An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21.
An ACYCLOVIR analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections.
A genus of the family HERPESVIRIDAE, subfamily ALPHAHERPESVIRINAE, consisting of herpes simplex-like viruses. The type species is HERPESVIRUS 1, HUMAN.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
An enzyme that catalyzes the transfer of 2-deoxy-D-ribose from THYMIDINE to orthophosphate, thereby liberating thymidine.
A GUANOSINE analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.
A pyrimidine nucleoside formed in the body by the deamination of CYTARABINE.
The type species of SIMPLEXVIRUS causing most forms of non-genital herpes simplex in humans. Primary infection occurs mainly in infants and young children and then the virus becomes latent in the dorsal root ganglion. It then is periodically reactivated throughout life causing mostly benign conditions.
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
Agents that inhibit PROTEIN KINASES.
Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
5-Thymidylic acid. A thymine nucleotide containing one phosphate group esterified to the deoxyribose moiety.
Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
Established cell cultures that have the potential to propagate indefinitely.
Phosphate esters of THYMIDINE in N-glycosidic linkage with ribose or deoxyribose, as occurs in nucleic acids. (From Dorland, 28th ed, p1154)
A cultured line of C3H mouse FIBROBLASTS that do not adhere to one another and do not express CADHERINS.
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.
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.
2'-Deoxyuridine. An antimetabolite that is converted to deoxyuridine triphosphate during DNA synthesis. Laboratory suppression of deoxyuridine is used to diagnose megaloblastic anemias due to vitamin B12 and folate deficiencies.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
The functional hereditary units of VIRUSES.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
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.
An enzyme that catalyzes reversible reactions of a nucleoside triphosphate, e.g., ATP, with a nucleoside monophosphate, e.g., UMP, to form ADP and UDP. Many nucleoside monophosphates can act as acceptor while many ribo- and deoxyribonucleoside triphosphates can act as donor. EC 2.7.4.4.
Genes that are used transgenically, i.e., via GENE TRANSFER TECHNIQUES to induce CELL DEATH.
DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.
An enzyme that catalyzes reversibly the phosphorylation of deoxycytidine with the formation of a nucleoside diphosphate and deoxycytidine monophosphate. Cytosine arabinoside can also act as an acceptor. All natural nucleoside triphosphates, except deoxycytidine triphosphate, can act as donors. The enzyme is induced by some viruses, particularly the herpes simplex virus (HERPESVIRUS HOMINIS). EC 2.7.1.74.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.
The rate dynamics in chemical or physical systems.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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 introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King & Stansfield, A Dictionary of Genetics, 4th ed)
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).
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.
A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
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.
An antineoplastic antimetabolite that is metabolized to fluorouracil when administered by rapid injection; when administered by slow, continuous, intra-arterial infusion, it is converted to floxuridine monophosphate. It has been used to treat hepatic metastases of gastrointestinal adenocarcinomas and for palliation in malignant neoplasms of the liver and gastrointestinal tract.
A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.
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.
A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
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.
A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
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.
Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).
A family of non-enveloped viruses infecting mammals (MASTADENOVIRUS) and birds (AVIADENOVIRUS) or both (ATADENOVIRUS). Infections may be asymptomatic or result in a variety of diseases.
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.
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.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.
A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.
A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.
ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.
A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.
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.
Biologically active DNA which has been formed by the in vitro joining of segments of DNA from different sources. It includes the recombination joint or edge of a heteroduplex region where two recombining DNA molecules are connected.
A purine or pyrimidine base bonded to DEOXYRIBOSE.
An analog of DEOXYURIDINE that inhibits viral DNA synthesis. The drug is used as an antiviral agent.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
Pyrimidines with a RIBOSE attached that can be phosphorylated to PYRIMIDINE NUCLEOTIDES.
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.
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
A family of enveloped, linear, double-stranded DNA viruses infecting a wide variety of animals. Subfamilies, based on biological characteristics, include: ALPHAHERPESVIRINAE; BETAHERPESVIRINAE; and GAMMAHERPESVIRINAE.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
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 mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.
An enzyme of the transferase class that catalyzes the reaction 5,10-methylenetetrahydrofolate and dUMP to dihydrofolate and dTMP in the synthesis of thymidine triphosphate. (From Dorland, 27th ed) EC 2.1.1.45.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
An enzyme that catalyzes the phosphorylation of uridine and cytidine to uridine 5'-phosphate and cytidine 5'-phosphate, respectively. ATP, dUTP, dGTP, and dATP are effective phosphate donors. EC 2.7.1.48.
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 mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
Proteins prepared by recombinant DNA technology.
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.
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.
Deoxyribonucleic acid that makes up the genetic material of viruses.
A folic acid derivative used as a rodenticide that has been shown to be teratogenic.
The introduction of functional (usually cloned) GENES into cells. A variety of techniques and naturally occurring processes are used for the gene transfer such as cell hybridization, LIPOSOMES or microcell-mediated gene transfer, ELECTROPORATION, chromosome-mediated gene transfer, TRANSFECTION, and GENETIC TRANSDUCTION. Gene transfer may result in genetically transformed cells and individual organisms.
A cell line derived from cultured tumor cells.
A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.
An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.
Elements of limited time intervals, contributing to particular results or situations.
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.
A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.
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.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
The making of a radiograph of an object or tissue by recording on a photographic plate the radiation emitted by radioactive material within the object. (Dorland, 27th ed)
A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.
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.
The type species of VARICELLOVIRUS causing CHICKENPOX (varicella) and HERPES ZOSTER (shingles) in humans.
The process by which a DNA molecule is duplicated.
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.
A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.
A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.
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.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.
A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.
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.
A group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. (Dorland, 27th ed.)
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.
An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
The type species of ORTHOPOXVIRUS, related to COWPOX VIRUS, but whose true origin is unknown. It has been used as a live vaccine against SMALLPOX. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of VACCINIA VIRUS.
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)
Drugs that are chemically similar to naturally occurring metabolites, but differ enough to interfere with normal metabolic pathways. (From AMA Drug Evaluations Annual, 1994, p2033)
The result of a positive or negative response (to drugs, for example) in one cell being passed onto other cells via the GAP JUNCTIONS or the intracellular milieu.
The relationship between the dose of an administered drug and the response of the organism to the drug.
An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.
Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.
Family of RNA viruses that infects birds and mammals and encodes the enzyme reverse transcriptase. The family contains seven genera: DELTARETROVIRUS; LENTIVIRUS; RETROVIRUSES TYPE B, MAMMALIAN; ALPHARETROVIRUS; GAMMARETROVIRUS; RETROVIRUSES TYPE D; and SPUMAVIRUS. A key feature of retrovirus biology is the synthesis of a DNA copy of the genome which is integrated into cellular DNA. After integration it is sometimes not expressed but maintained in a latent state (PROVIRUSES).
Enzymes that are part of the restriction-modification systems. They catalyze the endonucleolytic cleavage of DNA sequences which lack the species-specific methylation pattern in the host cell's DNA. Cleavage yields random or specific double-stranded fragments with terminal 5'-phosphates. The function of restriction enzymes is to destroy any foreign DNA that invades the host cell. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms. They are also used as tools for the systematic dissection and mapping of chromosomes, in the determination of base sequences of DNAs, and have made it possible to splice and recombine genes from one organism into the genome of another. EC 3.21.1.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
Nucleosides that have two hydroxy groups removed from the sugar moiety. The majority of these compounds have broad-spectrum antiretroviral activity due to their action as antimetabolites. The nucleosides are phosphorylated intracellularly to their 5'-triphosphates and act as chain-terminating inhibitors of viral reverse transcription.
Proteins found in any species of virus.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
Change brought about to an organisms genetic composition by unidirectional transfer (TRANSFECTION; TRANSDUCTION, GENETIC; CONJUGATION, GENETIC, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell's genome.
A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
The transfer of bacterial DNA by phages from an infected bacterium to another bacterium. This also refers to the transfer of genes into eukaryotic cells by viruses. This naturally occurring process is routinely employed as a GENE TRANSFER TECHNIQUE.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.
Rare mixed tumors of the brain and rarely the spinal cord which contain malignant neuroectodermal (glial) and mesenchymal components, including spindle-shaped fibrosarcoma cells. These tumors are highly aggressive and present primarily in adults as rapidly expanding mass lesions. They may arise in tissue that has been previously irradiated. (From Br J Neurosurg 1995 Apr;9(2):171-8)
A CELL LINE derived from the kidney of the African green (vervet) monkey, (CERCOPITHECUS AETHIOPS) used primarily in virus replication studies and plaque assays.
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.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
A purine or pyrimidine base bonded to a DEOXYRIBOSE containing a bond to a phosphate group.
A family of non-receptor, PROLINE-rich protein-tyrosine kinases.
A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.
An enzyme that catalyzes the acetylation of chloramphenicol to yield chloramphenicol 3-acetate. Since chloramphenicol 3-acetate does not bind to bacterial ribosomes and is not an inhibitor of peptidyltransferase, the enzyme is responsible for the naturally occurring chloramphenicol resistance in bacteria. The enzyme, for which variants are known, is found in both gram-negative and gram-positive bacteria. EC 2.3.1.28.
A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.
An inheritable change in cells manifested by changes in cell division and growth and alterations in cell surface properties. It is induced by infection with a transforming virus.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.
An experimental lymphocytic leukemia of mice.
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.
A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
A 195-kDa MAP kinase kinase kinase with broad specificity for MAP KINASE KINASES. It is found localized in the CYTOSKELETON and can activate a variety of MAP kinase-dependent pathways.
A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.
Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)
A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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.
Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
5-Bromo-2'-deoxycytidine. Can be incorporated into DNA in the presence of DNA polymerase, replacing dCTP.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
A class of organic compounds containing two ring structures, one of which is made up of more than one kind of atom, usually carbon plus another atom. The heterocycle may be either aromatic or nonaromatic.
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.
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.
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 serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.
The sum of the weight of all the atoms in a molecule.
The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.
Transport proteins that carry specific substances in the blood or across cell membranes.
A serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.
Proteins that are coded by immediate-early genes, in the absence of de novo protein synthesis. The term was originally used exclusively for viral regulatory proteins that were synthesized just after viral integration into the host cell. It is also used to describe cellular proteins which are synthesized immediately after the resting cell is stimulated by extracellular signals.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
An enzyme catalyzing the transfer of a phosphate group from 3-phospho-D-glycerate in the presence of ATP to yield 3-phospho-D-glyceroyl phosphate and ADP. EC 2.7.2.3.
A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
An enzyme that catalyzes the hydrolytic deamination of deoxycytidylic acid to deoxyuridylic acid and ammonia. It plays an important role in the regulation of the pool of deoxynucleotides in higher organisms. The enzyme also acts on some 5-substituted deoxycytidylic acids. EC 3.5.4.12.
A rather large group of enzymes comprising not only those transferring phosphate but also diphosphate, nucleotidyl residues, and others. These have also been subdivided according to the acceptor group. (From Enzyme Nomenclature, 1992) EC 2.7.

Transduction of glioma cells using a high-titer retroviral vector system and their subsequent migration in brain tumors. (1/2453)

The intracranial migration of transduced glioma cells was investigated in order to improve the treatment of malignant glioma by gene therapy using retroviral vectors. In this study, about half the volume of the tumor mass could be transduced in 14 days after only a single implantation of 3 x 10(5) retrovirus-producing cells into a tumor mass with a diameter of 5 mm. Moreover, we were able to follow the migration of glioma cells transduced by the lacZ-harboring retroviruses originating from the high-titer retrovirus-producing cells. Besides the importance of using a high-titer retroviral vector system, our results also indicate that the implantation site of the virus-producing cells and the interval between the implantation of the virus-producing cells and the subsequent administration of ganciclovir are important factors for the efficient killing of glioma cells.  (+info)

Identification of a cAMP response element within the glucose- 6-phosphatase hydrolytic subunit gene promoter which is involved in the transcriptional regulation by cAMP and glucocorticoids in H4IIE hepatoma cells. (2/2453)

The expression of a luciferase reporter gene under the control of the human glucose 6-phosphatase gene promoter was stimulated by both dexamethasone and dibutyryl cAMP in H4IIE hepatoma cells. A cis-active element located between nucleotides -161 and -152 in the glucose 6-phosphatase gene promoter was identified and found to be necessary for both basal reporter-gene expression and induction of expression by both dibutyryl cAMP and dexamethasone. Nucleotides -161 to -152 were functionally replaced by the consensus sequence for a cAMP response element. An antibody against the cAMP response element-binding protein caused a supershift in gel-electrophoretic-mobility-shift assays using an oligonucleotide probe representing the glucose 6-phosphatase gene promoter from nucleotides -161 to -152. These results strongly indicate that in H4IIE cells the glucose 6-phosphatase gene-promoter sequence from -161 to -152 is a cAMP response element which is important for the regulation of transcription of the glucose 6-phosphatase gene by both cAMP and glucocorticoids.  (+info)

Modulation of the cytotoxicity of 3'-azido-3'-deoxythymidine and methotrexate after transduction of folate receptor cDNA into human cervical carcinoma: identification of a correlation between folate receptor expression and thymidine kinase activity. (3/2453)

Cervical carcinoma is an AIDS-defining illness. The expression of folate receptors (FRs) in cervical carcinoma (HeLa-IU1) cells was modulated by stable transduction of FR cDNA encapsidated in recombinant adeno-associated virus-2 in the sense and antisense orientation (sense and antisense cells, respectively). Although sense cells proliferated slower than antisense or untransduced cells in vivo and in vitro in 2% (but not 10%) FCS, [methyl-3H]thymidine incorporation into DNA was significantly increased in sense cells in 10% serum; therefore, the basis for this discrepancy was investigated. The activity of thymidine kinase (TK) was subsequently directly correlated with the extent of FR expression in single cell-derived clones of transduced cells. This elevated TK activity was not a result of recruitment of the salvage pathway based on the presence of adequate dTTP pools, normal thymidylate synthase (TS) activity, persistence of increased thymidine incorporation despite the exogenous provision of excess 5,10-methylene-tetrahydrofolate, and documentation of adequate folates in sense cells. The increase in TK activity conferred significant biological properties to sense cells (but not antisense or untransduced cells) as demonstrated by augmented phosphorylation of 3'-azido-3'-deoxythymidine (AZT) and concomitantly greater sensitivity to the cytotoxic effects of AZT. Conversely, sense cells were highly resistant to methotrexate, but this was reversed by the addition of AZT. The direct correlation of FR expression and TK activity indicates a previously unrecognized consequence of FR overexpression.  (+info)

Elevated serum thymidine kinase levels identify a subgroup at high risk of disease progression in early, nonsmoldering chronic lymphocytic leukemia. (4/2453)

Chronic lymphocytic leukemia (CLL) shows a remarkably heterogeneous clinical outcome; survival ranges from several months in advanced stages to more than 10 years in early stages. The Binet and Rai staging systems distinguish three major prognostic subgroups, but do not accurately predict the individual risk of disease progression in early CLL (Binet stage A or Rai stage 0 to II). Because most newly diagnosed CLL patients present with early disease, it seems desirable to search for additional prognostic factors to identify early CLL patients at high risk of rapid progression. It has been shown that elevated serum thymidine kinase (s-TK) levels predict disease progression in CLL. Therefore, this study aimed to assess the prognostic value of s-TK in 122 previously untreated patients with Binet stage A CLL (mean age +/- SD, 58.7 +/- 8.5 years). In univariate analyses, 18 of the 22 parameters investigated predicted progression-free survival (PFS). In a stepwise multiple regression analysis, only three parameters provided independent prognostic information on PFS: s-TK greater than 7.1 U/L; presence of lymphadenopathy; and white blood cell (WBC) count greater than 75, 000/microL. When added to the classification of smoldering versus nonsmoldering CLL, s-TK levels separated two groups within the group of nonsmoldering stage A patients: patients with s-TK values greater than 7.1 U/L had a median PFS of 8 months, whereas patients with s-TK values +info)

Imaging adenoviral-directed reporter gene expression in living animals with positron emission tomography. (5/2453)

We are developing quantitative assays to repeatedly and noninvasively image expression of reporter genes in living animals, using positron emission tomography (PET). We synthesized positron-emitting 8-[18F]fluoroganciclovir (FGCV) and demonstrated that this compound is a substrate for the herpes simplex virus 1 thymidine kinase enzyme (HSV1-TK). Using positron-emitting FGCV as a PET reporter probe, we imaged adenovirus-directed hepatic expression of the HSV1-tk reporter gene in living mice. There is a significant positive correlation between the percent injected dose of FGCV retained per gram of liver and the levels of hepatic HSV1-tk reporter gene expression (r2 > 0.80). Over a similar range of HSV1-tk expression in vivo, the percent injected dose retained per gram of liver was 0-23% for ganciclovir and 0-3% for FGCV. Repeated, noninvasive, and quantitative imaging of PET reporter gene expression should be a valuable tool for studies of human gene therapy, of organ/cell transplantation, and of both environmental and behavioral modulation of gene expression in transgenic mice.  (+info)

Use of the Gal4-UAS technique for targeted gene expression in the zebrafish. (6/2453)

The most common way to analyze the function of cloned genes in zebrafish is to misexpress the gene product or an altered variant of it by mRNA injection. However, mRNA injection has several disadvantages. The GAL4-UAS system for targeted gene expression allows one to overcome some of these disadvantages. To test the GAL4-UAS system in zebrafish, we generated two different kinds of stable transgenic lines, carrying activator and effector constructs, respectively. In the activator lines the gene for the yeast transcriptional activator GAL4 is under the control of a given promoter, while in the effectors the gene of interest is fused to the sequence of the DNA-binding motif of GAL4 (UAS). Crosses of animals from the activator and effector lines show that effector genes are transcribed with the spatial pattern of the activators. This work smoothes the way for a novel method of misexpression of gene products in zebrafish in order to analyze the function of genes in developmental processes.  (+info)

Staurosporine blocked normal cells at G1/S boundary. (7/2453)

AIM: To reveal the regulating difference of G1/S-phase transition between normal and tumor cells by using staurosporine, an unspecific kinase inhibitor. METHODS: Flow cytometry, Dot blot, kinase activity assay, and electrophoresis. RESULTS: A 18-h treatment with staurosporine (5 micrograms.L-1) blocked normal cell line 2BS cells (normal human embryonic lung fibroblast, 5-20 passages) in G1 phase, decreased their thymidine kinase (TK) mRNA level and activity, and also dephosphorylated an intracellular 107 kDa protein. Meanwhile, all these effects in 2BS cells disappeared only by washing staurosporine away. Such kind of effects did not occur in tumor cell line BGC-823 cells (human stomach cancer cell). CONCLUSION: During the period of G1/S-phase transition, the kinases involved are more sensitive to staurosporine in normal cells than in tumor cells.  (+info)

Intronless mRNA transport elements may affect multiple steps of pre-mRNA processing. (8/2453)

We have reported recently that a small element within the mouse histone H2a-coding region permits efficient cytoplasmic accumulation of intronless beta-globin cDNA transcripts. This sequence lowers the levels of spliced products from intron-containing constructs and can functionally replace Rev and the Rev-responsive element (RRE) in the nuclear export of unspliced HIV-1-related mRNAs. In work reported here, we further investigate the molecular mechanisms by which this element might work. We demonstrate here through both in vivo and in vitro assays that, in addition to promoting mRNA nuclear export, this element acts as a polyadenylation enhancer and as a potent inhibitor of splicing. Surprisingly, two other described intronless mRNA transport elements (from the herpes simplex virus thymidine kinase gene and hepatitis B virus) appear to function in a similar manner. These findings prompt us to suggest that a general feature of intronless mRNA transport elements might be a collection of phenotypes, including the inhibition of splicing and the enhancement of both polyadenylation and mRNA export.  (+info)

TY - JOUR. T1 - Coexpression of herpesviral thymidine kinase reporter gene and VEGF gene for noninvasive monitoring of therapeutic gene transfer. T2 - An in vitro evaluation. AU - Anton, Martina. AU - Wittermann, Constanze. AU - Haubner, Roland. AU - Simoes, Marcus. AU - Reder, Sybille. AU - Essien, Bryan. AU - Wagner, Bettina. AU - Henke, Julia. AU - Erhardt, Wolf. AU - Noll, Steffi. AU - Hackett, Neil R.. AU - Crystal, Ronald G.. AU - Schwaiger, Markus. AU - Gansbacher, Bernd. AU - Bengel, Frank M.. PY - 2004/10/1. Y1 - 2004/10/1. N2 - Coexpression of a reporter gene and a therapeutic gene may allow for noninvasive monitoring of cardiac gene therapy. We sought to evaluate the usefulness of an adenoviral vector expressing mutant herpesviral thymidine kinase reporter gene (HSV1-sr39tk) and vascular endothelial growth factor (VEGF) 121 in independent expression cassettes (Ad4tk). Methods: Accumulation of 14C-2′-fluoro-5-methyl-1-β-D-arabinofuranosyluracil (FIAU) and ...
Toda la información sobre las últimas publicaciones científicas de la Clínica Universidad de Navarra. Transduction efficacy, antitumoral effect, and toxicity of adenovirus-mediated herpes simplex virus thymidine kinase/ ganciclovir therapy of hepatocellular carcinoma: the woodchuck animal model
All information about the latest scientific publications of the Clínica Universidad de Navarra. Transduction efficacy, antitumoral effect, and toxicity of adenovirus-mediated herpes simplex virus thymidine kinase/ ganciclovir therapy of hepatocellular carcinoma: the woodchuck animal model
Abstract We constructed a functional MoMuLV-based bicistronic retroviral vector encoding the herpes simplex virus type I thymidine kinase gene, which induces sensitivity to the prodrug ganciclovir (gcv), and the reporter beta-galactosidase gene (MFG-tk-IRES-lacZ). The U937 histiocytic cell line was transduced with this vector, and a clone (VB71) with high-level transgene expression was selected. Severe combined immunodeficient (SCID) mice were injected with VB71 cells to evaluate the role of long terminal repeat methylation in transgene silencing in vivo and to see whether 5-azacytidine (5 aza-C) demethylating agent prevented it. We found 5 aza-C maintained gene expression at high level in vitro. In vivo, time to tumor onset was significantly longer in SCID mice receiving the VB71 cells, 5 aza-C, and gcv compared with animals treated with either 5 aza-C or gcv alone. The number of injected tumor cells influences tumor onset time and the efficacy of 5 aza-C and gcv treatment. The standard ...
Summary Purified herpes simplex virus thymidine kinase has been used to immunize mice for the production of monoclonal antibodies to the enzyme. Monoclonal antibodies were successfully produced against both herpes simplex virus type 1 and type 2 enzymes. These antibodies should prove useful for detecting the enzyme under a variety of experimental conditions. We also demonstrate that the antibodies can provide an alternative method for obtaining large amounts of purified thymidine kinase.
TY - JOUR. T1 - Stem cells as vectors to deliver HSV/tk gene therapy for malignant gliomas. AU - Rath, Prakash. AU - Shi, Huidong. AU - Maruniak, Joel A.. AU - Litofsky, N. Scott. AU - Maria, Bernard L.. AU - Kirk, Mark D.. PY - 2009/10/12. Y1 - 2009/10/12. N2 - The prognosis of patients diagnosed with malignant gliomas including glioblastoma multiforme (GBM) is poor and there is an urgent need to develop and translate novel therapies into the clinic. Neural stem cells display remarkable tropism toward GBMs and thus may provide a platform to deliver oncolytic agents to improve survival. First we provide a brief review of clinical trials that have used intra-tumoral herpes simplex virus thymidine kinase (HSV/tk) gene therapy to treat brain tumors. Then, we review recent evidence that neural stem cells can be used to deliver HSV/tk to GBMs in animal models. While previous clinical trials used viruses or non-migratory vector-producing cells to deliver HSV/tk, the latter approaches were not ...
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Summary The induction of thymidine kinase (TK) and DNA polymerase was inhibited by interferon (IFN) in mouse L-cells infected with herpes simplex virus type 1 (HSV-1). The inhibitory activity of IFN at this early stage of HSV-1 replication was followed by a reduced virus yield and was dependent on the multiplicity of infection. The expression of a cloned thymidine kinase (tk) gene of HSV-1, in biochemically transformed L-cells (LTK+), was not affected by IFN. These same LTK+ cells, however, developed an antiviral state since, upon HSV-1 infection, the induction of TK and DNA polymerase of the replicating virus was inhibited by IFN. Furthermore, IFN inhibited the transactivation of the HSV-1 tk gene in the biochemically transformed LTK+ cells, which followed infection by a virus mutant defective in the tk gene (HSV-1 TK-). This transactivation is dependent on expression of immediate-early HSV-1 α-genes. These results indicate that IFN inhibits HSV-1 replication at an early step prior to DNA synthesis.
Thymidine kinases form part of the salvage pathway for pyrimidine deoxyribonucleotide synthesis. TKs are expressed in a variety of organisms from human to bacteria as well as in a number of viruses. The reaction catalysed by TK involves the transfer of a γ-phosphoryl moiety from ATP to 2deoxy-thymidine (dThd) to produce thymidine 5-monophosphate (dTMP). Certain TKs, such as those from herpes simplex virus type 1 (HSV-1) and varicella zoster virus (VZV) have, in addition, thymidylate kinase activity allowing the conversion of dTMP to thymidine 5-diphosphate (dTDP). TKs can be classified into two types which differ in several respects [1]. Type 1 TKs are of higher molecular weight, typically around 40 kDa, and are active as homodimers. This subfamily contains the HSV1, HSV2 and VZV TKs, and also mitochondrial TK.. TKs of type 2 include those from poxviridae such as vaccinia virus (VV) and variola virus, [2], as well as from human [3] hTK, (human type II thymidine kinase 1) and mouse [4]. Type ...
Mammals have two isoenzymes, that are chemically very different, TK1 and TK2. The former was first found in fetal tissue, the second was found to be more abundant in adult tissue, and initially they were termed fetal and adult thymidine kinase. Soon it was shown that TK1 is present in the cytoplasm only in anticipation of cell division (cell cycle-dependent),[10][11] whereas TK2 is located in mitochondria and is cell cycle-independent.[12][13] The two isoenzymes have different reaction kinetics and are inhibited by different inhibitors. The viral thymidine kinases differ completely from the mammalian enzymes both structurally and biochemically and are inhibited by inhibitors that do not inhibit the mammalian enzymes.[14][15][16] The genes of the two human isoenzymes were localized in the mid-1970s.[17][18] The gene for TK1 was cloned and sequenced.[19] The corresponding protein has a molecular weight of about 25 kD. Normally, it occurs in tissue as a dimer with a molecular weight of around 50 ...
Aims: Thymidine kinase 1 (TK1) is an enzyme involved in DNA synthesis and an important proliferation marker. We explored the association of preoperative serum TK1 activity with clinicopathological parameters and prognosis in terms of recurrence-free survival (RFS) in breast cancer (BC) patients. Patients and methods: TK1 activity in serum of 120 healthy women and 161 BC patients was measured by quantitative ELISA. Results: Serum TK1 activity in BC patients was significantly higher than in healthy women (P , 0.0001). In BC patients elevated TK1 activity was significantly associated with advanced T stage (P = 0.015), higher grade (P = 0.013), presence of tumor necrosis (P = 0.006), vascular invasion (P = 0.002), and lack of estrogen receptor (ER) and progesterone receptor (PR) expression (P = 0.0004 and P = 0.003). Higher TK1 activity was found in patients with BRCA1/2 mutations compared to those without the mutation (P = 0.004). Multivariate Cox proportional hazards analyses demonstrated that ...
TY - JOUR. T1 - Differences in thermostability of thymidine kinase isoenzymes in normal ovary and ovarian carcinoma. AU - Demeter, A.. AU - Abonyi, M.. AU - Look, K. Y.. AU - Keszler, G.. AU - Staub, M.. AU - Weber, G.. PY - 2001/4/17. Y1 - 2001/4/17. N2 - Thymidine kinase I (TK 1 EC. 2.7.1.21) the most specific and cell-cycle regulated salvage enzyme for pyrimidine nucleoside supply of DNA synthesis is a promising target to rationally designed chemo- and other therapies. The present study was undertaken to compare the heat stability of TK isoenzymes of both normal ovarian and epithelial ovarian cancer cells. Tissue extracts of epithelial ovarian carcinomas (N = 7) and normal ovaries (N=9) were analyzed for thymidine kinase activity using the polyethyleneimine-cellulose disc radioassay. The TK activity in extracts of ovarian carcinomas was 12-fold higher than in extracts of normal ovaries. The TK activity of ovarian carcinomas decreased significantly even after 30 minutes incubation at 37°C ...
Two plasmids containing nonoverlapping deletions of the herpes simplex virus thymidine kinase gene were introduced into thymidine kinase-deficient mouse L cells by DNA-mediated gene transfer. Thymidine kinase-producing transformants were generated by a mixture of the two plasmids at a frequency significantly greater than that generated by either plasmid alone. Southern blot analyses demonstrated that functional thymidine kinase genes were generated by homologous recombination between the two deletion mutants. ...
DI-fusion, le Dépôt institutionnel numérique de lULB, est loutil de référencementde la production scientifique de lULB.Linterface de recherche DI-fusion permet de consulter les publications des chercheurs de lULB et les thèses qui y ont été défendues.
9-(4-(18)F-Fluoro-3-[hydroxymethyl]butyl)guanine ((18)F-FHBG) is a sensitive and specific PET reporter probe for imaging the PET reporter genes, herpes simplex 1 thymidine kinase (HSV1-tk) and its mutant HSV1-sr39tk. (18)F-FHBG has suitable pharmacok
TY - JOUR. T1 - Glucocorticoid regulation of the genes encoding thymidine kinase, thymidylate synthase, and ornithine decarboxylase in P1798 cells. AU - Barbour, Karen W.. AU - Berger, Sondra H.. AU - Berger, Franklin G.. AU - Thompson, E. Aubrey. PY - 1988/1. Y1 - 1988/1. N2 - The expression of a number of genes was measured in P1798 cells treated for various periods of time with 0.1 mm dexamethasone. Thymidine kinase (TK) activity decreased under these conditions with 50% inhibition achieved within approximately 8 h. Decreased TK activity was associated with reduced abundance of TK mRNA. Analysis of nuclear tran-scription indicated that this was attributable to a decrease in the number of RNA polymerase II molecules engaged in transcription of the TK gene. With respect to TK, there was an overall correlation between enzyme activity, mRNA, and nuclear transcription. The data are consistent with the hypothesis that glucocorticoid inhibition of expression of TK is primarily due to inhibition of ...
TY - JOUR. T1 - Gene therapy for transplant arteriosclerosis. AU - Rekhter, M. D.. AU - Shah, N.. AU - Simari, R. D.. AU - Work, C.. AU - Kim, J. S.. AU - Nabel, G. J.. AU - Nabel, E. G.. AU - Gordon, D.. PY - 1997/12/1. Y1 - 1997/12/1. N2 - Transplant arteriosclerosis is a thickening of the intima that develops in arteries of transplanted organs. Smooth muscle cell (SMC) replication plays a central role in its pathogenesis. One strategy to selectively eliminate dividing cells is to express a herpesvirus thymidine kinase (tk) gene which phosphorylates the nucleoside analog, ganciclovir, into a toxic form which leads to cell killing. To evaluate a feasibility of transgene expression in arterial grafts, we performed ex vivo adenovirus (ADV)-mediated transfer of human placental alkaline phosphatase (hpAP) gene into aortas of donor rabbits, and then transplanted them into carotid artery of recipient rabbits. 2 days post-transplant luminal endothelial cells, adventitial cells, and medial SMCs ...
Local inflammatory response and vector spread after direct intraprostatic injection of a recombinant adenovirus containing the herpes simplex virus thymidine kinase gene and ganciclovir therapy in mice Academic Article ...
Thymidine kinase converts 5-fluorodeoxyuridine to 5-fluorodeoxyuridine monophosphate, which causes disruption of deoxynucleotide triphosphate ratios. The fission yeast Schizosaccharomyces pombe does not express endogenous thymidine kinase but 5-fluorodeoxyuridine inhibits growth when exogenous thymidine kinase is expressed. Unexpectedly, we found that 5-fluorodeoxyuridine causes S phase arrest even without thymidine kinase expression. DNA damage checkpoint proteins such as the 9-1-1 complex were required for viability in the presence of 5-fluorodeoxyuridine. We also found that strains with circular chromosomes, due to loss of pot1+, which have higher levels of replication stress, were more sensitive to loss of the 9-1-1 complex in the presence of 5-fluorodeoxyuridine. Thus, our results suggest that strains carrying circular chromosomes exhibit a greater dependence on DNA damage checkpoints to ensure viability in the presence of 5-fluorodeoxyuridine compared to stains that have linear ...
DNA containing the herpes simplex virus thymidine kinase (HSVtk) gene was used to transform wild-type tk+ mouse L cells to a tk++ status in vitro using methotrexate as a selective agent. HSVtk DNA was also used to transform mouse bone marrow cells in vitro. Transformed marrow cells injected into irradiated and methotrexate-treated recipient mice gave rise to proliferating cells which in some cases dominated the marrow population and which contained HSVtk gene sequences. ...
Cadee JA, van Luyn MJ, Brouwer LA, Plantinga JA, van Wachem PB, De Groot CJ, den OW, and Hennink WE. (2000). In vivo biocompatibility of dextran-based hydrogels. J Biomed Mater Res 50: 397-404. PubMed. de Vries EF, van WA, Harmsen MC, Mulder NH, Vaalburg W, and Hospers GA. (2000). [(11)C]FMAU and [(18)F]FHPG as PET tracers for herpes simplex virus thymidine kinase enzyme activity and human cytomegalovirus infections. Nucl Med Biol 27: 113-9. PubMed. Dijk F, Westerhof M, Busscher HJ, van Luyn MJ, and van Der Mei HC. (2000). In vitro formation of oropharyngeal biofilms on silicone rubber treated with a palladium/tin salt mixture. J Biomed Mater Res 51: 408-12. PubMed. Kas-Deelen AM, de Maar EF, Harmsen MC, Driessen C, van Son WJ, and The TH. (2000). Uninfected and cytomegalic endothelial cells in blood during cytomegalovirus infection: effect of acute rejection. J Infect Dis 181: 721-4. PubMed. Kas-Deelen AM, Harmsen MC, de Maar EF, Oost-Kort WW, Tervaert JW, Van Der Meer J, van Son WJ, and The ...
EBV Thymidine Kinase, 0.1 mg. Thymidine kinase (TK) belongs to a group of enzymes such as dihydrofolate reductase, thymidylate synthase, and DNA polymerase that are involved in DNA synthesis and precursor production.
Valaciclovir belongs to a family of molecules. Valaciclovir is a prodrug, an esterified version of aciclovir that has greater oral bioavailability (about 55%) than aciclovir (10-20%). It is converted by esterases to the active drug aciclovir, as well as the amino acid valine, via hepatic first-pass metabolism. Aciclovir is selectively converted into a monophosphate form by viral thymidine kinase, which is far more effective (3000 times) in phosphorylation of aciclovir than cellular thymidine kinase. Subsequently, the monophosphate form is further phosphorylated into the active triphosphate form, aciclo-GTP, by cellular kinases. Aciclo-GTP is a very potent inhibitor of viral DNA polymerase; it has approximately 100 times higher affinity to viral than cellular polymerase.[citation needed] Its monophosphate form also incorporates into the viral DNA, resulting in chain termination. It has also been shown that the viral enzymes cannot remove aciclo-GMP from the chain, which results in inhibition of ...
Moreover, mRNA level of FOXA2 was dramatically improved in S4 and S7 cells compared with undifferentiated cells, indicating the generation of definitive endoderm cells upon differentiation (Number?S11). the off-target effect, we therefore focused our effort in the current study within the insertion of a suicide gene into the locus for selective eradication of undifferentiated hPSCs. Two suicide strategies are widely used in cell-based therapy, including herpes simplex virus thymidine kinase (HSV-TK) and inducible caspsae-9 (iC9) (Zarogoulidis et?al., 2013). HSV-TK induces cell death by transforming the non-toxic prodrug ganciclovir (GCV) into a harmful form to block DNA replication (Moolten, 1986, Reardon, 1989). Multiple studies have demonstrated the effectiveness of expressing HSV-TK to kill undifferentiated hPSCs (Liang et?al., 2018, Schuldiner et?al., 2003). Since this system relies on cell division, it is not suitable for treating proliferating cells such as differentiated progenitor cells ...
Although acyclovir (ACV) is an effective antiviral agent, herpes simplex virus (HSV) that is resistant to treatment can be a serious clinical problem in immunocompromised patients. It has been estimated that ACV-resistant (ACVr) HSV appears in as many as 5% of this population upon treatment (4, 10). Clinically significant drug resistance implies evasion of drug action but retention of pathogenesis. The vast majority of mutations associated with clinical drug resistance occur in the viral thymidine kinase (TK) gene (tk), which encodes the enzyme that selectively activates ACV. The phenotypes of clinical isolates with mutant TKs typically fall into one of three categories: altered substrate specificity, low TK activity (TKL), or lack of measurable TK activity (TK−) (11, 12, 26). That viruses lacking TK activity are pathogenic has been puzzling. Although TK is not required for growth in cell culture, it is essential for pathogenesis in mouse models of HSV infection, in particular, for ...
The human growth hormone (hGH) transient assay system described here is based on the expression of hGH directed by cells transfected with hGH fusion genes. Levels of secreted hGH in the medium, measured by a simple radioimmunoassay, are proportional to both levels of cytoplasmic hGH mRNA and the amount of transfected DNA. The system is extremely sensitive, easy to perform, and is qualitatively different from other transient expression systems in that the medium is assayed and the cells themselves are not destroyed. The hGH transient assay system is appropriate for analyses of regulation of gene expression and was utilized here to investigate the effect of the simian virus 40 enhancer on the herpes simplex virus thymidine kinase promoter and the effect of zinc on the mouse metallothionein-I promoter. The expression of hGH can also be used as an internal control to monitor transfection efficiency along with any other transient expression system. All cell types tested thus far (including AtT-20, ...
Most individuals have no or only minimal signs or symptoms from HSV-1 or HSV-2 infection. ELLANSÉ™ with its four distinctive versions, lasting from 12 months up to 4 years, allow you to choose how long you would like the results to last, eliminating the need for frequent repeat treatments. Herpes infections are common among women of reproductive age (i.e., aged 15-44 years). Patients older than 65 years are usually considered ineligible for ASCT. In U. The sympathetic fibres parallel the parasympathetic fibres as they supply the same areas. Herpes simplex virus thymidine kinase (HSV-TK) is widely used in gene therapy.. TheBody. First, a lot of time and energy worrying that your partner will get herpes. The culprit responsible for cold sores is the herpes simplex virus. IgM antibodies are produced immediately after infection. What electrodesiccation uses in destroying chlamydia is an electric current. Make research projects and school reports about Canker Sores easy with credible articles ...
Multiple labs have reported that mammalian ovaries contain oogonial stem cells (OSCs), which can differentiate into oocytes that fertilize to produce offspring. However, the physiological relevance of these observations to adult ovarian function is unknown. Here we performed targeted and reversible ablation of premeiotic germ cells undergoing differentiation into oocytes in transgenic mice expressing the suicide gene, herpes simplex virus thymidine kinase (HSVtk), driven by the promoter of stimulated by retinoic acid gene 8 (Stra8), a germ cell-specific gene activated during meiotic commitment. Over a 21-day ablation phase induced by the HSVtk pro-drug, ganciclovir (GCV), oocyte numbers declined due to a disruption of new oocyte input. However, germ cell differentiation resumed after ceasing the ablation protocol, enabling complete regeneration of the oocyte pool. We next employed inducible lineage tracing to fate map, through Cre recombinase-mediated fluorescent reporter gene activation only in Stra8
It is called suicide gene therapy. And this is the concept: find a gene coding for an enzyme that human cells dont have. Insert that gene only into cancer cells--not normal cells. This enzyme works by taking a harmless pro-drug and converting it into a toxic compound. Early attempts at this therapy used the enzyme thymidine kinase from the herpes simplex virus. This enzyme converts the drug ganciclovir into a compound that stops DNA synthesis. If a cancer cell cant make new DNA, it will eventually die ...
Figure and Images: Expression of functional MMP-9 by GLV-1h255-infected tumor cells. (A) Expression cassettes of GLV-1h68 and GLV-1h255. In GLV-1h255 the insert in the Tk locus was replaced by the human mmp-9 gene under control of the PSE promoter. PSEL, synthetic early/late promoter; PSE, synthetic early promoter; P7.5, VACV p7.5 K early/late promoter; P11, VACV p11 late promoter; Tk, thymidine kinase locus, Ha, hemagglutinin locus. (B) Expression of virus-encoded MMP-9 (92 kDa) in GLV-1h255 infected PC-3 cells and supernatants in vitro, β-actin (42 kDa) was used as a loading control. (C) Activity of the MMP-9 protein was tested by gelatin zymography. Lysates and supernatants of infected A549 cells were isolated and separated by non-reducing SDS-PAGE. In zymography, cleavage of the substrate by MMP-9 resulted in a clear band. ...
BioAssay record AID 221799 submitted by ChEMBL: Compound was tested for antitumor activity against thymidine kinase deficient human B-lymphoblast Raji/0 cells.
The test item triethoxy(3-thiocyanatopropyl)silane was assessed for its potential to induce mutations at the mouse lymphoma thymidine kinase locus using the cell line L5178Y. The selection of the concentrations used in the main experiment was based on data from the pre-experiment. In the main experiment 1.3 mM (with metabolic activation) and 1 mM (without metabolic activation) were selected as the highest concentrations. The experiment with and without metabolic activation was performed as a 4 h short-term exposure assay. Based on the solubility test DMSO was used as solvent (final concentration 1% DMSO v/v). The test item was investigated at the following concentrations: with metabolic activation: 0.05, 0.1, 0.2, 0.5, 0.7, 0.9, 1.1 and 1.3 mM and without metabolic activation: 0.005, 0.01, 0.02, 0.05, 0.1, 0.2, 0.5 and 1 mM Precipitation of the test item was noted in the pre-experiment at a concentration of 2.5 mM. Growth inhibition was observed in the main experiment with and without metabolic ...
Acquistare indescribably forzest 20 buy online gli integratori che elencheremo in questo report è al 100% legale per la Legge Italiana. In another embodiment, a fusion protein comprised of a modified form of the tet repressor (TetR) and a transactivation domain or a domain (eg, a dimerization domain) which recruits a transcriptional activator (eg, an endogenous transcriptional activator) to interact with the fusion protein by a protein-protein interaction (eg, a non-covalent interaction) is introduced into a cell. Coli is also found in this environment ( 60, 61). Viral resistance to acyclovir may occur due to loss of thymidine kinase activity, levitra malaysia alterations in thymidine kinase substrate specificity, or decreased DNA-polymerase sensitivity. I have heard excellent things about blogenginenet! Im not very internet smart so Im not 100% certain? «Lady Gaga dedicates her new Little Monsters tattoo to her fans». The decision making it is only has not a new buy retin a cream ...
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The protein encoded by this gene is a cytosolic enzyme that catalyzes the addition of a gamma-phosphate group to thymidine. This creates dTMP and is the first step in the biosynthesis of dTTP, which is one component required for DNA replication. The encoded protein, whose levels fluctuate depending on the cell cycle stage, can act as a low activity dimer or a high activity tetramer. High levels of this protein have been used as a biomarker for diagnosing and categorizing many types of cancers. [provided by RefSeq, Oct 2016 ...
1E2P: The Effect of Substrate Binding on the Conformation and Structural Stability of Herpes Simplex Virus Type 1 Thymidine Kinase
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FLT was developed to provide a measure of tumor proliferation because it is taken up by cells and retained after phosphorylation by thymidine kinase 1. Thymidine kinase 1 increases as cells enter the DNA synthetic phase, and previous work has shown that FLT retention generally correlates with other measures of tumor proliferation. The most likely use of FLT will be in monitoring treatment response, but such studies need to consider the different methods for measuring FLT retention in tumors and their reproducibility.. The most common method of measuring tracer retention has been through the use of the semiquantitative approach of the SUV. The SUV uses the measurement of activity within a ROI along with the injected dose and the weight of the patient to calculate the desired variable. To take into account differences in the proportion of fat in patients, some investigators have adjusted the SUV by using lean body mass, ideal body weight, or even body surface area. When studying the ...
swd:Swoo_3233 K00857 thymidine kinase [EC:2.7.1.21] , (GenBank) Thymidine kinase (A) MAQLYFYYSAMNAGKSTSLLQSSYNYRERGMNTLVMTASIDDRYGVGKVASRIGIETDAQ VFGSDDNLAAMITSAHNEKQLHCILIDESQFLSKEQVKQLTHVVDNLDIPVLCYGLKTDF QGELFSGSQYLLAWADKLVELKTICHCGRKANMVLRLDGSGKPMRDGEQVAIGGNESYES VCRKHFREFLWD ...
gbr:Gbro_2907 K00857 thymidine kinase [EC:2.7.1.21] , (GenBank) Thymidine kinase (A) MSASAELVFYYGPMGAGKSTLALQTHFNQRQQGRSGVLLTKDDRSNRPLVTSRIGLAAEA IAVDDHTDVHALITGRGIPDFLVCDEAQFLTIAQVDQLAGLVDDHAVSVFAYGLLTDFRS VLFPGSARLVEIADEIHRMQAVVLCWCGRDACLNARIVNGRMVHAGELIAIGDTGDGPVH YRPLCRRHFTQGRIDAGGEPGPVDTNSQNPFSTG ...
Generation of MT-III-deficient mice. The mouse MT-III gene was isolated from a 129Sv genomic library (Palmiter et al., 1992). A disruption vector was constructed by replacing a 2.2 kbXhoI-NdeI region containing the promoter and exons 1 and 2 with a neomycin resistance cassette and inserting thymidine kinase genes at BamHI and BstEII sites in the 5′ and 3′ flanking regions, respectively. Electroporation and selection of AB1 embryonic stem cells was performed as described (Thomas et al., 1995). Colonies were screened for targeting by PCR and confirmed by Southern blot analysis of DNA digested withSstI by using a 0.6 kb BstEII-NdeI fragment as a probe. Eight positive clones were identified from 840 clones screened. Four clones were used to generate chimeric mice as described (Thomas et al., 1995), but only one clone transmitted through the germline, and it was used to establish a line of mice carrying the disrupted allele. F2 and F3 generation C57Bl/129Sv hybrid mice of both sexes were used in ...
Tk_AllocCursorFromObj(3) Tk Library Procedures Tk_AllocCursorFromObj(3) ______________________________________________________________________________ NAME Tk_AllocCursorFromObj, Tk_GetCursor, Tk_GetCursorFromObj, Tk_GetCursor- FromData, Tk_NameOfCursor, Tk_FreeCursorFromObj, Tk_FreeCursor - main- tain database of cursors SYNOPSIS #include ,tk.h, Tk_Cursor Tk_AllocCursorFromObj(interp, tkwin, objPtr) Tk_Cursor Tk_GetCursor(interp, tkwin, name) Tk_Cursor Tk_GetCursorFromObj(tkwin, objPtr) Tk_Cursor Tk_GetCursorFromData(interp, tkwin, source, mask, width, height, xHot, yHot, fg, bg) const char * Tk_NameOfCursor(display, cursor) Tk_FreeCursorFromObj(tkwin, objPtr) Tk_FreeCursor(display, cursor) ARGUMENTS Tcl_Interp *interp (in) Interpreter to use for error re- porting. Tk_Window tkwin (in) Token for window in which the cursor will be used. Tcl_Obj *objPtr (in/out) Description of cursor; see below for possible values. Internal rep will be modified to cache pointer to corresponding Tk_Cur- sor. char ...
Rabbit polyclonal antibody raised against synthetic peptide of TK1. A synthetic peptide corresponding to N-terminus of human TK1. (PAB5614) - Products - Abnova
TY - CHAP. T1 - Osteonectin promoter-mediated suicide gene therapy of prostate cancer. AU - Hsiao, Wan Chi. AU - Sung, Shian Ying. AU - Chung, Leland W.K.. AU - Hsieh, Chia Ling. PY - 2019/1/1. Y1 - 2019/1/1. N2 - Suicide gene therapy using the herpes simplex virus thymidine kinase (HSV-tk) gene, combined with the prodrug ganciclovir (GCV) medication, is a promising approach for the treatment of malignant tumors, including prostate cancer. The success of this therapeutic strategy requires tissue- or tumor-specific gene expression and efficient gene delivery. In this chapter, we describe the experimental protocols of key methodologies, including promoter construction, reporter assay, adenoviral vector construction and preparation, HSV-tk enzymatic assay and cytotoxicity assay to evaluate the specificity and efficacy of osteonectin promoter-mediated HSV-tk/GCV suicide gene therapy of prostate cancer.. AB - Suicide gene therapy using the herpes simplex virus thymidine kinase (HSV-tk) gene, combined ...
TY - JOUR. T1 - Construction of a differentiated human hepatocyte cell line expressing the herpes simplex virus-thymidine kinase gene. AU - Kobayashi, Naoya. AU - Miyazaki, Masahiro. AU - Westerman, Karen A.. AU - Noguchi, Hirofumi. AU - Sakaguchi, Masakiyo. AU - Totsugawa, Toshinori. AU - Watanabe, Takamasa. AU - Matsumura, Toshihisa. AU - Fujiwara, Toshiyoshi. AU - Leboulch, Philippe. AU - Tanaka, Noriaki. AU - Namba, Masayoshi. PY - 2001. Y1 - 2001. N2 - Transient support using a hybrid artificial liver (HAL) device is a promising treatment for the patients with acute liver failure. Primary human hepatocytes are an ideal source for HAL therapy; however, the number of human livers available for hepatocyte isolation is limited by competition for use in whole organ transplantation. To overcome this problem, we previously established a highly differentiated human fetal hepatocyte cell line OUMS-29. Considering the potential risk when using these genetically engineered cells in humans, additional ...
TY - JOUR. T1 - Enhanced combined tumor-specific oncolysis and suicide gene therapy for prostate cancer using M6 promoter. AU - Ahn, M.. AU - Lee, S. J.. AU - Li, Xiaochun. AU - Jiménez, J. A.. AU - Zhang, Y. P.. AU - Bae, K. H.. AU - Mohammadi, Y.. AU - Kao, Chinghai. AU - Gardner, Thomas. PY - 2009/1. Y1 - 2009/1. N2 - Enzyme pro-drug suicide gene therapy has been hindered by inefficient viral delivery and gene transduction. To further explore the potential of this approach, we have developed AdIU1, a prostate-restricted replicative adenovirus (PRRA) armed with the herpes simplex virus thymidine kinase (HSV-TK). In our previous Ad-OC-TK/ACV phase I clinical trial, we demonstrated safety and proof of principle with a tissue-specific promoter-based TK/pro-drug therapy using a replication-defective adenovirus for the treatment of prostate cancer metastases. In this study, we aimed to inhibit the growth of androgen-independent (AI), PSA/PSMA-positive prostate cancer cells by AdIU1. In vitro the ...
We have developed a novel model for depleting mouse hepatic stellate cells (HSCs) that has allowed us to clarify their contributions to hepatic injury and fibrosis. Transgenic (Tg) mice expressing the herpes simplex virus thymidine kinase gene (HSV-Tk) driven by the mouse GFAP promoter were used to render proliferating HSCs susceptible to killing in response to ganciclovir (GCV). Effects of GCV were explored in primary HSCs and in vivo. Panlobular damage was provoked to maximize HSC depletion by combining CCl4 (centrilobular injury) with allyl alcohol (AA) (periportal injury), as well as in a bile duct ligation (BDL) model. Cell depletion in situ was quantified using dual immunofluorescence (IF) for desmin and GFAP. In primary HSCs isolated from both untreated wild-type (WT) and Tg mice, GCV induced cell death in ∼50% of HSCs from Tg, but not WT, mice. In TG mice treated with CCl4+AA+GCV, there was a significant decrease in GFAP and desmin-positive cells, compared to WT mice (∼65% reduction; ...
Acyclovir is a potent and selective antiviral agent. Unfortunately, drug-resistant (acyclovir-resistant) mutants have already been reported in herpes simplex virus type 1 (HSV-1) orofacial infections. We have developed a laboratory acyclovir-resistant HSV-1 mutant. The natural course of acyclovir-resistant HSV-1 keratitis was found to be less virulent than that observed in wild type HSV-1 keratitis, but the rate of ganglionic latency was as high as that induced by the parental strain. In vitro studies and in vivo observation of rabbit corneas infected with acyclovir-resistant HSV-1 both demonstrated a significant sensitivity to vidarabine and bromovinyldeoxyuridine ([E]-5-[2-bromovinyl]-2-deoxyuridine). The thymidine kinase activity of the acyclovir-resistant mutant was 69% of that of the wild type HSV-1 ...
The herpesvirus family comprises several widespread infectious pathogens. They infect a variety of animal hosts, including humans and cause complex clinical outcomes. Recently, the possible correlation between genital infection by human herpesviruses (HHVs) and male infertility has attracted considerable attention. In this chaper, we investigated the mechanism of HHV‐1‐induced infertility in transgenic (Tg) rats and its possible correlation with infertility in human males. Ectopic expression of HHV‐1 thymidine kinase (TK) in the testis of Tg rats increased male infertility. In addition, truncated TK proteins were found in postmeiotic spermatids of Tg rat testis, leading to progressive degeneration of germ cells and vacuolization of the seminiferous epithelium. These findings suggest the possibility that a similar process occurs within HHV‐infected human germ cells.
TY - JOUR. T1 - Ablation of Neurogenesis Attenuates Recovery of Motor Function after Focal Cerebral Ischemia in Middle-Aged Mice. AU - Sun, Fen. AU - Wang, Xiaomei. AU - Mao, Xiao Ou. AU - Xie, Lin. AU - Jin, Kunlin. PY - 2012/10/26. Y1 - 2012/10/26. N2 - Depletion of neurogenesis worsens functional outcome in young-adult mice after focal cerebral ischemia, but whether a similar effect occurs in older mice is unknown. Using middle-aged (12-month-old) transgenic (DCX-TK(+)) mice that express herpes simplex virus thymidine kinase (HSV-TK) under control of the doublecortin (DCX) promoter, we conditionally depleted DCX-positive cells in the subventricular zone (SVZ) and hippocampus by treatment with ganciclovir (GCV) for 14 days. Focal cerebral ischemia was induced by permanent occlusion of the middle cerebral artery (MCAO) or occlusion of the distal segment of middle cerebral artery (dMCAO) on day 14 of vehicle or GCV treatment and mice were killed 24 hr or 12 weeks later. Increased infarct volume ...
Objective: Neural stem cells (NSC) have an inherent brain tumor tropism that can be exploited for targeted delivery of therapeutic genes to invasive gliomas. Here, we demonstrate that the non-invasive intranasal administration of tumor-targeting NSC is able to deliver a novel suicide gene (TK007) to intracerebrally growing human glioblastoma xenografts.. Method: Murine NSC were genetically modified to express the novel herpes simplex virus thymidine kinase variant (TK007). The biological activity of the NSC-mediated TK007/ganciclovir (GCV) system was assessed in cell survival and bystander assays using various human glioma cell lines. Therapeutic effects of intratumoral (3x105 cells) and intranasal (1.5x106) NSC-TK007 application alone and the sequential combination of both was tested using an intracranial U87 human glioblastoma model in nude mice. All animals received 50 mg/kg GCV i.p. for five consecutive days. Two control groups received either NaCl instead of GCV or NSC containing the empty ...
Preferred Name: Valacyclovir Definition: The hydrochloride salt of the L-valyl ester of the antiviral drug acyclovir. Orally administered, valacyclovir is rapidly converted to acyclovir which inhibits viral DNA replication after further conversion to the nucleotide analog acyclovir triphosphate by viral thymidine kinase, cellular guanyl cyclase, and a number of other cellular enzymes. Acyclovir triphosphate competitively inhibits viral DNA polymerase; incorporates into and terminates the growing viral DNA chain; and inactivates viral DNA polymerase. The greater antiviral activity of acyclovir against herpes simplex virus (HSV) compared with varicella-zoster virus (VZV) is due to its more efficient phosphorylation by HSV thymidine kinase. NCI-GLOSS Definition: A substance that is being studied in the prevention of fungal, bacterial, and viral infections in patients undergoing donor stem cell transplantation with cells that are infected with cytomegalovirus. It belongs to the family of drugs ...
Glioblastoma is a highly aggressive malignant tumor involving glial cells in the human brain. We used high-throughput sequencing to comprehensively profile the small RNAs expressed in glioblastoma and non-tumor brain tissues. MicroRNAs (miRNAs) made up the large majority of small RNAs, and we identified over 400 different cellular pre-miRNAs. No known viral miRNAs were detected in any of the samples analyzed. Cluster analysis revealed several miRNAs that were significantly down-regulated in glioblastomas, including miR-128, miR-124, miR-7, miR-139, miR-95, and miR-873. Post-transcriptional editing was observed for several miRNAs, including the miR-376 family, miR-411, miR-381, and miR-379. Using the deep sequencing information, we designed a lentiviral vector expressing a cell suicide gene, the herpes simplex virus thymidine kinase (HSV-TK) gene, under the regulation of a miRNA, miR-128, that was found to be enriched in non-tumor brain tissue yet down-regulated in glioblastomas, Glioblastoma cells
Thymidine kinase (TK) belongs to the group of oncofetal enzymes. It catalyzes thymidine transformation to thymidine monophosphate in the presence of ATP. Elevated serum levels of TK can be found above all in the acute stages of malignant diseases of the hematopoietic system, in the bronchoendogenic carcinoma, carcinoma of the prostate, testis, and bladder.. ...
ID PCP1 preliminary; circular DNA; SYN; 3600 BP. XX AC S62800; ATCC37351; XX DT 01-JUL-1993 (Rel. 7, Created) DT 01-JUL-1995 (Rel. 12, Last updated, Version 1) XX DE Vertebrate/E.coli plasmid vector pCP1 - incomplete. XX KW cloning vector. XX OS Cloning vector OC Artificial sequences; Cloning vehicles. XX RN [1] RC plasmid from pUC9 & vaccinia virus 7.5kDa gene RC pCP1 from pCAT & plasmid RC pMM24 from pMM23 & SV40 72-bp repeats RA Cochran M.A., Mackett M., Moss B.; RT Eukaryotic transient expression system dependent on transcription RT factors and regulatory DNA sequences of vaccinia virus; RL Proc. Natl. Acad. Sci. U.S.A. 82:19-23(1985). XX RN [2] RC plasmid from pBR328 RC pGS8 from plasmid & vaccinia virus TK gene RC pMM1 from pUC9 & vaccinia virus TK gene RC pMM2 from pUC9 & vaccinia virus TK gene RC pMM3 from pMM1 & pMM2 RC pMM4 from pMM3 RC pMM5 from pMM4 RC pGS15 from pUC9 & pAG4 RC pGS19 from pGS15 & linker RC pGS20, pGS21 from pGS19 & pGS8 RC [pGS30 from cat gene] RC pCAT from pBR328 ...
The bystander effect refers to the death of unmodified tumor cells when in contact with ganciclovir (GCV)-exposed, herpes simplex virus-thymidine kinase (HSV-TK)-modified tumor cells. Although the exact mechanism or mechanisms involved in mediating the bystander effect in vivo are unknown, our fin …
Reliable markers for monitoring bladder tumor therapy are needed to evaluate treatment effectiveness. Thymidine kinase 1 (TK1) is an enzyme involved in DNA synthesis and therefore proliferation-dependent. Serum concentration of TK1 (STK1) correlates with malignancy in various types of cancer, thus reflecting treatment results. This study explores for the first time the use of STK1 concentration, both as a prognostic marker and to monitor the outcome of bladder carcinoma surgery. STK1 in 56 bladder carcinoma patients was measured pre-operatively, and post-operatively at 1 week and 1, 3, and 6 months, using an immune ECL dot blot assay. An anti-TK1 chicken IgY antibody was used to determine STK1 concentrations. Mean pre-operative STK1 of bladder carcinoma patients was significantly higher than that of healthy individuals, with no overlap of individual values. STK1 concentrations increased significantly with tumor stage (I-III) and T-values (T1-T2), but not tumor grade (G1-G4). STK1 gradually ...
In the stab-injured spinal cord of GFAP-TK mice not given GCV, we found that all TK-expressing cells also expressed GFAP, and that ,98%, but not all, of GFAP-expressing reactive astrocytes also expressed detectable levels of transgene-derived TK (Fig. 2A-D,G). The inability to detect TK in all GFAP-expressing cells may be attributable to the discontinuous activity of the GFAP gene and differences in the intracellular half-life of the GFAP and TK proteins, as discussed elsewhere (Bush et al., 1999; Imura et al., 2003). We found no evidence for TK expression by cells that did not express GFAP.. To evaluate the degree of astrocyte cell division induced by SCI, we administered BrdU during the first 4 d after injury (Fig. 1A). At 14 d after injury, control mice exhibited many BrdU-labeled cells in tissue immediately adjacent to the stab wound (Fig. 2E,F); most of these BrdU-labeled cells expressed GFAP (Fig. 2H) and TK.. There was no qualitatively detectable difference in the response to SCI in all ...
AVIRAX Fabrigen Acyclovir Antiviral Action And Clinical Pharmacology: Acyclovir, a synthetic acyclic nucleoside analog, is a substrate with a high degree of specificity for herpes simplex and varicella-zoster specified thymidine kinase. Acyclovir is a poor substrate for host cell-specified thymidine kinase. Herpes simplex and varicella-zoster specified thymidine kinase transform acyclovir to its monophosphate which is then transformed by a number of cellular enzymes to acyclovir diphosphate and acyclovir triphosphate. Acyclovir triphosphate is both an inhibitor of, and a substrate for, herpesvirus-specified DNA polymerase. Although the cellular a-DNA polymerase in infected cells may also be inhibited by acyclovir triphosphate, this occurs only at concentrations of acyclovir triphosphate which are higher than those which inhibit the herpesvirus-specified DNA polymerase. Acyclovir is selectively converted to its active form in herpesvirus-infected cells and is thus preferentially taken up by these ...
The nucleotide sequence of the UL31 open reading frame is predicted to encode a basic protein with a hydrophilic amino terminus and a nuclear localization signal. To identify its gene product, we constructed a viral genome in which the thymidine kinase gene was inserted between the UL31 and UL32 open reading frames. The thymidine kinase gene was then deleted, and in the process, the 5 terminus of the UL31 open reading frame was replaced with a 64-bp sequence in frame with the complete, authentic sequence of the UL31 open reading frame. The inserted sequence encoded a hydrophilic epitope derived from glycoprotein B of human cytomegalovirus and for which a monoclonal antibody is available. We report that in infected cells, the tagged protein localized in and was dispersed throughout the nucleus. Nuclear fractionation studies revealed that the UL31 protein partitions with the nuclear matrix. The protein is phosphorylated in infected cells maintained in medium containing 32Pi. ...
The test substance was tested in an Ames test at concentrations up to the precipitation level (5000 ug/plate). In a plate incorporation and a pre-incubation assay (both performed in triplicate), the test substance did not induce mutations (base-pair substitution and frame-shift type) in Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537, as well as in E. coli WP2 uvr A both in presence and absence of metabolic activation (Harlan 2013j). The analogue is considered to be non mutagenic in the mouse lymphoma thymidine kinase locus using the cell line L5178Y (BSL2010e) and no chromosomal changes were observed in a chromosome aberration test in Chinese hamster lung fibroblasts (V79) (BSL 2010d). Both tests were performed in presence and absence of metabolic activation. Based on the similar outcome in the Ames test and the similarities between the test substance and the analogue, it is concluded that it is not expected that the test substance will induce mutagenic or clastogenic effects. No ...
A valid GLP study was performed to investigate the potential of the test item to induce mutations at the mouse lymphoma thymidine kinase locus using the cell line L5178Y. The method followed was that described in OECD TG 476. The assay was performed in three independent experiments, using two parallel cultures each. Experiment I, and II were performed with and without liver microsomal activation and a treatment period of 4 hours. The supplementary experiment III was solely performed with metabolic activation (4 hours treatment) to cover the cytotoxic range of approximately 10- 20% RTG that was not covered in the second experiment with metabolic activation. The concentration range of the main experiments was limited by the solubility of the test item in aqueous media and by cytotoxic effects. Relevant cytotoxic effects occurred at 40 µg/mL in the first experiment without metabolic activation and at 80.0 µg/mL in the presence of metabolic activation. In the second experiment cytotoxicity was ...
DiviTum™ assay determines the enzymatic activity of TK in patient samples. During the assay procedure, thymidine is replaced by its synthetic analog bromodeoxyuridine (BrdU), which gets phosphorylated and then incorporated into a synthetic DNA strand fixated in each well of a 96-well ELISA immunosorbent titer-plate.. The extent of BrdU incorporation depends on the activity of TK present in the serum sample; the more TK activity in the sample, the more BrdU is incorporated into synthetic DNA strands in the titer-plate well. The synthetic BrdU is then detected with anti-BrdU specific antibodies using the well-known ELISA assay technique. The DiviTum™ technology amplifies the signal, enabling the assay to measure thymidine kinase activity with high sensitivity.. ...
G207, a mutant herpes simplex virus (HSV) type 1, is safe when inoculated into recurrent malignant glioma. We conducted a phase 1 trial of G207 to demonstrate the safety of stereotactic intratumoral administration when given 24 hours prior to a single 5 Gy radiation dose in patients with recurrent m …
An enzyme (abbreviated tk) which plays an important role in the making of thymidine triphosphate from thymine -- the only way thymine, cytosine, and oth...
Acyclovir, famciclovir, and ganciclovir are guanosine analogs that are used as viral DNA polymerase inhibitors to treat HSV, VZV, and EBV. The three analogs require phosphorylation for activation. The first step in phosphorylation is monophosphorylation by the HSV/VZV thymidine kinase; further phosphorylation is then performed by the host cells to form the triphosphate. Finally, the drug is incorporated into the viral DNA molecule, terminating replication. Resistance arises when the virus lacks thymidine kinase and these analogs cannot be activated; therefore, cidofovir, which does not require phosphorylation by a viral kinase, must be used ...
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The GMO is a viral suspension of the recombinant virus JX-594. JX-594 is a non-integrative, replicative, propagative, recombinant VV derived from the commonly used commercial vaccine Wyeth strain. JX-594 differs by three genetic modifications from the wild type Wyeth strain: 1) disruption of the viral thymidine kinase (TK) gene by, 2) insertion of the human granulocyte macrophage-colony stimulating factor (hGM-CSF) gene and 3) insertion of the lacZ gene. ...
EBV and KSHV are associated with a variety of malignancies including some lymphomas, carcinomas and other malignancies. We anticipate that viral TK expression will differ among tumor types and will be adjusted with standard chemotherapies and some investigational agents. This exploratory study is aimed in part at evaluating whether standard regimens or investigational regimens might bring about sufficient activation of the EBV-TK or KSHV-TK in tumors to be therapeutically useful if used in conjunction with FIAU as a radiopharmaceutical ...
EBV and KSHV are associated with a variety of malignancies including some lymphomas, carcinomas and other malignancies. We anticipate that viral TK expression will differ among tumor types and will be adjusted with standard chemotherapies and some investigational agents. This exploratory study is aimed in part at evaluating whether standard regimens or investigational regimens might bring about sufficient activation of the EBV-TK or KSHV-TK in tumors to be therapeutically useful if used in conjunction with FIAU as a radiopharmaceutical ...
Beta-catenin/Tcf reporter mice. These mice express GFP gene under the control of the Tcf/Lef binding sites and a minimal thymidine kinase promoter from the TOPFLASH plasmid. Immunohistochemistry with a GFP antibody can be used to assess the Tg expression in the intestine. In other organs except for the intestine. In the splenocytes, expression of GFP was observed by FACS analysis, In other organs, the GFP expression patterns are not examined yet ...
SWISS-MODEL Template Library (SMTL) entry for 1qhi.1. HERPES SIMPLEX VIRUS TYPE-I THYMIDINE KINASE COMPLEXED WITH A NOVEL NON-SUBSTRATE INHIBITOR, 9-(4-HYDROXYBUTYL)-N2-PHENYLGUANINE
In anticipation of a phase I clinical trial in GBM patients using an immunotherapeutic approach that combines Ad-Flt3L with Ad-TK+GCV, it was critical to determine the optimal cytotoxic agent to use in this approach. Therefore, we compared the efficacy and neurotoxicity of Ad-TK+GCV with Ad vectors encoding the proapoptotic cytokines TNF-α, TRAIL, and FasL. Our hypothesis was that Ad-TK+GCV would exhibit superior efficacy and safety when compared with Ads expressing proapoptotic cytokines. Because Ad-TK kills proliferating cells in the presence of GCV (37), we expected this agent to have a powerful antitumor effect due to the presence of mitotic tumor cells within GBM. Also, the bystander effect of phosphorylated GCV would amplify the cytotoxic effect of this approach (37). The highest therapeutic efficacy was indeed achieved when using Ad-TK+GCV by itself for small tumors, and in combination with Ad-Flt3L for large tumors. Although all the proapoptotic Ads certainly induced apoptosis in vitro ...
Studying the biochemical determinants of FUra efficacy is still a major concern of todays chemotherapy (19, 20). Among the numerous factors likely to improve cell sensitivity, the role of tumoral enzymes involved in the conversion of prodrug FUra into active metabolites has been studied extensively. Because tumor response to fluoropyrimidines is multifactorial, determining a single marker of FUra efficiency remains hazardous and is often prone to controversy, even in vitro. For example, the activity of TK has been presented as a key determinant of response to FUra (21-23), whereas other studies have correlated high TK activity with resistance to fluoropyrimidine (24, 25), a fact that we experienced as well after transfecting the viral HSV1-TK gene into HT29 cells.4 Similarly, although UP has been described as an important enzyme responsible for FUra anabolism in several models (26), an attempt to modulate drug response after human UP transfection into MCF7 cells in our laboratory failed to ...
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The MTKP 97-12 cell line was produced by transfecting LMTK- cells with the expression plasmid pMTp97b that contains a cDNA sequence coding for the p97 melanoma associated antigen.
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... 1 Thymidine kinase from herpesvirus Thymidylate kinase Nucleoside-diphosphate kinase Thymidylate synthase ... Thymidine kinase is an enzyme, a phosphotransferase (a kinase): 2'-deoxythymidine kinase, ATP-thymidine 5'-phosphotransferase, ... One difficulty is that the poxvirus thymidine kinase belongs to the same family of thymidine kinases as the human thymidine ... Thymidine kinase 1 is such a salvage enzyme, whereas thymidine kinase 2 and thymidylate synthase are not cell cycle-dependent. ...
In enzymology, an ADP-thymidine kinase (EC 2.7.1.118) is an enzyme that catalyzes the chemical reaction ADP + thymidine ⇌ {\ ... displaystyle \rightleftharpoons } AMP + thymidine 5'-phosphate Thus, the two substrates of this enzyme are ADP and thymidine, ... The systematic name of this enzyme class is ADP:thymidine 5'-phosphotransferase. Other names in common use include ADP:dThd ... Falke D, Labenz J, Brauer D, Muller WE (1982). "Adenosine diphosphate: thymidine 5'-phosphotransferase, a new enzyme activity, ...
In enzymology, an AMP-thymidine kinase (EC 2.7.1.114) is an enzyme that catalyzes the chemical reaction AMP + thymidine ⇌ {\ ... the two substrates of this enzyme are AMP and thymidine, whereas its two products are adenosine and thymidine 5'-phosphate. ... The systematic name of this enzyme class is AMP:thymidine 5'-phosphotransferase. This enzyme is also called adenylate- ... Falke D, Labenz J, Brauer D, Muller WE (1982). "Adenosine diphosphate: thymidine 5'-phosphotransferase, a new enzyme activity, ...
... , soluble (gene name TK1), is a human thymidine kinase. Two forms of this protein have been identified in ... "Entrez Gene: Thymidine kinase 1, soluble". Huang DY, Chang ZF (June 2001). "Interaction of human thymidine kinase 1 with p21( ... "Co-purification of thymidylate kinase and cytosolic thymidine kinase from human term placenta by affinity chromatography". ... Thymidine kinase 1 has been shown to interact with P21. Click on genes, proteins and metabolites below to link to respective ...
... is a sub-family of thymidine kinases. Its presence in herpesvirus-infected cells is used to ... August 1998). "Exploring the active site of herpes simplex virus type-1 thymidine kinase by X-ray crystallography of complexes ... Trifluridine Brivudine Mutations in the gene coding thymidine kinase in herpes viruses can endow the virus with resistance to ... "Crystal structures of the thymidine kinase from herpes simplex virus type-1 in complex with deoxythymidine and ganciclovir". ...
... ". Zeman L, Lusena CV (March 1974). "DNA precursors and the absence of thymidine kinase in ... Thymidine kinase 2, mitochondrial is a protein that in humans is encoded by the TK2 gene. This gene encodes a ... This kinase is not present in yeast. GRCh38: Ensembl release 89: ENSG00000166548 - Ensembl, May 2017 GRCm38: Ensembl release 89 ... deoxyribonucleoside kinase that specifically phosphorylates thymidine, deoxycytidine, and deoxyuridine. The encoded enzyme ...
Thymidine kinase 1 is such a salvage enzyme, whereas thymidine kinase 2 is not cell cycle-dependent. Thymidine kinase is a ... Thymidine kinase is an enzyme, a phosphotransferase (a kinase): 2'-deoxythymidine kinase, ATP-thymidine 5'-phosphotransferase, ... Thymidine kinase Thymidylate kinase Nucleoside diphosphate kinase Thymidylate synthase Thymidine O'Neill KL, Buckwalter M, ... "Comparative study of the thymidine kinase and thymidylate kinase activities and of the feedbach inhibition of thymidine kinase ...
"Thymidine kinase". Medical Dictionary. Merriam-Webster. Retrieved 5 April 2013. Gentry GA (1992). "Viral thymidine kinases and ... encoding a thymidine kinase suicide gene, has progressed to phase III clinical trials. The herpes simplex virus thymidine ... The enzymes thymidine kinase and ribonucleotide reductase in cells are responsible for DNA synthesis and are only expressed in ... kinase phosphorylates the pro-drug, ganciclovir, which is then incorporated into DNA, blocking DNA synthesis. The tumour ...
Signal transduction Thymidine kinase Thymidine kinase in clinical chemistry Thymidylate kinase Wall-associated kinase Siebold C ... Kinases are classified into broad groups by the substrate they act upon: protein kinases, lipid kinases, carbohydrate kinases. ... It phosphorylates thymidine to create thymidine monophosphate (dTMP). This kinase uses an ATP molecule to supply the phosphate ... Thymidine kinase is one of the many nucleoside kinases that are responsible for nucleoside phosphorylation. ...
replacement of thymidine kinase (TK)). RCN was successful in 50% of voluntary participants allowing them to survive subsequent ...
Gentry GA (1992). "Viral thymidine kinases and their relatives". Pharmacology & Therapeutics. 54 (3): 319-55. doi:10.1016/0163- ...
Thymidine can be phosphorylated by thymidine kinase (TK). Uridine can be phosphorylated by uridine kinase (UK). Cytidine can be ... Deoxycytidine can be phosphorylated by deoxycytidine kinase (DCK). Adenosine uses the enzyme adenosine kinase, which is a very ...
Huang DY, Chang ZF (June 2001). "Interaction of human thymidine kinase 1 with p21(Waf1)". Biochem. J. 356 (Pt 3): 829-34. doi: ... Cyclin-Dependent+Kinase+Inhibitor+p21 at the US National Library of Medicine Medical Subject Headings (MeSH) Drosophila dacapo ... Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R, Beach D (1993). "p21 is a universal inhibitor of cyclin kinases". Nature. ... p21 is a potent cyclin-dependent kinase inhibitor (CKI). The p21 (CIP1/WAF1) protein binds to and inhibits the activity of ...
"Extending thymidine kinase activity to the catalytic repertoire of human deoxycytidine kinase". Biochemistry. 48 (6): 1256-63. ... Saada A, Shaag A, Mandel H, Nevo Y, Eriksson S, Elpeleg O (November 2001). "Mutant mitochondrial thymidine kinase in ... Cytidylate kinase or UMP-CMP kinase then adds the second phosphoryl group to form dFdCDP (gemcitabine diphosphate form), which ... Nucleoside-diphosphate kinase or nucleoside kinase A adds the third phosphoryl group to form dFdCTP (gemcitabine triphosphate ...
Thymidine kinase Thymidylate synthase Thymidine kinase in clinical chemistry Li C, Huang SH, Tang A, Drisco B, Zhang SQ, Seeger ... Thymidylate kinase (EC 2.7.4.9; dTMP kinase) catalyzes the phosphorylation of thymidine 5'-monophosphate (dTMP) to form ... thymidine 5'-phosphate ⇌ {\displaystyle \rightleftharpoons } ADP + thymidine 5'-diphosphate Thymidylate kinase is a ubiquitous ... Nelson DJ, Carter CE (1969). "Purification and characterization of Thymidine 5-monophosphate kinase from Escherichia coli B". J ...
"Induction of endogenous virus and of thymidine kinase by bromodeoxyuridine in cell cultures transformed by Friend virus". ... Induction of Endogenous Virus and of Thymidline Kinase. "Induction of Endogenous Virus and of Thymidline Kinase by ... "Identification and Characterization of Mitochondrial Factors Modulating Thymidine Kinase 2 Activity". Nucleosides, Nucleotides ... AZT is a thymidine analogue. AZT works by selectively inhibiting HIV's reverse transcriptase, the enzyme that the virus uses to ...
... the first betaherpesvirus with a thymidine kinase gene". Journal of General Virology. 87 (Pt 10): 2781-2789. doi:10.1099/vir. ...
Pellicer, A; Wigler, M; Axel, R; Silverstein, S (1978). "The transfer and stable integration of the HSV thymidine kinase gene ... "Transfer of purified herpes virus thymidine kinase gene to cultured mouse cells". Cell. 11 (1): 223-32. doi:10.1016/0092-8674( ...
In gene-deleted vaccines, the thymidine kinase gene has also been deleted; thus, the virus cannot infect and replicate in ...
Hamel, W; Magnelli, L; Chiarugi, VP; Israel, MA (June 1996). "Herpes simplex virus thymidine kinase/ganciclovir-mediated ... "Bystander killing of cancer cells by herpes simplex virus thymidine kinase gene is mediated by connexins". Proceedings of the ... of the herpes simplex virus thymidine kinase/ganciclovir system in vitro". Gene Ther. 3 (1): 85-92. PMID 8929915. Mesnil, Marc ...
An example would be thymidine kinase, which makes the host sensitive to ganciclovir selection. A distinction can be made ...
An example would be thymidine kinase, which makes the host sensitive to ganciclovir selection.[citation needed] Positive and ...
Griffiths A (December 2011). "Slipping and sliding: frameshift mutations in herpes simplex virus thymidine kinase and drug- ...
Viral proteins like viral thymidine kinase can be used for specific targeting of a drug. By introducing a prodrug only ... Glycogen synthase kinase 3 (GSK3) seems to be over-expressed in most cancer cells. GSK3 is involved in promoter activation ... kinase/Akt, heat shock protein 90, and mammalian target of rapamycin in transformed NK cells". Journal of Immunology. 174 (9): ...
FLT accumulates in proliferating cells where it indicates the activity of the enzyme thymidine kinase. Cell division can be ... FLT is phosphorylated as though it were thymidine, and is subsequently incorporated into DNA. Thymidine is essential for DNA ...
Thymidine kinase can then phosphorylate the 5'-carbon of this compound into thymidine monophosphate (TMP). Thymidylate kinase ... Uridine kinase (aka uridine-cytidine kinase) can then phosphorylate the 5'-carbon of this nucleoside into uridine monophosphate ... can phosphorylate TMP into thymidine diphosphate, which nucleoside diphosphate kinase can phosphorylate into thymidine ... which nucleoside diphosphate kinase can phosphorylate into uridine triphosphate. Thymidine phosphorylase or pyrimidine- ...
"Deoxyribonucleoside kinases in two aquatic bacteria with high specificity for thymidine and deoxyadenosine". FEMS Microbiology ... Several GST isozymes from various classes have been shown to inhibit the function of a kinase involved in the MAPK pathway that ... it is also supported by the fact that the transformed phenotype of tumor cells is associated with aberrantly regulated kinase ... regulates cell proliferation and death, preventing the kinase from carrying out its role in facilitating the signaling cascade ...
HSV or CMV particles can develop mutant protein kinases (thymidine kinase or UL97 protein kinase, respectively) that make them ... Frobert, E.; Ooka, T.; Cortay, J. C.; Lina, B.; Thouvenot, D.; Morfin, F. (March 2005). "Herpes Simplex Virus Thymidine Kinase ... However, unlike acyclovir and ganciclovir, foscarnet is not activated by viral protein kinases, making it useful in acyclovir- ... 2007). "Long-term foscarnet therapy remodels thymidine analogue mutations and alters resistance to zidovudine and lamivudine in ...
In this case the study uses the transfer of the Herpes simplex virus type I thymidine kinase (HSVtk) as the cytotoxic gene. ... "Bystander killing of cancer cells by herpes simplex virus thymidine kinase gene is mediated by connexins". Proceedings of the ...
CSF gene and deletion of the thymidine kinase gene which limits viral replication to cells with high levels of thymidine kinase ... Pexa-Vec has cancer selectivity through the deactivation of its thymidine kinase gene, and it has been engineered to express ... JX-929's tumor selectivity has been optimized through deletion of thymidine kinase and vaccinia growth factor. JX-929 has been ... thymidine kinase and vaccinia growth factor gene inactivation JX-929 (vvDD expressing CD for 5-FU pro-drug) experience in solid ...
Activation of E2F results in transcription of various genes like cyclin E, cyclin A, DNA polymerase, thymidine kinase, etc. ... Norbury C (1995). "Cdk2 protein kinase (vertebrates)". In Hardie DG, Hanks S (eds.). Protein kinase factsBook. Boston: Academic ... Additionally, CDK4/6 and CDK2 are also inactive because CDK4/6 are bound by INK4 family members (e.g., p16), limiting kinase ... Two families of genes, the cip/kip (CDK interacting protein/Kinase inhibitory protein) family and the INK4a/ARF (Inhibitor of ...
Protein kinases can also be inhibited by competition at the binding sites where the kinases interact with their substrate ... Methotrexate blocks the action of dihydrofolate reductase and thereby halts thymidine biosynthesis. This block of nucleotide ... Hence kinase inhibitors such as imatinib are frequently used to treat malignancies. Janus kinases are another notable example ... A notable class of kinase drug targets is the receptor tyrosine kinases which are essential enzymes that regulate cell growth; ...
The mitochondrial DNA base composition is thought to reflect its nucleotide-specific (guanine, cytosine, thymidine and adenine ... orchestrate DNA duplex opening and damage verification to coordinate repair with transcription and cell cycle via CAK kinase". ...
... with an inactive thymidine kinase gene. The preclinical pipeline of Genelux includes numerous genetically modified vaccinia ...
A protein kinase drifting around on the outer chloroplast membrane can use ATP to add a phosphate group to the Toc34 protein, ... List of sequenced plastomes Mitochondrial DNA Stocking, C. R. & Gifford, E. M. (1959). "Incorporation of thymidine into ... It can be regulated through phosphorylation, but by a different protein kinase than the one that phosphorylates Toc34. Its M- ...
... general anamnesis is combined with complete blood count and determination of lactate dehydrogenase or thymidine kinase in serum ...
Aciclovir acts as a nucleoside analog which specifically target herpes virus-infected cells using viral thymidine kinase (TK). ... Reactivation in HSV requires the stress response enzyme c-Jun N-terminal kinase (JNK), which is responsive to stressors such as ... which is subsequently phosphorylated to active aciclovir triphoshate by cellular kinases, thus selectively inhibiting viral DNA ...
... including thymidine kinase deficient (TK) and thymidylate synthase deficient (TS) were used in order to determinate the ...
Tseng CC, Zhang XY (2000). "Role of G protein-coupled receptor kinases in glucose-dependent insulinotropic polypeptide receptor ... Ding KH, Zhong Q, Isales CM (2003). "Glucose-dependent insulinotropic peptide stimulates thymidine incorporation in endothelial ...
... methanocarbathymidine that specifically inhibits growth of herpes simplex virus type 1 thymidine kinase-transduced osteosarcoma ...
... researchers were able to insert a herpes simplex virus thymidine kinase coding gene into tumor cells. This "suicide gene" is ...
... while thymidine is phosphorylated by thymidine kinase (TK); both HGPRT and TK are enzymes of the salvage pathway. On a HAT ... However, normal human and mouse cells can still multiply as they can utilize hypoxanthine and thymidine present in the medium ... This medium is supplemented with hypoxanthine, aminopterin and thymidine, hence the name HAT medium. Antimetabolite aminopterin ...
... in conjunction with the mitochondrial thymidine kinase, as part of the thymidine (dTTP)/dTMP substrate cycle. Since excess dTTP ... These treatments rely on the kinase activation of the analogs, which then are incorporated into the DNA of the tumor cell or ...
For example, a commonly studied strategy based on transfection of herpes simplex virus thymidine kinase (HSV-TK) along with ... Main mechanisms inducing cancer cells' deaths include: transgenic expression of thymidine kinases, cytosine deaminases, ...
Herpes simplex virus thymidine kinase (HSV-TK) and inducible caspase 9 (iCasp9) are two types of suicide genes that have been ...
The HSV virus used as an oncolytic virus has retained their native thymidine kinase gene which allows it to be targeted with ...
Signal transduction Thymidine kinase Thymidine kinase in clinical chemistry Thymidylate kinase Wall-associated kinase Walker JE ... Activation loop Autophosphorylation Ca2+/calmodulin-dependent protein kinase Cell signaling Cyclin-dependent kinase G protein- ... coupled receptor Nucleoside-diphosphate kinase Phosphatase Phosphatidylinositol phosphate kinases Phospholipid Phosphoprotein ... kinases and other ATP-requiring enzymes and a common nucleotide binding fold". The EMBO Journal. 1 (8): 945-51. doi:10.1002/j. ...
... thymidine and adenosine:[citation needed] Thymidine analogues: zidovudine (AZT) and stavudine (d4T) Cytidine analogues: ... This phosphorylation step is carried out by cellular kinase enzymes. NRTIs can induce mitochondrial impairment that leads to a ... Excision enhancement mutations, typically M41L, D67N, K70R, L210W, T215Y/F, and K219E/Q, are selected for by thymidine analogs ... AZT and D4T; and are therefore called thymidine analog mutations (TAMs). Other mutations including insertions and deletions in ...
... by a viral enzyme called thymidine kinase (TK), to which the drug has a high affinity (attraction). Phosphorylation by either ... Other articles where thymidine kinase is discussed: acyclovir: … ... by a viral enzyme called thymidine kinase (TK), to which the drug has a high affinity (attraction). Phosphorylation by either ...
section IV supra) disclosed a gene for rice thymidine kinase. Thus, the concept of a plant thymidine kinase was already ... iv) an isolated polynucleotide encoding a thymidine kinase enzyme derived from a plant, which thymidine kinase enzyme has a ... ii) an isolated polynucleotide encoding a thymidine kinase enzyme derived from a plant, which thymidine kinase enzyme, when ... iii) an isolated polynucleotide encoding a thymidine kinase enzyme derived from a plant, which thymidine kinase enzyme is ...
... deoxythymidine kinase, ATP-thymidine 5-phosphotransferase. Thymidine kinase is found in most living cells. Thymidine kinase is ... Thymidine kinase 2 mitochondrial, Mt-TK, TK2, MTTK, MTDPS2.. Introduction. Thymidine kinase 2 mitochondrial (TK2) is a member ... Thymidine kinases have a central function in the synthesis of DNA and thus in cell division, since they are part of the ... TK2 is a deoxyribonucleoside kinase which specifically phosphorylates thymidine, deoxycytidine, and deoxyuridine. TK2 localizes ...
Crystal structure of thymidine kinase from herpes simplex virus type 1 in complex with Me-ARA-EdU ... Thymidine kinase. A, B. 332. Human alphaherpesvirus 1 strain 17. Mutation(s): 0 Gene Names: TK, TK (UL23), UL23. EC: 2.7.1.21. ... Crystal structure of thymidine kinase from herpes simplex virus type 1 in complex with Me-ARA-EdU. *PDB DOI: 10.2210/pdb4OQX/ ...
Coexpression of Herpesviral Thymidine Kinase Reporter Gene and VEGF Gene for Noninvasive Monitoring of Therapeutic Gene ... Coexpression of Herpesviral Thymidine Kinase Reporter Gene and VEGF Gene for Noninvasive Monitoring of Therapeutic Gene ... Coexpression of Herpesviral Thymidine Kinase Reporter Gene and VEGF Gene for Noninvasive Monitoring of Therapeutic Gene ... Coexpression of Herpesviral Thymidine Kinase Reporter Gene and VEGF Gene for Noninvasive Monitoring of Therapeutic Gene ...
Noninvasive imaging of herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene expression is possible with a clinical gamma ... Noninvasive Imaging of Herpes Virus Thymidine Kinase Gene Transfer and Expression: A Potential Method for Monitoring Clinical ... Noninvasive Imaging of Herpes Virus Thymidine Kinase Gene Transfer and Expression: A Potential Method for Monitoring Clinical ...
Combination gene delivery of the cell cycle inhibitor p27 with thymidine kinase enhances prodrug cytotoxicity. In: Journal of ... Combination gene delivery of the cell cycle inhibitor p27 with thymidine kinase enhances prodrug cytotoxicity. Journal of ... Cytoxicity induced by the herpesvirus thymidine kinase (TK) gene in combination with prodrugs is dependent on cell growth and ... Dive into the research topics of Combination gene delivery of the cell cycle inhibitor p27 with thymidine kinase enhances ...
... thymidine 5-phosphotransferase, EC 2.7.1.21) gene has been cloned in Escherichia coli. A recombinat plasmid, pFG5, has been ... A herpes simplex virus DNA fragment that is produced by digestion with BamHI endonuclease and carries the thymidine kinase (TK ... Cloning of the active thymidine kinase gene of herpes simplex virus type 1 in Escherichia coli K-12. F. Colbere-Garapin 1, * S ... Cloning of the active thymidine kinase gene of herpes simplex virus type 1 in Escherichia coli K-12.. Proceedings of the ...
In this paper we present the nucleotide sequences of the thymidine kinase (TK) genes of two avian herpesviruses: a highly ... Nucleotide and Predicted Amino Acid Sequences of the Mareks Disease Virus and Turkey Herpesvirus Thymidine Kinase Genes; ... Comparison with Thymidine Kinase Genes of Other Herpesviruses. Journal of General Virology, 70 (11). pp. 3055-3065. ISSN 0022- ... Nucleotide and Predicted Amino Acid Sequences of the Mareks Disease Virus and Turkey Herpesvirus Thymidine Kinase Genes; ...
Mutation of Gln125 to Asn Selectively Abolishes the Thymidylate Kinase Activity of Herpes Simplex Virus Type 1 Thymidine Kinase ... Mutation of Gln125 to Asn Selectively Abolishes the Thymidylate Kinase Activity of Herpes Simplex Virus Type 1 Thymidine Kinase ...
Amplification of plasmid copy number by thymidine kinase expression in Saccharomyces cerevisiae ... Amplification of plasmid copy number by thymidine kinase expression in Saccharomyces cerevisiae ...
... suicide gene/prodrug systems consisting of herpes simplex virus thymidine kinase plus ganciclovir and hyperthermia were the ...
The TK2 gene provides instructions for making an enzyme called thymidine kinase 2 that functions within cell structures called ... Munch-Petersen B. Enzymatic regulation of cytosolic thymidine kinase 1 and mitochondrial thymidine kinase 2: a mini review. ... Thymidine kinase 2 is involved in the production and maintenance of mtDNA. Specifically, this enzyme plays a role in recycling ... Gotz A, Isohanni P, Pihko H, Paetau A, Herva R, Saarenpaa-Heikkila O, Valanne L, Marjavaara S, Suomalainen A. Thymidine kinase ...
Home , Resources , Infographics , AroCell and Corgenix establish the measurement of Thymidine Kinase. ... AroCell and Corgenix establish the measurement of Thymidine Kinase.. April 15, 2019 ...
Thymidine kinase. U94848. P: 5´-CGTATGGCAAACGAAGGAAAAATAGTTATAGTAGCCGCACTCGATGGGAC-3´ F: 5´-ATTCTGTGAGCGTATGGCAA-3´; R: 5´- ...
... dc.rights.license. Restricted to current Rensselaer ... The thymidine kinases of uninduced and induced Raji cells did not use CTP were not affected by EBV antiserat and were ... Two HSV-2 transformed cell lines showed no evidence of any viral thymidine kinase when tested for their CTP specificity or ... When ATP was omitted from the reaction mixture used in the thymidirte kinase assay, no thymidine monophosphate was formed by ...
Dog Thymidine Kinase (TK1) ELISA Kit. Catalogue Numbre: E-40TK, Supplied by Immunology Consultatnt Laboratory& Distributed by ... Dog Thymidine Kinase (TK1) ELISA Kit , E-40TK Immunology Consultant Laboratory Dog Thymidine Kinase (TK1) ELISA Kit , E-40TK. ( ... Dog Thymidine Kinase (TK1) ELISA Kit , E-40TK. Rating Required Select Rating. 1 star (worst). 2 stars. 3 stars (average). 4 ...
Preoperative Serum Thymidine Kinase Activity as Novel Monitoring, Prognostic, and Predicti Preoperative Serum Thymidine Kinase ... The aim of the study was to investigate serum thymidine kinase 1 (S-TK) activity as a diagnostic and prognostic marker for ... Serum thymidine kinase 1 activity may be a useful parameter for monitoring nTx efficacy. ...
Serum thymidine kinase 1 activity as a pharmacodynamic marker of cyclin-dependent kinase 4/6 inhibition in patients with early- ... Thymidine kinase is a proliferation marker downstream of the cyclin-dependent kinase 4/6 pathway. ... Circulating Tumor M2 pyruvate kinase and thymidine kinase 1 are potential predictors for disease recurrence in renal cell ... Serum thymidine kinase 1 levels correlates with FDG uptake and prognosis in patients with non-small cell lung cancer. Results ...
Plasma cell labeling index and β2-microglobulin predict survival independent of thymidine kinase and C-reactive protein in ... Plasma cell labeling index and β2-microglobulin predict survival independent of thymidine kinase and C-reactive protein in ...
Basic fibroblast growth factor enhancement of adenovirus-mediated delivery of the herpes simplex virus thymidine kinase gene ... an FGF2-redirected adenoviral vector carrying the gene for herpes simplex virus thymidine kinase (AdCMVHSV-TK) was shown to ...
Human TK1(Thymidine Kinase 1, Soluble) ELISA Kit. Human TK1(Thymidine Kinase 1, Soluble) ELISA Kit. Order Now: [email protected ... Human MAP2K1(Mitogen Activated Protein Kinase Kinase 1) ELISA Kit. *Human MARCKS(Myristoylated Alanine Rich Protein Kinase C ... Human MAP2K1(Mitogen Activated Protein Kinase Kinase 1) ELISA Kit. *Human MARCKS(Myristoylated Alanine Rich Protein Kinase C ... Description: Recombinant Human Thymidine Kinase 1, Soluble expressed in: Available from E.coli, Yeast, Baculovirus and ...
One strain had a deletion of the thymidine kinase gene; the second had a deletion of the thymidine kinase gene and insertion of ... Most reports of laboratory-acquired VACV infections were caused by thymidine kinase-deletion strains, which are sometimes ...
... thymidine incorporation into DNA. The kinetic parameters of thymidine kinase a regulatory enzyme for DNA synthesis was also ... Kinetic studies of thymidine kinase revealed that there was no change in the Michaelis -Menten constant (Km) whereas maximum ... Effect Insulin on DNA Synthesis and Kinetic Parameters of Thymidine Kinase During Liver Regenaration. Show full item record ... Effect Insulin on DNA Synthesis and Kinetic Parameters of Thymidine Kinase During Liver Regenaration. Dyuthi/Manakin Repository ...
Deletion of the thymidine kinase gene attenuates Caprine alphaherpesvirus 1 in goats. Jéssica Caroline Gomes Noll, **Lok ...
Ganciclovir is a selective antiviral activated only within infected cells by viral thymidine kinase. It is a viral DNA chain ... This is a prodrug that inhibits viral replication; it is activated by phosphorylation by virus-specific thymidine kinase. The ... Trifluridine is a pyrimidine (thymidine) analogue drug of choice in the United States for topical antiviral therapy for HSV ... It inhibits viral replication by incorporating into viral deoxyribonucleic acid (DNA) in place of thymidine. It is prescribed ...
... when levels of thymidine kinase I (TK1), the first enzyme in the pathway for incorporation of AZT into DNA, were determined by ...
in vitro mammalian cell gene mutation tests using the thymidine kinase gene. Target gene:. TK locus. Species / strain / cell ... OECD Guideline 490 (In Vitro Mammalian Cell Gene Mutation Tests Using the Thymidine Kinase Gene). Principles of method if other ...
Anti Thymidine Kinase Clone 2C5 , Gentaur $340.00 * Anti-4 Hydroxynonenal Antibody , Gentaur ...
Thymidine phosphorylase. AR. Late childhood Adolescence. dels/depl. muscle. MNGIE. TK2. 16q22-q23.1. Thymidine kinase 2. AR. ... Saada, A.; Shaag, A.; Mandel, H.; Nevo, Y.; Eriksson, S.; Elpeleg, O. Mutant mitochondrial thymidine kinase in mitochondrial ... Mutations in thymidine kinase gene with myopathy and SMA. Neurology 2002, 59, 1197-1202. [Google Scholar] [CrossRef] [PubMed] ... Elucidation of the tissue specificity in the mitochondrial thymidine kinase (TK2) deficiency. Mol. Genet. Metab. 2003, 79, 1-5 ...
  • by a viral enzyme called thymidine kinase (TK), to which the drug has a high affinity (attraction). (britannica.com)
  • TK2 is an enzyme, a phosphotransferase (a kinase): 2'-deoxythymidine kinase, ATP-thymidine 5'-phosphotransferase. (prospecbio.com)
  • The TK2 gene provides instructions for making an enzyme called thymidine kinase 2 that functions within cell structures called mitochondria, which are found in all tissues. (medlineplus.gov)
  • However thymidine monophosphate was formed by the mitochondrial enzyme when ATP was omitted from both the PAGE buffer and the reaction mixture. (rpi.edu)
  • However, it was found that when ATP was omitted from the PAGE buffer, the activity of the viral and mitochondrial thymidine kinase was not changed, although the cytosol enzyme could not be detected as expected. (rpi.edu)
  • The thymidine kinase of Raji cells which had been induced with iododeoxyuridine (Iudr) was examined to determine whether or not an enzyme of viral origin was present. (rpi.edu)
  • Herpes simplex virus Type 2 (HSV-2) also codes for a thymidine kinase which is different from the cytosol or mitochondrial forms of the enzyme. (rpi.edu)
  • Cells lytically infected with HSV-2 have a viral enzyme with a PAGE mobility intermediate between the cytosol and mitochondrial thymidine kinases. (rpi.edu)
  • Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human Thymidine Kinase 1, Soluble (TK1) in serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids. (kits-elisa.com)
  • Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Human Thymidine Kinase 1, Soluble (TK1) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids with no significant corss-reactivity with analogues from other species. (kits-elisa.com)
  • The kinetic parameters of thymidine kinase a regulatory enzyme for DNA synthesis was also studied in these groups. (cusat.ac.in)
  • Finally, when levels of thymidine kinase I (TK1), the first enzyme in the pathway for incorporation of AZT into DNA, were determined by Western blot analysis in all 19 NEMEC strains at 24 h of AZT exposure, higher TK1 protein levels were found in the 12 strains showing AZT-DNA incorporation, compared to the 7 showing no incorporation (p=0.0005, Mann-Whitney test). (cdc.gov)
  • The tomato gene in question codes for an enzyme called thymidine kinase. (news-medical.net)
  • Here, we report a novel interaction between the mitotic kinase, Aurora A, and the glycolytic enzyme, pyruvate kinase M2 (PKM2), in the interphase of the cell cycle. (jbc.org)
  • An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. (bvsalud.org)
  • We sought to evaluate the usefulness of an adenoviral vector expressing mutant herpesviral thymidine kinase reporter gene (HSV1-sr39tk) and vascular endothelial growth factor (VEGF) 121 in independent expression cassettes (Ad4tk). (snmjournals.org)
  • The feasibility of noninvasive imaging of cardiac transgene expression using PET and radiolabeled reporter probes for detection of adenovirally transfected herpesviral thymidine kinase reporter gene (HSV1-tk) has recently been demonstrated in small animals ( 1 ) and large animals ( 2 ). (snmjournals.org)
  • Cytoxicity induced by the herpesvirus thymidine kinase (TK) gene in combination with prodrugs is dependent on cell growth and leads to the elimination of genetically modified cells, thus limiting the duration of expression and efficacy of this treatment in vivo. (elsevier.com)
  • Cloning of the active thymidine kinase gene of herpes simplex virus type 1 in Escherichia coli K-12. (archives-ouvertes.fr)
  • ATP:thymidine 5'-phosphotransferase, EC 2.7.1.21) gene has been cloned in Escherichia coli. (archives-ouvertes.fr)
  • In a murine model of human ovarian carcinoma, an FGF2-redirected adenoviral vector carrying the gene for herpes simplex virus thymidine kinase (AdCMVHSV-TK) was shown to result in a significant prolongation of survival compared with the same number of particles of unmodified AdCMVHSV-TK. (uab.edu)
  • We investigated the efficacy of retrovirus-mediated gene transfer of the herpes simplex virus thymidine kinase (HSV-TK) gene to murine neuroblstoma cell lines [neuro-2a) in vitro and in vivo. (kribb.re.kr)
  • CAN-2409 (international non-proprietary name: aglatimagene besadenovec) is an adenovirus-based replication deficient engineered gene construct encoding the thymidine kinase gene derived from the herpes simplex virus. (candeltx.com)
  • The adenoviral construct is used as a vector to transport the thymidine kinase gene into the tumor cells at the site of injection. (candeltx.com)
  • Cells transduced with thymidine kinase gene undergo immunogenic cell death after exposure to these systemically administered prodrugs. (candeltx.com)
  • For the specific targeting of Ct-SLCO1B3 in RDEB-SCC, we employed spliceosome-mediated RNA trans -splicing (SMaRT) technology to replace the coding sequence of Ct-SLCO1B3 with that of the suicide gene herpes simplex virus 1 thymidine kinase (HSV1tk), thereby enabling tumor cells to convert the non-toxic prodrug ganciclovir (GCV) into an active drug which triggers apoptosis. (eb-researchnetwork.org)
  • The current US-licensed ORV consists of a rabies virus glycoprotein gene inserted into the thymidine kinase gene of an attenuated strain of the Copenhagen vaccinia virus (V-RG) ( 2 ). (cdc.gov)
  • HeLa cells that have been lytically infected or transformed with Herpes simplex virus Type 1 (HSV-1) have a viral thymidine kinase which is distinct from the cytosol and mitochondrial thymidinekinases. (rpi.edu)
  • Selective abolishment of pyrimidine nucleoside kinase activity of herpes simplex virus type 1 thymidine kinase by mutation of alanine-167 to tyrosine. (ox.ac.uk)
  • OBJECTIVES: Thymidine kinase (TK, EC 2.7.1.21) is a part of the pyrimidine salvage pathway, involved in DNA synthesis. (nel.edu)
  • The DiviTum ® TKa test performed on blood serum measures thymidine kinase activity (TKa) which reflects tumor cell proliferation. (biovica.com)
  • To demonstrate that low serum Thymidine Kinase 1 (sTK1) activity (=TKa) (measured with the DiviTum®TKa test) is associated with low risk for disease progression and long PFS and OS. (biovica.com)
  • Preoperative Serum Thymidine Kinase Activity as Novel Monitoring, Prognostic, and Predictive Biomarker in Pancreatic Cancer. (bvsalud.org)
  • The aim of the study was to investigate serum thymidine kinase 1 (S-TK) activity as a diagnostic and prognostic marker for patients with pancreatic ductal adenocarcinoma (PDAC). (bvsalud.org)
  • Serum thymidine kinase 1 activity may be a useful parameter for monitoring nTx efficacy . (bvsalud.org)
  • Description: Quantitativesandwich ELISA kit for measuring Human Thymidine Kinase 1, Soluble (TK1) in samples from serum, plasma, tissue homogenates. (kits-elisa.com)
  • To prevent background arising from spontaneous mutation, cells lacking TK have to be eliminated by culturing them in a culture medium (Dulbecco's modified Eagle's medium (DMEM) GlutaMAXTM - I) supplemented with 10% (v/v) of inactivated horse serum containing HMTG (Cole et al10): 15 μg/mL hypoxanthine, 0.3 μg/mL methotrexate, 9 μg/mL thymidine, 22.5 μg/mL glycine. (europa.eu)
  • Activity of serum thymidine kinase in non-Hodgkin lymphoma: relationship to other prognostic factors. (nih.gov)
  • Serum beta(2)-microglobulin and serum thymidine kinase are independent predictors of progression-free survival in chronic lymphocytic leukemia and immunocytoma. (nih.gov)
  • Thymidine kinase 2 mitochondrial (TK2) is a member of the DCK/DGK family. (prospecbio.com)
  • Munch-Petersen B. Enzymatic regulation of cytosolic thymidine kinase 1 and mitochondrial thymidine kinase 2: a mini review. (medlineplus.gov)
  • Ganciclovir is a selective antiviral activated only within infected cells by viral thymidine kinase. (medscape.com)
  • In contrast, a significant therapeutic effect was seen upon ganciclovir administration with a vector expressing thymidine kinase (TK) in the tumour stroma. (nature.com)
  • Ganciclovir is transformed by viral and cellular thymidine kinases (TK) to ganciclovir triphosphate, which works as an antiviral agent by inhibiting the synthesis of viral DNA in 2 ways: competitive inhibition of viral DNA-polymerase and direct incorporation into viral primer strand DNA, resulting in DNA chain termination and prevention of replication. (medscape.com)
  • Thymidine kinase converts ganciclovir to a number of toxic metabolites that end up inhibiting DNA polymerase, hence it is assumed to be active only in proliferating cells, which leaves differentiated cells refractory to this system. (scielo.cl)
  • Thymidine kinase converts generic, FDA-approved anti-herpes drugs, such as ganciclovir, acyclovir and valacyclovir, which are used as prodrugs, into a toxic nucleotide analogue. (candeltx.com)
  • In this paper we present the nucleotide sequences of the thymidine kinase (TK) genes of two avian herpesviruses: a highly oncogenic strain of Marek's disease virus (MDV strain RB1B) and its serologically related vaccine virus, the herpesvirus of turkeys (HVT strain Fc-126). (kent.ac.uk)
  • Thymidine kinase is present in 2 forms in mammalian cells, TK1 and TK2. (prospecbio.com)
  • Thymidine kinase is found in most living cells. (prospecbio.com)
  • Here, an effort was made to enhance TK/prodrug efficacy by coexpression of a cyclin-dependent kinase inhibitor (CKI), p27, to render cells resistant to TK/prodrug by inhibiting DNA synthesis. (elsevier.com)
  • The thymidine kinases of uninduced and induced Raji cells did not use CTP were not affected by EBV antiserat and were thermostable. (rpi.edu)
  • DiviTum can quantify the level of thymidine kinase released into the circulation from proliferating cells. (biovica.com)
  • Guanylate kinase then converts the monophosphate form into diphosphate and triphosphate analogues that inhibit viral DNA replication. (medscape.com)
  • TK2 is a deoxyribonucleoside kinase which specifically phosphorylates thymidine, deoxycytidine, and deoxyuridine. (prospecbio.com)
  • it is activated by phosphorylation by virus-specific thymidine kinase. (medscape.com)
  • Acyclovir is a prodrug activated by phosphorylation by virus-specific thymidine kinase (TK). (medscape.com)
  • Unity of the invention was given because no experimental work towards characterization, properties, use or biological function of plant thymidine kinases was accomplished prior to the priority date of the present invention. (epo.org)
  • When ATP was omitted from the reaction mixture used in the thymidirte kinase assay, no thymidine monophosphate was formed by the viral or cytosol enzymes. (rpi.edu)
  • The extent of cell proliferation in sham and hepatectomized- control, diabetic and insulin treated rats were monitored by determining DNA content and [3H]thymidine incorporation into DNA. (cusat.ac.in)
  • Kinetic studies of thymidine kinase revealed that there was no change in the Michaelis -Menten constant (Km) whereas maximum velocity (Vmax) was elevated in the diabetic hepatectomized groups compared to control and insulin treated hepatectomized groups. (cusat.ac.in)
  • Thus our study elucidates the role of insulin in thymidine kinase activity and DNA synthesis. (cusat.ac.in)
  • Trifluridine is a pyrimidine (thymidine) analogue drug of choice in the United States for topical antiviral therapy for HSV infection. (medscape.com)
  • Although combination chemotherapy regimens, including the nucleoside analogue fludarabine, were once the most commonly used first-line therapy in CLL, non-chemotherapy regimens (eg, with Bruton tyrosine kinase [BTK] inhibitors) are currently preferred in most cases. (medscape.com)
  • Thymidine kinases have a central function in the synthesis of DNA and thus in cell division, since they are part of the exceptional reaction chain to introduce deoxythymidine into the DNA. (prospecbio.com)
  • The DiviTum TKa test can detect an increase or decrease of Thymidine Kinase activity (TKa) level in the blood. (biovica.com)
  • The evidence demonstrates that measuring thymidine kinase activity (TKa) levels with the DiviTum TKa test provides important clinical information for the management of the disease. (biovica.com)
  • Document D8 did not deprive the invention of novelty since, as commented in the application as filed and also acknowledged in the International Search Report, it only disclosed a partial sequence insufficient for expression of the whole protein and it was completely silent about any possible use of rice thymidine kinase. (epo.org)
  • Here, we investigated the effects of glycogen synthase kinase 3 (GSK3) inhibition via lithium chloride (LiCl) treatment on SERCA uncoupling in skeletal muscle and UCP1 expression in adipose. (jbc.org)
  • They are heterozygous at the thymidine kinase (TK) locus which allows to detect mutation events at the TK-locus. (europa.eu)
  • It inhibits viral replication by incorporating into viral deoxyribonucleic acid (DNA) in place of thymidine. (medscape.com)
  • About two-thirds of the mutations that cause this condition change single protein building blocks (amino acids) in thymidine kinase 2. (medlineplus.gov)
  • Patients treated with Epirubicin and Docetaxel before surgery were followed by their thymidine kinase (TK1) levels in blood to directly observe treatment response. (globenewswire.com)
  • Two HSV-2 transformed cell lines showed no evidence of any viral thymidine kinase when tested for their CTP specificity or thermostability. (rpi.edu)