Thymidine kinase

Thymidine kinase

Crystal structure of a tetramer of thymidine kinase from U. urealyticum (where the monomers are color cyan, green, red, and magenta respectively) in complex with thymidine (space-filling model, carbon = white, oxygen = red, nitrogen = blue).[1]
Identifiers
EC number 2.7.1.21
CAS number 9002-06-6
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
Thymidine kinase
Identifiers
Symbol TK
Pfam PF00265
Pfam clan CL0023
InterPro IPR001267
PROSITE PDOC00524
Thymidine kinase 1, soluble
Identifiers
Symbol TK1
Entrez 7083
HUGO 11830
OMIM 188300
RefSeq NM_003258
UniProt P04183
Other data
EC number 2.7.1.21
Locus Chr. 17 q23.2-25.3
Thymidine kinase 2, mitochondrial
Identifiers
Symbol TK2
Entrez 7084
HUGO 11831
OMIM 188250
RefSeq NM_004614
UniProt O00142
Other data
EC number 2.7.1.21
Locus Chr. 16

Thymidine kinase is an enzyme, a phosphotransferase (a kinase): 2'-deoxythymidine kinase, ATP-thymidine 5'-phosphotransferase, EC 2.7.1.21.[2][3] It can be found in most living cells. It is present in two forms in mammalian cells, TK1 and TK2. Certain viruses also have genetic information for expression of viral thymidine kinases. Thymidine kinase catalyzes the reaction:

Thd + ATP → TMP + ADP

where Thd is (deoxy)thymidine, ATP is adenosine triphosphate, TMP is (deoxy)thymidine monophosphate and ADP is adenosine diphosphate. Thymidine kinases have a key function in the synthesis of DNA and thereby in cell division, as they are part of the unique reaction chain to introduce thymidine into the DNA. Thymidine is present in the body fluids as a result of degradation of DNA from food and from dead cells. Thymidine kinase is required for the action of many antiviral drugs. It is used to select hybridoma cell lines in production of monoclonal antibodies. In clinical chemistry it is used as a proliferation marker in the diagnosis, control of treatment and follow-up of malignant disease, mainly of hematological malignancies.

History

The incorporation of thymidine in DNA was demonstrated around 1950.[4] Somewhat later, it was shown that this incorporation was preceded by phosphorylation,[5] and, around 1960, the enzyme responsible was purified and characterized.[6][7]

Classification

Two different classes of thymidine kinases have been identified[8][9] and are included in this super family: one family groups together thymidine kinase from herpesvirus as well as cellular thymidylate kinases, the second family groups TK from various sources that include, vertebrates, bacteria, the bacteriophage T4, poxviruses, African swine fever virus (ASFV) and Fish lymphocystis disease virus (FLDV). The major capsid protein of insect iridescent viruses also belongs to this family. The Prosite pattern recognizes only the cellular type of thymidine kinases.

Isozymes

Mammals have two isoenzymes, that are chemically very different, TK1 and TK2. The former was first found in fetal tissue, the second was found to be more abundant in adult tissue, and initially they were termed fetal and adult thymidine kinase. Soon it was shown that TK1 is present in the cytoplasm only in anticipation of cell division (cell cycle-dependent),[10][11] whereas TK2 is located in mitochondria and is cell cycle-independent.[12][13] The two isoenzymes have different reaction kinetics and are inhibited by different inhibitors.

The viral thymidine kinases differ completely from the mammalian enzymes both structurally and biochemically and are inhibited by inhibitors that do not inhibit the mammalian enzymes.[14][15][16] The genes of the two human isoenzymes were localized in the mid-1970s.[17][18] The gene for TK1 was cloned and sequenced.[19] The corresponding protein has a molecular weight of about 25 kD. Normally, it occurs in tissue as a dimer with a molecular weight of around 50 kD. It can be activated by ATP. After activation, is a tetramer with a molecular weight around 100 kD.[20] However, the form of enzyme present in the circulation does not correspond to the protein as encoded by the gene: the main fraction of the active enzyme in the circulation has a molecular weight of 730 kD and is probably bound in a complex to other proteins. This complex is more stable and has a higher specific activity than any of the lower molecular weight forms.[21][22]

Recombinant TK1 cannot be activated and converted to a tetramer in this way, showing that the enzyme occurring in cells has been modified after synthesis.[20][23][24]

TK1 is synthesized by the cell during the S phase of cell division. After cell division is completed, TK1 is degraded intracellularly and does not pass to body fluids after normal cell division.[25][26][27][28] There is a feed-back regulation of the action of thymidine kinase in the cell: thymidine triphosphate (TTP), the product of the further phosphorylation of thymidine, acts as an inhibitor to thymidine kinase.[23] This serves to maintain a balanced amount of TTP available for nucleic acid synthesis, not oversaturating the system. 5'-Aminothymidine, a non-toxic analogue of thymidine, interferes with this regulatory mechanism and thereby increases the cytotoxicity of thymidine analogues used as antineoplastic drugs.[29][30][31][32][33][34][35] The reaction kinetics of thymidine and thymidine analogues phosphorylation is complicated and only partly known. The overall phosphorylation of thymidine to thymidine triphosphate does not follow Michaelis-Menten kinetics, and the various phosphates of thymidine and uridine interfere with the phosphorylation of each other.[36] The kinetics of TK from different species differ from each other's and also the different forms from a given species (monomer, dimer, tetramer and serum form) have different kinetic characteristics.

Genes for virus specific thymidine kinases have been identified in Herpes simplex virus, Varicella zoster virus and Epstein-Barr virus.[37][38][39][40][41][42][43]

+ ATP ---> + ADP

Thymidine reacts with ATP to give thymidine monophosphate and ADP.

Function

Thymidine monophosphate, the product of the reaction catalyzed by thymidine kinase, is in turn phosphorylated to thymidine diphosphate by the enzyme thymidylate kinase and further to thymidine triphosphate by the enzyme nucleoside diphosphate kinase. The triphosphate is included in a DNA molecule, a reaction catalyzed by a DNA polymerase and a complementary DNA molecule (or an RNA molecule in the case of reverse transcriptase, an enzyme present in retrovirus).

Thymidine monophosphate is also produced by the cell in a different reaction by methylation of deoxyuridine monophosphate, a product of other metabolic pathways unrelated to thymidine, by the enzyme thymidylate synthase. The second route is sufficient to supply thymidine monophosphate for DNA repair. When a cell prepares to divide, a complete new set-up of DNA is required, and the requirement for building blocks, including thymidine triphosphate, increases. Cells prepare for cell division by making some of the enzymes required during the division. They are not normally present in the cells and are downregulated and degraded afterwards. Such enzymes are called salvage enzymes. Thymidine kinase 1 is such a salvage enzyme, whereas thymidine kinase 2 and thymidylate synthase are not cell cycle-dependent.[44][45][46][47][48][49][50][51][52][53][54]

Deficiency

Thymidine kinase 2 is used by the cells for synthesis of mitochondrial DNA. Mutations in the gene for TK2 lead to a myopathic form of mitochondrial DNA depletion syndrome. This can be treated with deoxycytidine monophosphate / tymidine monophosphate supplementation.[55] Another reason for TK 2 deficiency may be oxidative stress induced S-glutathionylation and proteolytic degradation of mitochondrial thymidine kinase 2.[56] No syndrome caused by TK1 deficiency is known, probably as a defective TK1 gene would lead to fetal death.

Thymidine kinase during development

The formation of tetramer after modification of thymidine kinase 1 after synthesis enhances the enzyme activity. It has been suggested that this is a mechanism for regulation of the enzyme activity. The formation of tetramers is observed after the Dictyostelium development stage. Its use for fine regulation of DNA synthesis is suggested to have been established in warm blooded animals after they branched out from the vertebrates.[57] Also the development of thymidine kinase like enzymes in the development has been studied.[58]

Species distribution

Thymidine kinase is present in animals,[59][60][61][62][63][64][65] plants,[66][67] some bacteria, archeans[68][69][70] and virus. The thymidine kinases from pox viruses,[8][71] African swine fever virus,[9] Herpes simplex virus,[16][37][38][39][40][72][73][74] Varicella zoster virus and[41][75][76] Epstein- Barr virus[42] have been identified and to a varying degree characterized. The enzyme form in virus is different from that in other organisms.[16] Thymidine kinase is not present in fungi.[69][77][78][79]

Applications

Identification of dividing cells

The first indirect use of thymidine kinase in biochemical research was the identification of dividing cells by incorporation of radiolabeled thymidine and subsequent measurement of the radioactivity or autoradiography to identify the dividing cells. For this purpose tritiated thymidine is included in the growth medium.[80] In spite of errors in the technique, it is still used to determine the growth rate of malignant cells and to study the activation of lymphocytes in immunology.

PET scan of active tumors

3'-Deoxy-3'-[(18)F]fluorothymidine is a thymidine analog. Its uptake is regulated by thymidine kinase 1, and it is therefore taken up preferentially by rapidly proliferating tumor tissue. The fluorine isotope 18 is a positron emitter that is used in positron emission tomography (PET). This marker is therefore useful for PET imaging of active tumor proliferation, and compares favorably with the more commonly used marker 2-[(18)F]fluoro-2-deoxy-D-glucose.[81][82][83][84][85][86] A standardized protocol that will help comparison of clinical studies has been suggested.[87]

Selection of hybridomas

Hybridomas are cells obtained by fusing tumor cells (which can divide infinitely) and immunoglobulin-producing lymphocytes (plasma cells). Hybridomas can be expanded to produce large quantities of immunoglobulins with a given unique specificity (monoclonal antibodies). One problem is to single out the hybridomas from the large excess of unfused cells after the cell fusion. One common way to solve this is to use thymidine kinase negative (TK−) tumor cell lines for the fusion. The thymidine kinase negative cells are obtained by growing the tumor cell line in the presence of thymidine analogs, that kill the thymidine kinase positive (TK+) cells. The negative cells can then be expanded and used for the fusion with TK+ plasma cells. After fusion, the cells are grown in a medium with methotrexate[88] or aminopterin[89] that inhibit the enzyme dihydrofolate reductase thus blocking the de novo synthesis of thymidine monophosphate. One such medium that is commonly used is HAT medium, which contains hypoxanthine, aminopterinand thymidine. The unfused cells from the thymidine kinase-deficient cell line die because they have no source of thymidine monophosphate. The lymphocytes eventually die because they are not "immortal." Only the hybridomas that have "immortality" from their cell line ancestor and thymidine kinase from the plasma cell survive. Those that produce the desired antibody are then selected and cultured to produce the monoclonal antibody.[90][91][92][93][94] Hybridoma cells can also be isolated using the same principle as described with respect to another gene the HGPRT, which synthesizes IMP necessary for GMP nucleotide synthesis in the salvage pathway.

Study of chromosome structure

Molecular combing of DNA fibers can be used to monitor the structure of chromosomes in the budding yeast Saccharomyces cerevisiae. This provides DNA replication profiles of individual molecules. This requires that the yeast strains express thymidine kinase, which wild type yeasts so not, being fungi (see occurrence). Therefore. a gene for thymidine kinase must be incorporated in the genome.[95]

Clinical chemistry

Thymidine kinase is a salvage enzyme that is only present in anticipation of cell division. The enzyme is not set free from cells undergoing normal division where the cells have a special mechanism to degrade the proteins no longer needed after the cell division.[10] In normal subjects, the amount of thymidine kinase in serum or plasma is therefore very low. Tumor cells release enzyme to the circulation, probably in connection with the disruption of dead or dying tumor cells. The thymidine kinase level in serum therefore serves as a measure of malignant proliferation, indirectly as a measure of the aggressivity of the tumor.

Therapeutic applications

Some drugs are specifically directed against dividing cells. They can be used against tumors and viral diseases (both against retrovirus and against other virus), as the diseased cells replicate much more frequently than normal cells and also against some non-malignant diseases related to excessively rapid cell replication (for instance psoriasis). It has been suggested that the antiviral and anti-cancer activity of thymidine analogues is, at least partly, achieved by downregulation of mitochondrial thymidine kinase.[96]

Cytostatics

There are different classes of drugs directed against thymidine metabolism and thereby involving thymidine kinase that are used to control cancer associated cell division.[97][98][99][100][101][102] Chain terminators are thymidine analogues that are included in the growing DNA chain, but modified so that the chain cannot be further elongated. As analogs of thymidine, this type of drugs are readily phosphorylated to 5'-monophosphates. The monophosphate is further phosphorylated to the corresponding triphosphate and incorporated in the growing DNA chain. The analog has been modified so that it does not have the hydroxyl group in the 3'-position that is required for continued chain growth. In zidovudine (AZT; ATC:J05AF01) the 3'-hydroxyl group has been replaced by an azido group,[36][101] in stavudine (ATC: J05AF04) it has been removed without replacement.[103][104] AZT is used as substrate in one of the methods for determination of thymidine kinase in serum.[105] This implies that AZT interferes with this method and may be a limitation: AZT is a standard component of HAART therapy in HIV infection. One common consequence of AIDS is lymphoma and the most important diagnostic application of thymidine kinase determination is for monitoring of lymphoma.

Chemical structures of thymidine kinase substrate analogs
AZT 
Stavudine 
Idoxuridine 
Aciclovir 
Ganciclovir 

Other thymidine analogues, for instance Idoxuridine (ATC: J05AB02) act by blocking base pairing during subsequent replication cycles, thereby making the resulting DNA chain defective.[106] This may also be combined with radioactivity to achieve apoptosis of malignant cells.[107]

Antivirals

Some antiviral drugs, such as acyclovir (ATC: J05AB01) and ganciclovir (ATC: J05AB06) as well as other nucleoside analogs make use of the substrate specificity of viral thymidine kinase, as opposed to human thymidine kinases.[15] These drugs act as prodrugs, which in themselves are not toxic, but are converted to toxic drugs by phosphorylation by viral thymidine kinase. Cells infected with the virus therefore produce highly toxic triphosphates that lead to cell death. Human thymidine kinase, in contrast, with its more narrow specificity, is unable to phosphorylate and activate the prodrug. In this way, only cells infected by the virus are susceptible to the drug. Such drugs are effective only against viruses from the herpes group with their specific thymidine kinase.[108][109] In patients treated with this type of drugs, the development of antiviral drug resistance is frequently observed. Sequencing the thymidine kinase gene in Herpes simplex virus and Varicella zoster virus shows the rapid genetic variability and may facilitate the diagnosis of antiviral drug resistance.[16][76]

After smallpox was declared eradicated by WHO in December 1979, vaccination programs were terminated. A re-emergence of the disease either by accident or as a result of biological warfare would meet an unprotected population and could result in an epidemic that could be difficult to control. Mass vaccination would be unethical, as the only efficient vaccines against smallpox include live vaccinia virus with severe adverse effects on rare occasions. As one protective measure, large amounts of vaccine are kept in stock, but an efficient drug against smallpox has high priority. One possible approach would be to use the specificity of the thymidine kinase of poxvirus for the purpose, in a similar way that it is used for drugs against herpesvirus. One difficulty is that the poxvirus thymidine kinase belongs to the same family of thymidine kinases as the human thymidine kinases and thereby is more similar chemically. The structure of poxvirus thymidine kinases has therefore been determined to find potential antiviral drugs.[71] The search has, however, not yet resulted in a usable antiviral drug against poxviruses.

As a “suicide gene” in gene therapy

The herpesvirus thymidine kinase gene has also been used as a “suicide gene” as a safety system in gene therapy experiments, allowing cells expressing the gene to be killed using ganciclovir. This is desirable in case the recombinant gene causes a mutation leading to uncontrolled cell growth (insertional mutagenesis). The thymidine kinase produced by these modified cells may diffuse to neighboring cells, rendering them similarly susceptible to ganciclovir, a phenomenon known as the "bystander effect." This approach has been used to treat cancer in animal models, and is advantageous in that the tumor may be killed with as few as 10% of malignant cells expressing the gene.[110][111][112][113][114][115][116][117][118][119][120][121][122][123][124] A similar system has been tried using tomato thymidine kinase and AZT.[125][126]

Tumor marker genes

A similar use of the thymidine kinase makes use of the presence in some tumor cells of substances not present in normal cells (tumor markers). Such tumor markers are, for instance, CEA (carcinoembryonic antigen) and AFP (alpha fetoprotein). The genes for these tumor markers may be used as promoter genes for thymidine kinase. Thymidine kinase can then be activated in cells expressing the tumor marker but not in normal cells, such that treatment with ganciclovir kills only the tumor cells.[127][128][129][130][131][132] Such gene therapy-based approaches are still experimental, however, as problems associated with targeting the gene transfer to the tumor cells have not yet been completely solved.

Neutron capture therapy for tumors

Incorporation of a thymidine analogue with boron has been suggested and tried in animal models for boron neutron capture therapy of brain tumors A very extensive number of thymidine derivatives containing boron have been described.[133][134][135][136][137][138][139][140][141][142][143][144][145][146][147][148][149]

Antiparasitics

Introduction of a TK gene in a parasite genome makes it possible to incorporate BrdU and thereby makes the parasite sensitive to treatment with this drug has also been suggested and constitutes a sensitive indicator of replication of the parasite genome.[150]

Measurement

In serum and plasma

The level of thymidine kinase in serum or plasma is so low that the measurement is best based on the enzymatic activity. In commercial assays, this is done by incubation of a serum sample with a substrate analog and measurement of the amount of product formed.[72][73][74][105][151][152][153][154][155][156][157] Direct determination of the thymidine kinase protein by immunoassay has also been used.[158][159][160] The amounts of thymidine kinase found by this method does not correlate well with the enzyme activities. One reason for this is that a large amount of serum TK1 identified by immunoassay is not enzymatically active.[22][161]

In tissue

Thymidine kinase has been determined in tissue samples after extraction of the tissue. No standard method for the extraction or for the assay has been developed and TK determination in extracts from cells and tissues have not been validated in relation to any specific clinical question, see however Romain et al.[162] and Arnér et al.[163] A method has been developed for specific determination of TK2 in cell extracts using the substrate analog 5-Bromovinyl 2'-deoxyuridine.[164] In the studies referred to below the methods used and the way the results are reported are so different that comparisons between different studies are not possible. The TK1 levels in fetal tissues during development are higher than those of the corresponding tissues later.[165][166][167] Certain non-malignant diseases also give rise to dramatic elevation of TK values in cells and tissue: in peripheric lymphocytes during monocytosis[168] and in bone marrow during pernicious anemia.[169][170] As TK1 is present in cells during cell division, it is reasonable to assume that the TK activity in malignant tissue should be higher than in corresponding normal tissue. This is also confirmed in most studies.

Immunohistochemical staining

Antibodies against thymidine kinase are available for immunohistochemical detection.[171] Staining for thymidine kinase was found to be a reliable technique for identification of patients with stage 2 breast carcinoma. The highest number of patients identified was obtained by combination of thymidine kinase and Ki-67 staining.[172][173] The technique has also been validated for lung cancer,[172][174] for colorectal carcinima,[175] for lung cancer[176] and for renal cell carcinoma.[177]

Fluorescent staining

2'-deoxy-2',2'-difluoro-5-ethynyluridine (dF-EdU) binds to Herpes simplex virus thymidine kinase but, because of sterical hindrance, not to human thymidine kinase. This reagent together with a fluorescent azide cause fluorescence of infected cells but not of uninfected cells. Therefore, this substrate analog makes it possible to specifically stain infected cells.[178]

See also

References

  1. ↑ PDB: 2B8T​; Kosinska U, Carnrot C, Eriksson S, Wang L, Eklund H (December 2005). "Structure of the substrate complex of thymidine kinase from Ureaplasma urealyticum and investigations of possible drug targets for the enzyme". FEBS J. 272 (24): 6365–72. doi:10.1111/j.1742-4658.2005.05030.x. PMID 16336273.
  2. ↑ Kit S (1985). "Thymidine kinase". Microbiol. Sci. 2 (12): 369–75. PMID 3939993.
  3. ↑ Wintersberger E (1997). "Regulation and biological function of thymidine kinase". Biochem. Soc. Trans. 25 (1): 303–8. PMID 9056888.
  4. ↑ Reichard P, Estborn B (1951). "Utilization of desoxyribosides in the synthesis of polynucleotides". J. Biol. Chem. 188 (2): 839–46. PMID 14824173.
  5. ↑ Bessman MJ, Kornberg A, Lehman IR, Simms ES (1956). "Enzymic synthesis of deoxyribonucleic acid". Biochim. Biophys. Acta. 21 (1): 197–8. PMID 13363894.
  6. ↑ Bollum FJ, Potter VR (1958). "Incorporation of thymidine into deoxyribonucleic acid by enzymes from rat tissues". J. Biol. Chem. 233 (2): 478–82. PMID 13563524.
  7. ↑ Weissman SM, Smellie RM, Paul J (1960). "Studies on the biosynthesis of deoxyribonucleic acid by extracts of mammalian cells. IV. The phosphorylation of thymidine". Biochim. Biophys. Acta. 45: 101–10. doi:10.1016/0006-3002(60)91430-x. PMID 13784139.
  8. 1 2 Boyle DB, Coupar BE, Gibbs AJ, Seigman LJ, Both GW (1987). "Fowlpox virus thymidine kinase: nucleotide sequence and relationships to other thymidine kinases". Virology. 156 (2): 355–65. doi:10.1016/0042-6822(87)90415-6. PMID 3027984.
  9. 1 2 Blasco R, López-Otín C, Muñóz M, Bockamp EO, Simón-Mateo C, Viñuela E (1990). "Sequence and evolutionary relationships of African swine fever virus thymidine kinase". Virology. 178 (1): 301–4. doi:10.1016/0042-6822(90)90409-k. PMID 2389555.
  10. 1 2 Littlefield JW (1966). "The periodic synthesis of thymidine kinase in mouse fibroblasts". Biochim. Biophys. Acta. 114 (2): 398–403. doi:10.1016/0005-2787(66)90319-4. PMID 4223355.
  11. ↑ Bello LJ (1974). "Regulation of thymidine kinase synthesis in human cells". Exp. Cell Res. 89 (2): 263–74. doi:10.1016/0014-4827(74)90790-3. PMID 4457349.
  12. ↑ Berk AJ, Clayton DA (1973). "A genetically distinct thymidine kinase in mammalian mitochondria. Exclusive labeling of mitochondrial deoxyribonucleic acid". J. Biol. Chem. 248 (8): 2722–9. PMID 4735344.
  13. ↑ Berk AJ, Meyer BJ, Clayton DA (1973). "Mitochondrial-specific thymidine kinase". Arch. Biochem. Biophys. 154 (2): 563–5. PMID 4632422.
  14. ↑ Andrei G, Snoeck R (2011). "Emerging drugs for varicella-zoster virus infections". Expert Opinion on Emerging Drugs. 16 (3): 507–35. doi:10.1517/14728214.2011.591786. PMID 21699441.
  15. 1 2 Johnson VA, Hirsch MS (1990). "New developments in antiretroviral drug therapy for human immunodeficiency virus infections". AIDS Clinical Review: 235–72. PMID 1707295.
  16. 1 2 3 4 Schmidt S, Bohn-Wippert K, Schlattmann P, Zell R, Sauerbrei A (2015). "Sequence Analysis of Herpes Simplex Virus 1 Thymidine Kinase and DNA Polymerase Genes from over 300 Clinical Isolates from 1973 to 2014 Finds Novel Mutations That May Be Relevant for Development of Antiviral Resistance". Antimicrobial Agents and Chemotherapy. 59 (8): 4938–45. doi:10.1128/AAC.00977-15. PMC 4505214Freely accessible. PMID 26055375.
  17. ↑ Elsevier SM, Kucherlapati RS, Nichols EA, Creagan RP, Giles RE, Ruddle FH, Willecke K, McDougall JK (1974). "Assignment of the gene for galactokinase to human chromosome 17 and its regional localisation to band q21-22". Nature. 251 (5476): 633–6. doi:10.1038/251633a0. PMID 4371022.
  18. ↑ Willecke K, Teber T, Kucherlapati RS, Ruddle FH (1977). "Human mitochondrial thymidine kinase is coded for by a gene on chromosome 16 of the nucleus". Somatic Cell Genet. 3 (3): 237–45. doi:10.1007/bf01538743. PMID 605384.
  19. ↑ Flemington E, Bradshaw HD, Traina-Dorge V, Slagel V, Deininger PL (1987). "Sequence, structure and promoter characterization of the human thymidine kinase gene". Gene. 52 (2-3): 267–77. doi:10.1016/0378-1119(87)90053-9. PMID 3301530.
  20. 1 2 Welin M, Kosinska U, Mikkelsen NE, Carnrot C, Zhu C, Wang L, Eriksson S, Munch-Petersen B, Eklund H (2004). "Structures of thymidine kinase 1 of human and mycoplasmic origin". Proc. Natl. Acad. Sci. U.S.A. 101 (52): 17970–5. doi:10.1073/pnas.0406332102. PMC 539776Freely accessible. PMID 15611477.
  21. ↑ Karlström AR, Neumüller M, Gronowitz JS, Källander CF (1990). "Molecular forms in human serum of enzymes synthesizing DNA precursors and DNA". Mol. Cell. Biochem. 92 (1): 23–35. PMID 2155379.
  22. 1 2 Hanan S, Jagarlamudi KK, Liya W, Ellen H, Staffan E (2012). "Quaternary structures of recombinant, cellular, and serum forms of thymidine kinase 1 from dogs and humans". BMC Biochem. 13: 12. doi:10.1186/1471-2091-13-12. PMC 3411398Freely accessible. PMID 22741536.
  23. 1 2 Munch-Petersen B, Cloos L, Jensen HK, Tyrsted G (1995). "Human thymidine kinase 1. Regulation in normal and malignant cells". Adv. Enzyme Regul. 35: 69–89. doi:10.1016/0065-2571(94)00014-t. PMID 7572355.
  24. ↑ Li CL, Lu CY, Ke PY, Chang ZF (2004). "Perturbation of ATP-induced tetramerization of human cytosolic thymidine kinase by substitution of serine-13 with aspartic acid at the mitotic phosphorylation site". Biochem. Biophys. Res. Commun. 313 (3): 587–93. doi:10.1016/j.bbrc.2003.11.147. PMID 14697231.
  25. ↑ Zhu C, Harlow LS, Berenstein D, Munch-Petersen S, Munch-Petersen B (2006). "Effect of C-terminal of human cytosolic thymidine kinase (TK1) on in vitro stability and enzymatic properties". Nucleosides Nucleotides Nucleic Acids. 25 (9-11): 1185–8. doi:10.1080/15257770600894436. PMID 17065087.
  26. ↑ Potter VR (1963). "Feedback inhibition of thymidine kinase by thymidine triphosphate". Exp. Cell Res. 24: SUPPL9:259–62. PMID 14046233.
  27. ↑ Severin ES, Itkes AV, Kartasheva ON, Tunitskaya VL, Turpaev KT, Kafiani CA (1985). "Regulation of 2-5 A phosphodiesterase activity by cAMP-dependent phosphorylation: mechanism and biological role". Adv. Enzyme Regul. 23: 365–76. doi:10.1016/0065-2571(85)90056-1. PMID 3000146.
  28. ↑ Mikkelsen NE, Johansson K, Karlsson A, Knecht W, Andersen G, Piskur J, Munch-Petersen B, Eklund H (2003). "Structural basis for feedback inhibition of the deoxyribonucleoside salvage pathway: studies of the Drosophila deoxyribonucleoside kinase". Biochemistry. 42 (19): 5706–12. doi:10.1021/bi0340043. PMID 12741827.
  29. ↑ Fischer PH, Phillips AW (1984). "Antagonism of feedback inhibition. Stimulation of the phosphorylation of thymidine and 5-iodo-2'-deoxyuridine by 5-iodo-5'-amino-2',5'-dideoxyuridine". Mol. Pharmacol. 25 (3): 446–51. PMID 6727866.
  30. ↑ Fischer PH, Vazquez-Padua MA, Reznikoff CA (1986). "Perturbation of thymidine kinase regulation: a novel chemotherapeutic approach". Adv. Enzyme Regul. 25: 21–34. doi:10.1016/0065-2571(86)90006-3. PMID 3812083.
  31. ↑ Fischer PH, Vazquez-Padua MA, Reznikoff CA, Ratschan WJ (1986). "Preferential stimulation of iododeoxyuridine phosphorylation by 5'-aminothymidine in human bladder cancer cells in vitro". Cancer Res. 46 (9): 4522–6. PMID 3731105.
  32. ↑ Fischer PH, Fang TT, Lin TS, Hampton A, Bruggink J (1988). "Structure-activity analysis of antagonism of the feedback inhibition of thymidine kinase". Biochem. Pharmacol. 37 (7): 1293–8. doi:10.1016/0006-2952(88)90785-x. PMID 3355601.
  33. ↑ Vazquez-Padua MA, Kunugi K, Fischer PH (1989). "Enzyme regulatory site-directed drugs: study of the interactions of 5'-amino-2', 5'-dideoxythymidine (5'-AdThd) and thymidine triphosphate with thymidine kinase and the relationship to the stimulation of thymidine uptake by 5'-AdThd in 647V cells". Mol. Pharmacol. 35 (1): 98–104. PMID 2536472.
  34. ↑ Vazquez-Padua MA, Fischer PH, Christian BJ, Reznikoff CA (1989). "Basis for the differential modulation of the uptake of 5-iododeoxyuridine by 5'-aminothymidine among various cell types". Cancer Res. 49 (9): 2415–21. PMID 2706629.
  35. ↑ Vázquez-Padua MA (1994). "Modulation of thymidine kinase activity: a biochemical strategy to enhance the activation of antineoplastic drugs". P R Health Sci J. 13 (1): 19–23. PMID 8016290.
  36. 1 2 Sun R, Wang L (2014). "Thymidine kinase 2 enzyme kinetics elucidate the mechanism of thymidine-induced mitochondrial DNA depletion". Biochemistry. 53 (39): 6142–50. doi:10.1021/bi5006877. PMID 25215937.
  37. 1 2 McKnight SL (1980). "The nucleotide sequence and transcript map of the herpes simplex virus thymidine kinase gene". Nucleic Acids Res. 8 (24): 5949–64. doi:10.1093/nar/8.24.5949. PMC 328064Freely accessible. PMID 6258156.
  38. 1 2 Halliburton IW, Morse LS, Roizman B, Quinn KE (1980). "Mapping of the thymidine kinase genes of type 1 and type 2 herpes simplex viruses using intertypic recombinants". J. Gen. Virol. 49 (2): 235–53. doi:10.1099/0022-1317-49-2-235. PMID 6255066.
  39. 1 2 McDougall JK, Masse TH, Galloway DA (1980). "Location and cloning of the herpes simplex virus type 2 thymidine kinase gene". J. Virol. 33 (3): 1221–4. PMC 288658Freely accessible. PMID 6245273.
  40. 1 2 Kit S, Kit M, Qavi H, Trkula D, Otsuka H (1983). "Nucleotide sequence of the herpes simplex virus type 2 (HSV-2) thymidine kinase gene and predicted amino acid sequence of thymidine kinase polypeptide and its comparison with the HSV-1 thymidine kinase gene". Biochim. Biophys. Acta. 741 (2): 158–70. doi:10.1016/0167-4781(83)90056-8. PMID 6317035.
  41. 1 2 Sawyer MH, Ostrove JM, Felser JM, Straus SE (1986). "Mapping of the varicella zoster virus deoxypyrimidine kinase gene and preliminary identification of its transcript". Virology. 149 (1): 1–9. doi:10.1016/0042-6822(86)90081-4. PMID 3004022.
  42. 1 2 Littler E, Zeuthen J, McBride AA, Trøst Sørensen E, Powell KL, Walsh-Arrand JE, Arrand JR (1986). "Identification of an Epstein-Barr virus-coded thymidine kinase". EMBO J. 5 (8): 1959–66. PMC 1167064Freely accessible. PMID 3019675.
  43. ↑ Kit S, Dubbs DR (1963). "Acquisition of thymidine kinase activity by herpes simplex-infected mouse fibroblast cells". Biochem. Biophys. Res. Commun. 11: 55–9. doi:10.1016/0006-291x(63)90027-5. PMID 14033128.
  44. ↑ Schlosser CA, Steglich C, deWet JR, Scheffler IE (1981). "Cell cycle-dependent regulation of thymidine kinase activity introduced into mouse LMTK- cells by DNA and chromatin-mediated gene transfer". Proc. Natl. Acad. Sci. U.S.A. 78 (2): 1119–23. doi:10.1073/pnas.78.2.1119. PMC 319958Freely accessible. PMID 6940130.
  45. ↑ Coppock DL, Pardee AB (1987). "Control of thymidine kinase mRNA during the cell cycle". Mol. Cell. Biol. 7 (8): 2925–32. PMC 367911Freely accessible. PMID 3670299.
  46. ↑ Stewart CJ, Ito M, Conrad SE (1987). "Evidence for transcriptional and post-transcriptional control of the cellular thymidine kinase gene". Mol. Cell. Biol. 7 (3): 1156–63. PMC 365188Freely accessible. PMID 3561412.
  47. ↑ Piper AA, Tattersall MH, Fox RM (1980). "The activities of thymidine metabolising enzymes during the cell cycle of a human lymphocyte cell line LAZ-007 synchronised by centrifugal elutriation". Biochim. Biophys. Acta. 633 (3): 400–9. doi:10.1016/0304-4165(80)90198-1. PMID 6260157.
  48. ↑ Pelka-Fleischer R, Ruppelt W, Wilmanns W, Sauer H, Schalhorn A (1987). "Relation between cell cycle stage and the activity of DNA-synthesizing enzymes in cultured human lymphoblasts: investigations on cell fractions enriched according to cell cycle stages by way of centrifugal elutriation". Leukemia. 1 (3): 182–7. PMID 3669741.
  49. ↑ Sherley JL, Kelly TJ (1988). "Regulation of human thymidine kinase during the cell cycle". J. Biol. Chem. 263 (17): 8350–8. PMID 3372530.
  50. ↑ Gross MK, Kainz MS, Merrill GF (1987). "The chicken thymidine kinase gene is transcriptionally repressed during terminal differentiation: the associated decline in TK mRNA cannot account fully for the disappearance of TK enzyme activity". Dev. Biol. 122 (2): 439–51. doi:10.1016/0012-1606(87)90308-3. PMID 3596017.
  51. ↑ Kauffman MG, Kelly TJ (1991). "Cell cycle regulation of thymidine kinase: residues near the carboxyl terminus are essential for the specific degradation of the enzyme at mitosis". Mol. Cell. Biol. 11 (5): 2538–46. PMC 360023Freely accessible. PMID 1708095.
  52. ↑ Sutterluety H, Bartl S, Karlseder J, Wintersberger E, Seiser C (1996). "Carboxy-terminal residues of mouse thymidine kinase are essential for rapid degradation in quiescent cells". J. Mol. Biol. 259 (3): 383–92. doi:10.1006/jmbi.1996.0327. PMID 8676376.
  53. ↑ McAllister KA, Yasseen AA, McKerr G, Downes CS, McKelvey-Martin VJ (2014). "FISH comets show that the salvage enzyme TK1 contributes to gene-specific DNA repair". Frontiers in Genetics. 5: 233. doi:10.3389/fgene.2014.00233. PMC 4126492Freely accessible. PMID 25152750.
  54. ↑ Lee MH, Wang L, Chang ZF (2014). "The contribution of mitochondrial thymidylate synthesis in preventing the nuclear genome stress". Nucleic Acids Research. 42 (8): 4972–84. doi:10.1093/nar/gku152. PMC 4005647Freely accessible. PMID 24561807.
  55. ↑ Garone C, Garcia-Diaz B, Emmanuele V, Lopez LC, Tadesse S, Akman HO, Tanji K, Quinzii CM, Hirano M (2014). "Deoxypyrimidine monophosphate bypass therapy for thymidine kinase 2 deficiency". EMBO Molecular Medicine. 6 (8): 1016–27. doi:10.15252/emmm.201404092. PMC 4154130Freely accessible. PMID 24968719.
  56. ↑ Sun R, Eriksson S, Wang L (2012). "Oxidative stress induced S-glutathionylation and proteolytic degradation of mitochondrial thymidine kinase 2". J. Biol. Chem. 287 (29): 24304–12. doi:10.1074/jbc.M112.381996. PMC 3397856Freely accessible. PMID 22661713.
  57. ↑ Mutahir Z, Clausen AR, Andersson KM, Wisen SM, Munch-Petersen B, Piškur J (2013). "Thymidine kinase 1 regulatory fine-tuning through tetramer formation". The FEBS Journal. 280 (6): 1531–41. doi:10.1111/febs.12154. PMID 23351158.
  58. ↑ Konrad A, Lai J, Mutahir Z, Piškur J, Liberles DA (2014). "The phylogenetic distribution and evolution of enzymes within the thymidine kinase 2-like gene family in metazoa". Journal of Molecular Evolution. 78 (3-4): 202–16. doi:10.1007/s00239-014-9611-6. PMID 24500774.
  59. ↑ Larsdotter S, Nostell K, von Euler H (2015). "Serum thymidine kinase activity in clinically healthy and diseased horses: a potential marker for lymphoma". Veterinary Journal (London, England : 1997). 205 (2): 313–6. doi:10.1016/j.tvjl.2015.01.019. PMID 25744802.
  60. ↑ Jagarlamudi KK, Westberg S, Rönnberg H, Eriksson S (2014). "Properties of cellular and serum forms of thymidine kinase 1 (TK1) in dogs with acute lymphocytic leukemia (ALL) and canine mammary tumors (CMTs): implications for TK1 as a proliferation biomarker". BMC Veterinary Research. 10: 228. doi:10.1186/s12917-014-0228-1. PMC 4195903Freely accessible. PMID 25293656.
  61. ↑ Selting KA, Sharp CR, Ringold R, Knouse J (2015). "Serum thymidine kinase 1 and C-reactive protein as biomarkers for screening clinically healthy dogs for occult disease". Veterinary and Comparative Oncology. 13 (4): 373–84. doi:10.1111/vco.12052. PMID 23859156.
  62. ↑ Tawfeeq MM, Miura S, Horiuchi N, Kobayashi Y, Furuoka H, Inokuma H (2013). "Utility of serum thymidine kinase activity measurements for cases of bovine leukosis with difficult clinical diagnoses". The Journal of Veterinary Medical Science / the Japanese Society of Veterinary Science. 75 (9): 1167–72. doi:10.1292/jvms.12-0572. PMID 23628971.
  63. ↑ Sharif H, Hagman R, Wang L, Eriksson S (2013). "Elevation of serum thymidine kinase 1 in a bacterial infection: canine pyometra". Theriogenology. 79 (1): 17–23. doi:10.1016/j.theriogenology.2012.09.002. PMID 23102844.
  64. ↑ Taylor SS, Dodkin S, Papasouliotis K, Evans H, Graham PA, Belshaw Z, Westberg S, von Euler HP (2013). "Serum thymidine kinase activity in clinically healthy and diseased cats: a potential biomarker for lymphoma". Journal of Feline Medicine and Surgery. 15 (2): 142–7. doi:10.1177/1098612X12463928. PMID 23076596.
  65. ↑ Elliott JW, Cripps P, Blackwood L (2013). "Thymidine kinase assay in canine lymphoma". Veterinary and Comparative Oncology. 11 (1): 1–13. doi:10.1111/j.1476-5829.2011.00296.x. PMID 22236202.
  66. ↑ Pedroza-García JA, Nájera-Martínez M, de la Paz Sanchez M, Plasencia J (2015). "Arabidopsis thaliana thymidine kinase 1a is ubiquitously expressed during development and contributes to confer tolerance to genotoxic stress". Plant Molecular Biology. 87 (3): 303–15. doi:10.1007/s11103-014-0277-7. PMID 25537647.
  67. ↑ Clausen AR, Girandon L, Ali A, Knecht W, Rozpedowska E, Sandrini MP, Andreasson E, Munch-Petersen B, Piškur J (2012). "Two thymidine kinases and one multisubstrate deoxyribonucleoside kinase salvage DNA precursors in Arabidopsis thaliana". The FEBS Journal. 279 (20): 3889–97. doi:10.1111/j.1742-4658.2012.08747.x. PMID 22897443.
  68. ↑ Timm J, Bosch-Navarrete C, Recio E, Nettleship JE, Rada H, González-Pacanowska D, Wilson KS (2015). "Structural and Kinetic Characterization of Thymidine Kinase from Leishmania major". PLoS Neglected Tropical Diseases. 9 (5): e0003781. doi:10.1371/journal.pntd.0003781. PMC 4433323Freely accessible. PMID 25978379.
  69. 1 2 Grivell AR, Jackson JF (1968). "Thymidine kinase: evidence for its absence from Neurospora crassa and some other micro-organisms, and the relevance of this to the specific labelling of deoxyribonucleic acid". Journal of General Microbiology. 54 (2): 307–17. doi:10.1099/00221287-54-2-307. PMID 5729618.
  70. ↑ Tinta T, Christiansen LS, Konrad A, Liberles DA, Turk V, Munch-Petersen B, Piškur J, Clausen AR (2012). "Deoxyribonucleoside kinases in two aquatic bacteria with high specificity for thymidine and deoxyadenosine". FEMS Microbiology Letters. 331 (2): 120–7. doi:10.1111/j.1574-6968.2012.02565.x. PMID 22462611.
  71. 1 2 Black ME, Hruby DE (1990). "Quaternary structure of vaccinia virus thymidine kinase". Biochemical and Biophysical Research Communications. 169 (3): 1080–6. doi:10.1016/0006-291x(90)92005-k. PMID 2114104.
  72. 1 2 Gronowitz JS, Källander CF (1980). "Optimized assay for thymidine kinase and its application to the detection of antibodies against herpes simplex virus type 1- and 2-induced thymidine kinase". Infection and Immunity. 29 (2): 425–34. PMC 551136Freely accessible. PMID 6260651.
  73. 1 2 Gronowitz JS, Källander FR, Diderholm H, Hagberg H, Pettersson U (1984). "Application of an in vitro assay for serum thymidine kinase: results on viral disease and malignancies in humans". International Journal of Cancer. Journal International Du Cancer. 33 (1): 5–12. doi:10.1002/ijc.2910330103. PMID 6693195.
  74. 1 2 Gronowitz JS, Källander CF (1983). "A sensitive assay for detection of deoxythymidine kinase and its application to herpesvirus diagnosis". Current Topics in Microbiology and Immunology. 104: 235–45. PMID 6307593.
  75. ↑ Källander CF, Gronowitz JS, Olding-Stenkvist E (1983). "Rapid diagnosis of varicella-zoster virus infection by detection of viral deoxythymidine kinase in serum and vesicle fluid". Journal of Clinical Microbiology. 17 (2): 280–7. PMC 272623Freely accessible. PMID 6339548.
  76. 1 2 Brunnemann AK, Bohn-Wippert K, Zell R, Henke A, Walther M, Braum O, Maschkowitz G, Fickenscher H, Sauerbrei A, Krumbholz A (2015). "Drug resistance of clinical varicella-zoster virus strains confirmed by recombinant thymidine kinase expression and by targeted resistance mutagenesis of a cloned wild-type isolate". Antimicrob. Agents Chemother. 59 (5): 2726–34. doi:10.1128/AAC.05115-14. PMC 4394776Freely accessible. PMID 25712361.
  77. ↑ Rhind N (2015). "Incorporation of thymidine analogs for studying replication kinetics in fission yeast". Methods in Molecular Biology (Clifton, N.J.). 1300: 99–104. doi:10.1007/978-1-4939-2596-4_6. PMID 25916707.
  78. ↑ Rhind N (2009). "Incorporation of thymidine analogs for studying replication kinetics in fission yeast". Methods in Molecular Biology (Clifton, N.J.). 521: 509–15. doi:10.1007/978-1-60327-815-7_29. PMC 2861040Freely accessible. PMID 19563126.
  79. ↑ Sivakumar S, Porter-Goff M, Patel PK, Benoit K, Rhind N (2004). "In vivo labeling of fission yeast DNA with thymidine and thymidine analogs". Methods (San Diego, Calif.). 33 (3): 213–9. doi:10.1016/j.ymeth.2003.11.016. PMID 15157888.
  80. ↑ Johnson HA, Rubini JR, Cronkite EP, Bond VP (1960). "Labeling of human tumor cells in vivo by tritiated thymidine". Lab. Invest. 9: 460–5. PMID 14407455.
  81. ↑ Barthel H, Cleij MC, Collingridge DR, Hutchinson OC, Osman S, He Q, Luthra SK, Brady F, Price PM, Aboagye EO (2003). "3'-deoxy-3'-[18F]fluorothymidine as a new marker for monitoring tumor response to antiproliferative therapy in vivo with positron emission tomography". Cancer Res. 63 (13): 3791–8. PMID 12839975.
  82. ↑ Chao KS (2006). "Functional imaging for early prediction of response to chemoradiotherapy: 3'-deoxy-3'-18F-fluorothymidine positron emission tomography--a clinical application model of esophageal cancer". Semin. Oncol. 33 (6 Suppl 11): S59–63. doi:10.1053/j.seminoncol.2006.10.011. PMID 17178290.
  83. ↑ Salskov A, Tammisetti VS, Grierson J, Vesselle H (2007). "FLT: measuring tumor cell proliferation in vivo with positron emission tomography and 3'-deoxy-3'-[18F]fluorothymidine". Semin Nucl Med. 37 (6): 429–39. doi:10.1053/j.semnuclmed.2007.08.001. PMID 17920350.
  84. ↑ de Langen AJ, Klabbers B, Lubberink M, Boellaard R, Spreeuwenberg MD, Slotman BJ, de Bree R, Smit EF, Hoekstra OS, Lammertsma AA (2009). "Reproducibility of quantitative 18F-3'-deoxy-3'-fluorothymidine measurements using positron emission tomography". Eur. J. Nucl. Med. Mol. Imaging. 36 (3): 389–95. doi:10.1007/s00259-008-0960-5. PMID 18931838.
  85. ↑ Shields AF, Lawhorn-Crews JM, Briston DA, Zalzala S, Gadgeel S, Douglas KA, Mangner TJ, Heilbrun LK, Muzik O (2008). "Analysis and reproducibility of 3'-Deoxy-3'-[18F]fluorothymidine positron emission tomography imaging in patients with non-small cell lung cancer". Clin. Cancer Res. 14 (14): 4463–8. doi:10.1158/1078-0432.CCR-07-5243. PMC 3826917Freely accessible. PMID 18628460.
  86. ↑ Lamarca A, Asselin MC, Manoharan P, McNamara MG, Trigonis I, Hubner R, Saleem A, Valle JW (2015). "(18)F-FLT PET imaging of cellular proliferation in pancreatic cancer". Crit. Rev. Oncol. Hematol. 99: 158–69. doi:10.1016/j.critrevonc.2015.12.014. PMID 26778585.
  87. ↑ Peck M, Pollack HA, Friesen A, Muzi M, Shoner SC, Shankland EG, Fink JR, Armstrong JO, Link JM, Krohn KA (2015). "Applications of PET imaging with the proliferation marker [18F]-FLT". Q J Nucl Med Mol Imaging. 59 (1): 95–104. PMC 4415691Freely accessible. PMID 25737423.
  88. ↑ "Methotrexate". PubChem.
  89. ↑ "Aminopterin". PubChem.[ ]
  90. ↑ Köhler G, Milstein C (1975). "Continuous cultures of fused cells secreting antibody of predefined specificity". Nature. 256 (5517): 495–7. doi:10.1038/256495a0. PMID 1172191.
  91. ↑ Köhler G, Howe SC, Milstein C (1976). "Fusion between immunoglobulin-secreting and nonsecreting myeloma cell lines". Eur. J. Immunol. 6 (4): 292–5. doi:10.1002/eji.1830060411. PMID 825374.
  92. ↑ Köhler G, Milstein C (1976). "Derivation of specific antibody-producing tissue culture and tumor lines by cell fusion". Eur. J. Immunol. 6 (7): 511–9. doi:10.1002/eji.1830060713. PMID 825377.
  93. ↑ Köhler G, Pearson T, Milstein C (1977). "Fusion of T and B cells". Somatic Cell Genet. 3 (3): 303–12. PMID 305123.
  94. ↑ Milstein C, Adetugbo K, Cowan NJ, Kohler G, Secher DS (1978). "Expression of antibody genes in tissue culture: structural mutants and hybrid cells". Natl Cancer Inst Monogr (48): 321–30. PMID 107455.
  95. ↑ Gallo D, Wang G, Yip CM, Brown GW (2016). "Analysis of Replicating Yeast Chromosomes by DNA Combing". Cold Spring Harb Protoc. 2016 (2): pdb.prot085118. doi:10.1101/pdb.prot085118. PMID 26832684.
  96. ↑ Sun R, Eriksson S, Wang L (2014). "Down-regulation of mitochondrial thymidine kinase 2 and deoxyguanosine kinase by didanosine: implication for mitochondrial toxicities of anti-HIV nucleoside analogs". Biochemical and Biophysical Research Communications. 450 (2): 1021–6. doi:10.1016/j.bbrc.2014.06.098. PMID 24976398.
  97. ↑ Hirsch MS (1990). "Chemotherapy of human immunodeficiency virus infections: current practice and future prospects". The Journal of Infectious Diseases. 161 (5): 845–57. doi:10.1093/infdis/161.5.845. PMID 1691243.
  98. ↑ Lin TS, Neenan JP, Cheng YC, Prusoff WH (1976). "Synthesis and antiviral activity of 5- and 5'-substituted thymidine analogs". Journal of Medicinal Chemistry. 19 (4): 495–8. doi:10.1021/jm00226a009. PMID 177781.
  99. ↑ Helgstrand E, Oberg B (1980). "Enzymatic targets in virus chemotherapy". Antibiotics and Chemotherapy. 27: 22–69. PMID 6996606.
  100. ↑ Shannon WM, Schabel FM (1980). "Antiviral agents as adjuncts in cancer chemotherapy". Pharmacology & Therapeutics. 11 (2): 263–390. doi:10.1016/0163-7258(80)90034-0. PMID 7001501.
  101. 1 2 Sakamoto K, Yokogawa T, Ueno H, Oguchi K, Kazuno H, Ishida K, Tanaka N, Osada A, Yamada Y, Okabe H, Matsuo K (2015). "Crucial roles of thymidine kinase 1 and deoxyUTPase in incorporating the antineoplastic nucleosides trifluridine and 2'-deoxy-5-fluorouridine into DNA". International Journal of Oncology. 46 (6): 2327–34. doi:10.3892/ijo.2015.2974. PMC 4441292Freely accessible. PMID 25901475.
  102. ↑ Sun R, Eriksson S, Wang L (2014). "Zidovudine induces downregulation of mitochondrial deoxynucleoside kinases: implications for mitochondrial toxicity of antiviral nucleoside analogs". Antimicrobial Agents and Chemotherapy. 58 (11): 6758–66. doi:10.1128/AAC.03613-14. PMC 4249380Freely accessible. PMID 25182642.
  103. ↑ Hamamoto Y, Nakashima H, Matsui T, Matsuda A, Ueda T, Yamamoto N (1987). "Inhibitory effect of 2',3'-didehydro-2',3'-dideoxynucleosides on infectivity, cytopathic effects, and replication of human immunodeficiency virus". Antimicrobial Agents and Chemotherapy. 31 (6): 907–10. doi:10.1128/aac.31.6.907. PMC 284209Freely accessible. PMID 3039911.
  104. ↑ Baba M, Pauwels R, Herdewijn P, De Clercq E, Desmyter J, Vandeputte M (1987). "Both 2',3'-dideoxythymidine and its 2',3'-unsaturated derivative (2',3'-dideoxythymidinene) are potent and selective inhibitors of human immunodeficiency virus replication in vitro". Biochemical and Biophysical Research Communications. 142 (1): 128–34. doi:10.1016/0006-291x(87)90460-8. PMID 3028398.
  105. 1 2 Öhrvik A, Lindh M, Einarsson R, Grassi J, Eriksson S (2004). "Sensitive nonradiometric method for determining thymidine kinase 1 activity". Clinical Chemistry. 50 (9): 1597–606. doi:10.1373/clinchem.2003.030379. PMID 15247154.
  106. ↑ Prusoff WH (1959). "Synthesis and biological activities of iododeoxyuridine, an analog of thymidine". Biochimica et Biophysica Acta. 32 (1): 295–6. doi:10.1016/0006-3002(59)90597-9. PMID 13628760.
  107. ↑ Morgenroth A, Deisenhofer S, Glatting G, Kunkel FH, Dinger C, Zlatopolskiy B, Vogg AT, Kull T, Reske SN (2008). "Preferential tumor targeting and selective tumor cell cytotoxicity of 5-[131/125I]iodo-4'-thio-2'-deoxyuridine". Clinical Cancer Research. 14 (22): 7311–9. doi:10.1158/1078-0432.CCR-08-0907. PMID 19010846.
  108. ↑ Mar EC, Chiou JF, Cheng YC, Huang ES (1985). "Inhibition of cellular DNA polymerase alpha and human cytomegalovirus-induced DNA polymerase by the triphosphates of 9-(2-hydroxyethoxymethyl)guanine and 9-(1,3-dihydroxy-2-propoxymethyl)guanine". J. Virol. 53 (3): 776–80. PMC 254706Freely accessible. PMID 2983088.
  109. ↑ Weinschenk L, Schols D, Balzarini J, Meier C (2015). "Nucleoside Diphosphate Prodrugs: Nonsymmetric DiPPro-Nucleotides". Journal of Medicinal Chemistry. 58 (15): 6114–30. doi:10.1021/acs.jmedchem.5b00737. PMID 26125628.
  110. ↑ Nicholas TW, Read SB, Burrows FJ, Kruse CA (2003). "Suicide gene therapy with Herpes simplex virus thymidine kinase and ganciclovir is enhanced with connexins to improve gap junctions and bystander effects". Histology and Histopathology. 18 (2): 495–507. PMID 12647801.
  111. ↑ Preuss E, Muik A, Weber K, Otte J, von Laer D, Fehse B (2011). "Cancer suicide gene therapy with TK.007: superior killing efficiency and bystander effect". Journal of Molecular Medicine (Berlin, Germany). 89 (11): 1113–24. doi:10.1007/s00109-011-0777-8. PMID 21698427.
  112. ↑ Jones BS, Lamb LS, Goldman F, Di Stasi A (2014). "Improving the safety of cell therapy products by suicide gene transfer". Frontiers in Pharmacology. 5: 254. doi:10.3389/fphar.2014.00254. PMC 4245885Freely accessible. PMID 25505885.
  113. ↑ Rasekhian M, Teimoori-Toolabi L, Amini S, Azadmanesh K (2015). "An Enterovirus-Like RNA Construct for Colon Cancer Suicide Gene Therapy". Iranian Biomedical Journal. 19 (3): 124–32. PMC 4571007Freely accessible. PMID 26025964.
  114. ↑ Karjoo Z, Chen X, Hatefi A (2015). "Progress and problems with the use of suicide genes for targeted cancer therapy". Advanced Drug Delivery Reviews. 99: 113–28. doi:10.1016/j.addr.2015.05.009. PMID 26004498.
  115. ↑ Greco R, Oliveira G, Stanghellini MT, Vago L, Bondanza A, Peccatori J, Cieri N, Marktel S, Mastaglio S, Bordignon C, Bonini C, Ciceri F (2015). "Improving the safety of cell therapy with the TK-suicide gene". Frontiers in Pharmacology. 6: 95. doi:10.3389/fphar.2015.00095. PMC 4419602Freely accessible. PMID 25999859.
  116. ↑ Zhang TY, Huang B, Wu HB, Wu JH, Li LM, Li YX, Hu YL, Han M, Shen YQ, Tabata Y, Gao JQ (2015). "Synergistic effects of co-administration of suicide gene expressing mesenchymal stem cells and prodrug-encapsulated liposome on aggressive lung melanoma metastases in mice". Journal of Controlled Release. 209: 260–71. doi:10.1016/j.jconrel.2015.05.007. PMID 25966361.
  117. ↑ Chao CN, Huang YL, Lin MC, Fang CY, Shen CH, Chen PL, Wang M, Chang D, Tseng CE (2015). "Inhibition of human diffuse large B-cell lymphoma growth by JC polyomavirus-like particles delivering a suicide gene". Journal of Translational Medicine. 13: 29. doi:10.1186/s12967-015-0389-0. PMC 4312600Freely accessible. PMID 25623859.
  118. ↑ Fang CY, Tsai YD, Lin MC, Wang M, Chen PL, Chao CN, Huang YL, Chang D, Shen CH (2015). "Inhibition of human bladder cancer growth by a suicide gene delivered by JC polyomavirus virus-like particles in a mouse model". The Journal of Urology. 193 (6): 2100–6. doi:10.1016/j.juro.2015.01.084. PMID 25623749.
  119. ↑ Wu JX, Liu SH, Nemunaitis JJ, Brunicardi FC (2015). "Liposomal insulin promoter-thymidine kinase gene therapy followed by ganciclovir effectively ablates human pancreatic cancer in mice". Cancer Letters. 359 (2): 206–10. doi:10.1016/j.canlet.2015.01.002. PMC 4336837Freely accessible. PMID 25596375.
  120. ↑ Hsu C, Abad JD, Morgan RA (2013). "Characterization of human T lymphocytes engineered to express interleukin-15 and herpes simplex virus-thymidine kinase". The Journal of Surgical Research. 184 (1): 282–9. doi:10.1016/j.jss.2013.03.054. PMC 3759574Freely accessible. PMID 23582229.
  121. ↑ Mutahir Z, Larsen NB, Christiansen LS, Andersson KM, Rico R, Wisen SM, Clausen AR, Munch-Petersen B, Piškur J (2011). "Characterization of oligomeric and kinetic properties of tomato thymidine kinase 1". Nucleosides Nucleotides Nucleic Acids. 30 (12): 1223–6. doi:10.1080/15257770.2011.597629. PMID 22132978.
  122. ↑ Kotini AG, de Stanchina E, Themeli M, Sadelain M, Papapetrou EP (2016). "Escape Mutations, Ganciclovir Resistance, and Teratoma Formation in Human iPSCs Expressing an HSVtk Suicide Gene". Mol Ther Nucleic Acids. 5: e284. doi:10.1038/mtna.2015.57. PMC 4884789Freely accessible. PMID 26836371.
  123. ↑ Cong X, Lei JL, Xia SL, Wang YM, Li Y, Li S, Luo Y, Sun Y, Qiu HJ (2016). "Pathogenicity and immunogenicity of a gE/gI/TK gene-deleted pseudorabies virus variant in susceptible animals". Vet. Microbiol. 182: 170–7. doi:10.1016/j.vetmic.2015.11.022. PMID 26711045.
  124. ↑ Ji N, Weng D, Liu C, Gu Z, Chen S, Guo Y, Fan Z, Wang X, Chen J, Zhao Y, Zhou J, Wang J, Ma D, Li N (2015). "Adenovirus-mediated delivery of herpes simplex virus thymidine kinase administration improves outcome of recurrent high-grade glioma". Oncotarget. 7: 4369–78. doi:10.18632/oncotarget.6737. PMC 4826211Freely accessible. PMID 26716896.
  125. ↑ Christiansen LS, Egeblad L, Munch-Petersen B, Piškur J, Knecht W (2015). "New Variants of Tomato Thymidine Kinase 1 Selected for Increased Sensitivity of E. coli KY895 towards Azidothymidine". Cancers. 7 (2): 966–80. doi:10.3390/cancers7020819. PMC 4491694Freely accessible. PMID 26061968.
  126. ↑ Stedt H, Samaranayake H, Kurkipuro J, Wirth G, Christiansen LS, Vuorio T, Määttä AM, Piškur J, Ylä-Herttuala S (2015). "Tomato thymidine kinase-based suicide gene therapy for malignant glioma--an alternative for Herpes Simplex virus-1 thymidine kinase". Cancer Gene Ther. 22 (3): 130–7. doi:10.1038/cgt.2014.76. PMID 25613481.
  127. ↑ Hart IR (1996). "Tissue specific promoters in targeting systemically delivered gene therapy". Seminars in Oncology. 23 (1): 154–8. PMID 8607025.
  128. ↑ Wills KN, Huang WM, Harris MP, Machemer T, Maneval DC, Gregory RJ (1995). "Gene therapy for hepatocellular carcinoma: chemosensitivity conferred by adenovirus-mediated transfer of the HSV-1 thymidine kinase gene". Cancer Gene Therapy. 2 (3): 191–7. PMID 8528962.
  129. ↑ Ido A, Nakata K, Kato Y, Nakao K, Murata K, Fujita M, Ishii N, Tamaoki T, Shiku H, Nagataki S (1995). "Gene therapy for hepatoma cells using a retrovirus vector carrying herpes simplex virus thymidine kinase gene under the control of human alpha-fetoprotein gene promoter". Cancer Research. 55 (14): 3105–9. PMID 7541712.
  130. ↑ Kanai F, Shiratori Y, Yoshida Y, Wakimoto H, Hamada H, Kanegae Y, Saito I, Nakabayashi H, Tamaoki T, Tanaka T, Lan KH, Kato N, Shiina S, Omata M (1996). "Gene therapy for alpha-fetoprotein-producing human hepatoma cells by adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene". Hepatology (Baltimore, Md.). 23 (6): 1359–68. doi:10.1002/hep.510230611. PMID 8675152.
  131. ↑ Garver RI, Goldsmith KT, Rodu B, Hu PC, Sorscher EJ, Curiel DT (1994). "Strategy for achieving selective killing of carcinomas". Gene Therapy. 1 (1): 46–50. PMID 7584059.
  132. ↑ Hart IR (1996). "Transcriptionally targeted gene therapy". Current Topics in Microbiology and Immunology. 213 (3): 19–25. PMID 8815006.
  133. ↑ Byun Y, Thirumamagal BT, Yang W, Eriksson S, Barth RF, Tjarks W (2006). "Preparation and biological evaluation of 10B-enriched 3-[5-{2-(2,3-dihydroxyprop-1-yl)-o-carboran-1-yl}pentan-1-yl]thymidine (N5-2OH), a new boron delivery agent for boron neutron capture therapy of brain tumors". Journal of Medicinal Chemistry. 49 (18): 5513–23. doi:10.1021/jm060413w. PMID 16942024.
  134. ↑ Thirumamagal BT, Johnsamuel J, Cosquer GY, Byun Y, Yan J, Narayanasamy S, Tjarks W, Barth RF, Al-Madhoun AS, Eriksson S (2006). "Boronated thymidine analogues for boron neutron capture therapy". Nucleosides, Nucleotides & Nucleic Acids. 25 (8): 861–6. doi:10.1080/15257770600793844. PMID 16901817.
  135. ↑ Narayanasamy S, Thirumamagal BT, Johnsamuel J, Byun Y, Al-Madhoun AS, Usova E, Cosquer GY, Yan J, Bandyopadhyaya AK, Tiwari R, Eriksson S, Tjarks W (2006). "Hydrophilically enhanced 3-carboranyl thymidine analogues (3CTAs) for boron neutron capture therapy (BNCT) of cancer". Bioorganic & Medicinal Chemistry. 14 (20): 6886–99. doi:10.1016/j.bmc.2006.06.039. PMID 16831554.
  136. ↑ Byun Y, Narayanasamy S, Johnsamuel J, Bandyopadhyaya AK, Tiwari R, Al-Madhoun AS, Barth RF, Eriksson S, Tjarks W (2006). "3-Carboranyl thymidine analogues (3CTAs) and other boronated nucleosides for boron neutron capture therapy". Anti-cancer Agents in Medicinal Chemistry. 6 (2): 127–44. doi:10.2174/187152006776119171. PMID 16529536.
  137. ↑ Byun Y, Yan J, Al-Madhoun AS, Johnsamuel J, Yang W, Barth RF, Eriksson S, Tjarks W (2005). "Synthesis and biological evaluation of neutral and zwitterionic 3-carboranyl thymidine analogues for boron neutron capture therapy". Journal of Medicinal Chemistry. 48 (4): 1188–98. doi:10.1021/jm0491896. PMID 15715485.
  138. ↑ Barth RF, Yang W, Al-Madhoun AS, Johnsamuel J, Byun Y, Chandra S, Smith DR, Tjarks W, Eriksson S (2004). "Boron-containing nucleosides as potential delivery agents for neutron capture therapy of brain tumors". Cancer Research. 64 (17): 6287–95. doi:10.1158/0008-5472.CAN-04-0437. PMID 15342417.
  139. ↑ Al-Madhoun AS, Johnsamuel J, Barth RF, Tjarks W, Eriksson S (2004). "Evaluation of human thymidine kinase 1 substrates as new candidates for boron neutron capture therapy". Cancer Research. 64 (17): 6280–6. doi:10.1158/0008-5472.CAN-04-0197. PMID 15342416.
  140. ↑ Johnsamuel J, Lakhi N, Al-Madhoun AS, Byun Y, Yan J, Eriksson S, Tjarks W (2004). "Synthesis of ethyleneoxide modified 3-carboranyl thymidine analogues and evaluation of their biochemical, physicochemical, and structural properties". Bioorganic & Medicinal Chemistry. 12 (18): 4769–81. doi:10.1016/j.bmc.2004.07.032. PMID 15336255.
  141. ↑ Byun Y, Yan J, Al-Madhoun AS, Johnsamuel J, Yang W, Barth RF, Eriksson S, Tjarks W (2004). "The synthesis and biochemical evaluation of thymidine analogues substituted with nido carborane at the N-3 position". Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine. 61 (5): 1125–30. doi:10.1016/j.apradiso.2004.05.023. PMID 15308203.
  142. ↑ Yan J, Naeslund C, Al-Madhoun AS, Wang J, Ji W, Cosquer GY, Johnsamuel J, Sjöberg S, Eriksson S, Tjarks W (2002). "Synthesis and biological evaluation of 3'-carboranyl thymidine analogues". Bioorganic & Medicinal Chemistry Letters. 12 (16): 2209–12. doi:10.1016/s0960-894x(02)00357-8. PMID 12127539.
  143. ↑ Barth RF, Yang W, Wu G, Swindall M, Byun Y, Narayanasamy S, Tjarks W, Tordoff K, Moeschberger ML, Eriksson S, Binns PJ, Riley KJ (2008). "Thymidine kinase 1 as a molecular target for boron neutron capture therapy of brain tumors". Proceedings of the National Academy of Sciences of the United States of America. 105 (45): 17493–7. doi:10.1073/pnas.0809569105. PMC 2582264Freely accessible. PMID 18981415.
  144. ↑ Agarwal HK, McElroy CA, Sjuvarsson E, Eriksson S, Darby MV, Tjarks W (2013). "Synthesis of N3-substituted carboranyl thymidine bioconjugates and their evaluation as substrates of recombinant human thymidine kinase 1". Eur J Med Chem. 60: 456–68. doi:10.1016/j.ejmech.2012.11.041. PMC 3587680Freely accessible. PMID 23318906.
  145. ↑ Hasabelnaby S, Goudah A, Agarwal HK, abd Alla MS, Tjarks W (2012). "Synthesis, chemical and enzymatic hydrolysis, and aqueous solubility of amino acid ester prodrugs of 3-carboranyl thymidine analogs for boron neutron capture therapy of brain tumors". Eur J Med Chem. 55: 325–34. doi:10.1016/j.ejmech.2012.07.033. PMC 3432695Freely accessible. PMID 22889558.
  146. ↑ Sjuvarsson E, Damaraju VL, Mowles D, Sawyer MB, Tiwari R, Agarwal HK, Khalil A, Hasabelnaby S, Goudah A, Nakkula RJ, Barth RF, Cass CE, Eriksson S, Tjarks W (2013). "Cellular influx, efflux, and anabolism of 3-carboranyl thymidine analogs: potential boron delivery agents for neutron capture therapy". J. Pharmacol. Exp. Ther. 347 (2): 388–97. doi:10.1124/jpet.113.207464. PMC 3807065Freely accessible. PMID 24006340.
  147. ↑ Agarwal HK, Khalil A, Ishita K, Yang W, Nakkula RJ, Wu LC, Ali T, Tiwari R, Byun Y, Barth RF, Tjarks W (2015). "Synthesis and evaluation of thymidine kinase 1-targeting carboranyl pyrimidine nucleoside analogs for boron neutron capture therapy of cancer". Eur J Med Chem. 100: 197–209. doi:10.1016/j.ejmech.2015.05.042. PMC 4501388Freely accessible. PMID 26087030.
  148. ↑ Barth RF, Yang W, Nakkula RJ, Byun Y, Tjarks W, Chu Wu L, Binns PJ, Riley KJ (2015). "Evaluation of TK1 targeting carboranyl thymidine analogs as potential delivery agents for neutron capture therapy of brain tumors". Appl Radiat Isot. 106: 251–5. doi:10.1016/j.apradiso.2015.06.031. PMID 26282567.
  149. ↑ Khalil A, Ishita K, Ali T, Tjarks W (2013). "N3-substituted thymidine bioconjugates for cancer therapy and imaging". Future Med Chem. 5 (6): 677–92. doi:10.4155/fmc.13.31. PMC 3816973Freely accessible. PMID 23617430.
  150. ↑ Merrick CJ (2015). "Transfection with thymidine kinase permits bromodeoxyuridine labelling of DNA replication in the human malaria parasite Plasmodium falciparum". Malar. J. 14 (1): 490. doi:10.1186/s12936-015-1014-7. PMC 4668656Freely accessible. PMID 26630917.
  151. ↑ WO application 2006000246, "A method and kit for determination of thymidine kinase activity and use thereof", published 2006-02-24, assigned to Gronowitz JS
  152. ↑ von Euler HP, Öhrvik AB, Eriksson SK (2006). "A non-radiometric method for measuring serum thymidine kinase activity in malignant lymphoma in dogs". Research in Veterinary Science. 80 (1): 17–24. doi:10.1016/j.rvsc.2005.05.001. PMID 16140350.
  153. ↑ Pagaduan JV, Ramsden M, O'Neill K, Woolley AT (2015). "Microchip immunoaffinity electrophoresis of antibody-thymidine kinase 1 complex". Electrophoresis. 36 (5): 813–7. doi:10.1002/elps.201400436. PMC 4346389Freely accessible. PMID 25486911.
  154. ↑ Stålhandske P, Wang L, Westberg S, von Euler H, Groth E, Gustafsson SA, Eriksson S, Lennerstrand J (2013). "Homogeneous assay for real-time and simultaneous detection of thymidine kinase 1 and deoxycytidine kinase activities". Anal. Biochem. 432 (2): 155–64. doi:10.1016/j.ab.2012.08.004. PMID 22902741.
  155. ↑ Sharif H, von Euler H, Westberg S, He E, Wang L, Eriksson S (2012). "A sensitive and kinetically defined radiochemical assay for canine and human serum thymidine kinase 1 (TK1) to monitor canine malignant lymphoma". Vet. J. 194 (1): 40–7. doi:10.1016/j.tvjl.2012.03.006. PMID 22516918.
  156. ↑ Chen ZH, Huang SQ, Wang Y, Yang AZ, Wen J, Xu XH, Chen Y, Chen QB, Wang YH, He E, Zhou J, Skog S (2011). "Serological thymidine kinase 1 is a biomarker for early detection of tumours--a health screening study on 35,365 people, using a sensitive chemiluminescent dot blot assay". Sensors (Basel). 11 (12): 11064–80. doi:10.3390/s111211064. PMC 3251970Freely accessible. PMID 22247653.
  157. ↑ Nisman B, Allweis T, Kadouri L, Mali B, Hamburger T, Baras M, Gronowitz S, Peretz T (2013). "Comparison of diagnostic and prognostic performance of two assays measuring thymidine kinase 1 activity in serum of breast cancer patients". Clin. Chem. Lab. Med. 51 (2): 439–47. doi:10.1515/cclm-2012-0162. PMID 23093267.
  158. ↑ He Q, Zou L, Zhang PA, Lui JX, Skog S, Fornander T (2000). "The clinical significance of thymidine kinase 1 measurement in serum of breast cancer patients using anti-TK1 antibody". The International Journal of Biological Markers. 15 (2): 139–46. PMID 10883887.
  159. ↑ Kimmel N, Friedman MG, Sarov I (1982). "Enzyme-linked immunosorbent assay (ELISA) for detection of herpes simplex virus-specific IgM antibodies". Journal of Virological Methods. 4 (4-5): 219–27. doi:10.1016/0166-0934(82)90068-4. PMID 6286702.
  160. ↑ Huang S, Lin J, Guo N, Zhang M, Yun X, Liu S, Zhou J, He E, Skog S (2011). "Elevated serum thymidine kinase 1 predicts risk of pre/early cancerous progression". Asian Pacific Journal of Cancer Prevention. 12 (2): 497–505. PMID 21545220.
  161. ↑ Kiran Kumar J, Sharif H, Westberg S, von Euler H, Eriksson S (2013). "High levels of inactive thymidine kinase 1 polypeptide detected in sera from dogs with solid tumours by immunoaffinity methods: implications for in vitro diagnostics". Vet. J. 197 (3): 854–60. doi:10.1016/j.tvjl.2013.05.036. PMID 23831216.
  162. ↑ Romain S, Spyratos F, Guirou O, Deytieux S, Chinot O, Martin PM (1994). "Technical evaluation of thymidine kinase assay in cytosols from breast cancers. EORTC Receptor Study Group Report". European Journal of Cancer (Oxford, England : 1990). 30A (14): 2163–5. PMID 7857717.
  163. ↑ Arnér ES, Spasokoukotskaja T, Eriksson S (1992). "Selective assays for thymidine kinase 1 and 2 and deoxycytidine kinase and their activities in extracts from human cells and tissues". Biochemical and Biophysical Research Communications. 188 (2): 712–8. doi:10.1016/0006-291x(92)91114-6. PMID 1359886.
  164. ↑ Wang L, Eriksson S (2008). "5-Bromovinyl 2'-deoxyuridine phosphorylation by mitochondrial and cytosolic thymidine kinase (TK2 and TK1) and its use in selective measurement of TK2 activity in crude extracts". Nucleosides, Nucleotides & Nucleic Acids. 27 (6): 858–62. doi:10.1080/15257770802146510. PMID 18600552.
  165. ↑ Herzfeld A, Greengard O (1980). "Enzyme activities in human fetal and neoplastic tissues". Cancer. 46 (9): 2047–54. doi:10.1002/1097-0142(19801101)46:9<2047::aid-cncr2820460924>3.0.co;2-q. PMID 6253048.
  166. ↑ Machovich R, Greengard O (1972). "Thymidine kinase in rat tissues during growth and differentiation". Biochimica et Biophysica Acta. 286 (2): 375–81. doi:10.1016/0304-4165(72)90273-5. PMID 4660462.
  167. ↑ Herzfeld A, Raper SM, Gore I (1980). "The ontogeny of thymidine kinase in tissues of man and rat". Pediatric Research. 14 (12): 1304–10. doi:10.1203/00006450-198012000-00006. PMID 7208144.
  168. ↑ Schollenberger S, Taureck D, Wilmanns W (1972). "[Enzymes of thymidine and thymidylate metabolism in normal and pathological blood and bone marrow cells]". Blut (in German). 25 (5): 318–34. PMID 4508724.
  169. ↑ Nakao K, Fujioka S (1968). "Thymidine kinase activity in the human bone marrow from various blood diseases". Life Sciences. 7 (8): 395–9. doi:10.1016/0024-3205(68)90039-8. PMID 5649653.
  170. ↑ Wickramasinghe SN, Olsen I, Saunders JE (1975). "Thymidine kinase activity in human bone marrow cells". Scandinavian Journal of Haematology. 15 (2): 139–44. PMID 1059244.
  171. ↑ Kuroiwa N, Nakayama M, Fukuda T, Fukui H, Ohwada H, Hiwasa T, Fujimura S (2001). "Specific recognition of cytosolic thymidine kinase in the human lung tumor by monoclonal antibodies raised against recombinant human thymidine kinase". Journal of Immunological Methods. 253 (1-2): 1–11. doi:10.1016/s0022-1759(01)00368-4. PMID 11384664.
  172. 1 2 He Q, Mao Y, Wu J, Decker C, Merza M, Wang N, Eriksson S, Castro J, Skog S (2004). "Cytosolic thymidine kinase is a specific histopathologic tumour marker for breast carcinomas". International Journal of Oncology. 25 (4): 945–53. PMID 15375544.
  173. ↑ Mao Y, Wu J, Wang N, He L, Wu C, He Q, Skog S (2002). "A comparative study: immunohistochemical detection of cytosolic thymidine kinase and proliferating cell nuclear antigen in breast cancer". Cancer Investigation. 20 (7-8): 922–31. doi:10.1081/cnv-120005905. PMID 12449723.
  174. ↑ Mao Y, Wu J, Skog S, Eriksson S, Zhao Y, Zhou J, He Q (2005). "Expression of cell proliferating genes in patients with non-small cell lung cancer by immunohistochemistry and cDNA profiling". Oncology Reports. 13 (5): 837–46. PMID 15809747.
  175. ↑ Wu J, Mao Y, He L, Wang N, Wu C, He Q, Skog S (2000). "A new cell proliferating marker: cytosolic thymidine kinase as compared to proliferating cell nuclear antigen in patients with colorectal carcinoma". Anticancer Research. 20 (6C): 4815–20. PMID 11205225.
  176. ↑ Li HX, Lei DS, Wang XQ, Skog S, He Q (2005). "Serum thymidine kinase 1 is a prognostic and monitoring factor in patients with non-small cell lung cancer". Oncol. Rep. 13 (1): 145–9. PMID 15583816.
  177. ↑ Kruck S, Hennenlotter J, Vogel U, Schilling D, Gakis G, Hevler J, Kuehs U, Stenzl A, Schwentner C (2012). "Exposed proliferation antigen 210 (XPA-210) in renal cell carcinoma (RCC) and oncocytoma: clinical utility and biological implications". BJU Int. 109 (4): 634–8. doi:10.1111/j.1464-410X.2011.10392.x. PMID 21711439.
  178. ↑ Neef AB, Pernot L, Schreier VN, Scapozza L, Luedtke NW (2015). "A Bioorthogonal Chemical Reporter of Viral Infection". Angewandte Chemie International Edition in English. 54 (27): 7911–4. doi:10.1002/anie.201500250. PMID 25974835.

External links

This article is issued from Wikipedia - version of the 11/8/2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.