Dataset Information

Evaluation of serum thymidine kinase 1 activity as a biomarker for treatment effectiveness and prediction of relapse in dogs with non-Hodgkin lymphoma.

ABSTRACT:

Background

Serum thymidine kinase 1 (sTK1) activity is closely correlated with DNA synthesis.

Objectives

Evaluate sTK1 activity as a biomarker for treatment response and early detection of relapse in dogs with lymphoma.

Animals

Ninety-seven client-owned dogs with naive or relapsed lymphoma and 23 healthy dogs.

Methods

Prospective study. Serum TK1 activity measured by refined ELISA-based method (DiviTum assay, Biovica International) before treatment, at clinical response, and every 4?weeks until relapse or last follow-up.

Results

Serum TK1 activity was ?20 Du/L in 96% (22/23) of healthy dogs. Pretreatment sTK1 activity was >20 Du/L in 88% (85/97) dogs with lymphoma. At clinical response, sTK1 activity was significantly lower in dogs with complete (CR, n?=?36) versus partial (PR, n?=?29) response (P 2.7-fold value measured at clinical response) predicted relapse at subsequent 4-week assessment with a Se 61% and Sp 88% (AUC, 0.79; 95%-CI, 0.64-0.95; P =?.004).

Conclusions and clinical importance

Monitoring sTK1 activity could help to detect complete responders and early disease progression in dogs with lymphoma.

SUBMITTER: Boye P

PROVIDER: S-EPMC6639481 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Evaluation of serum thymidine kinase 1 activity as a biomarker for treatment effectiveness and prediction of relapse in dogs with non-Hodgkin lymphoma.

Boyé Pierre P Floch Franck F Serres François F Geeraert Kévyn K Clerson Pierre P Siomboing Xavier X Bergqvist Mattias M Sack Gabriel G Tierny Dominique D

Journal of veterinary internal medicine 20190525 4

<h4>Background</h4>Serum thymidine kinase 1 (sTK1) activity is closely correlated with DNA synthesis.<h4>Objectives</h4>Evaluate sTK1 activity as a biomarker for treatment response and early detection of relapse in dogs with lymphoma.<h4>Animals</h4>Ninety-seven client-owned dogs with naive or relapsed lymphoma and 23 healthy dogs.<h4>Methods</h4>Prospective study. Serum TK1 activity measured by refined ELISA-based method (DiviTum assay, Biovica International) before treatment, at clinical respo ...[more]

PMID: 31129922

Similar Datasets

Project description:BACKGROUND:Thymidine kinase 1 (TK1) plays a key role in the synthesis of deoxythymidine triphosphate (dTTP) and is thus important for DNA replication and cell proliferation. The expression of TK1 is highest during S-phase, and it is rapidly degraded after mitosis. In cancer cells, TK1 is upregulated, resulting in leakage of excess TK1 into the blood. Consequently, serum TK1 has been used as a diagnostic and prognostic cancer biomarker, mainly in human medicine. The aims of this work were to characterize equine TK1 and to evaluate its suitability as a serum biomarker for equine lymphoma. RESULTS:Equine TK1 was cloned, expressed in E. coli and affinity purified. The purified recombinant horse TK1 showed broad substrate specificity, phosphorylating pyrimidine deoxyribo- and ribonucleosides and, to some extent, purine deoxynucleosides, including anticancer and antiviral nucleoside analogues. ATP was the preferred phosphate donor. Serum TK1 activity was measured in samples collected from horses with confirmed or suspected lymphoma and control horses with and without concurrent diseases. Serum TK1 activity levels were significantly higher in horses with lymphoma (p < 0.0005) and suspected lymphoma (p < 0.02) and in tumour-free groups with diverse diseases (p < 0.03) than in controls without concurrent diseases. There was a significant difference between the lymphoma group and the tumour-free group with diverse diseases (p < 0.0006). Furthermore, receiver operating characteristic analysis revealed a sensitivity of 0.86, a specificity of 0.95 and an AUC (area under the curve) of 0.92 compared to the controls without concurrent diseases, with a sensitivity of 0.97, a specificity of 0.71 and an AUC of 0.88 when compared with the tumour-free group with diverse diseases. CONCLUSION:Equine TK1 showed high specific activity and broader substrate specificity than human TK1. Anticancer and antiviral thymidine analogues were efficiently phosphorylated by horse TK1, suggesting that these analogues might be good candidates for chemotherapy in horses. Serum TK1 activity was significantly higher in horses with lymphoma than in controls. ROC analysis indicated that serum TK1 could serve as a promising cancer biomarker in horses.

Project description:IntroductionDogs play an important role in society, which increased during the covid epidemics. This has led to a much higher workload for the veterinarians. Therefore, there is a need for efficient diagnostic tools to identify risk of malignant diseases. Here the development of a new test that can solve some of these problems is presented. It is based on serum Thymidine Kinase 1 (TK1), which is a biomarker for cell proliferation and cell lysis.MethodsAnti-TK1 monoclonal antibodies were produced against two different epitopes, the active site of the TK1 protein and the C-terminal region of canine TK1. The antibodies were developed with hybridoma technology and validated using dot blot, Quartz Crystal Microbalance (QCM) technology, western blots, immunoprecipitation (IP), and enzyme-linked immunosorbent assay (ELISA). Clinical evaluation of Canine TK1 ELISA was done by using sera from 131 healthy dogs and 93 dogs with lymphoma. The two selected Anti-TK1 monoclonal antibodies have Kd values in the range of 10-9 M and further analysis with dot and western blots confirmed the high affinity binding of these antibodies. A sandwich Canine TK1 ELISA was developed using the anti-TK1 antibodies, and TK1 concentrations in serum samples were determined using dog recombinant TK1 as a standard.ResultsSerum TK1 protein levels were significantly higher in dogs with lymphoma compared to those in healthy dogs (p < 0.0001). Receiver operating curve analysis showed that the canine TK1-ELISA obtain a sensitivity of 0.80, at a specificity of 0.95. Moreover, the Canine TK1 ELISA has a positive predictive value (PPV) of 97%, and the negative predictive value (NPV) of 83%, reflecting the proportion of test results that are truly positive and negative. Furthermore, Canine TK1 ELISA had significantly higher capacity to differentiate dogs with T-cell lymphoma from those with B-cell lymphoma compared to earlier used TK1 activity assays.DiscussionThese results demonstrate that the Canine TK1 ELISA can serve as an efficient tool in the diagnosis and management of dogs with lymphomas.

Dataset Information

Evaluation of serum thymidine kinase 1 activity as a biomarker for treatment effectiveness and prediction of relapse in dogs with non-Hodgkin lymphoma.

Background

Objectives

Animals

Methods

Results

Conclusions and clinical importance

Publications

Evaluation of serum thymidine kinase 1 activity as a biomarker for treatment effectiveness and prediction of relapse in dogs with non-Hodgkin lymphoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets