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Molecular properties of serum thymidine kinase 1 and use of the canine enzyme in disease monitoring

Sharif, Hanan Mohamed (2012). Molecular properties of serum thymidine kinase 1 and use of the canine enzyme in disease monitoring. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis agriculturae Sueciae, 1652-6880 ; 2012:51
ISBN 978-91-576-7698-6
[Doctoral thesis]

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Abstract

Thymidine kinase 1 (ATP: thymidine 5'-phosphotransferase, EC 2.7.1.21, TK1) catalyzes the transfer of the gamma phosphate group from a phosphate donor to the 5´- hydroxyl group of thymidine to form thymidine monophosphate, which is converted to thymidine triphosphate and then utilized in DNA synthesis. TK1 activity markedly increases in G1 and S phase of the cell cycle and is found mainly in dividing cells, but also in an extracellular form in the blood. Increased serum TK1 levels are considered as a sensitive and useful marker for cell proliferation and detection of malignancy in clinical medicine.

The aim of this study was to investigate the molecular characteristics of canine thymidine kinase 1 and utilize several anti-TK1 antibodies to a better understanding its role in disease prognostics, risk assessment, and monitoring of cancer development.

Study I was undertaken to clarify the structure of recombinant, cellular and serum TK1 in order to improve the usefulness of serum TK1 (STK1) as a proliferation biomarker in neoplastic diseases. Several forms of STK1 were observed with different enzymatic activities. The active form of STK1 was found mainly as an oligomer. Dimer and tetramer forms of STK1 were also seen in serum by immunoaffinity method, but they were enzymatically less active. Study II described a sensitive method using a [3H]-deoxythymidine phosphorylation assay to measure STK1 activity in dogs and humans with hematologic malignancies and dogs with solid tumors. The results revealed that the dThd phosphorylation assay was suitable for measurement of TK1 in hematologic malignancy (lymphoma and leukemia) and provided valuable information regarding the disease recurrence. Significant correlation was observed between the [3H]-dThd assay and the TK1 activity assays, TK-REA and TK Liaison. However, STK1 activity levels in dogs with solid tumors were very low. Therefore, another method to determine the levels of TK1 in serum based on immunoaffinity techniques was performed in study III. The concentration of STK1 protein in dogs with solid tumors was much higher than expected from the activity. Thus, methods to determine STK1 protein are more sensitive than activity tests in solid tumors. Study IV revealed that serum TK1 activity was elevated in 41% of bitches with pyometra, and thus TK1 determinations may be clinically valuable also in some non-neoplastic diseases.

Authors/Creators:Sharif, Hanan Mohamed
Title:Molecular properties of serum thymidine kinase 1 and use of the canine enzyme in disease monitoring
Series/Journal:Acta Universitatis agriculturae Sueciae (1652-6880)
Year of publishing :2012
Volume:2012:51
Number of Pages:73
Papers/manuscripts:
NumberReferences
I.Sharif H., Kiran KJ., Wang L., He E., Eriksson S. (2012). Quaternary structure of recombinant, cellular, and serum forms of thymidine kinase 1 from dogs and humans. BMC Biochemistry Journal 13 (12), 1-10.
II.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. The Veterinary Journal (In press).
III.Sharif H*., Kumar KJ*., Westberg S., Von Euler H., Eriksson S. (2012). Determination of serum thymidine kinase 1 polypeptide and activity levels in dogs with hematologic malignancy and solid tumour. (Manuscript). * First authorship shared
IV.Sharif H., Hagman R., Wang L., Eriksson S. (2012). Elevation of serum thymidine kinase 1 activity in a bacterial infection: Canine pyometra. (Submitted for publication).
Place of Publication:Uppsala
Publisher:Dept. of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences
Associated Programs and Other Stakeholders:SLU - Research Areas for the Future > Future Animal Health and Welfare
ISBN for printed version:978-91-576-7698-6
ISSN:1652-6880
Language:English
Publication Type:Doctoral thesis
Full Text Status:Public
Agris subject categories.:L Animal production > L50 Animal physiology and biochemistry
L Animal production > L73 Animal diseases
Subjects:(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Medical Bioscience
Agrovoc terms:dogs, thymidine, enzymes, genetic markers, neoplasms, pyometra, animal diseases, human diseases, blood serum, diagnosis, monitoring
Keywords:blood biomarkers, thymidine kinase, cell proliferation biomarker, canine pyometra, radio-enzymatic assay, solid tumor, hematologic malignancy
URN:NBN:urn:nbn:se:slu:epsilon-e-586
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-586
ID Code:8999
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Anatomy, Physiology and Biochemistry
Deposited By: Hanan Sharif
Deposited On:27 Aug 2012 06:48
Metadata Last Modified:02 Dec 2014 10:51

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