Clinical observations reveal that an augmented pace of T-cell recovery after chemotherapy correlates with improved tumor-free survival, suggesting the add-back of T cells after chemotherapy may improve outcomes. To evaluate adoptive immunotherapy treatment for B-lineage non-Hodgkin lymphoma (NHL), we expanded T cells from client-owned canines diagnosed with NHL on artificial antigen presenting cells (aAPC) in the presence of human interleukin (IL)-2 and IL-21. Graded doses of autologous T cells were infused after CHOP chemotherapy and persisted for 49 days, homed to tumor, and significantly improved survival. Serum thymidine kinase changes predicted T-cell engraftment, while anti-tumor effects correlated with neutrophil-to-lymphocyte ratios and granzyme B expression in manufactured T cells. Therefore, chemotherapy can be used to modulate infused T-cell responses to enhance anti-tumor effects. The companion canine model has translational implications for human immunotherapy which can be readily exploited since clinical-grade canine and human T cells are propagated using identical approaches.

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Adoptive T-cell therapy improves treatment of canine non-Hodgkin lymphoma post chemotherapy.

Background The prognostic value of the concentration of serum thymidine kinase 1 (S-TK1) with regard to recurrence in low risk breast cancer patients, 3 months after surgery was evaluated. Patients and methods The concentration of S-TK1 in serum was determined in 120 breast cancer patients at the time of surgery and in 67 patients 3 months after surgery, by anti-TK1 chicken IgY antibody, using a dot-blot immuno-assay. The S-TK1 concentration was compared with the serological activity of thymidine kinase (STK) and of carbohydrate antigen (CA 15-3). Results A statistically significant trend (unadjusted) was found for recurrence (distant or loco-regional) in patients with a higher S-TK1 concentration, as compared with patients with a lower S-TK1 concentration. A multivariate analysis gave the same results. The hazard rate ratio for developing distant and/or loco-regional recurrence in patients with a higher S-TK1 concentration was about six to seven times higher than in patients with a lower S-TK1 concentration. Conclusion Our results indicate that the S-TK1 concentration is higher in patients developing distant and/or loco-regional recurrence 3 months post-surgery.

Thymidine kinase 1 in serum predicts increased risk of distant or loco-regional recurrence following surgery in patients with early breast cancer.

Despite extensive progress in treatment for cancer in recent decades, the early diagnosis for gastric cancer (GC) and colorectal cancer (CRC) remains poor. In this study, we explore the diagnostic value of joint detection of thymidine kinase 1 (TK1), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9) and carbohydrate antigen 72-4 (CA 72-4) in the diagnosis of GC and CRC, and to evaluated the relationship between TK1 expression and clinical pathological characteristics in the patients. Serum TK1, CA 19-9, CA 72-4 and CEA levels were measured in 169 patients with GC, 344 patients with CRC and 75 healthy controls using electro-chemiluminescence. The TK1 concentration was significantly higher in patients with cancer than in healthy controls and patients with clinical stage Ⅲ+Ⅳ had higher TK1 levels than clinical stage Ⅰ+Ⅱ (P 0.05). Moreover, the AUCs varied significantly between the combination tests and single biomarker tests (Z test, P<0.01). In conclusion, serum TK1 may be an independent tumor marker for GC and CRC patients, and the combination of TK1, CA 19-9 and CA 72-4 and CEA performed even better. This study suggests that combination detection of four tumor markers may prove to be useful for the diagnosis of GC and CRC.

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Clinical significance and diagnostic capacity of serum TK1, CEA, CA 19-9 and CA 72-4 levels in gastric and colorectal cancer patients.

Thymidine kinase and cancer monitoring

Thymidine kinase 1 (TK 1-fetal) is a cell cycle-dependent marker that increases dramatically during the S-phase of the cell cycle. In this review, the authors discuss serum levels of thymidine kinase in a variety of neoplasias. Determination of thymidine kinase helps to monitor the follow-up of solid tumours and haematological malignancies as well as indicating the efficacy of adjuvant and palliative chemotherapy. Elevated levels of thymidine kinase must always be interpreted together with a detailed knowledge of the patient's condition because nonspecific elevations of serum levels (inflammatory and autoimmune diseases) must be excluded.

The role of thymidine kinase in cancer diseases.

Tumor-related biomarkers are used for the diagnosis, prognosis and monitoring of treatments and follow-up of cancer patients, although only a few are fully accepted for the detection of invisible/visible tumors in health screening. Thymidine kinase 1 (TK1), a cell cycle-dependent and thus a proliferation-related marker, has been extensively studied during the last decades, using both biochemical and immunological techniques. Therefore, TK1 is an emerging potential proliferating biomarker in oncology that may be used for the prognosis and monitoring of tumor therapy, relapse and survival. In addition, TK1 concentration in serum (STK1p) is a useful biomarker in healthy screening for the detection of potential malignancy development as well as the identification of early-stage tumors, with a few false-positive cases (ROC value, 0.96; tumor proliferation sensitivity, 0.80; specificity, 0.99). In this review, we examine results regarding the expression of STK1p and TK1 in relation to cancer patients and STK1p in health screening published between 2000 and 2012. The use of tumor-related markers recommended by international cancer organizations is also discussed. This review provides valuable information for applications in tumor patients, in health screening and for cancer research.

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The proliferation marker thymidine kinase 1 in clinical use (Review)

Serological thymidine kinase 1 (STK1) is a reliable proliferation marker for prognosis, monitoring tumour therapy, and relapse. Here we investigated the use of STK1 in health screening for early detection of pre-malignant and malignant diseases. The investigation was based on 35,365 participants in four independent health screening studies in China between 2005-2011. All participants were clinically examined. The concentration of STK1 was determined by a sensitive chemiluminescent dot blot ECL assay. The ROCvalue of the STK1 assay was 0.96. At a cut-off STK1 value of 2.0 pM, the likelihood (+) value was 236.5, and the sensitivity and the specificity were 0.78 and 0.99, respectively. The relative number of city-dwelling people with elevated STK1 values (≥2.0 pM) was 0.8% (198/26,484), while the corresponding value for the group of oil-field workers was 5.8% (514/8,355). The latter group expressed significantly higher frequency of refractory anaemia, fatty liver, and obesity, compared to the city dwellers, but no cases of breast hyperplasia or prostate hyperplasia. Furthermore, people working in oil drilling/oil transportation showed higher STK1 values and higher frequency of pre-malignancies and benign diseases than people working in the oil-field administration. In the STK1 elevated group of the city-dwelling people, a statistically significantly higher number of people were found to have malignancies, pre-malignancies of all types, moderate/severe type of hyperplasia of breast or prostate, or refractory anaemia, or to be at high risk for hepatitis B, compared to people with normal STK1 values (<2.0 pM). No malignancies were found in the normal STK1 group. In the elevated STK1 group 85.4% showed diseases linked to a higher risk for pre-/early cancerous progression, compared to 52.4% of those with normal STK1 values. Among participants with elevated STK1 values, 8.8% developed new malignancies or progress in their pre-malignancies within 5 to 72 months, compared to 0.2% among people with normal STK1 values. People who showed elevated STK1 values were at about three to five times higher risk to develop malignancies compared to a calculated risk based on a cancer incidence rate of 0.2-0.3%. We conclude that serological TK1 protein concentration is a reliable marker for risk assessment of pre/early cancerous progression.

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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

Background
Thymidine kinase 1 in serum (STK1) has been found to be a reliable proliferation marker in clinical trials. In this study, we examined the significance of STK1 in routine clinical settings.

Serum thymidine kinase 1 correlates to clinical stages and clinical reactions and monitors the outcome of therapy of 1,247 cancer patients in routine clinical settings

BACKGROUND: The role of serum tumour markers is to reveal tumours not yet visible by imaging techniques. Here we examine the use of serum thymidine kinase 1 protein (STK1) in health screening. PATIENTS AND METHODS: Persons (n = 11,880) participating in health screening programs in China, during 2005-2007, were tested for STK1. STK1 was measured by a sensitive chemiluminescence dot-blot assay. Medical examination of participants was carried out in parallel. RESULTS: The proportion of STK1-positive (> 2 pM) individuals was 0.5%, corresponding to the cancer incidence rate of China. No malignant cases were found in the STK1-negative group, but two pre-malignant and one malignant case were found in the STK1-positive group. The low frequency of malignancies found was probably due to the relatively young population (mean age 40.4 +/- 13.4 years). In the STK1-positive group, there were 24% of persons with benign diseases (breast, liver, kidney), 37% with proliferative tissues (breast, prostate), 13% with fatty liver, 9% with inflammatory reactions/virus infections (three hepatitis B virus-positive persons) and 17% showed other types of physiological changes not directly related to proliferation. In the STK1-positive group, a significantly (p 2 pM may indicate an early risk for development of malignancies years later.

Serological thymidine kinase 1 (STK1) indicates an elevated risk for the development of malignant tumours.

This study was performed to examine possible use of thymidine kinase 1 concentration in serum (STK1) for prognosis of non-Hodgkin’s lymphoma patients following chemotherapy treatment. The STK1 levels of 37 patients were determined by enhanced chemiluminescent dot-blot assay on the day before chemotherapy, and on day 1 and day 28 after start of the treatment. The specificity and sensitivity was evaluated by Western blot with anti-TK1 IgY antibody and by receiver operating characteristic (ROC) analysis. Western blot and ROC analysis of TK1 in serum showed high specificity and sensitivity. The mean STK1 level of the non-Hodgkin’s lymphoma patients was significantly higher compared to healthy persons (p < 0.001). The mean STK1 level increased significantly (p < 0.001) on day 1 and then declined, reaching on day 28 values corresponding to those of healthy persons. The mean STK1 values before treatment and at 1 and 28 days after start of the treatment also correlated significantly with the clinical response (CR, PR and NR) and five-year survival. Although the number of patients was limited in this study, TK1 in serum might possess an important reference value in the evaluation of treatment and prognosis of non-Hodgkin’s lymphoma following chemotherapy.

Ji Zhou

Papers

The proliferation marker thymidine kinase 1 in clinical use (Review)

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

Serum thymidine kinase 1 correlates to clinical stages and clinical reactions and monitors the outcome of therapy of 1,247 cancer patients in routine clinical settings

Serological thymidine kinase 1 (STK1) indicates an elevated risk for the development of malignant tumours.

Serum thymidine kinase 1 concentration as a prognostic factor of chemotherapy-treated non-Hodgkin’s lymphoma patients