, associate with the cell surface, and degrade the ECM. A study of all 11 members of ...
... cell reproduction, and cell regeneration in humans and other animals. It is thus important in human development. It is a type ... a 53-year-old female with carcinoma of the breast and widespread skeletal metastases; a 68-year-old female with advanced ... an emerging role for xenobiotic-metabolizing enzymes and the transcription factors regulating their expression. A review". ... Contributes to the maintenance and function of pancreatic islets. *Stimulates the immune system ...
"Retinoic acid induces embryonal carcinoma cells to differentiate into neurons and glial cells". The Journal of Cell Biology. ... usually transcription factors, introduced in the cells. The starting material can be either pluripotent stem cells (PSCs), or ... cell type affected in diseases are a major focus of research, this includes hepatocytes, Langerhans islet beta-cells, ... Historically, embryonic carcinoma (EC) cells have also been used. Fibroblasts or other differentiated cell types have been used ...
positive regulation of transcription from RNA polymerase II promoter. • negative regulation of cell proliferation. • signal ... Transcriptional mechanisms of FZD5 in undifferentiated human ES cells, fetal liver/spleen, adult colon, pancreatic islet, and ... "A novel frizzled gene identified in human esophageal carcinoma mediates APC/beta-catenin signals". Proc. Natl. Acad. Sci. U.S. ... cell maturation. • Wnt signaling pathway. • embryonic camera-type eye development. • multicellular organism development. • cell ...
... induces tumor suppressive properties in human hepatocellular carcinoma-derived cells, Huh7 and Hep3B cell lines, ... "GDF11 modulates NGN3+ islet progenitor cell number and promotes beta-cell differentiation in pancreas development". Development ... transcription factors. These effects suggest an "anti-hypertrophic effect", aiding in the reversal process of age-related ... "Cell. 153 (4): 828-39. doi:10.1016/j.cell.2013.04.015. PMC 3677132. PMID 23663781.. ...
... cell reproduction, and cell regeneration in humans and other animals. It is thus important in human development. GH also ... a 53-year-old female with carcinoma of the breast and widespread skeletal metastases; a 68-year-old female with advanced ... an emerging role for xenobiotic-metabolizing enzymes and the transcription factors regulating their expression. A review". ... Contributes to the maintenance and function of pancreatic islets. *Stimulates the immune system ...
The Medical Subject Headings indexing system refers to "islet cell carcinoma", which is subdivided into gastrinoma, glucagonoma ... for example the transcription factor PELP1.[45][46] ... "Islet Cell Tumors of the Pancreas / Endocrine Neoplasms of the ... Other exocrine cancers include adenosquamous carcinomas, signet ring cell carcinomas, hepatoid carcinomas, colloid carcinomas, ... "islet cell cancers",[28] even though it is now known that they do not actually arise from islet cells as previously thought.[27 ...
"The C cells (parafollicular cells) of the thyroid gland and medullary thyroid carcinoma. A review". The American Journal of ... which bind with hormone response elements and transcription factors to modulate DNA transcription.[30][31] In addition to these ... Islets of pancreas. *Alpha cell. *Beta cell. *PP cell. *Delta cell. *Epsilon cell ... parafollicular cells.[4] These cells secrete calcitonin and so are also called C cells.[16] ...
These complexes inhibit calcineurin, block dephosphorylation of the transcription factor NFAT of activated T-cells and its ... "Gingival squamous cell carcinoma diagnosed on the occasion of osteonecrosis of the jaw in a patient with chronic GVHD". Rinsho ... cells in the graft itself that causes it but cells in the graft that make the recipient's T cells act like donor T cells. It ... T-cells and guest B-cells. In the final phase, these effector cells migrate to target organs and mediate tissue damage, ...
"Protein prenylation in glucose-induced insulin secretion from the pancreatic islet beta cell: a perspective". Journal of ... The sterol response elements then facilitate increased transcription of various other proteins, most notably, LDL receptor. The ... hepatocellular carcinoma,[98] and possibly prostate cancer.[99][100] They appear to have no effect on the risk of lung cancer,[ ... "Cell. 161 (1): 161-172. doi:10.1016/j.cell.2015.01.036. PMC 4525717. PMID 25815993.. ...
... re-aggregating cells,[31][32] cockroach hemocyte capsules,[33] rabbit skin,[34] chick embryos,[35] human islet of Langerhans,[ ... "Gap junction blockage interferes with neuronal and astroglial differentiation of mouse P19 embryonal carcinoma cells". Dev. ... "eat-5 and unc-7 represent a multigene family in Caenorhabditis elegans involved in cell-cell coupling". J. Cell Biol. 134 (2): ... "Connexin43 modulates cell polarity and directional cell migration by regulating microtubule dynamics". PLoS ONE. 6 (10): e26379 ...
Hepatocellular carcinoma cell proliferation may arise from miR-21 interaction with MAP2K3, a tumor repressor gene. Optimal ... a transcription factor that activates a series of transcription events in the nucleus accumbens that ultimately result in ... "A pancreatic islet-specific microRNA regulates insulin secretion". Nature. 432 (7014): 226-30. Bibcode:2004Natur.432..226P. doi ... and cell cycle in mice lacking miRNA-1-2". Cell. 129 (2): 303-17. doi:10.1016/j.cell.2007.03.030. PMID 17397913. Thum T, ...
CD47 knockdown acutely increases mRNA levels of c-Myc and other stem cell transcription factors in cells in vitro and in vivo. ... "Neo-β Cell Islets" from Intestinal Crypts". Cell Reports. 6 (6): 1046-1058. doi:10.1016/j.celrep.2014.02.013. PMC 4245054. PMID ... teratoma-initiating embryonic-like carcinoma cells during differentiation. The survival of these teratoma-initiating cells is ... human iPS cell-derived myeloid cell lines as unlimited cell source for dendritic cell-like antigen-presenting cells". Gene ...
... produced by antigen-presenting cells (APCs). M1-activated macrophages express transcription factors such as Interferon- ... Cucak H, Grunnet LG, Rosendahl A (January 2014). "Accumulation of M1-like macrophages in type 2 diabetic islets is followed by ... February 2017). "Heterogeneity of macrophage infiltration and therapeutic response in lung carcinoma revealed by 3D organ ... for example apoptotic cells, symbiont cells, gametes and cells of the embryo in the uterus). M2 macrophages hence govern ...
... they cannot penetrate cell membranes. Thus, GH exerts some of its effects by binding to receptors on target cells, where it ... a 53-year-old female with carcinoma of the breast and widespread skeletal metastases; a 68-year-old female with advanced ... an emerging role for xenobiotic-metabolizing enzymes and the transcription factors regulating their expression. A review". ... liver uptake of glucose Promotes gluconeogenesis in the liver Contributes to the maintenance and function of pancreatic islets ...
Title: MLL3 and MLL4 Methyltransferases Bind to the MAFA and MAFB Transcription Factors to Regulate Islet β-Cell Function. ... Downregulation of MLL3 in esophageal squamous cell carcinoma is required for the growth and metastasis of cancer cells. Xia M, ... Title: Downregulation of MLL3 in esophageal squamous cell carcinoma is required for the growth and metastasis of cancer cells. ... inactivation of MLL3 and TET2 may play an important role in the tumorigenesis process of HTLV-I-induced acute adult T-cell ...
Islets cells display a strong staining, whereas epithelial cells of the pancreatic duct (arrow) or acinar cells are negative ... Chretien S., Dubart A., Beaupain D., Raich N., Grandchamp B., Rosa J., Goossens M., Romeo P. H. Alternative transcription and ... In pancreatic carcinoma tissues, the cellularity of the carcinoma cells was relatively low (approximately 10-50%), but we still ... Cell Lines and Tissue Samples.. Three pancreatic adenocarcinoma cell lines were used in this study. The BxPC3 and PSN1 cell ...
Iwafuchi-Doi M, Zaret KS (June 2016). "Cell fate control by pioneer transcription factors". Development. 143 (11): 1833-7. doi: ... knockout studies show that Foxa2 is important for the formation of pancreatic islets and maturation of alpha and beta cells, ... Single nucleotide polymorphisms in the FOXA2 gene are associated with hepatocellular carcinoma, especially in males. This ... December 2012). "Foxa2 and H2A.Z mediate nucleosome depletion during embryonic stem cell differentiation". Cell. 151 (7): 1608- ...
... islet cell tumors of the pancreas, and pheochromocytoma.. The cellular transcription factor Elongin (SIII) has been identified ... Comprehensive molecular characterization of clear cell renal cell carcinoma. Cancer Genome Atlas Research Network. ... Carcinoma and Birt Hogg Dubé syndrome and Hereditary Leiomyomatosis Renal Cell Carcinoma and Succinate Dehydrogenase Renal Cell ... von Hippel-Lindau and clear cell renal carcinoma), the gene for Hereditary Papillary Renal Carcinoma (MET oncogene, type I ...
... and lipoid cell morphology in an 80-year-old female who was admitted to our hospital with mictritional pain and bilateral ... We present very rare variants of urothelial carcinoma featuring nested, plasmacytoid, ... 14576499 - Analysis of expression profiles of islet-associated transcription and growth factors du.... ... Carcinoma, Transitional Cell / pathology*. Diagnosis, Differential. Fatal Outcome. Female. Humans. Keratins / metabolism. ...
TTC39B is expressed in a multitude of tissues: testis, lung, islets of langerhans, pancreas, kidney, pooled germ cell tumors, ... cell-cycle, transcription, and protein transport complexes. Two more TPR domains are found in the TTC39B protein: TPR1 which ... breast carcinoma, etc. There are five different transcript variants for the TTC39B gene. Isoform 1 is the longest transcript ... The transcription start site for TTC39B protein isoform 1 is located from base pairs 15,307,340 to 15,307,389 and has a length ...
... , Xing Xu, Yudong Zheng, Lian ... is a compound derived from Streptomyces achromogenes that has been used for the treatment of pancreatic β cell carcinoma. Due ... Forkhead box O (FoxO) is a transcription factor that plays an important role in the differentiation, proliferation and survival ... Islet β cells are the only cells that secrete insulin, the maintenance of normal amount and function of insulin is necessary ...
Molecular targeted therapy for carcinoid and islet-cell carcinoma. Best Pract Res Clin Endocrinol Metab 21 (1): 163-72, 2007. [ ... an intestinal transcription factor in endocrine tumors of the small intestine, suggests an origin from an epithelial precursor ... Poorly differentiated carcinomas (small cell and fewer large cell), which are highly malignant and carry a poor prognosis. ... In addition, in the WHO classification scheme, GI NETs have been grouped with pancreatic NETS (islet cell tumors) and labeled ...
No islet cell tumors were observed, even among animals ,2 years of age. Under our experimental conditions, the proliferative ... Cyclin D1 may thus be considered a potential candidate to augment the beta-cell population ex vivo as a prelude to islet ... We expressed cyclin D1 in the beta-cells of mice and islet hyperplasia developed in a time-dependent manner. The hyperplastic ... have implicated the G1-S transition as a key regulatory checkpoint governing the proliferation of pancreatic islet cells. ...
Molecular targeted therapy for carcinoid and islet-cell carcinoma. Best Pract Res Clin Endocrinol Metab 21 (1): 163-72, 2007. ... an intestinal transcription factor in endocrine tumors of the small intestine, suggests an origin from an epithelial precursor ... Poorly differentiated carcinomas (small cell and fewer large cell), which are highly malignant and carry a poor prognosis. ... Goblet cell carcinoids are classified according to the carcinoma scheme.[2]. This staging classification applies to carcinoids ...
Loss of ARNT/HIF1beta mediates altered gene expression and pancreatic-islet dysfunction in human type 2 diabetes. Cell. 122:337 ... Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol. 16:4604-4613 ... Aryl hydrocarbon receptor nuclear translocator promotes the proliferation and invasion of clear cell renal cell carcinoma cells ... The role of hypoxia and cancer stem cells in renal cell carcinoma pathogenesis. Stem Cell Rev Rep. 11:919-943. 2015. View ...
Retinoic acid stimulates erythropoietin gene transcription in embryonal carcinoma cells through the direct repeat of a steroid/ ... Synonyms: ICRF, Islet cells regeneration factor, Islet of Langerhans regenerating protein, Lithostathine-1-alpha, P19, ... ... Expression of multiple heparin-binding growth factor species by murine embryonal carcinoma and embryonic stem cells. Heath, J.K ... Embryonal carcinoma P19 cells produce erythropoietin constitutively but express lactate dehydrogenase in an oxygen-dependent ...
Molecular targeted therapy for carcinoid and islet-cell carcinoma. Best Pract Res Clin Endocrinol Metab 21 (1): 163-72, 2007. ... an intestinal transcription factor in endocrine tumors of the small intestine, suggests an origin from an epithelial precursor ... Poorly differentiated carcinomas (small cell and fewer large cell), which are highly malignant and carry a poor prognosis. ... aAdapted from Cell TypeLocationSecretory ProductG cell Gastric antrum and duodenumGastrinECL cell Gastric fundus and ...
Islet Studies. *. Cell Cycle Regulation of the Pdx1 Transcription Factor in Developing Pancreas and Insulin-Producing β-Cells ... anti-miR-21 treatment of mammary carcinoma cells increased apoptosis and decreased cell proliferation (49). A similar mechanism ... Insulin-secreting cell line culture and pancreatic islet isolation.. The insulin-secreting cell line MIN6B1 and INS-1E were ... miR-21 is strongly upregulated in cytokine-treated β-cells and in NOD mice during islet inflammation. In myeloma cells, the ...
Expressed by beta-islet cell of pancreas Pancreas. Insulin-promoting factor-1 (PDX-1). Pancreatic islet. Transcription factor ... Pluripotent Stem Cells. Alkaline phosphatase. Embryonic stem (ES), embryonal carcinoma (EC). Elevated expression of this enzyme ... Pancreatic islet. Expressed by gamma-islet cell of pancreas. Somatostatin. Pancreatic islet. Expressed by delta-islet cell of ... Pancreatic islet. Expressed by alpha-islet cell of pancreas. Insulin. Pancreatic islet. ...
von Hippel Lindau syndrome = hemangioblastoma of the CNS/retina, pheochromocytoma, renal cell carcinoma, pancreatic ... MEN 1 = hyperparathyroidism, pancreatic islet cell tumors, pituitary adenomas. May also have cutaneous manifestations ( ... in which the iodide suppresses gene transcription of TPO. Give sodium iodide 1 g IV or SSKI 5 drops orally q 6 h. ... MEN 2A = medullary thyroid carcinoma, hyperparathyroidism, pheochromocytoma. MEN 2B = medullary thyroid carcinoma, ...
Transforming growth factor-beta/Smad3 signaling regulates insulin gene transcription and pancreatic islet beta-cell function. J ... and pancreatic diseases like pancreatitis and pancreatic carcinoma (13,14). During embryogenesis, TGFβ signaling regulates the ... Percentage of BrdU+ β cells, Ki-67+ β cells, BrdU+ duct cells, and β-cell mass/area was quantified on the basis of at least six ... Duct- to islet-cell differentiation and islet growth in the pancreas of duct-ligated adult rats. Diabetologia 1995;38:1405-1411 ...
... non-small cell neuroendocrine carcinoma was made after a histological analysis and immunostaining. We attempted to highlight ... Our review of the literature revealed that further research is needed, focusing on neuroendocrine carcinomas of the esophagus ... High-grade neuroendocrine carcinoma (NEC) of the esophagus is an extremely aggressive and rare disease, which is still not well ... weakly positive for Islet-1, but negative for p40, keratin 5/6, and thyroid transcription factor (TTF-1), as shown in Figure 3 ...
Keywords: head and neck cancer, squamous cell carcinoma, programmed cell death 1, programmed cell death ligand 1, immunotherapy ... Groundbreaking progress has been achieved in the treatment of recurrent/metastatic head and neck squamous cell carcinoma (HNSCC ... and programmed cell death ligand 1 (PD-L1) has shown enormous development prospects for HNC treatment. ... With the development of cancer molecular biology and immunology, targeted therapy for immune checkpoints of programmed cell ...
... for this transcription element are recognized in human being insulinomas lymphomas head and neck squamous cell carcinomas as ... We demonstrate that within mature islets endogenous PAX4 marks predominantly a subset of islet β-cells which on one hand is ... PAX4 is a key regulator of pancreatic islet advancement whilst Acarbose in adult acute overexpression protects β-cells against ... Our data recommend PAX4 defines an expandable β-cell sub people within adult islets. During embryogenesis both exocrine and ...
Sox17 and Sox4 differentially regulate β-catenin/T-cell factor activity and proliferation of colon carcinoma cells. Mol Cell ... Use of differentiating adult stem cells (marrow stromal cells) to identify new downstream target genes for transcription ... Tissue-specific knockout of SOX4 in the pancreas results in failure of normal development of pancreatic islets ( 4). SOX4 ... 1C). EGFR is expressed in RWPE-1 cells, but not in LNCaP cells, and SOX4 did not bind to these sequences in LNCaP cells (data ...
... is a glucose-sensing transcription factor that mediates the induction of glycolytic and lipogenic genes in response to glucose ... Seino Y et al (1993) Abnormal facilitative glucose transporter gene expression in human islet cell tumors. J Clin Endocrinol ... Genomic analysis of ChREBP target gene expression in human hepatocellular carcinoma cell line HEPG2 by ChIP-sequencing showed ... transcription factor expressed in liver, white and brown adipose tissues, intestine, muscle, and pancreatic β-cells [21, 22]. ...
Forskolin suppresses insulin gene transcription in islet beta-cells through a protein kinase A-independent pathway. Cell Signal ... Enteric neuronal autoantibodies in pseudoobstruction with small-cell lung carcinoma. Gastroenterology. 1991 Jan; 100(1):137-42 ... Forskolin surpresses insulin gene transcription in islet beta cells through a protein kinase A-independent pathway. Cellular ... 1999 Cell signaling and transcription regulation in acinar epithelial cells. Curr Opin Gastroenterol. 1998; 16(1):1-5. ...
Knocking down SNRPN blocked the cell cycle at the G2/M phase transition and promoted tumor cell apoptosis, inhibiting the ... Knocking down SNRPN blocked the cell cycle at the G2/M phase transition and promoted tumor cell apoptosis, inhibiting the ... Both in vitro and in vivo experiments confirmed that high expression of SNRPN was associated with tumor proliferation, cell ... Both in vitro and in vivo experiments confirmed that high expression of SNRPN was associated with tumor proliferation, cell ...
Phase II trial of chlorozotocin and fluorouracil in islet cell carcinoma: a Southwest Oncology Group study. Bukowski, R.M., ... The insulin gene is transcribed in the human thymus and transcription levels correlated with allelic variation at the INS VNTR- ... Anatomical context of Islets of Langerhans. *When beta cells were lacking in islet-cell tumors or in the pancreas of a patient ... Immunofluorescence revealed an islet-cell cytoplasmic antibody (ICA) in 20 patients with IDDM and an islet-cell-surface ...
The NEUROD1 gene encodes a member of the NeuroD family of basic-loop-helix transcription factors. The NEUROD 1 was first ... Immunoperoxidase of monoclonal antibody to NEUROD1 on formalin-fixed paraffin-embedded human ovary, clear cell carcinoma. [ ... and endocrine islet cells. NeuroD1 regulates the expression of numerous genes including the insulin gene. Mutations in the ... The NEUROD1 gene encodes a member of the NeuroD family of basic-loop-helix transcription factors. The NEUROD 1 was first ...
In the pancreas, PAXs proteins play a critical role in islet cell differentiation. We recently observed that islet cells show ... thyroid SCC / thyroid squamous cell carcinoma. * PAX8 is an excellent marker for confirming primary thyroid tumor in metastasis ... PAXs (paired box) genes encode a family of transcription factors that regulate organogenesis and cell-lineage specification in ... thyroid carcinoma.. * Pax8 is expressed in 79% of thyroid anaplastic carcinomas to a variable extent, whereas TTF-1 and TTF-2 ...
Transcription profiling by array of human pancreatic islet cells after in vitro expansion ... Tags: adenoma, cancer, carcinoma, duct, invasive carcinoma, main pancreatic duct, mucinous adenoma, mucinous neoplasm, pancreas ... Tags: beta cell, cell, hand, insulin, pancreas, pancreatic islet, right, stem cell ... Tags: bone, bone marrow, brain, cell, cerebellum, colon, cortex, genome, gland, heart, intestine, kidney, liver, lung, muscle, ...
"Long non-coding RNA MEG3 inhibits adipogenesis and promotes osteogenesis of human adipose-derived mesenchymal stem cells via ... Expression, regulation and roles of miR-26a and MEG3 in tongue squamous cell carcinoma ... of human adipose-derived stromal cells by retinoblastoma binding protein 2 repression of RUNX2-activated transcription ... Epigenetic regulation of the DLK1-MEG3 microRNA cluster in human type 2 diabetic islets ...
The shRNA against HPV16 E6 or E7 was delivered by adenovirus into esophageal squamous cell carcinoma (ESCC) cells with high HPV ... Pancreatic β-cell DNA was identified in the circulation of patients with recently diagnosed type-1 diabetes and islet-graft ... transcription quantitative PCR and investigated protein expression in B-lymphoblastoid cell lines and primary dendritic cells ... Peripheral blood mononuclear cells from the patient showed decreased frequency of CTLA-4(high) cells in CD4(+)FOXP3(+) cells ...
  • The incidence of carcinoma of the pancreas is associated with a high mortality rate. (
  • Germline mutations in the VHL gene predispose individuals to a variety of tumors, including renal carcinoma, CNS hemangioblastoma, islet cell tumors of the pancreas, and pheochromocytoma. (
  • Dysregulation of FOXA transcription factors have been linked to several types of human cancers, including acute myeloid leukemia and cancer of the esophagus, lung, thyroid, pancreas, breast and prostate. (
  • Focal regions of nestin-positive cells are also identified in large, small, and centrolobular ducts of the rat pancreas. (
  • Upon confluence, they are able to differentiate into cells that express liver and exocrine pancreas markers, such as α-fetoprotein and pancreatic amylase, and display a ductal/endocrine phenotype with expression of CK19, neural-specific cell adhesion molecule, insulin, glucagon, and the pancreas/duodenum specific homeodomain transcription factor, IDX-1. (
  • The identification of NIP cells within the pancreatic islets themselves suggest possibilities for treatment of diabetes, whereby NIP cells isolated from pancreas biopsies could be expanded ex vivo and transplanted into the donor/recipient. (
  • The mammalian pancreas consists of three distinct tissue types: the ductal tree, the exocrine acini that produce digestive enzymes, and the endocrine islets of Langerhans. (
  • Ductal cells of the adult pancreas include latent progenitor cells of the islet endocrine cells that can be induced to differentiate into islet endocrine cells given the appropriate morphogen stimuli-a process referred to as neogenesis ( 2 - 6 ). (
  • The differentiation of duct cells of the pancreas into endocrine hormone-producing cells is believed to recapitulate the embryonic development (ontogeny) of the pancreas, whereby the exocrine and endocrine pancreases arise from the differentiation and proliferation of patterned endodermal cells in the early embryonic foregut that first form a ductal tree by branching morphogenesis ( 1 ). (
  • Tissue-specific knockout of SOX4 in the pancreas results in failure of normal development of pancreatic islets ( 4 ). (
  • In the pancreas, PAXs proteins play a critical role in islet cell differentiation. (
  • In 2011, we described a robust protocol of targeted oncogenesis in human fetal pancreas and produced the first functional human β cell line, and in subsequent years additional lines with specific traits. (
  • β cells reside in the pancreas and are organized in clusters of endocrine cells called islets of Langerhans. (
  • Over the past century - mainly since 1921, when Banting and Best started treating diabetic dogs with pancreas extracts - our understanding of how β cells develop, grow, function, survive, and die in physiological and pathological conditions has improved impressively. (
  • Approximately 90% of the pancreas is exocrine tissue, comprising acinar cells that synthesize and secrete digestive enzymes and ductal cells that secrete and channel the fluid that transports the acinar enzymes to the duodenum. (
  • About 1% of the pancreas is endocrine tissue, comprising four principal cell types synthesizing insulin (β-cells), glucagon (α-cells), somatostatin (δ-cells), and pancreatic polypeptide (PP cells) organized into islets scattered throughout the exocrine pancreas. (
  • Databases show MPP7 is highly expressed in mouse pancreas and is expressed in human islets. (
  • This population is highly proliferative, capable of differentiation toward the myriad cell types of the mature adult pancreas and produces basal amounts of insulin. (
  • We theorize that using this cell population, in addition to a bioreactor type culture mechanism that mimics the niche of the in vivo pancreas, we can create a viable cell source of insulin-producing cells that can be used for the transplant and treatment of diabetes. (
  • She is currently focusing her attention on methods of transplanting human fetal progenitor cells from the liver and pancreas. (
  • The size of the pancreas is determined by intrinsic factors, such as the number of progenitor cells, and by extrinsic signals that control the fate and proliferation of those progenitors. (
  • Although we have shown that the Wnt signaling component β-catenin is selectively required in mouse embryos for the generation of exocrine acinar cells, this protein has been ascribed various functions in the postnatal pancreas, including proliferation and regeneration of islet as well as acinar cells. (
  • Addressing these questions in the pancreas, a bifunctional organ comprising anatomically distinct endocrine and exocrine cell types, has implications for several devastating diseases, including diabetes, pancreatitis and pancreatic cancer. (
  • In the endocrine pancreas, BETA2 null mice show moderate reduction in the number of beta cells and a slight reduction in alpha cell number ( 24 ), with essentially normal POMC expression in the corticotrophs of the anterior pituitary ( 16 ). (
  • Pancreas organogenesis is regulated by the interaction of distinct signaling pathways that promote or restrict morphogenesis and cell differentiation. (
  • Shh-/- and Shh-/-;Ihh+/- mutants have a threefold increase in pancreas mass, and a fourfold increase in pancreatic endocrine cell numbers. (
  • 2 Islet-1 exhibits strong nuclear staining in the islets of normal pancreas and tumor cells of the pancreatic neuroendocrine tumor. (
  • The objective of this review is to discuss similarities and differences between the neoplastic lesions of the pancreas and biliary tract with potential implications on a common origin from similar stem/progenitor cells. (
  • The endocrine cells of the rat pancreatic islets of Langerhans, including insulin-producing β-cells, turn over every 40-50 days by processes of apoptosis and the proliferation and differentiation of new islet cells (neogenesis) from progenitor epithelial cells located in the pancreatic ducts. (
  • 1-3 Islet-1 plays an important role in the embryogenesis and differentiation of the insulin producing pancreatic beta cells within the islets of Langerhans. (
  • Pancreatic Neuroendocrine Tumors (PanNETs) arise from cells of the Islets of Langerhans. (
  • Using beta-cell growth factors to enhance human pancreatic Islet transplantation. (
  • Islet transplantation offers a potential cure for type I diabetes mellitus. (
  • The aim of this thesis was to establish the effects of rapamycin, one of the primary immunosuppressants used in islet transplantation, on murine β cells and islets and elucidate the mechanisms of any toxicity seen. (
  • ud This work brings into question the use of rapamycin as an immunosuppressant in islet transplantation and also highlights the key role of PKB in β cell survival. (
  • 2006). A significant role for histocompatibility in human islet transplantation. (
  • 2001). Autoantibody response to islet transplantation in type 1 diabetes. (
  • Islet transplantation has proven effective at curing diabetes, but its use is severely limited due to the necessity for a large number of transplantable islets as well as a shortage of suitable donors. (
  • Improved outcomes in islet isolation and transplantation by the use of a novel hemoglobin-based O2 carrier. (
  • Robotic-assisted laparoscopic distal pancreatectomy of a redo case combined with autologous islet transplantation for chronic pancreatitis. (
  • No treatments have been devised that increase beta-cell mass in vivo in humans, and transplantation of beta-cells is extremely limited due to lack of appropriate donors. (
  • For these reasons, increasing functional beta-cell mass in vitro, or in vivo prior to or after transplantation, has become a "Holy Grail" of diabetes research. (
  • In the context of islet studies and transplantation, 1 islet equivalent (IEQ) is often considered as a size of 150 mm, consisting of an average 2,500 cells. (
  • Unlike whole organ transplantation where revascularization occurs through surgical anastomosis of vessels, the revascularization of islets requires the formation of vessel patencies either through inosculation of host and recipient microvessels or through neo-vessel penetration into the islet. (
  • Oh E., Stull N.D., Mirmira R.G., and Thurmond D.C. (2014) Syntaxin 4 upregulation improves islet function and transplantation success. (
  • Forkhead box O (FoxO) is a transcription factor that plays an important role in the differentiation, proliferation and survival of various cells such as adipocytes, hepatocytes, and islet β cells. (
  • SOX4 is a critical developmental transcription factor in vertebrates and is required for precise differentiation and proliferation in multiple tissues. (
  • These studies suggest a critical role for SOX4 in cell fate decisions and differentiation. (
  • SNRPN also plays a role in regulating osteoblastic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) by increasing runt-related transcription factor 2 (Runx2) expression at the RNA splicing level ( 10 ). (
  • The NEUROD 1 was first described by Lee et al (1995) who observed that the gene was transiently expressed in subsets of neuronal cells of the central and peripheral nervous system at the time of their terminal differentiation into mature neurons. (
  • NEUROD1 is involved in the regulation of several cell differentiation pathways including the development of retinal ganglion cell, inner ear sensory neurons, and endocrine islet cells. (
  • The culture medium contained KnockOut Dulbecco's modified minimal essential medium (a serum-free substitute for the 20% fetal bovine serum used in the 1998 experiments), and basic FGF, which is necessary to maintain cell proliferation and prevent differentiation. (
  • Plays a role in the regulation of proliferation, survival and differentiation of many different cell types and also in metabolism and inflammation. (
  • If the location of the primary malignancy is not determined, treatment is often initiated based on the grade and level of differentiation of the tumor, with well- and moderately differentiated tumors treated as carcinoid tumors, whereas poorly differentiated tumors are treated similarly to small cell tumors. (
  • Since joining the lab, he has developed three projects: (1) Dissecting the transcription factor network controlling pancreatic beta cell differentiation by using high-throughput screening techniques to discover novel small molecule inducers that are able to promote regeneration of pancreatic endocrine cells. (
  • Proliferation and differentiation characteristics of HPC cells are the focus of ongoing studies. (
  • suggesting that this gene is required not only for differentiation of acinar cells but also for their normal maintenance. (
  • Moreover, RBP2 siRNA is sufficient to promote senescence and differentiation in pRB-defective tumor cells in vitro ( 9 , 10 ). (
  • The basic helix-loop-helix protein BETA2/NeuroD activates transcription of the secretin gene and is essential for terminal differentiation of secretin-producing enteroendocrine cells. (
  • Islet-1, a human insulin gene enhancer-binding protein, is a transcription factor involved in the differentiation of the neuroendocrine pancreatic cells. (
  • Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. (
  • RT "CDK6 blocks differentiation: coupling cell proliferation to the block RT to differentiation in leukemic cells. (
  • 2005, "Efficient Differentiation of Human Embryonic Stem Cells to Definitive Endoderm," Nature Biotechnology, 23(12):1534-1541. (
  • 2002, "Growth Inhibitors Promote Differentiation of Insulin-Producing Tissue from Embryonic Stem Cells," PNAS, vol. 99(25)16105-16110. (
  • PAX8 is shown to be involved in tumor cell proliferation and differentiation, signal transduction, apoptosis, cell polarity and transport, cell motility and adhesion. (
  • 1. A method of producing liver precursor cells, said method comprising the steps of obtaining a cell population comprising definitive endoderm cells and providing said cell population with a BMP family growth factor and an FGF family growth factor for a time sufficient to allow the differentiation of liver precursor cells from said definitive endoderm cells. (
  • Immunohistochemically, the cancer cells were positive for cytokeratin, epithelial membrane antigen, but not for vimentin, S-100, or hematopoietic markers of plasma cells such as CD79alpha and CD38. (
  • Although the cellular origin of NETs of the GI tract is uncertain, consistent expression of cytokeratins in NETs and the expression of the caudal-related homeodomain protein 2 (CdX2 protein), an intestinal transcription factor in endocrine tumors of the small intestine, suggests an origin from an epithelial precursor cell. (
  • Consistent but weaker staining for Pax8 is also identified in the epithelial cells of remnant thymic tissue located in the periphery of the tumors. (
  • Hepatic Oval cells are small, oval shaped epithelial cells identified in the liver during normal embryonic development. (
  • Immunoreactive gp-340 was also found in epithelial cells of the small intestine and in the ducts of salivary glands. (
  • Three collectins are known in humans: mannan-binding lectin (MBL), a serum protein, and the lung surfactant proteins A and D (SP-A and SP-D), which are produced by epithelial cells mainly in the lung. (
  • SP-D is mainly produced by alveolar type II cells but is also present in sweat, salivary, tear, and mammary glands and in epithelial cells throughout the gastrointestinal tract. (
  • In contrast, PPAR γ was also shown to induce a mesenchymal transformation in epithelial intestinal cells. (
  • Our results indicate that troglitazone induced a mesenchymal-like transformation in M1 and IMCD-K2 epithelial cells independently of PPAR γ . (
  • An example of this was found in the intestine where activation of PPAR γ was shown to induce a mesenchymal transition in epithelial intestinal cell line [ 7 ]. (
  • Epithelial cells form organized cell-cell adhesion junctions preventing movement of individual cells and producing a tight epithelial surface. (
  • The transformation of EMT is described as the process in which epithelial cells that function as ion and fluid transporters lose their epithelial polarity, cellular adhesion molecules, and reorganize their actin cytoskeleton from a cortical bundle formation that supported adhesion molecules into stress fibers containing de novo expressed α -smooth muscle actin ( α -SMA) that supports migration. (
  • Role of mitochondrial hOGG1 and aconitase in oxidant-induced lung epithelial cell apoptosis. (
  • We report here that overexpression of mitochondria-targeted human alpha-hOgg1 (mt-hOgg1) in human lung adenocarcinoma cells with some alveolar epithelial cell characteristics (A549 cells) prevents oxidant-induced mitochondrial dysfunction and apoptosis by preserving mitochondrial aconitase. (
  • Proliferation, cell migration and cell adhesion all must be tightly controlled in order to prevent either inflammatory diseases or epithelial cancers. (
  • Isolating highly enriched populations of circulating epithelial cells and other rare cells from blood using a magnetic sweeper device. (
  • RT "Cyclin-dependent kinase 6 inhibits proliferation of human mammary RT epithelial cells. (
  • During the acquisition of EMT characteristics, cancer cells lose the epithelial markers, such as E-cadherin, and gain the mesenchymal markers, such as vimentin, fibronectin and N-cadherin ( 13 ). (
  • Soluble molecules secreted from breast tumor cells, but not normal breast epithelial cells, induced IL-23 protein secretion in dendritic cells via induction of p19 mRNA expression. (
  • In contrast, benign tumors showed weak expression or no expression of COX-2, and only islet cells displayed COX-2 expression in normal pancreatic tissues. (
  • Furthermore, consistent with the results at protein levels, reverse transcription-PCR analyses indicated that COX-2 mRNA was overexpressed in 7 of 13 (54%) carcinomas, but in none of 3 benign tumors. (
  • Carcinoid tumors are rare, slow-growing tumors that originate in cells of the diffuse neuroendocrine system. (
  • the term should not be used to describe pancreatic NETs or islet cell tumors. (
  • 6 ] (Refer to the PDQ summary on Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Treatment for more information. (
  • Most NETs of the small and large intestines occur sporadically, while others may occur within the background of an inherited neoplasia syndrome such as multiple endocrine neoplasia type 1 (MEN1) or neurofibromatosis type 1 (NF1) (e.g., gastrin-producing G-cell tumors and somatostatin-producing D-cell tumors of the duodenum, respectively). (
  • Individual carcinoid tumors have specific histologic and immunohistochemical features based on their anatomic location and endocrine cell type. (
  • In a subset of cases, additional markers, including but not limited to thyroid transcription factor-1 (TTF1), RCC, and Wilms tumor-1 (WT1), may be needed to distinguish between the 3 most common PAX8-positive tumors. (
  • They are considered neural tumors derived from cells of the neural crest. (
  • Neuroendocrine tumors (NETs) are formed from cells of the nervous and endocrine systems. (
  • In collaboration with Matthew Meyerson (Broad Institute, Dana-Farber Cancer Institute) and Chrissie Thirwell ( University College London Cancer Institute), Dr. Nakakura is studying the causes of small intestine neuroendocrine tumors utilizing state-of-the art genetic and epigenetic technologies of primary tumors and single cell analyses of precursor lesions. (
  • The RIP1-Tag2 transgenic mouse model overexpresses SV40 T antigen under the control of the insulin promoter, resulting in development of islet cell tumors 4 . (
  • Here, using a genetic targeting strategy, we investigated the contribution of Hif-1α to the changes of tumor phenotype in the Vegf -deleted islet tumors in RIP1-Tag2 mice. (
  • Chromosomal localization of PTCH2 places it on chromosome 1p33-34, a region deleted in some germ cell tumors, raising the possibility that PTCH2 may be a tumor suppressor in Dhh target cells (Carpenter, 1998). (
  • To date, one truncating mutation was identified in a medulloblastoma and a change in a splice donor site in a basal cell carcinoma, suggesting that the gene plays a role in the development of some tumors (Smyth, 1999). (
  • Islet 1 (Isl1) Expression is a reliable marker for pancreatic endocrine tumors and their metastases. (
  • Value of Islet 1 and PAX8 in identifying metastatic neuroendocrine tumors of pancreatic origin. (
  • They are distinguished into two broad categories: 1) Tumors identified as small cell lung carcinomas with biology and natural history of a high-grade malignancy and characteristics of small cell undifferentiated or anaplastic appearance by light microscopy. (
  • Over 90% of thyroid tumors arise from follicular thyroid cells. (
  • Expression of PAX8 is increased in neoplastic renal tissues, Wilms tumors, ovarian cancer and Müllerian carcinomas. (
  • Re-activation of PAX8 (or Pax2) expression has been reported in pediatric Wilms Tumors, almost all subtypes of renal cell carcinoma, nephrogenic adenomas, ovarian cancer cells, bladder, prostate, and endometrial carcinomas. (
  • Aryl hydrocarbon receptor nuclear translocator (ARNT) is a transcription factor that has been reported to play a vital role in regulating glycolysis, angiogenesis and apoptosis. (
  • OBJECTIVE Pancreatic β-cells exposed to proinflammatory cytokines display alterations in gene expression resulting in defective insulin secretion and apoptosis. (
  • Prolonged exposure to cytokines leads to decreased capacity of β-cells to produce and release insulin in response to secretagogues and, in the long term, to destruction of the cells by apoptosis or necrosis. (
  • Knocking down SNRPN blocked the cell cycle at the G2/M phase transition and promoted tumor cell apoptosis, inhibiting the progression of colorectal cancer. (
  • ud This thesis has demonstrated that rapamycin treatment results in significant reductions in glucose stimulated insulin secretion in the MIN6 mouse insulinoma cell line and isolated rat islets, as well as increased apoptosis in these cell types. (
  • Increased albumin concentration reduces apoptosis and improves functionality of human islets. (
  • The gene encodes a transcription factor involved in several biological processes, most noticeably in cell proliferation and, oddly enough, apoptosis (programmed cell death). (
  • The effects of miR-195 overexpression on cell cycle progression and apoptosis and its effects on the expression of Cyclin D1 and Bcl-2 were examined in transfected TSCC cell lines (SCC-15 and Cal27) using fluorescence-activated cell sorting assays, luciferase reporter assays, and Western blots. (
  • Overexpression of miR-195 inhibited cell cycle progression, promoted apoptosis, and reduced Cyclin D1 and Bcl-2 expression in two TSCC cell lines. (
  • Bcl-2 is one of the key regulators of apoptosis and confers a survival advantage to cells by protecting them from apoptotic death [21] . (
  • The resulting changes in cellular function are known as the 'hallmarks of cancer' ( 3 ) and may be described as: self-sufficient growth signals, insensitive anti-growth signals, evading apoptosis (process of programmed cell death), unlimited replication and sustained angiogenesis (growth of new blood vessels from pre-existing ones), tissue invasion and metastasis (spread of cancer), unstable genome, infection and inflammation and cancer metabolic phenotype. (
  • Apoptosis and cell proliferation in proliferative retinal disorders: PCNA, Ki-67, caspase-3, and PARP expression. (
  • Previous studies have reported that oridonin can inhibit proliferation, induce cell cycle arrest and apoptosis and metastasis in many cancers ( 4 - 7 ), but the definite molecular action mechanisms of inhibition of pancreatic cancer have not yet been clarified. (
  • To investigate whether Potentilla discolor Bunge (PDB) extracts could protect islet β cells and promote cell proliferation and insulin secretion. (
  • Cell viability, insulin secretion and gene expression were measured to investigate the protective effects of PDB extract on RIN-m5f β cells damaged by streptozotocin. (
  • PDB extracts inhibited cell damage, improved cell viability, promoted insulin secretion, and increased protein level of p-Fox O1 in RIN-m5f β cells in a dose-dependent manner. (
  • Islet β cells are the only cells that secrete insulin, the maintenance of normal amount and function of insulin is necessary for the body to secret adequate insulin to maintain the balance of the body. (
  • In diabetic rat model, PDB not only significantly reduced blood glucose but also promoted the repair of β cells and the release of insulin [ 5 ]. (
  • The prolyl isomerase Pin1 increases β-cell proliferation and enhances insulin secretion. (
  • PPARβ/δ affects pancreatic β cell mass and insulin secretion in mice. (
  • We assessed the involvement of the microRNAs affected in cytokine-mediated β-cell failure by modifying their expression in insulin-secreting MIN6 cells. (
  • Insulin release from pancreatic β-cells is essential for blood glucose homeostasis. (
  • Diabetes develops if the amount of insulin released by β-cells is insufficient to cover the metabolic demand. (
  • Nestin-positive cells within pancreatic islets express neither the hormones insulin, glucagon, somatostatin, or pancreatic polypeptide nor the markers of vascular endothelium or neurons, such as collagen IV and galanin. (
  • Embedded in the exocrine tissue are the islets (which contain α-, β-, δ-, and PP-cells that produce the hormones glucagon, insulin, somatostatin, and pancreatic polypeptide, respectively) involved in the regulation of physiological nutrient homeostasis ( 1 ). (
  • 4 Insulin Biosynthesis, Secretion, And action o Insulin is produced in the beta cells of the pancreatic islets. (
  • o Glucose is the key regulator of insulin secretion by the pancreatic beta cells. (
  • By generating a new mouse model, she identified that intestinal stem cells can be reprogrammed into insulin-producing cells in vivo. (
  • Insulin is produced in β cells, and its secretion into the bloodstream is tightly regulated to control glucose homeostasis. (
  • In people with type 1 diabetes, β cells are selectively destroyed by an autoimmune attack, creating an absolute insulin deficiency. (
  • The potential roles of MPP7 mutations in diabetes and perturbed islet cell polarity in insulin secretion warrant further study. (
  • 2002). Activation of phosphatidylinositol 3-kinase contributes to insulin-like growth factor I-mediated inhibition of pancreatic beta-cell death. (
  • 2006). Autocrine insulin action activates Akt and increases survival of isolated human islets. (
  • An alternative therapy would include a robust, easily accessible cellular population to replace damaged islets and restore insulin secretion. (
  • Deregulated expression of c-Myc in pancreatic islets results in islet involution and onset of diabetes due to the loss of insulin production. (
  • The biologic impacts of MIF overexpression on insulin secretion function of mice islets and β cells (HIT-T15) were investigated in vitro. (
  • The insulin secretion function of both islets and HIT-T15 cells was impaired by indirect co-cultured with PC cells or treated with conditioned media from them. (
  • Stable MIF knock-down significantly decreased the diabetogenic effect of PC cells, while MIF knock-in HPDE6 cells demonstrated a strong inhibitory effect on insulin secretion function of islets and HIT-T15 cells. (
  • MIF is up-regulated in patients with pancreatic cancer and causes dysfunction of insulin secretion in β-cells. (
  • BETA2/NeuroD, a basic helix-loop-helix (bHLH) transcription factor that was originally identified as a transactivator of the insulin gene ( 25 ) and as a neurogenic factor in Xenopus embryos ( 15 ), was subsequently shown to bind the secretin gene E-box as a heterodimer with the ubiquitously expressed bHLH protein E12 or E47 ( 22 ). (
  • Whereas genetic studies indicate that Pbx1 regulates the development and function of insulin-producing pancreatic β-cells, the role of Meis family members in β-cells is still unknown. (
  • My main research focus has been on SNARE ( S oluble N SF A ttachment protein RE ceptor) proteins which play essential roles in cellular exocytosis and their binding partners, which are involved in the mobilization and trafficking of intercellular granules such as insulin granules in the pancreatic islet beta cells, as well as GLUT4 containing vesicles in the skeletal muscle and fat. (
  • Ramalingam L., Oh E., and Thurmond D.C. (2013) Novel roles for insulin receptor (IR) in adipocytes and skeletal muscle cells via new and unexpected substrates. (
  • Munc18c Phosphorylation by the Insulin Receptor Links Cell Signaling Directly to SNARE Exocytosis. (
  • Overexpression of COX-2 in carcinoma tissues was also confirmed by Western blot analysis. (
  • Forkhead box protein A2 (FOXA2), also known as hepatocyte nuclear factor 3-beta (HNF-3B), is a transcription factor that plays an important role during development, in mature tissues and, when dysregulated or mutated, also in cancer. (
  • Consistent with its role as a pioneering transcription factor, FOXA2 is expressed in early development and essential for the development and homeostasis of various cell types and tissues. (
  • In the present study, ARNT expression was detected in tissues from patients with renal cell carcinoma (RCC) and in RCC cell lines. (
  • It was found that ARNT protein expression was elevated both in tissues from patients with clear cell RCC (ccRCC) and in different RCC cell lines. (
  • In recent years, scientists have discovered a wide array of stem cells that have unique capabilities to self-renew, grow indefinitely, and differentiate or develop into multiple types of cells and tissues. (
  • So, how do scientists identify these rare type of cells found in many different cells and tissues-a process that is much akin to finding a needle in a haystack? (
  • A second method uses stem cell markers and their fluorescent tags to visually assess cells as they exist in tissues. (
  • Often researchers want to assess how stem cells appear in tissues and in doing so they use a microscope to evaluate them rather than the FACS instrument. (
  • Methods Expression levels of ciRS-7, miR-7 and three miR-7-targeted mRNAs in 108 pairs of HCC and their matched non-tumor tissues were examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). (
  • Telomerase activity and long telomeres are characteristic of proliferating cells in embryonic tissues and of germ cells. (
  • The exocrine-endocrine relationship begins at the inception of pancreogenesis: both tissues are derived from a common endodermal cell lineage (for reviews, see references 34 and 73 ). (
  • BETA2 is expressed in a very limited number of tissues, including neurons, the anterior pituitary, pancreatic islets, and enteroendocrine cells. (
  • Distinguishable components of this process are known from histopathological studies (fibrosis, angiogenesis, and immune reactions) and from biochemical analyses that have revealed, for example, that elevated levels of proteases may mediate the migration of tumor cells through normal tissues. (
  • Degradation of the cell cycle and the proliferation of malignant cells results in the loss of control mechanisms that ensure the normal function of tissues. (
  • The PAX gene family has an important role in the formation of tissues and organs during embryonic development and maintaining the normal function of some cells after birth. (
  • We found that Th17 cells were increased in the peripheral blood, spleen, and tumor tissues of mammary gland tumor-bearing mice. (
  • The Th17 cell survival factor, IL-23, was also overexpressed in tumor tissues isolated from mice and human breast cancer patients. (
  • Trainees will learn how to prepare cells and tissues for 3D imaging, and how to perform fluorescent in situ hybridization (FISH) followed by 3D imaging and analysis. (
  • Crown antibodies pass additional stringent quality requirements, including extended control sets, uniform results against multiple biologically relevant cell lines and tissues, and function in multiple applications. (
  • A strong expression of COX-2 protein was present in 23 of 52 (44%) pancreatic carcinomas, a moderate expression was present in 24 of 52 (46%) pancreatic carcinomas, and a weak expression was present in 5 of 52 (10%) pancreatic carcinomas. (
  • One example is that ectopic expression of FOXA2 together with HNF4A drives transdifferentiation of fibroblasts to hepatocyte-like cells. (
  • ARNT disruption using siRNA knockdown inhibited the migratory abilities and cell proliferation, potentially by altering the glycolysis pathway in vitro , as evidenced by decreased M2 type acetone kinase, 6‑phosphofructo‑2‑kinase/fructose‑2,6‑bisphosphatase 3 and hexokinase 2 expression. (
  • Gunton JE, Kulkarni RN, Yim S, Okada T, Hawthorne WJ, Tseng YH, Roberson RS, Ricordi C, OConnell PJ, Gonzalez FJ and Kahn CR: Loss of ARNT/HIF1beta mediates altered gene expression and pancreatic-islet dysfunction in human type 2 diabetes. (
  • RESEARCH DESIGN AND METHODS We used global microarray profiling and real-time PCR analysis to detect changes in microRNA expression in β-cells exposed to cytokines and in islets of pre-diabetic NOD mice. (
  • RESULTS We found that IL-1β and TNF-α induce the expression of miR-21, miR-34a, and miR-146a both in MIN6 cells and human pancreatic islets. (
  • Cytokines induce modifications in gene expression through the activation of different transcription factors ( 1 , 3 ) that lead to upregulation of proteins exerting harmful actions on β-cells ( 6 , 7 ). (
  • In addition to transcription factors, other regulatory molecules make an important contribution to the control of gene expression ( 8 ). (
  • Here, we have identified the direct transcriptional targets of SOX4 using a combination of genome-wide localization chromatin immunoprecipitation-chip analysis and transient overexpression followed by expression profiling in a prostate cancer model cell line. (
  • To date, three studies have used expression profiling of cells after either small interfering RNA (siRNA) knockdown or overexpression of SOX4 to identify candidate downstream target genes ( 9 , 11 , 18 ). (
  • We investigated the expression patterns of ChREBP and glucose transporters (GLUTs) in human hepatocellular carcinoma (HCC) and their association with HCC progression. (
  • Both in vitro and in vivo experiments confirmed that high expression of SNRPN was associated with tumor proliferation, cell cycle, and metastasis. (
  • They also showed that ectopic expression of the NEUROD1 gene could convert non-neuronal cells to neuronal cells. (
  • Western Blot analysis of NEUROD1 expression in transfected 293T cell line by NEUROD1 monoclonal antibody (M01), clone 3H8.Lane 1: NEUROD1 transfected lysate(39.9 KDa).Lane 2: Non-transfected lysate. (
  • Expression data of human induced pluripotent stem cells (hiPSCs), human embryonic stem cells (hESCs) and those differentiated cells. (
  • Using quantitative chromatin immunoprecipitation and expression assays, we show that FoxM1 is essential for transcription of the mitotic regulatory genes Cdc25B, Aurora B kinase, survivin, centromere protein A (CENPA), and CENPB. (
  • Upon PDGF stimulation, stimulates vascular smooth muscle cell proliferation by regulating CCND1 and CCND2 expression. (
  • Divergence of islet and acinar cell lineages may occur by modification of a pancreatic regulatory network through the differential expression of regulatory molecules such as transcription factors (or possibly by the differential use of a shared factor) to activate exocrine or endocrine-specific gene sets. (
  • Alternatively, the translocation may cause islet cell dysfunction by altering MPP7 expression in a subtle or tissue-specific fashion. (
  • 1996). Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA. (
  • therefore, tools to selectively target epigenetic modifications in the desired cell type and strategies to more efficiently correct aberrant gene expression in disease are needed. (
  • Expression of these genes will be altered in human beta-cells via shRNA-mediated gene suppression and locus-specific epigenetic targeting. (
  • Telocytes are large but rare mesenchymal cells that are marked by Foxl1 and PDGFRα expression and form a subepithelial plexus that extends from the stomach to the colon. (
  • The expression of secretin, a peptide hormone, is restricted to S-type enteroendocrine cells present primarily in the small intestine and in the colon. (
  • Analysis of the secretin gene promoter by transient expression assays identified an enhancer between −174 and −53 bp 5′ of the transcription initiation site. (
  • The enhancer was necessary and sufficient for high levels of reporter gene expression in secretin-expressing cell lines but had no activity in cell lines that did not express their endogenous secretin gene ( 38 ). (
  • Hypoxia inducible factor-1α (HIF-1α) is a transcription factor that regulates gene expression under hypoxic conditions 7 . (
  • Using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), we evaluated miR-195 expression in TSCC samples from 81 patients. (
  • Jia L-f, Wei S-b, Gong K, Gan Y-h, Yu G-y (2013) Prognostic Implications of MicoRNA miR-195 Expression in Human Tongue Squamous Cell Carcinoma. (
  • Genome-wide transcriptome analyses are routinely used to monitor tissue-, disease- and cell type-specific gene expression, but it has been technically challenging to generate expression profiles from single cells. (
  • We found that although gene expression estimates from single cells have increased noise, hundreds of differentially expressed genes could be identified using few cells per cell type. (
  • Applying Smart-Seq to circulating tumor cells from melanomas, we identified distinct gene expression patterns, including candidate biomarkers for melanoma circulating tumor cells. (
  • A process is provided of introducing an RNA into a living cell to inhibit gene expression of a target gene in that cell. (
  • c) introducing the RNA into the target cell, thereby inhibiting expression of the target gene. (
  • This regulatory module appears to function broadly as we also identify Meis3 regulation of cell survival and PDK1 expression in ovarian carcinoma cells, suggesting a unique function for Meis3 beyond the traditional roles for TALE homeodomain factors during embryogenesis. (
  • Endoderm-Specific Gene Expression in Embryonic Stem Cells Differentiated to Embryoid Bodies," Exp Cell Res. (
  • [6] This nuclear protein is involved in thyroid follicular cell development and expression of thyroid-specific genes. (
  • Bandyopadhyay S, Valdor R, Macian F. Tle4 regulates epigenetic silencing of gamma interferon expression during effector T helper cell tolerance. (
  • protein up-regulates heat shock protein 70 expression via E2F1 transcription factor 1, promoting Wasf3/Wave3/MMP9 signaling and bladder cancer invasion. (
  • miR-200b-3p can inhibit the EMT and oridonin can inhibit the expression of ZEB1, N-cadherin and fibronectin but not increase the expression of E-cadherin, while the cell adhesion molecules ICAM-1 and VCAM-1 were decreased by oridonin in BxPC-3 and PANC-1 cells and the cytoskeleton was altered by oridonin in PANC-1 cells compared with the control. (
  • One important mechanism of endocrine disruption is altered gene expression, mediated by inappropriate activation or deactivation of receptors that act as transcription factors. (
  • Abgent has over fifteen years of experience producing recombinant proteins in E. coli and mammalian cells (CHO and HEK293, etc), and we have added a powerful yeast expression platform to our menu of services. (
  • This feature has been observed both in vitro and in vivo, where FOXA transcription factors can bind nucleosome-bound target DNA sequences. (
  • CONCLUSIONS Our data identify miR-21, miR-34a, and miR-146a as novel players in β-cell failure elicited in vitro and in vivo by proinflammatory cytokines, notably during the development of peri-insulitis that precedes overt diabetes in NOD mice. (
  • After their isolation, these nestin-positive cells have an unusually extended proliferative capacity when cultured in vitro (∼8 months), can be cloned repeatedly, and appear to be multipotential. (
  • Over the past decades, β cell protection has been extensively investigated in rodents both in vivo and in vitro using isolated islets or rodent β cell lines. (
  • Much of our understanding comes from rodent models in which the phenotype of β cells from wild-type and transgenic mice and rats was analyzed first in vivo and, once islet isolation procedures were established ( 6 ), expanded upon in vitro. (
  • The Sca-1+ HPC cells can be continuously cultivated over 30 passages in vitro and are non-tumorigenic. (
  • Encapsulation of human islets in novel inhomogeneous alginate-ca2+/ba2+ microbeads: in vitro and in vivo function. (
  • For example, in vitro studies of neoplastic cells in culture, which are commonly investigated, are inadequate experimental systems through which to address major features of tumor invasion. (
  • Embryonic Stem Cells Express Neuronal Properties in Vitro," Dev Biol. (
  • In vitro, oridonin had a certain effect on the migration in BxPC-3 and PANC-1 cells, but not though type III EMT by miR-200-3p/ZEB1 axis, and may be related to type Ⅱ EMT, tumor microenvironment or altering the cytoskeleton. (
  • FoxO1 regulates the number of and function of β cells, and plays an important role in the development of diabetes [ 3 , 4 ]. (
  • Taken together, these results demonstrate that FoxM1 regulates transcription of cell cycle genes critical for progression into S-phase and mitosis. (
  • Negatively regulates myeloid progenitor cell proliferation by repressing RUNX1 in a NBRE site-independent manner. (
  • Islet Coordinately Regulates Motor Axon Guidance and Dendrite Targeting through the Frazzled/DCC Receptor. (
  • Csk differentially regulates Src64 during distinct morphological events in Drosophila germ cells. (
  • Three-amino-acid-loop-extension homeodomain factor Meis3 regulates cell survival via PDK1. (
  • Here we show that Meis3 is abundantly expressed in pancreatic islets and β-cells and that it regulates β-cell survival. (
  • These changes of adhesion molecules were not observed in the primary culture of the tumor cells under hypoxic conditions. (
  • Figure 4: Single-cell transcriptomes of circulating tumor cells. (
  • Tumor microenvironment is composed of tumor cells, fibroblasts, endothelial cells, and infiltrating immune cells. (
  • The cross-talk between tumor cells and other tumor-associated cells may lead to either blocking tumor formation or enhancing tumor formation and/or progression. (
  • Using three-dimensional (3D) imaging, trainees will examine the positions of telomeres, centromeres and chromosomes in nuclei of normal and tumor cells. (
  • Downregulation of MLL3 in esophageal squamous cell carcinoma is required for the growth and metastasis of cancer cells. (
  • Groundbreaking progress has been achieved in the treatment of recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). (
  • Approximately 90% of HNC is head and neck squamous cell carcinoma (HNSCC), with ≈650,000 new cases reported annually worldwide. (
  • But little is known about the dysregulation of miR-195 in tongue squamous cell carcinoma (TSCC). (
  • Head and neck squamous cell carcinoma, including cancers of oral cavity, oropharynx, larynx, and hypopharynx, represents the sixth most frequent solid cancer around the world [1] . (
  • Tongue squamous cell carcinoma (TSCC) is the most common type of oral cancer and is well-known for its high rate of proliferation and nodal metastasis [2] . (
  • A) Oral squamous cell carcinoma (OSCC) of the lateral edge of the tongue ( 13 ). (
  • Due to its toxicity to islet β cells, STZ has been used to induce cell or animal model of diabetes [ 2 ]. (
  • Recently, ARNT has been reported to a play role in pancreatic‑islet function in type 2 diabetes. (
  • Type 1 diabetes is an autoimmune disease characterized by an inflammatory response against pancreatic islets, leading to selective and progressive β-cell loss ( 1 ). (
  • Although the etiology differs from that of type 1 diabetes, immune-cell infiltration and decrease in functional β-cell mass are also observed in type 2 diabetes ( 3 ). (
  • Proinflammatory cytokines such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and γ-interferon (IFN-γ), produced by infiltrating leukocytes and by islet cells, play a central role in β-cell failure and in the development of diabetes ( 1 , 3 - 5 ). (
  • Patients with type 1 or type 2 diabetes have an insufficiency in their functional β cell mass. (
  • To advance diabetes treatment and to work toward a cure, a better understanding of how to protect the pancreatic β cells against autoimmune or metabolic assaults (e.g., obesity, gestation) will be required. (
  • Next, we discuss the use of such functional human β cell lines and share some perspectives on their use to advance diabetes research. (
  • 2006). Ablation of PDK1 in pancreatic beta cells induces diabetes as a result of loss of beta cell mass. (
  • Her research focuses on restorative therapy to replace lost islet mass in the treatment of Type I diabetes. (
  • 2) Isolating and characterizing a human pancreatic stem/progenitor cell population and developing a long-lasting functional pancreatic islet for long-term correction of diabetes based on native pancreatic islet matrix. (
  • We suggest that loss of Wnt-β-catenin activity is unlikely to drive islet dysfunction, as occurs in type 2 diabetes, but that β-catenin is likely to promote human acinar cell proliferation following injury, and might therefore contribute to the resolution of acute or chronic pancreatitis. (
  • There are two major forms of diabetes and both are associated with decreased beta-cell mass. (
  • To date, I have published 10 first author manuscripts in journals such as Cell Metabolism, Journal of Cell Biology, Diabetes, JCEM and JBC with an additional 17 co-author manuscripts. (
  • Overexpression of cyclin D1 in pancreatic beta-cells in vivo results in islet hyperplasia without hypoglycemia. (
  • PAX8 is expressed in normal pancreatic islet cells and in a high proportion of primary and metastatic PETs. (
  • Ewing sarcoma (ES): A highly malignant, metastatic, primitive small round cell tumor of bone and soft tissue that affects children and adolescents. (
  • 1-3 Islet-1 has been shown to be a reliable marker for the detection of primary and metastatic pancreatic neuroendocrine neoplasms. (
  • Because Desert Hedgehog (Dhh) is expressed specifically in the testis and is required for germ cell development, it is likely that PTCH2 mediates Dhh activity in vivo. (
  • The VHL tumor suppressor gene is the gene for both von Hippel-Lindau disease as well as sporadic, clear-cell renal carcinoma. (
  • However, the administration to rats of islet trophic factors such as glucose or glucagon-like peptide 1 for 48 h results in a doubling of islet cell mass, suggesting that islet progenitor cells may reside within the islets themselves. (
  • We propose that these nestin-positive islet-derived progenitor (NIP) cells are a distinct population of cells that reside within pancreatic islets and may participate in the neogenesis of islet endocrine cells. (
  • The NIP cells that also reside in the pancreatic ducts may be contributors to the established location of islet progenitor cells. (
  • The sex determining region Y-box 4 ( SOX4 ) gene is a developmental transcription factor important for progenitor cell development and Wnt signaling ( 1 , 2 ). (
  • Whereas SOX2 is critical for maintenance of stem cells ( 7 ), SOX4 may specify transit-amplifying progenitor cells that are the immediate daughters of adult stem cells and have been proposed to be the population that gives rise to cancer stem cells. (
  • Provided herein are compositions and methods using stem/progenitor cells in a therapeutic approach for treatment of or promotion of healing of acute and chronic wounds. (
  • 10. sup.6 stem/progenitor cells/cm.sup. (
  • 2. The composition of claim 1, stem/progenitor cells are selected from the group consisting of bone marrow derived cells, hematopoietic stem cells, mesenchymal stem cells, peripheral blood stem cells, and mixtures and combinations thereof. (
  • 3. The composition of claim 1, wherein the stem/progenitor cells are bone marrow derived cells. (
  • 4. The composition of claim 1, wherein the stem/progenitor cells are mesenchymal stem cells. (
  • 8. The method of claim 6, stem/progenitor cells are bone marrow derived cells, hematopoietic stem cells, mesenchymal stem cells, peripheral blood stem cells, and mixtures and combinations thereof. (
  • We have isolated a pancreatic progenitor cell, using stem cell antigen 1 (Sca-1), a marker of hematopoietic stem cells. (
  • Dr. Cui's research interests are in stem/progenitor cells and regenerative medicine. (
  • This involves re-endothelialization of vascular channels and parenchymal repopulation with hepatic stem/progenitor cells into decellularized liver biomatrix scaffold. (
  • Her post-doctoral research includes isolating and establishing Sca-1 positive hepatic progenitor cell lines from wild type adult mice. (
  • Glucagonoma is a rare neuroendocrine tumor (NET) of the pancreatic alpha cells that results in the overproduction of the hormone glucagon. (
  • Hepatocellular carcinoma results from chronic cyclin D1 overexpression in transgenic mice. (
  • Hepatocyte growth factor overexpression in the islet of transgenic mice increases beta cell proliferation, enhances islet mass, and induces mild hypoglycemia. (
  • We further show an increase of these microRNAs in islets of NOD mice during development of pre-diabetic insulitis. (
  • 1995). A selective decrease in the beta cell mass of human islets transplanted into diabetic nude mice. (
  • Rachael Turner, a graduate student in Dr. Reid's lab and whom Dr. Gerber mentors, is using different gel type materials to transplant cells into mice livers and study the effects and how effective the gels are at keeping the cells alive and localized in the liver. (
  • To address whether β-catenin remains important for the maintenance and expansion of mature acinar cells, we have established a system to follow the behavior and fate of β-catenin-deficient cells during postnatal growth and regeneration in mice. (
  • Conditional gene ablation of Porcupine (Porcn), which is required for functional maturation of all Wnt proteins, in Foxl1+ telocytes causes cessation of Wnt signaling to intestinal crypts, loss of stem cell proliferation, and death of mutant mice within four days of tamoxifen treatment. (
  • Secretin-expressing enteroendocrine cells are totally absent in BETA2 null mice ( 24 ). (
  • No remarkable changes were observed in the islet-specific Hif-1α- null mice ( RipCre/Hif-1α fl/fl ) as previously reported 17 , 18 . (
  • Activating transcription factor 3 promotes loss of the acinar cell phenotype in response to cerulein-induced pancreatitis in mice. (
  • R&D systems, Cytokine bulletin 2007: TGF-beta Superfamily Signaling in ES cells (Mice are Not Men) p. 1-3. (
  • BxPC-3 and PANC-1 cells were treated with oridonin or transfected by miR-200b-3p, those cells were used for western blot assay, Transwell assay, ELISA, immunofluorescence staining, tumorigenesis assay in nude mice and immunohistochemical assay to verify the effects of oridonin or miR-200b-3p on pancreatic cancer. (
  • The level of cyclooxygenase (COX)-2 has been investigated recently in various human carcinomas. (
  • Induction of beta-cell proliferation and retinoblastoma protein phosphorylation in rat and human islets using adenovirus-mediated transfer of cyclin-dependent kinase-4 and cyclin D1. (
  • Researchers now know that many different types of stem cells exist but they all are found in very small populations in the human body, in some cases 1 stem cell in 100,000 cells in circulating blood. (
  • Here we show that rat and human pancreatic islets contain a heretofore unrecognized distinct population of cells that express the neural stem cell-specific marker nestin. (
  • Immunoperoxidase of monoclonal antibody to NEUROD1 on formalin-fixed paraffin-embedded human ovary, clear cell carcinoma. (
  • Furthermore, she applied her cell biology expertise and tissue engineering techniques to develop a biomimetic platform for long-term human islet culture and beta cell research. (
  • Here, we show that both early-passage Foxm1(-)(/)(-) mouse embryonic fibroblasts (MEFs) and human osteosarcoma U2OS cells depleted of FoxM1 protein by small interfering RNA fail to grow in culture due to a mitotic block and accumulate nuclear levels of cyclin-dependent kinase inhibitor (CDKI) proteins p21(Cip1) and p27(Kip1). (
  • Transferring these rodent data to humans has long been challenging, at least partly for technical reasons: primary human islet preparations were scarce and functional human β cell lines were lacking. (
  • In this Review, we first explain how we developed the human β cell lines and why we think we succeeded where others, despite major efforts, did not. (
  • An increase in human islet preparations available for research has improved our understanding of what a human β cell is, but the material remains scarce, its availability is unpredictable, and the quality is variable. (
  • To grow cultures of human ES cells, Thomson and his collaborators used 36 fresh or frozen embryos generated in IVF laboratories from couples undergoing treatment for infertility. (
  • From the 14 embryos that developed to the blastocyst stage, they established 5 human ES cell lines-H1, H7, H9, H13 and H14 [ 35 ]. (
  • To generate human ES cell cultures, cells from the inner cell mass of a human blastocyst were cultured in a multi-step process. (
  • The five original human ES cell lines continued to divide without differentiating for 5 to 6 months [ 35 ]. (
  • Human somatic cells, however, do not show telomerase activity and their telomeres are considerably shorter. (
  • 2001). AKT1/PKBalpha kinase is frequently elevated in human cancers and its constitutive activation is required for oncogenic transformation in NIH3T3 cells. (
  • 1992). AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas. (
  • 2008). Antiproinflammatory effects of sirolimus on human islet preparations. (
  • 1999). Auto- and alloimmune reactivity to human islet allografts transplanted into type 1 diabetic patients. (
  • 1988). Automated method for isolation of human pancreatic islets. (
  • Improved human pancreatic islet purification with the refined UIC-UB density gradient. (
  • Intra-ductal glutamine administration reduces oxidative injury during human pancreatic islet isolation. (
  • We demonstrated that these TALE-DNMTs direct DNA methylation specifically to the targeted gene locus in human cells. (
  • Epigenomic rejuvenation of human pancreatic beta-cells. (
  • Our previous studies clearly show that adult human beta-cells can be induced to replicate, and - importantly - that cells can maintain normal glucose responsiveness after cell division. (
  • We will focus on mechanisms derived from studies of non-neoplastic human disease as well as age-related phenotypic changes in human beta-cells. (
  • Success will be assessed in transplanted human islets by determination of beta-cell replication rate and retention of function. (
  • Selected genes will then be targeted as in Aim 1 to improve human beta-cell function, as assessed by glucose responsiveness. (
  • Mutations of the human Patched gene (PTCH) have been identified in individuals with the nevoid basal cell carcinoma syndrome (NBCCS) as well as in sporadic basal cell carcinomas and medulloblastomas. (
  • Rodent islets are primarily composed of β-cells located in the center with other cell types in the periphery, human islets exhibit interconnected α- and β-cells [ 3 - 13 , 14 ]. (
  • Importantly, human cells express all of the HR genes needed to carry out gene targeting [1] . (
  • 2005, "TGFb/Activin/Nodal Signaling is Necessary for the Maintenance of Pluripotency in Human Embryonic Stem Cells," Development, 132:1273-1282. (
  • Several known tumor suppressor genes like TP53 and WT1 have been identified as transcriptional targets in human astrocytoma cells. (
  • The mechanism may be related to increased phosphorylation of Fox O1, which increases the number and improves the function of β cells. (
  • Li W, Qiu Y, Hao J, Zhao C, Deng X and Shu G: Dauricine upregulates the chemosensitivity of hepatocellular carcinoma cells: Role of repressing glycolysis via miR-199a:HK2/PKM2 modulation. (
  • The effect of Scutellaria baicalensis on the signaling network in hepatocellular carcinoma cells. (
  • The cellular transcription factor Elongin (SIII) has been identified as a functional target of the VHL protein. (
  • The VHL protein is found both in the nucleus and in the cytosol of transiently transfected cells. (
  • Most TPR-containing proteins are associated with multiprotein complexes, and there is extensive evidence indicating that TPR motifs are important to the functioning of chaperone, cell-cycle, transcription, and protein transport complexes. (
  • The transcription start site for TTC39B protein isoform 1 is located from base pairs 15,307,340 to 15,307,389 and has a length of 50 bp. (
  • Ramil CP, Dong M, An P, Lewandowski TM, Yu Z, Miller LJ , Lin Q. Spirohexene-Tetrazine Ligation Enables Bioorthogonal Labeling of Class B G Protein-Coupled Receptors in Live Cells. (
  • Coexpressed Class B G Protein-Coupled Secretin and GLP-1 Receptors Self- and Cross-Associate: Impact on Pancreatic Islets. (
  • SOX4 is a 47-kDa protein that is encoded by a single exon and contains a conserved high-mobility group DNA-binding domain (DBD) related to the TCF/LEF family of transcription factors that mediate transcriptional responses to Wnt signals. (
  • SOX4 is up-regulated at the mRNA and protein level in prostate cancer cell lines and patient samples, and this up-regulation is correlated with Gleason score or tumor grade ( 9 ). (
  • Carbohydrate response element binding protein (ChREBP) is a glucose-sensing transcription factor that mediates the induction of glycolytic and lipogenic genes in response to glucose. (
  • The NEUROD1 protein forms heterodimers with other bHLH proteins and activates the transcription of a large set of genes that contain the E-box DNA sequence 5'-CANNTG'-3. (
  • In Min 6 insulinoma cells Petersen et al (2002) were able to conclude that MEK-ERK associated phosphorylation of the serine 274 on NEUROD1 induces the translocation of the protein to the nucleus and that this may normally be associated with cell glucose concentration. (
  • The translocation breakpoints are associated with Nuclear Receptor Subfamily 4, Group A, Member 3 (on chromosome 9) and either Ewing Sarcome Breakpoint Region 1 (on chromosome 22), RNA Polymerase II, TATA Box-Binding Protein-Associated Factor, 68-KD (on chromosome 17), or Transcription factor 12 (on chromosome 15). (
  • It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. (
  • Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. (
  • However, the chromosome 10 breakpoint was 220 kilobases 5' to the Membrane Protein, Palmitoylated 7 ( MPP7 ) gene, which encodes a protein required for proper cell polarity. (
  • whereas mTORC2 plays a key role in regulating cell survival via protein kinase B (PKB). (
  • Thus, Finb/RREB-1 does not function as a classical activator of transcription that recruits an activation domain to a DNA-protein complex. (
  • Activating transcription factor 3 (ATF3) is a key mediator of the unfolded protein response, a pathway rapidly activated during pancreatic insult. (
  • We further identify the 3-phosphoinositide-dependent protein kinase 1 (PDK1), a well-known kinase involved in the PI3K-Akt signaling pathway, as a direct Meis3 target, which mediates its role in β-cell survival. (
  • 2004, "BMP4 Supports Self-Renewal of Embryonic Stem Cells by Inhibiting Mitogen-Activated Protein Kinase Pathways," PNAS, 101(16):6027-6032. (
  • [8] A fusion protein, PAX8-PPAR-γ , is implicated in some follicular thyroid carcinomas and follicular-variant papillary thyroid carcinoma. (
  • Polycomb group protein ezh2 controls actin polymerization and cell signaling. (
  • Furthermore, blocking protein kinase A (PKA) by H89 completely abrogated the inductive effects of tumor-conditioned medium and PGE 2 on p19 transcription, whereas the cAMP active analog, Forskolin, mimics the PGE 2 effect. (
  • Data regarding carcinoids and other NETs, such as poorly differentiated neuroendocrine carcinomas, may be combined in some epidemiologic and clinical studies, rendering separate consideration difficult. (
  • A diagnosis of poorly differentiated (high-grade) non-small cell neuroendocrine carcinoma was made after a histological analysis and immunostaining. (
  • Moreover, overexpression of p16 in these cells reversed the proliferative phenotype, demonstrating the specificity of our epigenetic targeting. (
  • Oridonin or overexpression of miR‑200b-3p can inhibit the cell migration in BxPC-3 and PANC-1 cells. (
  • Conditional knockout studies show that Foxa2 is important for the formation of pancreatic islets and maturation of alpha and beta cells, thereby being essential for glucose homeostasis. (
  • Cancer cells acquire energy from glucose to satisfy their high metabolic demands. (
  • Plays a role in glucose transport by regulating translocation of the SLC2A4 glucose transporter to the cell surface (PubMed:24022864). (
  • β-cell, the central regulator of glucose homeostasis is the largest cellular component of islets in most species [ 12 , 13 ]. (
  • In Aim 1, we will target the genes altered in patients with marked beta-cell hyperplasia, such as those suffering from Beckwith-Wiedemann Syndrome or Multiple Endocrine Neoplasia. (
  • In islets, induces type B pancreatic cell proliferation through up-regulation of genes that activate cell cycle, as well as genes that cause degradation of the CDKN1A (By similarity). (
  • The invasive growth of malignant cells induces an admixture of host reactions including desmoplasia, angiogenesis, and immune reactions. (
  • Taken together, our results indicate that tumor-secreted PGE 2 induces IL-23, but not IL-12, production in the tumor microenvironment, leading to Th17 cell expansion. (
  • Thus, FOXA2 have important roles in cell type specification by promoting chromatin accessibility for the binding of lineage- or tissue-specific factors The FOXA factors also facilitate the maintenance of cell identity by bookmarking cell type-specific genes so that these genes can be rapidly reactivated after cytokinesis. (
  • Eukaryotic cells contain hundreds of noncoding RNAs called microRNAs (miRNAs) that associate with the 3′ untranslated region of mRNAs ( 9 ), potentially inhibiting messenger translation of thousands of genes ( 10 , 11 ). (
  • PAXs (paired box) genes encode a family of transcription factors that regulate organogenesis and cell-lineage specification in multiple organ systems . (
  • Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. (
  • Although there are 12 different cdk genes, only 5 have been shown to directly drive the cell cycle. (
  • Once stabilized, HIF-1α heterodimerizes with HIF-1β to act as a transcription factor, controlling a wide range of genes involved in the hypoxic response. (
  • Although down-regulation of genes that promote the mature acinar cell fate is required to reduce injury associated with pancreatitis, the factors that promote this repression are unknown. (
  • [8] PAX8 and other transcription factors play a role in binding to DNA and regulating the genes that drive thyroid hormone synthesis (Tg, TPO, Slc5a5 and Tshr). (
  • Also, six new putative disease markers were identified, including energy metabolism, cytoskeleton and cell signaling proteins. (
  • Greater telomere length is associated with immortalized cell lines such as embryonic stem cells and cancer cells. (
  • High levels of telomerase activity are detected in embryonic stem cells and cancer cells, whereas little or no telomerase activity is present in most mature, differentiated cell types. (
  • Tracing the derivation of embryonic stem cells from the inner cell mass by single-cell RNA-Seq analysis. (
  • 2004. Self-renewal of teratocarcinoma and embryonic stem cells. (
  • 2003, "Role of ERas in Promoting Tumour-Like Properties in Mouse Embryonic Stem Cells," Nature, 423:541-545. (
  • 2004, "Development of Definitive Endoderm from Embryonic Stem Cells in Culture," Development, 131 (7):1651-1662. (
  • And, when scientists examine these cells under a microscope, they look just like any other cell in the tissue where they are found. (
  • She then conducted postdoctoral studies in tissue plasticity and cell fate decision at University of Pennsylvania. (
  • 1 The H9.1 and H9.2 clonal cell lines were produced by first plating 105 of the parent H9 cells per well in tissue-culture plates. (
  • Using pancreatic islets as a model for vascularized tissue, this review will present a general overview of EC behaviour dynamics in sprouting angiogenesis, particularly focusing on the interplay between VEGF and Notch pathways. (
  • Pancreatic islets are highly vascularized and receive 10% of the pancreatic blood flow despite comprising of only 1-2% of the overall tissue mass [ 1 ]. (
  • Islets represent endocrine "island" clusters, embedded and scattered within large amounts of exocrine acinar tissue [ 2 ]. (
  • The capillary network within islets is about five times denser in comparison with exocrine tissue [ 16 ]. (
  • Our findings suggest that COX-2 inhibitors might be potentially effective against pancreatic carcinomas and that COX-2 may be involved in certain biological processes in pancreatic islets. (
  • Scientists have taken advantage of the biological uniqueness of stem cell receptors and chemical properties of certain compounds to tag or "mark" cells. (
  • The next stage is to gain an understanding of the biological processes involved from c-Myc activation, to tumour growth and finally to islet tumour involution. (
  • Our protocol will be useful for addressing fundamental biological problems requiring genome-wide transcriptome profiling in rare cells. (
  • The hope is that using such systems-level approaches to analysing and modelling complex biological systems will provide insights into the inner working of the cell, biological function and disease. (
  • Inner medullary collecting duct cells (IMCD-K2) and mouse cortical collecting duct cells (M1), representing the cortical and medullary collecting duct, were exposed to 5-10 μ M troglitazone for 24 hours. (
  • Islet-1 (EP283) on medullary thyroid carcinoma. (
  • PAX-8 is key if differential is lung adenocarcinoma vs. thyroid carcinoma. (
  • Dr. Lauwers' areas of clinical focus include luminal malignancies of the gut (particularly esophageal and gastric adenocarcinoma) and hepatocellular carcinoma. (
  • Both can evolve to invasive carcinomas, respectively cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC). (
  • mediates CREB-induced neuronal survival, and during hippocampus development, plays a critical role in pyramidal cell survival and axonal guidance. (
  • Is required for S phase entry of the cell cycle and survival of smooth muscle cells by inducing CCND1, resulting in RB1 phosphorylation. (
  • A better understanding of molecular mechanisms associated with intra-islet EC cross-talk and its micro-environment may present exciting new perspectives on islet graft to host revascularization and in supporting islet graft survival. (
  • Rapid and adequate revascularization is critical for survival and function of transplanted islets [ 19 - 21 ]. (
  • This study was conducted to determine whether the number and microlocalization of macrophages, mature dendritic cells and cytotoxic T cells in non-small cell lung cancer are associated with patient's survival time. (
  • Correlation of the cell numbers and patient's survival time was analyzed using the Statistical Package for the Social Sciences (version 13.0). (
  • The number of macrophages in the tumor islets was positively associated with patient's survival time, whereas the number of macrophages in the tumor stroma was negatively associated with patient's survival time in both univariate and multivariate analyses. (
  • The number of mature dendritic cells in the tumor islets and stroma, tumor islets only, or tumor stroma only was positively associated with patient's survival time in a univariate analysis but not in a multivariate analysis. (
  • The number of macrophages in the tumor islets or stroma is an independent predictor of survival time in NSCLC patients. (
  • Counting macrophages in the tumor islets or stroma is more useful in predicting patient's survival time than counting mature dendritic cells or cytotoxic T cells. (
  • In order to identify new prognostic factors that can guide clinical practice, we have previously found that the number of tumor-associated macrophages (TAMs) in the tumor islets is positively associated with survival time in the patients with NSCLC [ 6 ]. (
  • In addition to suggesting functional links between nuclear pore complex architecture and cancer cell survival, the culture system provides a novel experimental window into the dynamics of tumor cell drug resistance and dormancy. (
  • In acinar cell lines the activity is mediated by a complex comprising PDX1, PBX1b, and MRG1 (MEIS2). (
  • The endocrine and exocrine compartments are structurally and functionally integrated through an islet-acinar portal blood system that facilitates the regulation of acinar cell functions directly by islet peptide hormones ( 81 ). (
  • We find that β-catenin is continuously required for the establishment and maintenance of acinar cell mass, extending from embryonic specification through juvenile and adult self-renewal and regeneration. (
  • Coating the surface of every cell in the body are specialized proteins, called receptors, that have the capability of selectively binding or adhering to other "signaling" molecules. (
  • Normally, cells use these receptors and the molecules that bind to them as a way of communicating with other cells and to carry out their proper functions in the body. (
  • Stem cell markers are given short-hand names based on the molecules that bind to the stem cell surface receptors. (
  • Researchers use the signaling molecules that selectively adhere to the receptors on the surface of the cell as a tool that allows them to identify stem cells. (
  • Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). (
  • Whether the constituents of a network are molecules, cells or living organisms, the network provides a framework to model the complex events that emerge from interactions among these parts. (
  • Tumor cell-derived molecules such as cytokines and lipid mediators play a critical role in inducing chronic inflammation in the tumor microenvironment. (
  • Our review of the literature revealed that further research is needed, focusing on neuroendocrine carcinomas of the esophagus and how this entity differs from some of the more well-known neuroendocrine neoplasms in terms of management. (
  • Neuroendocrine carcinoma of the esophagus is classified within the gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) based on the 2010 World Health Organization (WHO) classification system. (
  • Neuroendocrine cells are widely distributed throughout the body, and neoplasms from these dispersed cells can arise at many sites. (
  • PAX8/PPARy rearrangement account for 30-40% of conventional type follicular carcinomas [14] and less than 5% of oncocytic carcinomas (aka Hurthle-Cell Neoplasms). (
  • The genomic structure of PTCH2 has been characterized and single-stranded conformational polymorphism analysis was used to search for PTCH2 mutations in basal cell carcinomas and medulloblastomas in NBCCS patients. (
  • Mutations in this gene have been associated with thyroid dysgenesis , thyroid follicular carcinomas and atypical follicular thyroid adenomas . (