Genomes and Genes
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 18.104.22.168.
Publications358 found, 100 shown here
- Suicide gene therapy mediated by the Herpes Simplex virus thymidine kinase gene/Ganciclovir system: fifteen years of applicationC 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)...
- Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic miceT G Bush
Medical Research Council Cambridge Centre for Brain Repair, and Department of Anatomy, University of Cambridge, United Kingdom
Neuron 23:297-308. 1999....
- Validation of FLT uptake as a measure of thymidine kinase-1 activity in A549 carcinoma cellsJanet 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.
- Imaging tri-fusion multimodality reporter gene expression in living subjectsPritha 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 ..
- Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathyA 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...
- Comparison of radiolabeled nucleoside probes (FIAU, FHBG, and FHPG) for PET imaging of HSV1-tk gene expressionJuri Gelovani Tjuvajev
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
J Nucl Med 43:1072-83. 2002The 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-..
- Human pharmacokinetic and dosimetry studies of [(18)F]FHBG: a reporter probe for imaging herpes simplex virus type-1 thymidine kinase reporter gene expressionS 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...
- Thymidine kinase 2 (H126N) knockin mice show the essential role of balanced deoxynucleotide pools for mitochondrial DNA maintenanceHasan 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...
- Progressive loss of mitochondrial DNA in thymidine kinase 2-deficient miceXiaoshan Zhou
Department of Laboratory Medicine, Karolinska Institute, S 141 86 Huddinge, Sweden
Hum Mol Genet 17:2329-35. 2008Deficient enzymatic activity of the mitochondrial deoxyribonucleoside kinases deoxyguanosine kinase (DGUOK) or thymidine kinase 2 (TK2) cause mitochondrial DNA (mtDNA)-depletion syndromes in humans...
- The "bystander effect": tumor regression when a fraction of the tumor mass is genetically modifiedS M Freeman
Clinical Immunology Unit, University of Rochester Medical School, New York 14642
Cancer Res 53:5274-83. 1993Tumor cells expressing the herpes simplex virus thymidine kinase (HSV-TK) gene are sensitive to the drug ganciclovir (GCV)...
- A mutant herpes simplex virus type 1 thymidine kinase reporter gene shows improved sensitivity for imaging reporter gene expression with positron emission tomographyS 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...
- Mammalian deoxyribonucleoside kinasesE S Arner
Medical Nobel Institute for Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Sweden
Pharmacol Ther 67:155-86. 1995The mammalian deoxyribonucleoside kinases are deoxycytidine kinase, thymidine kinase 1 and 2 and deoxyguanosine kinase...
- Chemotherapy delivered after viral immunogene therapy augments antitumor efficacy via multiple immune-mediated mechanismsZvi 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...
- Systemic cancer therapy with a tumor-selective vaccinia virus mutant lacking thymidine kinase and vaccinia growth factor genesJ 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 ..
- Thymidine kinase 2 mutations in autosomal recessive progressive external ophthalmoplegia with multiple mitochondrial DNA deletionsHenna 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...
- 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 expressionShahriar 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...
- Regulation by degradation, a cellular defense against deoxyribonucleotide pool imbalancesChiara 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...
- Fusion enzymes containing HSV-1 thymidine kinase mutants and guanylate kinase enhance prodrug sensitivity in vitro and in vivoA Ardiani
School of Molecular Biosciences, Washington State University, Pullman, WA 99164 6534, USA
Cancer Gene Ther 17:86-96. 2010Herpes simplex virus thymidine kinase (HSVTK) with ganciclovir (GCV) is currently the most widely used suicide gene/prodrug system in cancer gene therapy...
- Selective removal of undifferentiated embryonic stem cells from differentiation cultures through HSV1 thymidine kinase and ganciclovir treatmentOrtwin 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 ..
- Thymidine kinase gene modified bone marrow mesenchymal stem cells as vehicles for antitumor therapyChao 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 ..
- Current progress in suicide gene therapy for cancerKazuyuki 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, ..
- Systemic efficacy of combined suicide/cytokine gene therapy in a murine model of hepatocellular carcinomaAnna 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...
- Human amniotic fluid-derived stem cells expressing cytosine deaminase and thymidine kinase inhibits the growth of breast cancer cells in cellular and xenograft mouse modelsN 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),..
- Thymidine kinase 1 expression defines an activated G1 state of the cell cycle as revealed with site-specific antibodies and ArrayScan assaysFabio Gasparri
Biology Department, Oncology, Nerviano Medical Sciences, Nerviano, Italy
Eur J Cell Biol 88:779-85. 2009b>Thymidine kinase 1 (TK1) is a DNA salvage enzyme involved in the synthesis of thymidine triphosphate needed during S phase...
- Alpha-fetoprotein-thymidine kinase-luciferase knockin mice: a novel model for dual modality longitudinal imaging of tumorigenesis in liverXincheng 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...
- 8-[18F]Fluoropenciclovir: an improved reporter probe for imaging HSV1-tk reporter gene expression in vivo using PETM 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...
- A phase I clinical trial of thymidine kinase-based gene therapy in advanced hepatocellular carcinomaB 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...
- In vivo biological activity of the histone deacetylase inhibitor LAQ824 is detectable with 3'-deoxy-3'-[18F]fluorothymidine positron emission tomographyJulius 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...
- Regulation and functional contribution of thymidine kinase 1 in repair of DNA damageYen 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 ..
- A heterotypic bystander effect for tumor cell killing after adeno-associated virus/phage-mediated, vascular-targeted suicide gene transferMartin 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 ..
- Essential protective roles of reactive astrocytes in traumatic brain injuryD 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...
- 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...
- Selective ablation of human embryonic stem cells expressing a "suicide" geneMaya 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...
- Onset and organ specificity of Tk2 deficiency depends on Tk1 down-regulation and transcriptional compensationBeatriz Dorado
Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
Hum Mol Genet 20:155-64. 2011Deficiency of thymidine kinase 2 (TK2) is a frequent cause of isolated myopathy or encephalomyopathy in children with mitochondrial DNA (mtDNA) depletion...
- Thymidine kinase 2 defects can cause multi-tissue mtDNA depletion syndromeAlexandra 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...
- Correlation between MIB-1 and other proliferation markers: clinical implications of the MIB-1 cutoff valueFrederique 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...
- Molecular imaging of embryonic stem cell misbehavior and suicide gene ablationFeng 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...
- Transcription factors of the Sp1 family: interaction with E2F and regulation of the murine thymidine kinase promoterH 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...
- A sensitive and kinetically defined radiochemical assay for canine and human serum thymidine kinase 1 (TK1) to monitor canine malignant lymphomaH Sharif
Department of Anatomy, Swedish University of Agricultural Sciences, BMC, P O Box 575, S 751 23 Uppsala, Sweden
Vet J 194:40-7. 2012b>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...
- Construction and identification of recombinant vectors carrying herpes simplex virus thymidine kinase and cytokine genes expressed in gastric carcinoma cell line SGC7901Jian 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. 2004To 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.
- HSV type 1 thymidine kinase protein accumulation in round spermatids induces male infertility by spermatogenesis disruption and apoptotic loss of germ cellsLi yi Cai
Division of Life Science, Graduate School of Agriculture, Meiji University, Kawasaki, Kanagawa 214 8571, Japan
Reprod Toxicol 27:14-21. 2009HSV type 1 thymidine kinase (HSV1-TK)-introduced transgenic rodents and HSV-infected humans were reported to suffer male infertility...
- 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 cellsM 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-..
- Tumor cell apoptosis induces tumor-specific immunity in a CC chemokine receptor 1- and 5-dependent manner in miceNoriho 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)...
- A spectrophotometric assay for quantitative determination of kcat of herpes simplex virus type 1 thymidine kinase substratesP 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...
- mtDNA depletion myopathy: elucidation of the tissue specificity in the mitochondrial thymidine kinase (TK2) deficiencyAnn Saada
Metabolic Disease Unit, Shaare Zedek Medical Center, Post Office Box 3235, IL 91031 Jerusalem, Israel
Mol Genet Metab 79:1-5. 2003Decreased mitochondrial thymidine kinase (TK2) activity is associated with mitochondrial DNA (mtDNA) depletion and respiratory chain dysfunction and is manifested by isolated, fatal skeletal myopathy...
- AdvHSV-tk gene therapy with intravenous ganciclovir improves survival in human malignant glioma: a randomised, controlled studyArto 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...
- The uptake of 3'-deoxy-3'-[18F]fluorothymidine into L5178Y tumours in vivo is dependent on thymidine kinase 1 protein levelsHenryk 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. 2005The 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.
- 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 koiB 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...
- A scalable approach to prevent teratoma formation of human embryonic stem cellsZhili 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, ..
- Ablation of tumor-derived stem cells transplanted to the central nervous system by genetic modification of embryonic stem cells with a suicide geneJuyeon 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)..
- Adjuvant adenovirus-mediated delivery of herpes simplex virus thymidine kinase administration improves outcome of liver transplantation in patients with advanced hepatocellular carcinomaNing 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 ..
- Noninvasive molecular imaging of hypoxia in human xenografts: comparing hypoxia-induced gene expression with endogenous and exogenous hypoxia markersFuqiu 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), ..
- Two novel mutations in thymidine kinase-2 cause early onset fatal encephalomyopathy and severe mtDNA depletionNicole Lesko
Department of Laboratory Medicine, Division of Metabolic Diseases, Karolinska Institutet, Stockholm, Sweden
Neuromuscul Disord 20:198-203. 2010Deficiency of thymidine kinase-2 (TK2) has been described in children with early onset fatal skeletal myopathy...
- Phase I study of adenoviral delivery of the HSV-tk gene and ganciclovir administration in patients with current malignant brain tumorsT 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...
- Gene therapy: the first approved gene-based medicines, molecular mechanisms and clinical indicationsJ 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.
- High serum thymidine kinase 1 level predicts poorer survival in patients with chronic lymphocytic leukemiaSergej 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. 2010Serum 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...
- Thymidine kinase and cancer monitoringStefan 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...
- 4- to 6-week-old adult-born hippocampal neurons influence novelty-evoked exploration and contextual fear conditioningChristine 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...
- High thymidine kinase 1 (TK1) expression is a predictor of poor survival in patients with pT1 of lung adenocarcinomaYan Xu
Department of Pathology, Nanjing Jinling Hospital, Nanjing University Medical School, 305 Zhongshangdong Road, Nanjing, 210002, Jiangsu Province, China
Tumour Biol 33:475-83. 2012In 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...
- Comparative aspects of the proliferation marker thymidine kinase 1 in human and canine tumour diseasesH 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 ..
- 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 modelsMarco 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 ..
- Deoxyribonucleotide metabolism in cycling and resting human fibroblasts with a missense mutation in p53R2, a subunit of ribonucleotide reductaseGiovanna 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 ..
- Adenovirus-mediated gene transfer of enhanced Herpes simplex virus thymidine kinase mutants improves prodrug-mediated tumor cell killingRainer Wiewrodt
Department of Medicine, Philadelphia, Pennsylvania 19194, USA
Cancer Gene Ther 10:353-64. 2003The 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 ..
- 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 productionQiao 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...
- Ultrasound-targeted microbubble destruction mediated herpes simplex virus-thymidine kinase gene treats hepatoma in miceShiji 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. 2010The 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.
- A novel G-quadruplex motif modulates promoter activity of human thymidine kinase 1Richa 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)...
- 3'-[4-Aryl-(1,2,3-triazol-1-yl)]-3'-deoxythymidine analogues as potent and selective inhibitors of human mitochondrial thymidine kinaseSara 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-..
- Advances in imaging gene-directed enzyme prodrug therapySrabani 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-..
- Liver failure caused by herpes simplex virus thymidine kinase plus ganciclovir therapy is associated with mitochondrial dysfunction and mitochondrial DNA depletionMaite Herraiz
Division of Hepatology and Gene Therapy, University of Navarra, Medical School Pamplona, 31008 Pamplona, Spain
Hum Gene Ther 14:463-72. 2003Herpes simplex virus thymidine kinase (HSV-tk) converts ganciclovir (GCV) into an active compound, which can be incorporated into DNA molecules and terminate DNA synthesis...
- Serum thymidine kinase activity in dogs with malignant lymphoma: a potent marker for prognosis and monitoring the diseaseHenrik 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. 2004Serum thymidine kinase (sTK) activity was evaluated as a tumor marker for canine malignant lymphoma (ML)...
- pRL-TK induction can cause misinterpretation of gene promoter activitySimone A Osborne
School of Biomolecular and Biomedical Science, Griffith University, Nathan, QLD, Australia 4111
Biotechniques 33:1240-2. 2002
- 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 drugsYury Likar
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
J Nucl Med 49:713-20. 2008The 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...
- Mitotic degradation of human thymidine kinase 1 is dependent on the anaphase-promoting complex/cyclosome-CDH1-mediated pathwayPo 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. 2004The expression of human thymidine kinase 1 (hTK1) is highly dependent on the growth states and cell cycle stages in mammalian cells...
- 3'-(1,2,3-Triazol-1-yl)-3'-deoxythymidine analogs as substrates for human and Ureaplasma parvum thymidine kinase for structure-activity investigationsJay 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...
- Cytosolic thymidine kinase is a specific histopathologic tumour marker for breast carcinomasQimin He
Department of Oncology Clinical Research Laboratory, Novum, KFC, Karolinska University Hospital, S 141 86 Stockholm, Sweden
Int J Oncol 25:945-53. 2004b>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...
- Thymidine kinase, thymidylate synthase, and dihydropyrimidine dehydrogenase profiles of cell lines of the National Cancer Institute's Anticancer Drug ScreenJ 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...
- Noninvasive detection of therapeutic cytolytic T cells with 18F-FHBG PET in a patient with gliomaShahriar 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.
- Connexin over-expression differentially suppresses glioma growth and contributes to the bystander effect following HSV-thymidine kinase gene therapyTomas 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...
- The anti-glioma effect of suicide gene therapy using BMSC expressing HSV/TK combined with overexpression of Cx43 in glioma cellsQ 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 ..
- Imaging colon cancer response following treatment with AZD1152: a preclinical analysis of [18F]fluoro-2-deoxyglucose and 3'-deoxy-3'-[18F]fluorothymidine imagingMaxim A Moroz
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Clin Cancer Res 17:1099-110. 2011....
- Enhanced combined tumor-specific oncolysis and suicide gene therapy for prostate cancer using M6 promoterM 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)...
- Optimizing prostate cancer suicide gene therapy using herpes simplex virus thymidine kinase active site variantsAllan J Pantuck
Department of Urology, School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
Hum Gene Ther 13:777-89. 2002The herpes simplex virus (HSV) thymidine kinase gene (tk) forms the basis of a widely used strategy for suicide gene therapy...
- 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 effectsBin 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...
- Structure-guided engineering of human thymidine kinase 2 as a positron emission tomography reporter gene for enhanced phosphorylation of non-natural thymidine analog reporter probeDean 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...
- Correlation of 18F-FLT uptake with equilibrative nucleoside transporter-1 and thymidine kinase-1 expressions in gastrointestinal cancerReiko Kameyama
Department of Radiology, Faculty of Medicine, Kagawa University, Kagawa, Japan
Nucl Med Commun 32:460-5. 2011We 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 ..
- Oncolytic adenoviruses armed with thymidine kinase can be traced by PET imaging and show potent antitumoural effects by ganciclovir dosingDaniel Abate-Daga
Institut d Investigacions Biomediques August Pi i Sunyer IDIBAPS, Barcelona, Spain
PLoS ONE 6:e26142. 2011Replication-competent adenoviruses armed with thymidine kinase (TK) combine the concepts of virotherapy and suicide gene therapy...
- Influence of the bystander effect on HSV-tk/GCV gene therapy. A reviewIngrid 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...
- Potent tumor-specific immunity induced by an in vivo heat shock protein-suicide gene-based tumor vaccineWenhong 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...
- Non-invasive in vivo imaging with radiolabelled FIAU for monitoring cancer gene therapy using herpes simplex virus type 1 thymidine kinase and ganciclovirWin 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...
- Prognostic importance of thymidine kinase in colorectal and breast cancerS Svobodova
Third Internal Medicine Clinic, General Faculty Hospital Prague, First Medical School Prague Charles University, Prague, Czech Republic
Anticancer Res 27:1907-9. 2007b>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...
- Characterization of a thymidine kinase-deficient mutant of equine herpesvirus 4 and in vitro susceptibility of the virus to antiviral agentsWalid 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 ..
- Multimodality imaging of lymphocytic migration using lentiviral-based transduction of a tri-fusion reporter geneYoung 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...
- Comparison of [18F]FHPG and [124/125I]FIAU for imaging herpes simplex virus type 1 thymidine kinase gene expressionP 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...
- Different regulation of thymidine kinase during the cell cycle of normal versus DNA tumor virus-transformed cellsM Hengstschlager
Institute of Molecular Biology, Vienna Biocenter, University of Vienna, Austria
J Biol Chem 269:13836-42. 1994We 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...
- Gamma camera dual imaging with a somatostatin receptor and thymidine kinase after gene transfer with a bicistronic adenovirus in miceKurt 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...
- Molecular-genetic PET imaging using an HSV1-tk mutant reporter gene with enhanced specificity to acycloguanosine nucleoside analogsAmer 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) ..
- Somatic expression of herpes thymidine kinase in mice following injection of a fusion gene into eggsR L Brinster
Cell 27:223-31. 1981A 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-..
- 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 cancerSvend 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 ..
- Replication-competent adenovirus-mediated suicide gene therapy with radiation in a preclinical model of pancreatic cancerSvend 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...
- Monitoring adenoviral DNA delivery, using a mutant herpes simplex virus type 1 thymidine kinase gene as a PET reporter geneQ 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 ..
- Repetitive noninvasive monitoring of HSV1-tk-expressing T cells intravenously infused into nonhuman primates using positron emission tomography and computed tomography with 18F-FEAUGianpietro 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 ..
- Regulation of HSV-1 Gene Expression and Replication by Nuclear Hormone ReceptorsSHAOCHUNG 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)...
- N-methanocarbathymidine (N-MCT) for the Treatment of Herpes and Pox Virus InfectiAquilur Rahman; Fiscal Year: 2010..N-MCT is activated only in virus-infected cells by the HSV thymidine kinase (TK)...
- Mechanism of Irradiation Pulmonary FibrosisJoel 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 ..
- Neonatal Chemoselection Following Ex Vivo Gene Transfer For Hereditary DisordersKARIN 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...
- Engineering the Brain Immune System for Tumor TherapyMaria 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)]...
- T-cell Therapy for B-lineage Acute Lymphoblastic LeukemiaLaurence 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)...
- A Targeted Preemptive Approach to Addressing Mitochondrial Toxicity of NucleosideJohn 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)...
- Genetic correction of human beta-thalassemic induced pluripotent stem cellsEIRINI 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 ..
- In vivo imaging of encapsulated stem cells in mouse models of tumor resectionKhalid 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...
- Gutless Adenovirus Mediated Gene Therapy for GliomaMaria 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 ..
- Molecular Determinants Affecting FLT-PET in Colorectal CancerHENRY 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...
- Genetic correction of human beta-thalassemic induced pluripotent stem cellsEIRINI 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 ..
- Targeting Nanoparticle DNA Delivery to Prostate TumorsJanet 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...
- Fluorescence enhanced optical tomographyEva 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...
- Enhancing Suicide Gene Therapy Through Mechanism-Based ApproachesDonna 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, ..
- BETR Therapy for Herpesvirus-Associated TumorsMartin 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)...
- IMAGING T CELLS BY POSITRON EMISSION TOMOGRAPHYShahriar 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 ..
- GFI-1 and Osteoblast Suppression in Multiple MyelomaGARSON 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 ..
- Targeting Adenovirus for Gene Therapy of Uterine LeiomyomaAyman 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...
- Lentivirus-based positive/negative selection in minimally ablative transplantsKARIN L GAENSLER; Fiscal Year: 2013..with tricistronic lentiviral vectors containing P140K-O6-methylguanine-methyltransferase (MGMTP140K), HSV-Thymidine kinase (TKHSV) and eGFP...
- Mechanisms of Genetic Reversion in Ichthyosis With ConfettiKeith 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 ..
- 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...
- Imaging Cellular Stress and Treatment Response Using Positron Emission TomographyANTHONY 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...
- [F18]FMAU in Prostate CancerHossein 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...
- Engineering Polymers For Gene Therapy of Head CancerHamid Ghandehari; Fiscal Year: 2013..Gene-directed enzyme prodrug therapy (GDEPT) using adenovirus with herpes simplex virus thymidine kinase (Ad...
- Novel molecular imaging approaches to monitor gene and cell-based therapiesShahriar 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...
- Oral prodrug of a novel antiviral that blocks neuronal reactivation of HSVGeorge 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 ..
- Imaging Cytolytic T Cells in Cancer Patients Using PET Reporter Genes/Reporter PrSanjiv 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)...
- Role of NG2 in diabetic nephropathyVesselina 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 ..
- The 26S Proteasome in Cancer Stem CellsFrank 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...
- PDX-1 is a Therapeutic Target for Pancreatic CancerFRANCIS 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 ..
- Molecular Imaging of Stem Cell Transplantation in the HeartJuri 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 ..
- Role of Fibroblasts in CancerRaghu 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 ..
- Mitochondrial Toxicity of Antiviral NucleosidesEdward 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 ..
- Human Pharmacogenetics and Human Liver RegenerationGARY 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 ..
- Injectable reporters to image tumors and guide resectionRoger 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...
- Virus-Targeted Therapy for MalignanciesSUSAN PARK PERRINE; Fiscal Year: 2011..cells can be killed by nucleoside analog antiviral drugs like ganciclovir, which target the viral thymidine kinase (TK) enzyme...
- CARDIOMYOPATHY IN AIDSWilliam Lewis; Fiscal Year: 2009..b>Thymidine kinase 2 (TK2;phosphorylates pyrimidines intramitochondrially) is evaluated with "dominant negative" mutant TGs...
- Targeted Therapy for Burkitt Lymphoma in Resource Poor SettingsGlen 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...
- TK-based Infection ImagingMartin 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...
- Investigation of herpes simplex virus -1 neurotropism in SCID DRG xenograftsAnn 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) ..
- Boronated nucleosides for neutron capture therapy of brain tumorsWerner 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...
- Effect of maternal care on neurogenesis and behaviorArie 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 ..
- Clinical and Immunologic Evaluation of ProstAtak for Prostate CancerEstuardo Aguilar-Cordova; Fiscal Year: 2013..A secondary objective is to prospectively evaluate surrogate end-points for early stage prostate cancer. ..
- 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...
- Retroviral replicating vector for prodrug activator gene therapyDouglas 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)...
- 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...
- Molecular Sensors for Imaging Histone Methylations in Living AnimalsRamasamy Paulmurugan; Fiscal Year: 2013..achieved by developing: 1) Optical bioluminescence (Split-Luciferase-complementation), and 2) microPET (Split-Thymidine kinase complementation) imaging sensors...
- MECHANISMS REGULATING HSV TK EXPRESSION DURING INFECTIONDonald 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...
- Acquired mtDNA depletion and nucleoside reverse transciptase inhibitorsWilliam 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)...
- 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...
- Targeting of EBV Latency in Burkitt's LymphomaJuan 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...
- Targeted Gene Therapy for LymphomaBruce 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...
- Nucleoside Transporters In HAART Mitochondrial ToxicityJohn 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...
- MODELS OF IN VIVO MYOMETRIAL GENE TRANSFERGregory 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 ..
- Phase II SBIR: WHI-07: A Novel Dual-Function MicrobicideOSMOND D CRUZ; Fiscal Year: 2005..WHI-07 was rationally designed to bypass the thymidine kinase dependency of ZDV activation in genital tract secretions...
- ZIDOVUDINE METABOLISM: REBRETRON TREATED HUMAN PATIENTSJose Rodriguez; Fiscal Year: 2003..ZDV-MP and ZDV-TP), by increasing thymidine triphosphate (dTTP) intracellular concentrations which inhibits thymidine kinase 1...
- ALTERED MECHANICAL LOADS AND SKELETAL MUSCLE PHENOTYPERichard Tsika; Fiscal Year: 2009..in muscle cells, and that the dbetaNRE-S element confers Pur-dependent decreased activation of a minimal thymidine kinase promoter...
- Stem cells as vehicles for therapeutic nanoparticle delivery to breast cancerDeryl 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, ..
- Enhancing Suicide Gene Therapy Through Mechanism-Based ApproachesDonna 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, ..
- IMPROVING SUICIDE GENES FOR CANCER GENE THERAPYMargaret 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...
- DLI using genetically modified T cells: Phase 1 trialJohn 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 ..
- MOLECULAR ANALYSIS OF CARCINOGEN-INDUCED MUTATIONSNorman 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...
- EXPERIMENTAL THERAPEUTICS EXPLOITING FOLATE RECEPTORSASOK 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 ..
- Gene Therapy for RetinoblastomaRichard 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...
- GENE-BASED THERAPIES AND IMAGING OF MALIGNANT GLIOMASKevin 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...
- New imaging agents for studying gene expressionHANK 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)...
- DRUGS TO PREVENT RECURRENT HERPESVIRUS INFECTIONSGeorge Wright; Fiscal Year: 2001..We have established that inhibitors of the HSV thymidine kinase (TK) prevent recurrent infections in animal models...