thymidine kinase

Summary

Summary: 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.

Top Publications

  1. ncbi Suicide gene therapy mediated by the Herpes Simplex virus thymidine kinase gene/Ganciclovir system: fifteen years of application
    C Fillat
    Programa Gens i Malaltia, Centre de Regulacio Genomica, Barcelona, Spain
    Curr Gene Ther 3:13-26. 2003
  2. ncbi Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice
    T G Bush
    Medical Research Council Cambridge Centre for Brain Repair, and Department of Anatomy, University of Cambridge, United Kingdom
    Neuron 23:297-308. 1999
  3. ncbi Validation of FLT uptake as a measure of thymidine kinase-1 activity in A549 carcinoma cells
    Janet S Rasey
    Department of Radiation Oncology, University of Washington School of Medicine, Seattle, Washington 98195, USA
    J Nucl Med 43:1210-7. 2002
  4. pmc Imaging tri-fusion multimodality reporter gene expression in living subjects
    Pritha Ray
    Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
    Cancer Res 64:1323-30. 2004
  5. ncbi Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy
    A Saada
    The Metabolic Disease Unit, Shaare Zedek Medical Center, Faculty of Medicine, The Hebrew University, Jerusalem 91031, Israel
    Nat Genet 29:342-4. 2001
  6. ncbi Comparison of radiolabeled nucleoside probes (FIAU, FHBG, and FHPG) for PET imaging of HSV1-tk gene expression
    Juri Gelovani Tjuvajev
    Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Nucl Med 43:1072-83. 2002
  7. ncbi Human pharmacokinetic and dosimetry studies of [(18)F]FHBG: a reporter probe for imaging herpes simplex virus type-1 thymidine kinase reporter gene expression
    S Yaghoubi
    Crump Institute for Molecular Imaging, UCLA--DOE Laboratory of Structural Biology and Molecular Medicine, UCLA School of Medicine, University of California, Los Angeles, 90095-1770, USA
    J Nucl Med 42:1225-34. 2001
  8. pmc Thymidine kinase 2 (H126N) knockin mice show the essential role of balanced deoxynucleotide pools for mitochondrial DNA maintenance
    Hasan O Akman
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    Hum Mol Genet 17:2433-40. 2008
  9. ncbi Progressive loss of mitochondrial DNA in thymidine kinase 2-deficient mice
    Xiaoshan Zhou
    Department of Laboratory Medicine, Karolinska Institute, S 141 86 Huddinge, Sweden
    Hum Mol Genet 17:2329-35. 2008
  10. ncbi The "bystander effect": tumor regression when a fraction of the tumor mass is genetically modified
    S M Freeman
    Clinical Immunology Unit, University of Rochester Medical School, New York 14642
    Cancer Res 53:5274-83. 1993

Detail Information

Publications358 found, 100 shown here

  1. ncbi Suicide gene therapy mediated by the Herpes Simplex virus thymidine kinase gene/Ganciclovir system: fifteen years of application
    C Fillat
    Programa Gens i Malaltia, Centre de Regulacio Genomica, Barcelona, Spain
    Curr Gene Ther 3:13-26. 2003
    ..The first GDEPT system described was the thymidine kinase gene of the Herpes Simplex virus (HSVtk) in combination with the prodrug Ganciclovir (GCV)...
  2. ncbi Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice
    T G Bush
    Medical Research Council Cambridge Centre for Brain Repair, and Department of Anatomy, University of Cambridge, United Kingdom
    Neuron 23:297-308. 1999
    ....
  3. ncbi Validation of FLT uptake as a measure of thymidine kinase-1 activity in A549 carcinoma cells
    Janet S Rasey
    Department of Radiation Oncology, University of Washington School of Medicine, Seattle, Washington 98195, USA
    J Nucl Med 43:1210-7. 2002
    ..We tested the accuracy with which FLT uptake predicted the activity of cytosolic thymidine kinase-1 (TK(1)), an enzyme that is upregulated before and during DNA synthesis.
  4. pmc Imaging tri-fusion multimodality reporter gene expression in living subjects
    Pritha Ray
    Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
    Cancer Res 64:1323-30. 2004
    ..gene encoding the monomeric red fluorescence protein (mrfp1), and a mutant herpes simplex virus type 1 sr39 thymidine kinase [HSV1-truncated sr39tk (ttk); a PET reporter gene] was found to preserve the most activity for each protein ..
  5. ncbi Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy
    A Saada
    The Metabolic Disease Unit, Shaare Zedek Medical Center, Faculty of Medicine, The Hebrew University, Jerusalem 91031, Israel
    Nat Genet 29:342-4. 2001
    ..Two of the four human deoxyribonucleoside kinases, deoxyguanosine kinase (dGK) and thymidine kinase-2 (TK2), are expressed in mitochondria...
  6. ncbi Comparison of radiolabeled nucleoside probes (FIAU, FHBG, and FHPG) for PET imaging of HSV1-tk gene expression
    Juri Gelovani Tjuvajev
    Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Nucl Med 43:1072-83. 2002
    The efficacy of 3 radiolabeled probes of current interest for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk) expression in vivo with PET, including (124)I- or (131)I-labeled 2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-..
  7. ncbi Human pharmacokinetic and dosimetry studies of [(18)F]FHBG: a reporter probe for imaging herpes simplex virus type-1 thymidine kinase reporter gene expression
    S Yaghoubi
    Crump Institute for Molecular Imaging, UCLA--DOE Laboratory of Structural Biology and Molecular Medicine, UCLA School of Medicine, University of California, Los Angeles, 90095-1770, USA
    J Nucl Med 42:1225-34. 2001
    ..18)F]FHBG) has been used as a reporter probe to image expression of herpes simplex virus type-1 thymidine kinase (HSV1-tk) reporter gene in living animals...
  8. pmc Thymidine kinase 2 (H126N) knockin mice show the essential role of balanced deoxynucleotide pools for mitochondrial DNA maintenance
    Hasan O Akman
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    Hum Mol Genet 17:2433-40. 2008
    ..MtDNA depletion has been associated with mutations in nine autosomal genes, including thymidine kinase (TK2), which encodes a ubiquitous mitochondrial protein...
  9. ncbi Progressive loss of mitochondrial DNA in thymidine kinase 2-deficient mice
    Xiaoshan Zhou
    Department of Laboratory Medicine, Karolinska Institute, S 141 86 Huddinge, Sweden
    Hum Mol Genet 17:2329-35. 2008
    Deficient enzymatic activity of the mitochondrial deoxyribonucleoside kinases deoxyguanosine kinase (DGUOK) or thymidine kinase 2 (TK2) cause mitochondrial DNA (mtDNA)-depletion syndromes in humans...
  10. ncbi The "bystander effect": tumor regression when a fraction of the tumor mass is genetically modified
    S M Freeman
    Clinical Immunology Unit, University of Rochester Medical School, New York 14642
    Cancer Res 53:5274-83. 1993
    Tumor cells expressing the herpes simplex virus thymidine kinase (HSV-TK) gene are sensitive to the drug ganciclovir (GCV)...
  11. pmc A mutant herpes simplex virus type 1 thymidine kinase reporter gene shows improved sensitivity for imaging reporter gene expression with positron emission tomography
    S S Gambhir
    The Crump Institute for Biological Imaging, University of California Department of Energy Laboratory of Structural Biology and Molecular Medicine, University of California School of Medicine, Los Angeles, CA 90095 1770, USA
    Proc Natl Acad Sci U S A 97:2785-90. 2000
    ..detection of lower levels of PET reporter gene expression by utilizing a mutant herpes simplex virus type 1 thymidine kinase (HSV1-sr39tk) as a PET reporter gene...
  12. ncbi Mammalian deoxyribonucleoside kinases
    E S Arner
    Medical Nobel Institute for Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Sweden
    Pharmacol Ther 67:155-86. 1995
    The mammalian deoxyribonucleoside kinases are deoxycytidine kinase, thymidine kinase 1 and 2 and deoxyguanosine kinase...
  13. pmc Chemotherapy delivered after viral immunogene therapy augments antitumor efficacy via multiple immune-mediated mechanisms
    Zvi G Fridlender
    Thoracic Oncology Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Mol Ther 18:1947-59. 2010
    ..This approach is currently being tested in a clinical trial and could be applied to other trials of viral immunogene therapy...
  14. ncbi Systemic cancer therapy with a tumor-selective vaccinia virus mutant lacking thymidine kinase and vaccinia growth factor genes
    J A McCart
    Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892-1502, USA
    Cancer Res 61:8751-7. 2001
    ..To enhance the tumor specificity of this vector, we have developed a combined thymidine kinase-deleted (TK-) and vaccinia growth factor-deleted (VGF-) vaccinia virus and investigated its properties in ..
  15. ncbi Thymidine kinase 2 mutations in autosomal recessive progressive external ophthalmoplegia with multiple mitochondrial DNA deletions
    Henna Tyynismaa
    Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, Haartmaninkatu 8, Helsinki 00290, Finland
    Hum Mol Genet 21:66-75. 2012
    ..identified compound heterozygous mutations, leading to two amino acid alterations R225W and a novel T230A in thymidine kinase 2 (TK2) in arPEO patients...
  16. ncbi Preclinical safety evaluation of 18F-FHBG: a PET reporter probe for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk) or mutant HSV1-sr39tk's expression
    Shahriar S Yaghoubi
    Department of Radiology, Molecular Imaging Program at Stanford, Bio X Program, Stanford University School of Medicine, California, USA
    J Nucl Med 47:706-15. 2006
    ..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...
  17. ncbi Regulation by degradation, a cellular defense against deoxyribonucleotide pool imbalances
    Chiara Rampazzo
    Department of Biology, University of Padova, Via Ugo Bassi 58B, 35131 Padova, Italy
    Mutat Res 703:2-10. 2010
    ..The role of some relevant enzymes is illustrated with data obtained by chemical or genetic manipulation of their expression in cultured mammalian cells...
  18. pmc Fusion enzymes containing HSV-1 thymidine kinase mutants and guanylate kinase enhance prodrug sensitivity in vitro and in vivo
    A Ardiani
    School of Molecular Biosciences, Washington State University, Pullman, WA 99164 6534, USA
    Cancer Gene Ther 17:86-96. 2010
    Herpes simplex virus thymidine kinase (HSVTK) with ganciclovir (GCV) is currently the most widely used suicide gene/prodrug system in cancer gene therapy...
  19. ncbi Selective removal of undifferentiated embryonic stem cells from differentiation cultures through HSV1 thymidine kinase and ganciclovir treatment
    Ortwin Naujok
    Institute of Clinical Biochemistry, Hannover Medical School, 30625, Hannover, Germany
    Stem Cell Rev 6:450-61. 2010
    ..Use of the HSV1 thymidine kinase and eGFP under the control of the Oct4 promoter allowed the destruction of undifferentiated ES cells by ..
  20. ncbi Thymidine kinase gene modified bone marrow mesenchymal stem cells as vehicles for antitumor therapy
    Chao Song
    Stem Cells and Regeneration Program, School of Biomedical Sciences and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT Hong Kong, People s Republic of China
    Hum Gene Ther 22:439-49. 2011
    ..When infected with herpes simplex virus thymidine kinase (TK) gene by lentiviral transduction, TK-BMSCs maintained their tumor tropism capabilities and significantly ..
  21. ncbi Current progress in suicide gene therapy for cancer
    Kazuyuki Yazawa
    Michael E DeBakey Department of Surgery, Baylor College of Medicine, 6550 Fannin, Suite 1661, Houston, Texas 77030, USA
    World J Surg 26:783-9. 2002
    ..A number of suicide gene systems have been identified, including the herpes simplex virus thymidine kinase gene, the cytosine deaminase gene, the varicella-zoster virus thymidine kinase gene, the nitroreductase gene, ..
  22. ncbi Systemic efficacy of combined suicide/cytokine gene therapy in a murine model of hepatocellular carcinoma
    Anna Lisa Stefani
    Department of Histology, Microbiology and Medical Biotechnologies, University of Padova, Padova, Italy
    J Hepatol 42:728-35. 2005
    ..The aim of the study was to evaluate the in vitro and in vivo efficacy of combined gene therapy of HCC with two different MoMLV-derived retroviral vectors, an MFG- and a LXSN-derived vector, both containing HSV-TK and hIL-2...
  23. ncbi Human amniotic fluid-derived stem cells expressing cytosine deaminase and thymidine kinase inhibits the growth of breast cancer cells in cellular and xenograft mouse models
    N H Kang
    Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea
    Cancer Gene Ther 19:412-9. 2012
    ..in order to express two suicide genes encoding bacterial cytosine deaminase (CD) and herpes simplex virus thymidine kinase (HSV-TK) that convert non-toxic prodrugs, 5-fluorocytosine (5-FC) and mono-phosphorylate ganciclovir (GCV-MP),..
  24. ncbi Thymidine kinase 1 expression defines an activated G1 state of the cell cycle as revealed with site-specific antibodies and ArrayScan assays
    Fabio Gasparri
    Biology Department, Oncology, Nerviano Medical Sciences, Nerviano, Italy
    Eur J Cell Biol 88:779-85. 2009
    b>Thymidine kinase 1 (TK1) is a DNA salvage enzyme involved in the synthesis of thymidine triphosphate needed during S phase...
  25. pmc Alpha-fetoprotein-thymidine kinase-luciferase knockin mice: a novel model for dual modality longitudinal imaging of tumorigenesis in liver
    Xincheng Lu
    Case Comprehensive Cancer Centre, Case Western Reserve University, Cleveland, OH 44106, USA
    J Hepatol 55:96-102. 2011
    ..We aimed to take advantage of the dramatic re-expression of the Afp gene in HCC to develop a hepatocarcinogenesis reporter (HCR) mouse model for dual-modality, longitudinal in vivo imaging of liver tumor development, and progression...
  26. ncbi 8-[18F]Fluoropenciclovir: an improved reporter probe for imaging HSV1-tk reporter gene expression in vivo using PET
    M Iyer
    Crump Institute for Molecular Imaging, UCLA/Department of Energy Laboratory of Structural Biology and Molecular Medicine, UCLA-Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, California 90095-1770, USA
    J Nucl Med 42:96-105. 2001
    ..compared it with 8-[18F]fluoroganciclovir (FGCV) for monitoring the expression of herpes simplex virus type 1 thymidine kinase (HSV1 -tk) reporter gene in cell culture and in vivo...
  27. ncbi A phase I clinical trial of thymidine kinase-based gene therapy in advanced hepatocellular carcinoma
    B Sangro
    Liver Unit, Clinica Universitaria, Pamplona, Spain
    Cancer Gene Ther 17:837-43. 2010
    ..safety of intratumoral administration of a first-generation adenoviral vector encoding herpes simplex virus thymidine kinase (HSV-TK) gene (Ad...
  28. ncbi In vivo biological activity of the histone deacetylase inhibitor LAQ824 is detectable with 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography
    Julius Leyton
    Molecular Therapy and Cancer Cell Biology, Imperial College London, Faculty of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom
    Cancer Res 66:7621-9. 2006
    ..We initially showed that thymidine kinase 1 (TK1; EC2.7.1...
  29. pmc Regulation and functional contribution of thymidine kinase 1 in repair of DNA damage
    Yen Ling Chen
    Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, No 1, Section 1, Jen Ai Road, Taipei 100, Taiwan
    J Biol Chem 285:27327-35. 2010
    ..Here we investigated the regulation of thymidine kinase 1 (TK1) in response to DNA damage and found that genotoxic insults in tumor cells cause up-regulation and ..
  30. pmc A heterotypic bystander effect for tumor cell killing after adeno-associated virus/phage-mediated, vascular-targeted suicide gene transfer
    Martin Trepel
    Department of Oncology and Hematology, University Medical Center Hamburg Eppendorf, Hamburg, Germany
    Mol Cancer Ther 8:2383-91. 2009
    ..We recently reported that selective systemic delivery of suicide genes such as herpes simplex virus thymidine kinase (HSVtk) to tumor endothelial cells through a novel targeted adeno-associated virus/phage vector leads to ..
  31. ncbi Essential protective roles of reactive astrocytes in traumatic brain injury
    D J Myer
    Department of Neurobiology, University of California Los Angeles, CA 90095 1763, USA
    Brain 129:2761-72. 2006
    ..different severities in transgenic mice that express a glial fibrillary acidic protein-herpes simplex virus-thymidine kinase transgene...
  32. ncbi Mitochondrial deoxynucleotide pools in quiescent fibroblasts: a possible model for mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)
    Paola Ferraro
    Department of Biology, The University of Padova, 35131 Padova, Italy
    J Biol Chem 280:24472-80. 2005
    ..Other dNTPs are marginally affected. Deoxyuridine does not increase the normal dNTP pools but gives rise to a small dUTP and a large dUMP pool, both turning over rapidly. We discuss these results in relation to MNGIE...
  33. ncbi Selective ablation of human embryonic stem cells expressing a "suicide" gene
    Maya Schuldiner
    Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem, Israel
    Stem Cells 21:257-65. 2003
    ..these potential problems, we genetically engineered human ES cell lines to express the herpes simplex virus thymidine kinase (HSV-tk) gene. Expression of the HSV-tk protein renders the ES cells sensitive to the U.S...
  34. pmc Onset and organ specificity of Tk2 deficiency depends on Tk1 down-regulation and transcriptional compensation
    Beatriz Dorado
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    Hum Mol Genet 20:155-64. 2011
    Deficiency of thymidine kinase 2 (TK2) is a frequent cause of isolated myopathy or encephalomyopathy in children with mitochondrial DNA (mtDNA) depletion...
  35. ncbi Thymidine kinase 2 defects can cause multi-tissue mtDNA depletion syndrome
    Alexandra Götz
    Research Programme of Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
    Brain 131:2841-50. 2008
    ..b>Thymidine kinase 2 (TK2) has been reported to cause a myopathic form of MDS...
  36. ncbi Correlation between MIB-1 and other proliferation markers: clinical implications of the MIB-1 cutoff value
    Frederique Spyratos
    Laboratoire d Oncobiologie, Centre Rene Huguenin, Saint Cloud, France
    Cancer 94:2151-9. 2002
    ..The objectives of this study were to compare MIB-1 evaluation to other methods of measuring cell proliferation, with a view to refining the cutoff used to classify tumors with low and high proliferation rates in therapeutic trials...
  37. ncbi Molecular imaging of embryonic stem cell misbehavior and suicide gene ablation
    Feng Cao
    The Department of Radiology and Bio X Program, Stanford University School of Medicine, Stanford, California 94305 5344, USA
    Cloning Stem Cells 9:107-17. 2007
    ..of monomeric red fluorescence protein (mrfp), firefly luciferase (Fluc), and herpes simplex virus truncated thymidine kinase (HSV-ttk) reporter genes...
  38. ncbi Transcription factors of the Sp1 family: interaction with E2F and regulation of the murine thymidine kinase promoter
    H Rotheneder
    Vienna Biocenter, University of Vienna, Austria
    J Mol Biol 293:1005-15. 1999
    ..of the Sp1 family to interact with E2F-1 and to regulate the activity of the E2F and Sp1 dependent murine thymidine kinase promoter...
  39. ncbi A sensitive and kinetically defined radiochemical assay for canine and human serum thymidine kinase 1 (TK1) to monitor canine malignant lymphoma
    H Sharif
    Department of Anatomy, Swedish University of Agricultural Sciences, BMC, P O Box 575, S 751 23 Uppsala, Sweden
    Vet J 194:40-7. 2012
    b>Thymidine kinase 1 (TK1) is a cell cycle regulated enzyme with maximum expression during the S phase. Serum TK1 (S-TK1) is a unique biomarker for cell proliferation...
  40. ncbi Construction and identification of recombinant vectors carrying herpes simplex virus thymidine kinase and cytokine genes expressed in gastric carcinoma cell line SGC7901
    Jian Hua Zhang
    Department of Biomedical Engineering, School of Life Science and Technology, Xi an Jiaotong University, 28 West Xianning Road, Xi an 710049, Shaanxi Province, China
    World J Gastroenterol 10:26-30. 2004
    To construct and identify the recombinant vectors carrying herpes simplex virus thymidine kinase (HSV-TK) and tumor necrosis factor alpha (TNF-alpha) or interleukin-2 (IL-2) genes expressed in gastric carcinoma cell line SGC7901.
  41. ncbi HSV type 1 thymidine kinase protein accumulation in round spermatids induces male infertility by spermatogenesis disruption and apoptotic loss of germ cells
    Li yi Cai
    Division of Life Science, Graduate School of Agriculture, Meiji University, Kawasaki, Kanagawa 214 8571, Japan
    Reprod Toxicol 27:14-21. 2009
    HSV type 1 thymidine kinase (HSV1-TK)-introduced transgenic rodents and HSV-infected humans were reported to suffer male infertility...
  42. ncbi Expression of herpes simplex virus-thymidine kinase gene controlled by a promoter region of the midkine gene confers selective cytotoxicity to ganciclovir in human carcinoma cells
    M Miyauchi
    Division of Pathology, Chiba Cancer Center Research Institute, Chiba, Japan
    Int J Cancer 91:723-7. 2001
    ..Regulated expression of the herpes simplex virus-thymidine kinase (HSV-TK) gene under the control of the MK promoter conferred increased sensitivity to ganciclovir (GCV) on MK-..
  43. ncbi Tumor cell apoptosis induces tumor-specific immunity in a CC chemokine receptor 1- and 5-dependent manner in mice
    Noriho Iida
    Cancer Research Institute, Kanazawa University, Kanazawa 920 0934, Japan
    J Leukoc Biol 84:1001-10. 2008
    ..We injected mice with a murine hepatoma cell line, BNL 1ME A.7R.1 (BNL), transfected with HSV-thymidine kinase (tk) gene and then treated the animals with ganciclovir (GCV)...
  44. ncbi A spectrophotometric assay for quantitative determination of kcat of herpes simplex virus type 1 thymidine kinase substrates
    P Schelling
    Department of Applied BioSciences, Swiss Federal Institute of Technology (ETH, Winterthurerstrasse 190, , CH-8057, Switzerland
    Anal Biochem 295:82-7. 2001
    ..to determine the in vitro catalytic turnover constant of several substrates of herpes simplex virus type 1 thymidine kinase is presented in this study...
  45. ncbi mtDNA depletion myopathy: elucidation of the tissue specificity in the mitochondrial thymidine kinase (TK2) deficiency
    Ann Saada
    Metabolic Disease Unit, Shaare Zedek Medical Center, Post Office Box 3235, IL 91031 Jerusalem, Israel
    Mol Genet Metab 79:1-5. 2003
    Decreased mitochondrial thymidine kinase (TK2) activity is associated with mitochondrial DNA (mtDNA) depletion and respiratory chain dysfunction and is manifested by isolated, fatal skeletal myopathy...
  46. ncbi AdvHSV-tk gene therapy with intravenous ganciclovir improves survival in human malignant glioma: a randomised, controlled study
    Arto Immonen
    Department of Neurosurgery, University of Kuopio, A I Virtanen Institute, Finland
    Mol Ther 10:967-72. 2004
    ..The treatment was well tolerated. It is concluded that AdvHSV-tk gene therapy with GCV is a potential new treatment for operable primary or recurrent high-grade glioma...
  47. ncbi The uptake of 3'-deoxy-3'-[18F]fluorothymidine into L5178Y tumours in vivo is dependent on thymidine kinase 1 protein levels
    Henryk Barthel
    Molecular Therapy and PET Oncology Research Group, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK
    Eur J Nucl Med Mol Imaging 32:257-63. 2005
    The aim of this study was to investigate the role of thymidine kinase 1 (TK1) protein in 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) positron emission tomography (PET) studies.
  48. pmc Cloning of the koi herpesvirus genome as an infectious bacterial artificial chromosome demonstrates that disruption of the thymidine kinase locus induces partial attenuation in Cyprinus carpio koi
    B Costes
    Immunology Vaccinology B43b, Department of Infectious and Parasitic Diseases, Faculty of Veterinary Medicine, University of Liege, B 4000 Liege, Belgium
    J Virol 82:4955-64. 2008
    ..This goal was achieved by the insertion of a loxP-flanked BAC cassette into the thymidine kinase (TK) locus...
  49. pmc A scalable approach to prevent teratoma formation of human embryonic stem cells
    Zhili Rong
    Division of Biological Sciences, University of California at San Diego, La Jolla, California 92093 0322, USA
    J Biol Chem 287:32338-45. 2012
    ..By introducing a hyperactive variant of herpes simplex virus thymidine kinase gene into the 3'-untranslated region of the endogenous NANOG gene of hESCs through homologous recombination, ..
  50. ncbi Ablation of tumor-derived stem cells transplanted to the central nervous system by genetic modification of embryonic stem cells with a suicide gene
    Juyeon Jung
    Department of Genetic Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA
    Hum Gene Ther 18:1182-92. 2007
    ..A lentiviral vector carrying the herpes simplex virus thymidine kinase (HSVtk) and green fluorescent protein (GFP) genes was used to genetically modify murine ESCs (HSVtk+GFP+ ESCs)..
  51. ncbi Adjuvant adenovirus-mediated delivery of herpes simplex virus thymidine kinase administration improves outcome of liver transplantation in patients with advanced hepatocellular carcinoma
    Ning Li
    Beijing Youan Hospital, Capital Medical University, China
    Clin Cancer Res 13:5847-54. 2007
    ..Adenovirus-mediated delivery of herpes simplex virus thymidine kinase (ADV-TK) therapy is an established adjuvant treatment in cancer, and we evaluated its potential as an ..
  52. pmc Noninvasive molecular imaging of hypoxia in human xenografts: comparing hypoxia-induced gene expression with endogenous and exogenous hypoxia markers
    Fuqiu He
    Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Cancer Res 68:8597-606. 2008
    ..A hypoxia-inducible dual reporter herpes simplex virus type 1 thymidine kinase and enhanced green fluorescence protein (HSV1-TKeGFP), under the control of hypoxia response element (9HRE), ..
  53. ncbi Two novel mutations in thymidine kinase-2 cause early onset fatal encephalomyopathy and severe mtDNA depletion
    Nicole Lesko
    Department of Laboratory Medicine, Division of Metabolic Diseases, Karolinska Institutet, Stockholm, Sweden
    Neuromuscul Disord 20:198-203. 2010
    Deficiency of thymidine kinase-2 (TK2) has been described in children with early onset fatal skeletal myopathy...
  54. ncbi Phase I study of adenoviral delivery of the HSV-tk gene and ganciclovir administration in patients with current malignant brain tumors
    T W Trask
    Department of Neurosurgery, Baylor College of Medicine, Houston, Texas 77030, USA
    Mol Ther 1:195-203. 2000
    ..x 10(12) vector particles (VP) of a replication-defective adenoviral vector bearing the herpes simplex virus thymidine kinase gene driven by the Rous sarcoma virus promoter (Adv.RSVtk), followed by ganciclovir (GCV) treatment...
  55. ncbi Gene therapy: the first approved gene-based medicines, molecular mechanisms and clinical indications
    J K Räty
    Department of Biotechnology and Molecular Medicine, A I Virtanen Institute for Molecular Sciences, University of Kuopio, Finland
    Curr Mol Pharmacol 1:13-23. 2008
    ..market approval, based on p53 expression (Gendicine and Advexin), conditionally replicative adenoviruses (Oncorine) and thymidine kinase + ganciclovir therapy (Cerepro), are introduced with emphasis on the molecular mechanisms of action.
  56. ncbi High serum thymidine kinase 1 level predicts poorer survival in patients with chronic lymphocytic leukemia
    Sergej N Konoplev
    Division of Pathology and Laboratory Medicine, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Am J Clin Pathol 134:472-7. 2010
    Serum thymidine kinase 1 (TK1) levels have been reported to have prognostic significance in patients with chronic lymphocytic leukemia (CLL). Until recently, serum TK1 levels were assessed using inconvenient radioenzyme assays...
  57. ncbi Thymidine kinase and cancer monitoring
    Stefan Aufderklamm
    Department of Urology, Eberhard Karls University, Tubingen, Germany
    Cancer Lett 316:6-10. 2012
    ..Herein, we summarize the status of TK1 for cancer monitoring and point out its use as a proliferation marker. A comprehensive overview about the association of TK-1 with various entities is given...
  58. pmc 4- to 6-week-old adult-born hippocampal neurons influence novelty-evoked exploration and contextual fear conditioning
    Christine A Denny
    Department of Biological Sciences, Columbia University, New York, New York, USA
    Hippocampus 22:1188-201. 2012
    ..These data suggest that the transient enhancement of plasticity observed in young adult-born neurons contributes to cognitive functions...
  59. ncbi High thymidine kinase 1 (TK1) expression is a predictor of poor survival in patients with pT1 of lung adenocarcinoma
    Yan Xu
    Department of Pathology, Nanjing Jinling Hospital, Nanjing University Medical School, 305 Zhongshangdong Road, Nanjing, 210002, Jiangsu Province, China
    Tumour Biol 33:475-83. 2012
    In this study, we explore the association of thymidine kinase 1 (TK1) expression in tumour tissues with clinical pathological parameters and prognosis in patients with pathological T1 (pT1) lung adenocarcinoma...
  60. ncbi Comparative aspects of the proliferation marker thymidine kinase 1 in human and canine tumour diseases
    H von Euler
    Center of Clinical Comparative Oncology C3O, Department of Clinical Sciences, Swedish University of Agricultural Sciences SLU, Uppsala, Sweden
    Vet Comp Oncol 9:1-15. 2011
    ..The S phase-specific protein thymidine kinase 1 (TK1) can be used in immunohistochemistry for RNA/protein expression in tissue specimens and for activity ..
  61. pmc Herpes simplex virus type 1 thymidine kinase-armed bovine herpesvirus type 4-based vector displays enhanced oncolytic properties in immunocompetent orthotopic syngenic mouse and rat glioma models
    Marco Redaelli
    Dipartimento di Salute Animale, Sezione di Malattie Infettive degli Animali, Universita di Parma, via del Taglio 8 43126 Parma, Italy
    Neuro Oncol 14:288-301. 2012
    ..In the present study, a herpes simplex virus type 1 thymidine kinase suicide gene-armed BoHV-4 was constructed, characterized, and proven to be highly efficient in killing by ..
  62. pmc Deoxyribonucleotide metabolism in cycling and resting human fibroblasts with a missense mutation in p53R2, a subunit of ribonucleotide reductase
    Giovanna Pontarin
    Department of Biology, University of Padova, Padova, Italy
    J Biol Chem 286:11132-40. 2011
    ..mtDNA was not affected. Also, nuclear DNA synthesis and the cell cycle-regulated enzymes R2 and thymidine kinase 1 decreased strongly, but the mutant cell populations retained unexpectedly larger amounts of the two enzymes ..
  63. ncbi Adenovirus-mediated gene transfer of enhanced Herpes simplex virus thymidine kinase mutants improves prodrug-mediated tumor cell killing
    Rainer Wiewrodt
    Department of Medicine, Philadelphia, Pennsylvania 19194, USA
    Cancer Gene Ther 10:353-64. 2003
    The Herpes simplex virus 1 (HSV) thymidine kinase (tk) suicide gene together with ganciclovir (GCV) have been successfully used for the in vivo treatment of various solid tumors and for the ablation of unwanted transfused stem cells in ..
  64. pmc The Epstein-Barr virus (EBV)-encoded protein kinase, EBV-PK, but not the thymidine kinase (EBV-TK), is required for ganciclovir and acyclovir inhibition of lytic viral production
    Qiao Meng
    Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin Madison, Madison, WI 53706, USA
    J Virol 84:4534-42. 2010
    ..virus (EBV)-infected cells is mediated primarily by the EBV-encoded protein kinase (EBV-PK), the EBV-encoded thymidine kinase (EBV-TK), or both is controversial...
  65. pmc Ultrasound-targeted microbubble destruction mediated herpes simplex virus-thymidine kinase gene treats hepatoma in mice
    Shiji Zhou
    Department of Hepatobiliary Surgery, Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, PR China
    J Exp Clin Cancer Res 29:170. 2010
    The purpose of the study was to explore the anti-tumor effect of ultrasound -targeted microbubble destruction mediated herpes simplex virus thymidine kinase (HSV-TK) suicide gene system on mice hepatoma.
  66. ncbi A novel G-quadruplex motif modulates promoter activity of human thymidine kinase 1
    Richa Basundra
    Proteomics and Structural Biology Unit, Institute of Genomics and Integrative Biology, CSIR, Delhi, India
    FEBS J 277:4254-64. 2010
    ..we identified a characteristic potential G-quadruplex-forming sequence element within the promoter of human thymidine kinase 1 (TK1)...
  67. ncbi 3'-[4-Aryl-(1,2,3-triazol-1-yl)]-3'-deoxythymidine analogues as potent and selective inhibitors of human mitochondrial thymidine kinase
    Sara Van Poecke
    Laboratory for Medicinal Chemistry FFW, Ghent University, Harelbekestraat 72, 9000 Gent, Belgium
    J Med Chem 53:2902-12. 2010
    ..to increase the potency and selectivity of earlier identified substrate-based inhibitors of mitochondrial thymidine kinase 2 (TK-2), we now describe the synthesis of new thymidine analogues containing a 4- or 5-substituted 1,2,3-..
  68. ncbi Advances in imaging gene-directed enzyme prodrug therapy
    Srabani Bhaumik
    GE Global Research Center, Research Circle, Niskayuna NY 12309, USA
    Curr Pharm Biotechnol 12:497-507. 2011
    ..In this review, we present three most promising suicide gene/prodrug combinations (1) herpes simplex virus thymidine kinase (HSV-TK) with ganciclovir (GCV), (2) cytosine deaminase (CD) from bacteria or yeast with 5-fluorocytodine (5-..
  69. ncbi Liver failure caused by herpes simplex virus thymidine kinase plus ganciclovir therapy is associated with mitochondrial dysfunction and mitochondrial DNA depletion
    Maite Herraiz
    Division of Hepatology and Gene Therapy, University of Navarra, Medical School Pamplona, 31008 Pamplona, Spain
    Hum Gene Ther 14:463-72. 2003
    Herpes simplex virus thymidine kinase (HSV-tk) converts ganciclovir (GCV) into an active compound, which can be incorporated into DNA molecules and terminate DNA synthesis...
  70. ncbi Serum thymidine kinase activity in dogs with malignant lymphoma: a potent marker for prognosis and monitoring the disease
    Henrik von Euler
    Faculty of Veterinary Medicine and Animal Science, Department of Small Animal Clinical Sciences, Swedish University of Agricultural Sciences SLU, S 750 07 Uppsala, Sweden
    J Vet Intern Med 18:696-702. 2004
    Serum thymidine kinase (sTK) activity was evaluated as a tumor marker for canine malignant lymphoma (ML)...
  71. ncbi pRL-TK induction can cause misinterpretation of gene promoter activity
    Simone A Osborne
    School of Biomolecular and Biomedical Science, Griffith University, Nathan, QLD, Australia 4111
    Biotechniques 33:1240-2. 2002
  72. pmc A new acycloguanosine-specific supermutant of herpes simplex virus type 1 thymidine kinase suitable for PET imaging and suicide gene therapy for potential use in patients treated with pyrimidine-based cytotoxic drugs
    Yury Likar
    Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Nucl Med 49:713-20. 2008
    The herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene is widely used as a suicide gene in combination with ganciclovir (GCV) and as a nuclear imaging reporter gene with an appropriate reporter probe...
  73. pmc Mitotic degradation of human thymidine kinase 1 is dependent on the anaphase-promoting complex/cyclosome-CDH1-mediated pathway
    Po Yuan Ke
    Graduate Institute of Biochemistry and Molecular Biology, National Taiwan University College of Medicine, No 1, Section 1 Jen Ai Road, Taipei 100, Taiwan, Republic of China
    Mol Cell Biol 24:514-26. 2004
    The expression of human thymidine kinase 1 (hTK1) is highly dependent on the growth states and cell cycle stages in mammalian cells...
  74. ncbi 3'-(1,2,3-Triazol-1-yl)-3'-deoxythymidine analogs as substrates for human and Ureaplasma parvum thymidine kinase for structure-activity investigations
    Jay Lin
    Department of Anatomy, Physiology and Biochemistry, Veterinary Medical Biochemistry, Swedish University Agricultural Sciences, Uppsala, Sweden
    Bioorg Med Chem 18:3261-9. 2010
    ..parvum (Up) causes opportunistic infections and relies on salvage of nucleosides for DNA synthesis and Up thymidine kinase (UpTK) provides the necessary thymidine nucleotides...
  75. ncbi Cytosolic thymidine kinase is a specific histopathologic tumour marker for breast carcinomas
    Qimin He
    Department of Oncology Clinical Research Laboratory, Novum, KFC, Karolinska University Hospital, S 141 86 Stockholm, Sweden
    Int J Oncol 25:945-53. 2004
    b>Thymidine kinase 1 (TK1), an enzyme involved in the synthesis of precursors for DNA, and thus proliferation dependent, has been suggested as a good tumour marker...
  76. ncbi Thymidine kinase, thymidylate synthase, and dihydropyrimidine dehydrogenase profiles of cell lines of the National Cancer Institute's Anticancer Drug Screen
    J L Grem
    Developmental Therapeutics Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute at the National Naval Medical Center, Bethesda, Maryland 20889, USA
    Clin Cancer Res 7:999-1009. 2001
    ..EXPERIMENTAL DESIGN: Thymidine kinase (TK) activity was assessed by conversion of [(3)H]thymidine to [(3)H]TMP...
  77. pmc Noninvasive detection of therapeutic cytolytic T cells with 18F-FHBG PET in a patient with glioma
    Shahriar S Yaghoubi
    Multimodality Molecular Imaging Lab, Department of Radiology and Bioengineering, Stanford University, Stanford, CA, USA
    Nat Clin Pract Oncol 6:53-8. 2009
    ..engineered to express the interleukin 13 zetakine gene (which encodes a receptor protein that targets these T cells to tumor cells) and the herpes simplex virus 1 thymidine kinase (HSV1 tk) suicide gene, and PET imaging reporter gene.
  78. ncbi Connexin over-expression differentially suppresses glioma growth and contributes to the bystander effect following HSV-thymidine kinase gene therapy
    Tomas Jimenez
    Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario, Canada
    Cell Commun Adhes 13:79-92. 2006
    ..These studies indicate that connexins have unique properties that contribute to their tumor suppressive function...
  79. ncbi The anti-glioma effect of suicide gene therapy using BMSC expressing HSV/TK combined with overexpression of Cx43 in glioma cells
    Q Huang
    Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, People s Republic of China
    Cancer Gene Ther 17:192-202. 2010
    ..The herpes simplex virus thymidine kinase (HSV-TK)/ganciclovir (GCV) suicide gene therapy with a potent bystander effect has been considered as one of ..
  80. pmc Imaging colon cancer response following treatment with AZD1152: a preclinical analysis of [18F]fluoro-2-deoxyglucose and 3'-deoxy-3'-[18F]fluorothymidine imaging
    Maxim A Moroz
    Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Clin Cancer Res 17:1099-110. 2011
    ....
  81. pmc Enhanced combined tumor-specific oncolysis and suicide gene therapy for prostate cancer using M6 promoter
    M Ahn
    Department of Urology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Cancer Gene Ther 16:73-82. 2009
    ..have developed AdIU1, a prostate-restricted replicative adenovirus (PRRA) armed with the herpes simplex virus thymidine kinase (HSV-TK)...
  82. ncbi Optimizing prostate cancer suicide gene therapy using herpes simplex virus thymidine kinase active site variants
    Allan J Pantuck
    Department of Urology, School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
    Hum Gene Ther 13:777-89. 2002
    The herpes simplex virus (HSV) thymidine kinase gene (tk) forms the basis of a widely used strategy for suicide gene therapy...
  83. ncbi Co-expression of herpes simplex virus thymidine kinase and Escherichia coli nitroreductase by an hTERT-driven adenovirus vector in breast cancer cells results in additive anti-tumor effects
    Bin Yu
    National Engineering Laboratory for AIDS Vaccine, The Ministry of Education, College of Life Science, Jilin University, Changchun 130012, PR China
    Oncol Rep 26:255-64. 2011
    ..Previous studies suggested that combining herpes simplex virus thymidine kinase (HSV-TK) and ganciclovir (GCV) with Escherichia coli nitroreductase (Coli...
  84. pmc Structure-guided engineering of human thymidine kinase 2 as a positron emission tomography reporter gene for enhanced phosphorylation of non-natural thymidine analog reporter probe
    Dean O Campbell
    Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA 90095, USA
    J Biol Chem 287:446-54. 2012
    ..Here we describe a new PRG-PRP system that employs, as the PRG, a mutated form of human thymidine kinase 2 (TK2) and 2'-deoxy-2'-18F-5-methyl-1-β-L-arabinofuranosyluracil (L-18F-FMAU) as the PRP...
  85. ncbi Correlation of 18F-FLT uptake with equilibrative nucleoside transporter-1 and thymidine kinase-1 expressions in gastrointestinal cancer
    Reiko Kameyama
    Department of Radiology, Faculty of Medicine, Kagawa University, Kagawa, Japan
    Nucl Med Commun 32:460-5. 2011
    We examined equilibrative nucleoside transporter-1 (ENT1) and thymidine kinase-1 (TK1) messenger ribonucleic acid (mRNA) expressions in cancer tissue samples to elucidate the mechanism of 3'-deoxy-3'-F-fluorothymidine (FLT) uptake by ..
  86. pmc Oncolytic adenoviruses armed with thymidine kinase can be traced by PET imaging and show potent antitumoural effects by ganciclovir dosing
    Daniel Abate-Daga
    Institut d Investigacions Biomediques August Pi i Sunyer IDIBAPS, Barcelona, Spain
    PLoS ONE 6:e26142. 2011
    Replication-competent adenoviruses armed with thymidine kinase (TK) combine the concepts of virotherapy and suicide gene therapy...
  87. ncbi Influence of the bystander effect on HSV-tk/GCV gene therapy. A review
    Ingrid J van Dillen
    Department of Medical Oncology, Groningen University Hospital, PO Box 30 001, 9700 RB Groningen, The Netherlands
    Curr Gene Ther 2:307-22. 2002
    ..of the most frequently studied therapeutic strategies is based on transfection with the herpes simplex virus thymidine kinase gene (HSV-tk), followed by ganciclovir administration...
  88. ncbi Potent tumor-specific immunity induced by an in vivo heat shock protein-suicide gene-based tumor vaccine
    Wenhong Ren
    Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030, USA
    Cancer Res 64:6645-51. 2004
    ..a recombinant replication-defective adenovirus (Ad-HT) that coexpresses HSP70 and a herpes simplex virus thymidine kinase suicide gene...
  89. ncbi Non-invasive in vivo imaging with radiolabelled FIAU for monitoring cancer gene therapy using herpes simplex virus type 1 thymidine kinase and ganciclovir
    Win Ping Deng
    Graduate Institute of Biomedical Materials, Taipei Medical University, Taipei, Taiwan
    Eur J Nucl Med Mol Imaging 31:99-109. 2004
    ..FIAU) as an enzyme substrate for monitoring retroviral vector-mediated herpes simplex virus type 1 thymidine kinase gene ( HSV1-tk) transgene expression. Iodine-131 labelled FIAU was prepared by a no-carrier-added (n.c.a...
  90. ncbi Prognostic importance of thymidine kinase in colorectal and breast cancer
    S Svobodova
    Third Internal Medicine Clinic, General Faculty Hospital Prague, First Medical School Prague Charles University, Prague, Czech Republic
    Anticancer Res 27:1907-9. 2007
    b>Thymidine kinase (TK) plays an essential role in the processing of thymidine within the cell and therefore it is an important marker of proliferation, particularly in tumor cells...
  91. ncbi Characterization of a thymidine kinase-deficient mutant of equine herpesvirus 4 and in vitro susceptibility of the virus to antiviral agents
    Walid Azab
    Department of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1 1 1 Yayoi, Bunkyo ku, Tokyo 113 8657, Japan
    Antiviral Res 85:389-95. 2010
    ..A thymidine kinase (TK)-deletion mutant has been generated by using bacterial artificial chromosome (BAC) technology to ..
  92. ncbi Multimodality imaging of lymphocytic migration using lentiviral-based transduction of a tri-fusion reporter gene
    Young J Kim
    Division of Head and Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
    Mol Imaging Biol 6:331-40. 2004
    ..migration into a tumor site by positron emission tomography (PET), using retroviral transduction of mutated thymidine kinase (sr39TK) reporter genes into immunized T-lymphocytes...
  93. ncbi Comparison of [18F]FHPG and [124/125I]FIAU for imaging herpes simplex virus type 1 thymidine kinase gene expression
    P Brust
    Institute of Bioinorganic and Radiopharmaceutical Chemistry, Forschungszentrum, Rossendorf, Germany
    Eur J Nucl Med 28:721-9. 2001
    ..methyl] guanine, [18F]FHPG) have been proposed for the non-invasive imaging of herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene expression...
  94. ncbi Different regulation of thymidine kinase during the cell cycle of normal versus DNA tumor virus-transformed cells
    M Hengstschlager
    Institute of Molecular Biology, Vienna Biocenter, University of Vienna, Austria
    J Biol Chem 269:13836-42. 1994
    We compared the cell cycle regulation of thymidine kinase (TK) after centrifugal elutriation in normal human and mouse cells (primary cells, diploid fibroblasts) with its expression in cells transformed with different DNA tumor viruses...
  95. ncbi Gamma camera dual imaging with a somatostatin receptor and thymidine kinase after gene transfer with a bicistronic adenovirus in mice
    Kurt R Zinn
    Depts of Radiology, University of Alabama at Birmingham, Boshell Bldg, BDB 11, 1530 3rd Ave S, Birmingham, AL 35294 0012, USA
    Radiology 223:417-25. 2002
    ..To compare two systems for assessing gene transfer to cancer cells and xenograft tumors with noninvasive gamma camera imaging...
  96. ncbi Molecular-genetic PET imaging using an HSV1-tk mutant reporter gene with enhanced specificity to acycloguanosine nucleoside analogs
    Amer M Najjar
    Experimental Diagnostic Imaging, University of Texas M D Anderson Cancer Center, Houston, Texas, USA
    J Nucl Med 50:409-16. 2009
    ..Using herpes simplex virus-1 thymidine kinase (HSV1-tk) mutants with narrower substrate specificities in combination with wild-type HSV1-tk (wtHSV1-tk) ..
  97. ncbi Somatic expression of herpes thymidine kinase in mice following injection of a fusion gene into eggs
    R L Brinster
    Cell 27:223-31. 1981
    A plasmid, designated pMK, containing the structural gene for thymidine kinase from herpes simplex virus (HSV) fused to the promoter/regulatory region of the mouse metallothionein-I gene, was injected into the pronucleus of fertilized one-..
  98. ncbi Phase I study of replication-competent adenovirus-mediated double-suicide gene therapy in combination with conventional-dose three-dimensional conformal radiation therapy for the treatment of newly diagnosed, intermediate- to high-risk prostate cancer
    Svend O Freytag
    Department of Radiation Oncology, Henry Ford Health System, One Ford Place, Detroit, Michigan 48202, USA
    Cancer Res 63:7497-506. 2003
    ..of a replication-competent, oncolytic adenovirus containing a cytosine deaminase (CD)/herpes simplex virus thymidine kinase (HSV-1 TK) fusion gene concomitant with increasing durations of 5-fluorocytosine and valganciclovir prodrug ..
  99. ncbi Replication-competent adenovirus-mediated suicide gene therapy with radiation in a preclinical model of pancreatic cancer
    Svend O Freytag
    Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan 48202, USA
    Mol Ther 15:1600-6. 2007
    ..adenovirus and also to the cytotoxic effects of the yeast cytosine deaminase (yCD) and herpes simplex virus thymidine kinase (HSV-1 TK(SR39)) genes in vitro...
  100. ncbi Monitoring adenoviral DNA delivery, using a mutant herpes simplex virus type 1 thymidine kinase gene as a PET reporter gene
    Q Liang
    Crump Institute for Molecular Imaging, UCLA School of Medicine, Los Angles, CA, USA
    Gene Ther 9:1659-66. 2002
    ..Herpes simplex virus 1 thymidine kinase (HSV1-tk) is currently under intensive investigation as a reporter gene for in vivo imaging of reporter gene ..
  101. pmc Repetitive noninvasive monitoring of HSV1-tk-expressing T cells intravenously infused into nonhuman primates using positron emission tomography and computed tomography with 18F-FEAU
    Gianpietro Dotti
    Department of Experimental Diagnostic Imaging, The University of Texas, USA
    Mol Imaging 8:230-7. 2009
    ..activated and transduced with a retroviral vector encoding for the sr39 mutant herpes simplex virus 1 thymidine kinase (sr39HSV1-tk) reporter gene can be detected after intravenous infusion in discrete lymphoid organs and in ..

Research Grants68

  1. Regulation of HSV-1 Gene Expression and Replication by Nuclear Hormone Receptors
    SHAOCHUNG VICTOR HSIA; Fiscal Year: 2013
    ..genome, we identified thyroid hormone receptor responsive elements (TREs) in the regulatory regions of HSV-1 thymidine kinase (TK), latency-associated transcript (LAT), and infected cell protein 0 (ICP0)...
  2. N-methanocarbathymidine (N-MCT) for the Treatment of Herpes and Pox Virus Infecti
    Aquilur Rahman; Fiscal Year: 2010
    ..N-MCT is activated only in virus-infected cells by the HSV thymidine kinase (TK)...
  3. Mechanism of Irradiation Pulmonary Fibrosis
    Joel S Greenberger; Fiscal Year: 2012
    ..We will use female C57BL/6J mice and HSV-TK (Herpes Simplex Virus-Thymidine Kinase)-CCSP+ transgenic mice (which have gancyclovir sensitive Clara Cell Secretory Protein positive lung stem ..
  4. Neonatal Chemoselection Following Ex Vivo Gene Transfer For Hereditary Disorders
    KARIN L GAENSLER; Fiscal Year: 2012
    ..HYPOTHESIS 3: HSC transduction with a positive/negative lentiviral vector incorporating MGMT and thymidine kinase (TK) will enable negative selection of proliferating alloreactive T cells...
  5. Engineering the Brain Immune System for Tumor Therapy
    Maria G Castro; Fiscal Year: 2013
    ..tumor antigens to the DCs, tumor cells are killed using conditional cytotoxicity [herpes simplex virus type 1 thymidine kinase (TK) plus ganciclovir (GCV)]...
  6. T-cell Therapy for B-lineage Acute Lymphoblastic Leukemia
    Laurence J N Cooper; Fiscal Year: 2013
    ..Beauty (SB) system has been combined with electroporation to introduce the CAR as well as co-express HSV-1 thymidine kinase (TK) for imaging by positron emission tomography (PET)...
  7. A Targeted Preemptive Approach to Addressing Mitochondrial Toxicity of Nucleoside
    John K Buolamwini; Fiscal Year: 2013
    ..are sequentially phosphorylated starting with rate-limiting monophosphorylation by mitochondrial-specific thymidine kinase 2 (TK-2) and/or deoxyguanosine kinase (dGK)...
  8. Genetic correction of human beta-thalassemic induced pluripotent stem cells
    EIRINI PAPAPETROU; Fiscal Year: 2012
    ..An Herpes Simplex Virus-thymidine kinase (HSV-tk) "suicide gene" with regulated expression by tissue-specific promoters/enhancers and/or miR- NAs to ..
  9. In vivo imaging of encapsulated stem cells in mouse models of tumor resection
    Khalid A Shah; Fiscal Year: 2013
    ..To ensure the safety of our approach, we will ultimately engineer human MSC-Enb-TRAIL to express HSV-thymidine kinase (TK), an activatable cellular suicide gene that will allow us to selectively eradicate MSC post-GBM treatment...
  10. Gutless Adenovirus Mediated Gene Therapy for Glioma
    Maria G Castro; Fiscal Year: 2011
    ..fms-like tyrosine kinase 3 ligand (FltSL) (to recruit DCs to the brain), and herpes simplex virus type 1 thymidine kinase (HSV1-TK) that through the phosphorylation of the prodrug GCV (GCV) induces tumor cell death, making ..
  11. Molecular Determinants Affecting FLT-PET in Colorectal Cancer
    HENRY C MANNING; Fiscal Year: 2010
    ..Upon internalization, [18F]-FLT is monophosphorylated in a reaction catalyzed by the cytosolic enzyme thymidine kinase 1 (TK1) which results in intracellular trapping and accumulation...
  12. Genetic correction of human beta-thalassemic induced pluripotent stem cells
    EIRINI PAPAPETROU; Fiscal Year: 2013
    ..An Herpes Simplex Virus-thymidine kinase (HSV-tk) "suicide gene" with regulated expression by tissue-specific promoters/enhancers and/or miR- NAs to ..
  13. Targeting Nanoparticle DNA Delivery to Prostate Tumors
    Janet A Sawicki; Fiscal Year: 2010
    ..genes, a gene encoding diphtheria toxin and a fusion gene encoding cytosine deaminase + herpes simplex virus thymidine kinase to primary and metastatic prostate tumors. Our specific aims are to: 1...
  14. Fluorescence enhanced optical tomography
    Eva M Sevick-Muraca; Fiscal Year: 2012
    ..guanine ([18F]-FHBG) and optical analogs in animals with tumors stably transfected to express viral thymidine kinase (vTK) to quantify gene expression with PET and optical tomography with Dr...
  15. Enhancing Suicide Gene Therapy Through Mechanism-Based Approaches
    Donna S Shewach; Fiscal Year: 2012
    ..We have focused on the herpes simplex virus thymidine kinase (HSV-TK), the initial activator of the antiviral drug ganciclovir (GCV) to its cytotoxic triphosphate, ..
  16. BETR Therapy for Herpesvirus-Associated Tumors
    Martin G Pomper; Fiscal Year: 2013
    ..on the metabolic concentration of a radiolabeled low molecular weight substrate in tumors mediated by the EBV thymidine kinase (TK)...
  17. IMAGING T CELLS BY POSITRON EMISSION TOMOGRAPHY
    Shahriar Yaghoubi; Fiscal Year: 2013
    ..This will be accomplished by coexpressing a mutant of herpes simplex virus-1 thymidine kinase (sr39tk) with the CD19-specific CAR in T cells using the Sleeping Beauty (SB) transposon/transposase system ..
  18. GFI-1 and Osteoblast Suppression in Multiple Myeloma
    GARSON DAVID ROODMAN; Fiscal Year: 2013
    ..model of MM-induced OB suppression using 5TGM1 MM cells (which we modified to express GFP for detection and thymidine kinase, which allows them to be selectively killed by ganciclovir) demonstrate a persistent inhibition of OB ..
  19. Targeting Adenovirus for Gene Therapy of Uterine Leiomyoma
    Ayman Al-Hendy; Fiscal Year: 2013
    ..lesions;dominant negative estrogen receptor (DN-ER), dominant negative progesterone receptor (DN- PR) or thymidine kinase/ganciclovir (TK/GCV) approach...
  20. Lentivirus-based positive/negative selection in minimally ablative transplants
    KARIN L GAENSLER; Fiscal Year: 2013
    ..with tricistronic lentiviral vectors containing P140K-O6-methylguanine-methyltransferase (MGMTP140K), HSV-Thymidine kinase (TKHSV) and eGFP...
  21. Mechanisms of Genetic Reversion in Ichthyosis With Confetti
    Keith A Choate; Fiscal Year: 2013
    ..be examined via stable expression in a human cell line which is heterozygous for a functional allele at the thymidine kinase (TK) locus, conferring sensitivity to trifluorothymidine (TFT) and allowing detection of spontaneous and ..
  22. Airway Goblet Cells: Friend or Foe?
    David A Stoltz; Fiscal Year: 2012
    ..goblet cell and mucus biology by conditionally targeting airway goblet cells with the herpes virus type 1 thymidine kinase system in wild-type and CF pigs...
  23. Imaging Cellular Stress and Treatment Response Using Positron Emission Tomography
    ANTHONY FRANK SHIELDS; Fiscal Year: 2012
    ..Our work, and that of others, has demonstrated that FMAU is retained by the action of thymidine kinase 2 (TK2), a mitochondrial enzyme. We have found that increased retention reflects cellular stress...
  24. [F18]FMAU in Prostate Cancer
    Hossein Jadvar; Fiscal Year: 2010
    ..FMAU, first developed in our laboratory, is a thymidine analog that is phosphorylated by thymidine kinase and incorporated in the DNA and therefore is useful for imaging tumor proliferation...
  25. Engineering Polymers For Gene Therapy of Head Cancer
    Hamid Ghandehari; Fiscal Year: 2013
    ..Gene-directed enzyme prodrug therapy (GDEPT) using adenovirus with herpes simplex virus thymidine kinase (Ad...
  26. Novel molecular imaging approaches to monitor gene and cell-based therapies
    Shahriar Yaghoubi; Fiscal Year: 2013
    ..Our new current PRG being developed is a point mutant (N44D) of the human thymidine kinase 2 (tk2) gene. L-[18F]FMAU and L- [18F]FEAU, two hTK2-N44D substrates, are our new PRPs...
  27. Oral prodrug of a novel antiviral that blocks neuronal reactivation of HSV
    George E Wright; Fiscal Year: 2012
    ..We have pioneered the study of selective inhibitors of the herpes virus-specific thymidine kinase (TK), the enzyme responsible both for "activation" of anti-herpes nucleoside analogs and for reactivation of ..
  28. Imaging Cytolytic T Cells in Cancer Patients Using PET Reporter Genes/Reporter Pr
    Sanjiv S Gambhir; Fiscal Year: 2012
    ..18F]FHBG, which can be used for monitoring the trafficking of cells expressing the Herpes Simplex Virus 1 Thymidine Kinase (HSV1-TK or mutant HSV1-sr39TK)...
  29. Role of NG2 in diabetic nephropathy
    Vesselina G Cooke; Fiscal Year: 2010
    ..transgenic mice in which mesangial cells are transgenically tagged with yellow fluorescent protein or viral thymidine kinase (to ablate proliferating mesangial cells at specific time points using ganciclovir) and evaluate the ..
  30. The 26S Proteasome in Cancer Stem Cells
    Frank Pajonk; Fiscal Year: 2013
    ..Furthermore, we have used the same degron to destabilize thymidine kinase and to target it using ganciclovir, in so doing eliminating CICs from glioblastoma cell populations...
  31. PDX-1 is a Therapeutic Target for Pancreatic Cancer
    FRANCIS CHARLES BRUNICARDI; Fiscal Year: 2012
    ..Preliminary data also demonstrate that viral thymidine kinase expression using rat insulin promoter-thymidine kinase gene therapy (RIP-TK) in PC cells in mice can be ..
  32. Molecular Imaging of Stem Cell Transplantation in the Heart
    Juri G Gelovani; Fiscal Year: 2010
    ..This construct will encode for a constitutively expressed "beacon" reporter gene-the truncated human thymidine kinase type two fused with red fluorescent protein (hTK2RFP)-and a "sensor" reporter gene, consisting of the herpes ..
  33. Role of Fibroblasts in Cancer
    Raghu Kalluri; Fiscal Year: 2010
    ..specific ablation of FSP1+/alphaSMA- fibroblasts using transgenic mice, which harbor FSP1 promoter driven thymidine kinase protein (FSP1-tk), demonstrate that FSP1+ fibroblasts are critical for the formation of metastasis without a ..
  34. Mitochondrial Toxicity of Antiviral Nucleosides
    Edward E McKee; Fiscal Year: 2010
    ..Since AZT is a competitive inhibitor of thymidine kinase 2, we will also test the effects of thymidine and uridine on reversing AZT toxicity, and on reversing changes ..
  35. Human Pharmacogenetics and Human Liver Regeneration
    GARY A PELTZ; Fiscal Year: 2013
    ..To do this, a highly immunocompromised (NOG) mouse was genetically engineered to express a thymidine kinase transgene in the liver, which enabled the temporally controlled and tissue-specific ablation of mouse liver ..
  36. Injectable reporters to image tumors and guide resection
    Roger Y Tsien; Fiscal Year: 2013
    ..tomography (PET), combining best available versions of far-red fluorescent protein, firefly luciferase, and thymidine kinase, expressed as separate but genetically linked proteins separated by self-cleaving viral 2A sequences...
  37. Virus-Targeted Therapy for Malignancies
    SUSAN PARK PERRINE; Fiscal Year: 2011
    ..cells can be killed by nucleoside analog antiviral drugs like ganciclovir, which target the viral thymidine kinase (TK) enzyme...
  38. CARDIOMYOPATHY IN AIDS
    William Lewis; Fiscal Year: 2009
    ..b>Thymidine kinase 2 (TK2;phosphorylates pyrimidines intramitochondrially) is evaluated with "dominant negative" mutant TGs...
  39. Targeted Therapy for Burkitt Lymphoma in Resource Poor Settings
    Glen N Barber; Fiscal Year: 2010
    ..effect by both blocking a vital survival factor and inducing the EBV gene expression including viral thymidine kinase (vTK), which phosphorylates the thymidine analogue, AZT...
  40. TK-based Infection Imaging
    Martin G Pomper; Fiscal Year: 2013
    ..positron emission tomography (PET) that directly radiolabels and images bacteria by virtue of the bacterial thymidine kinase (TK) enzyme, which can be tagged with [124I]FIAU...
  41. Investigation of herpes simplex virus -1 neurotropism in SCID DRG xenografts
    Ann M Arvin; Fiscal Year: 2010
    ..through the evaluation of recombinant HSV-1 strains, in particular we will examine the requirement for HSV-1 thymidine kinase (TK) during initial infection and persistence in DRG, and gD mutants for their capacity for viral entry;(3) ..
  42. Boronated nucleosides for neutron capture therapy of brain tumors
    Werner Tjarks; Fiscal Year: 2013
    ..The mechanism of action of 3CTAs is primarily based on their ability to function as substrates of human thymidine kinase 1 (TK1), which is only active in proliferating cells...
  43. Effect of maternal care on neurogenesis and behavior
    Arie Kaffman; Fiscal Year: 2010
    ..In order to test this hypothesis we have generated transgenic mice that express thymidine kinase in neural stem cells (NSC) and show that exposure of NSC from these mice to Ganciclovir abolishes ..
  44. Clinical and Immunologic Evaluation of ProstAtak for Prostate Cancer
    Estuardo Aguilar-Cordova; Fiscal Year: 2013
    ..A secondary objective is to prospectively evaluate surrogate end-points for early stage prostate cancer. ..
  45. Molecular imaging of cell-based therapeutics using an engineered human enzyme.
    Arnon Lavie; Fiscal Year: 2013
    ..To circumvent this, we will employ a modified version of human thymidine kinase 2 (TK2) as the source for the unique enzymatic activity...
  46. Retroviral replicating vector for prodrug activator gene therapy
    Douglas J Jolly; Fiscal Year: 2012
    ..We have now constructed RRV expressing an optimized Herpes simplex thymidine kinase (HSV-TK) prodrug activator gene (RRV-TK in this proposal)...
  47. In situ Redirection of T cell Specificity and Imaging of Targeted CAR Expression.
    Pin Wang; Fiscal Year: 2013
    ..can specifically transduce T cells in situ with tumor-antigen specific CAR genes and herpes simplex virus-1 thymidine kinase (HSV1tk), a positron emission tomography reporter (PET) gene...
  48. Molecular Sensors for Imaging Histone Methylations in Living Animals
    Ramasamy Paulmurugan; Fiscal Year: 2013
    ..achieved by developing: 1) Optical bioluminescence (Split-Luciferase-complementation), and 2) microPET (Split-Thymidine kinase complementation) imaging sensors...
  49. MECHANISMS REGULATING HSV TK EXPRESSION DURING INFECTION
    Donald M Coen; Fiscal Year: 2010
    ..A focus of these studies is the HSV thymidine kinase (tk) gene and the gene it overlaps, UL24. HSV and other herpesviruses are important human pathogens...
  50. Acquired mtDNA depletion and nucleoside reverse transciptase inhibitors
    William Lewis; Fiscal Year: 2010
    ..Pyrimidine NRTIs compete with dThd for phosphorylation to monophosphates (-MP) by thymidine kinase (cytoplasmic TK1 and mitochondrial TK2 isoforms) and to diphosphates (-DP) by thymidylate kinase (TMPK)...
  51. Enzyme-delivery scaffold technology for targeted cancer killing.
    Arnon Lavie; Fiscal Year: 2013
    ..version of human deoxycytidine kinase (dCKEN), which is a novel enzyme variant that has been endowed with thymidine kinase activity...
  52. Targeting of EBV Latency in Burkitt's Lymphoma
    Juan Carlos Ramos; Fiscal Year: 2010
    ..Commonly available chemotherapeutic agents are known to induce the EBV lytic cycle including viral thymidine kinase and thereby potentiate phosphorylation of AZT...
  53. Targeted Gene Therapy for Lymphoma
    Bruce F Smith; Fiscal Year: 2010
    ..Finally, the ability of these vectors to deliver the Herpes Simplex thymidine kinase gene to tumor cells will be evaluated in dogs with spontaneously occurring lymphoma...
  54. Nucleoside Transporters In HAART Mitochondrial Toxicity
    John Buolamwini; Fiscal Year: 2006
    ..nucleosides are sequentially phosphorylated by mitochondrial kinases such as the mitochondrial-specific thymidine kinase (TK-2) and others to yield the active triphosphate metabolites, which then inhibit mtDNA synthesis...
  55. MODELS OF IN VIVO MYOMETRIAL GENE TRANSFER
    Gregory Christman; Fiscal Year: 2001
    ..Recently, gene transfer has been shown to be effective in vascular smooth muscle using the herpes virus thymidine kinase/ganciclovir (HSV-tk/GCV) cytotoxic gene therapy approach to ablate smooth muscle proliferation following ..
  56. Phase II SBIR: WHI-07: A Novel Dual-Function Microbicide
    OSMOND D CRUZ; Fiscal Year: 2005
    ..WHI-07 was rationally designed to bypass the thymidine kinase dependency of ZDV activation in genital tract secretions...
  57. ZIDOVUDINE METABOLISM: REBRETRON TREATED HUMAN PATIENTS
    Jose Rodriguez; Fiscal Year: 2003
    ..ZDV-MP and ZDV-TP), by increasing thymidine triphosphate (dTTP) intracellular concentrations which inhibits thymidine kinase 1...
  58. ALTERED MECHANICAL LOADS AND SKELETAL MUSCLE PHENOTYPE
    Richard Tsika; Fiscal Year: 2009
    ..in muscle cells, and that the dbetaNRE-S element confers Pur-dependent decreased activation of a minimal thymidine kinase promoter...
  59. Stem cells as vehicles for therapeutic nanoparticle delivery to breast cancer
    Deryl Troyer; Fiscal Year: 2009
    ..In specific aim 1, we will engineer UCMS cells with a suicide gene (thymidine kinase), load them with several multiple nanogel therapeutic combinations, coculture them with breast cancer cells, ..
  60. Enhancing Suicide Gene Therapy Through Mechanism-Based Approaches
    Donna Shewach; Fiscal Year: 2007
    ..We have focused on the herpes simplex virus thymidine kinase (HSV-TK), the initial activator of the antiviral drug ganciclovir (GCV) to its cytotoxic triphosphate, ..
  61. IMPROVING SUICIDE GENES FOR CANCER GENE THERAPY
    Margaret Black; Fiscal Year: 2009
    ..Current protocols to elicit tumor reduction utilize Herpes Simplex Virus type 1 (HSV) thymidine kinase (TK) with the prodrug ganciclovir (GCV), or the E...
  62. DLI using genetically modified T cells: Phase 1 trial
    John Dipersio; Fiscal Year: 2005
    ..The central hypotheses of this study are the following: Retroviral mediated transfer of a chimeric CD34-Thymidine Kinase (CD34-TK75) suicide gene into human T cells to control GvHD can be performed safely, and will result in ..
  63. MOLECULAR ANALYSIS OF CARCINOGEN-INDUCED MUTATIONS
    Norman Drinkwater; Fiscal Year: 1992
    ..the oriP element from Epstein-Barr virus, a bacterial plasmid replicon, and the herpes simplex virus type 1 thymidine kinase (HSV-tK) gene, replicate as plasmids and are stably maintained in human cells...
  64. EXPERIMENTAL THERAPEUTICS EXPLOITING FOLATE RECEPTORS
    ASOK ANTONY; Fiscal Year: 2002
    ..enter cells via FR, thereby predicting a lower IC50 with less systemic toxicity; and third, the increase in thymidine kinase (TK) activity which accompanies FR overexpression will render these cells hypersensitive to otherwise ..
  65. Gene Therapy for Retinoblastoma
    Richard Hurwitz; Fiscal Year: 2003
    ..Numerous preclinical and clinical trials have shown that adenoviral vectors used to deliver the Herpes thymidine kinase gene followed by ganciclovir can be safely administered...
  66. GENE-BASED THERAPIES AND IMAGING OF MALIGNANT GLIOMAS
    Kevin Judy; Fiscal Year: 2003
    ..associated with the intracranial administration of two new recombinant adenovirus expressing herpes virus thymidine kinase (H5.001RSVtk) or interferon-beta (H5.010CMVINF beta) in patients with malignant gliomas...
  67. New imaging agents for studying gene expression
    HANK KUNG; Fiscal Year: 2007
    ..We propose to develop F-18 and 1-123 labeled nucleosides as selective substrates of herpes simplex thymidine kinase (HSV1-TK) in conjunction with positron computed tomography (PET)...
  68. DRUGS TO PREVENT RECURRENT HERPESVIRUS INFECTIONS
    George Wright; Fiscal Year: 2001
    ..We have established that inhibitors of the HSV thymidine kinase (TK) prevent recurrent infections in animal models...