Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 10 isoenzyme markers discussed here represent those that in the author's judgment show promise as effective tumor markers. The relative usefulness of these isoenzymes as tumor markers is summarized in Table 6. Each isoenzyme is evaluated by a rating system, with a scale of 0-5 points in each of seven categories. The hypothetical ideal tumor marker received 5 points in all seven categories for a total score of 35. Unfortunately, less than perfect scores ranging from 9 to 26 were found for the 10 isoenzymes evaluated here. The five best isoenzymes were neuron-specific enolase (26 points), prostatic acid phosphatase (23 points), placental alkaline phosphatase (20 points), thymidine kinase 1 (16 points), and lactate dehydrogenase 1 (16 points). In general, low isoenzyme scores can be attributed to the problems exhibited by all tumor markers: insensitivity to early-stage malignancies and false-positive elevations in nonmalignant diseases. Nevertheless, each of the 10 isoenzymes described here has potential clinical usefulness to support a diagnosis of cancer and/or to assist in the monitoring of therapy.
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PMID:Serum isoenzymes in cancer diagnosis and management. 210 May 75

The loss of expression of the enzyme O6-methylguanine-DNA methyltransferase (the Mex- phenotype), which often results from cellular transformation, confers hypersensitivity to alkylating agents. We have observed two unrelated examples in which human cell lines have undergone a spontaneous alteration in their Mex phenotype during propagation in vitro. The change was reversible and was not the result of mutation. In both cases a loss of methyltransferase expression was accompanied by a simultaneous loss of expression of two metabolically unrelated enzymes: thymidine kinase and galactokinase. "Reversion" to methyltransferase expression was accompanied by simultaneous reexpression of both kinase activities. A third example of this coordinate gene regulation was seen with the Burkitt's lymphoma cell line Raji which expresses methyltransferase, thymidine kinase, and galactokinase at high levels. A thymidine kinase- Raji cell line derived by bromodeoxyuridine mutagenesis that is also Mex- was found to be galactokinase-. It appears that methyltransferase expression may in some instances be coordinately regulated with the tk and glk loci which are closely linked on human chromosome 17.
Cancer Res 1990 Mar 01
PMID:Coregulation of the human O6-methylguanine-DNA methyltransferase with two unrelated genes that are closely linked. 213 69

A bacterial expression system which produces large amounts of the Epstein-Barr-virus-coded thymidine kinase has been developed and used to produce protein for Western blot analysis of a number of human antisera. Interestingly, only sera from nasopharyngeal carcinoma (NPC) patients had any detectable IgA antibody which reacted with the EBV TK. These findings provided the basis for ELISA tests using a crude lysate of the E. coli cells expressing the EBV TK as target antigen. Sera from NPC patients showed high levels of IgA reactive antibodies in this test while other sera did not.
Int J Cancer 1990 Jun 15
PMID:Immunological response of nasopharyngeal carcinoma patients to the Epstein-Barr-virus-coded thymidine kinase expressed in Escherichia coli. 216 95

The respective pretreatment prognostic impacts of the following markers were evaluated in 125 patients with small cell lung cancer (SCLC): lactic dehydrogenase (LDH), serum thymidine kinase (S-TK), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and tissue polypeptide antigen (TPA). More traditional clinical and serologic markers were also evaluated. Univariate analysis showed that all of the biochemical markers mentioned above, the Karnofsky index (KI) and the patient's sex were related to both the stage of disease (limited/extensive disease: LD/ED) and to survival. The strongest marker for the clinical stage was S-TK, whereas TPA showed the strongest relationship with survival. Multivariate analyses produced a model consisting of S-TK, CEA, NSE, and the patient's sex for determining the clinical stage. To compare the prognostic capacity of easily determined biochemical and simple clinical variables to the more resource-demanding variable of the clinical stage, three multivariate analyses in relation to survival were performed: (1) biochemical markers and simple clinical variables; (2) LD/ED and simple clinical variables; and (3) all available variables. The model obtained from the first analysis included TPA, KI, age, and the patient's sex; the model from the second analyses included LD/ED, patient's age, and KI; and the model from the third analysis, TPA, KI, age, sex, and LD/ED. Indices based on these three multivariate models were calculated for each patient and the prognostic capacity of these indices was compared. Pretreatment serum marker levels also had the capacity to predict both the grade and the duration of the response to therapy.
Cancer 1990 Aug 15
PMID:Clinical and serologic markers of stage and prognosis in small cell lung cancer. A multivariate analysis. 216 41

The carboxyl-terminal one-third of human topoisomerase II polypeptide expressed in Escherichia coli was used as antigen to generate polyclonal antibodies in rabbits. With the use of antiserum, DNA topoisomerase II levels of phytohemagglutinin-stimulated human lymphocytes were measured by immunoblotting. Our results showed that the increase in intracellular topoisomerase II level paralleled the entry of cells into proliferation. We also found that the increase in the topoisomerase II level resulted from an increase in the amount of topoisomerase II mRNA. The time course study indicated that the appearance of topoisomerase II mRNA was first observed at 36 h after phytohemagglutinin stimulation. The maximal level of topoisomerase II mRNA was seen at 45 h after stimulation. The same RNA blot was rehybridized with a thymidine kinase probe. The maximal level of thymidine kinase mRNA was observed at 39 h after phytohemagglutinin stimulation. In a comparison of the time course of topoisomerase II gene expression with that of [3H]thymidine incorporation and thymidine kinase gene expression, it was found that the expression of the topoisomerase II gene was later than the onset of DNA replication. Thus, this study suggests that topoisomerase I, which is constantly expressed throughout the cell cycle, might participate in the initiation of DNA replication, while topoisomerase II is involved in solving the DNA topological problems accompanying DNA strand separation during DNA replication.
Cancer Res 1990 Sep 01
PMID:Induction of topoisomerase II gene expression in human lymphocytes upon phytohemagglutinin stimulation. 216 62

The activities of five enzymes, orotate phosphoribosyltransferase (OPRTase), uridine kinase (UR kinase), thymidine kinase (TdR kinase), uridine phosphorylase (UR Prylase) and thymidine phosphorylase (TdR Prylase), were examined in subcultured human acute leukemia cell lines (HL-60, CCRF-CEM), subcultured human solid tumor cell lines (Colo-205, HeLa-S3) and human cancerous tissues with a view to compare the activation of 5-fluorouracil in them. There was no significant difference in the activity of any enzyme between HL-60 and CCRF-CEM, Colo-205 and HeLa-S3, and human lung cancerous tissue and human colon cancerous tissue. Compared between the acute leukemia cell lines and the solid tumor cell lines, the UR kinase activity was high in both cell lines. The OPRTase and UR Prylase activities were low in the solid tumor cell lines. In the cancerous tissues, both the UR kinase and TdR kinase activities were low, but the UR Prylase and TdR Prylase activities were markedly high. The results suggest that the intracellular activation of 5-fluorouracil varies with different human cancerous cells. When the anti-cancer activity of 5-fluorouracil is tested in vitro, the difference of fluoropyrimidine metabolism in subcultured cell lines from that in the cancerous tissue should be taken in account.
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PMID:[Activities of enzymes converting 5-fluorouracil to 5-fluorouridine-5' monophosphate and 5-fluorodeoxyuridine-5' monophosphate in subcultured cell lines and solid tumor tissues]. 216 17

Attempts have been made to use enzyme assays primarily in tissue, to predict risk of colon cancer in high risk colon cancer families, and in patients with polyposis. Efforts have also been made to predict recurrence in surgically "cured" cancer patients. The use of thymidine kinase, ornithine decarboxylase, LDH isoenzymes, and other enzymes for these purposes will be reviewed.
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PMID:Enzymes used in predicting high risk to colon cancer. 217 52

5' Amino-5'-deoxythymidine (5'-AdThd) has been demonstrated previously to antagonize dTTP-mediated feedback inhibition of purified thymidine kinase from 647V, a human bladder cancer cell line. Low concentrations of 5'-AdThd (3-30 microM) have also been shown to stimulate cellular uptake of iododeoxyuridine (IdUrd) in 647V cells at clinically relevant IdUrd concentrations (2 microM). We report that the combination of 30 microM 5'-AdThd plus 2 microM IdUrd results in a significant increase of IdUrd replacement of thymidine (dThd) (18%) in the DNA of 647V cells over that obtained by exposure to 2 microM IdUrd alone (7.9%). However, increasing the 5'-AdThd concentration to 300 microM inhibited the incorporation of IdUrd into DNA (3%). IdUrd-induced radiosensitization of 647V cells, as measured by clonogenic survival, was enhanced by coincubation with 30 microM 5'-AdThd, while 300 microM 5'-AdThd reduced the IdUrd radiosensitization. Additionally, radiation-induced single strand break generation when IdUrd was incorporated into 647V DNA, as measured by rapid alkaline elution, was also enhanced by coincubation with 30 microM 5'-AdThd, while 300 microM 5'-AdThd resulted in a decrease in the number of single strand breaks produced. In T24, another bladder cancer cell line, and SV-HUC-TT1, a tumorigenic cell line derived from SV-HUC, 3-10 microM 5'-AdThd was also able to enhance IdUrd replacement of dThd in DNA. However, no stimulation of dThd replacement by 5'-AdThd occurred in SV-HUC, a prototypic "normal" bladder urothelial cell line. Since 5'-AdThd is not a substrate for mammalian thymidine kinase and has little or no cytotoxicity in vitro and in vivo, it may be a selective modulator of IdUrd radiosensitization of human bladder carcinoma and should be tested in vivo.
Cancer Res 1990 Aug 15
PMID:Modulation of IdUrd-DNA incorporation and radiosensitization in human bladder carcinoma cells. 219 32

The enzyme thymidine kinase is associated with DNA synthesis. Thymidine kinase serum levels were studied in normal controls (n = 20), patients with primary breast cancer (n = 60), patients with systemic breast cancer (n = 20) and as a non-cancer disease control group in patients with inflammatory gastrointestinal disorders (n = 20). Comparison of pretreatment values in the cancer patients with the normal controls showed a significant difference between the three groups in relation to stage of disease: mean values 4.22 (+/- 1.08), 6.22 (+/- 2.24) and 9.79 (+/- 7.56) pmol ml-1 h-1 for normal controls, operable breast cancer and systemic breast cancer respectively (P less than 0.005; analysis of variance). Patients with systemic breast cancer had a significantly elevated serum thymidine kinase level compared to controls (P less than 0.01) and patients with primary operable cancer (P less than 0.05). Patients with primary operable cancer had significantly higher serum thymidine kinase levels over normal controls (P less than 0.01). Mean serum TK in patients with inflammatory gastrointestinal diseases was similar to normal controls but significantly less than both patients with primary operable breast cancer and patients with systemic breast cancer. Twenty patients with operable breast cancer were followed up after primary surgery by serial 3-monthly thymidine kinase levels in the disease free interval. Four patients have developed systemic recurrence with a rise in the mean thymidine kinase value to 14.3 pmol ml-1 h-1. Ten patients with advanced breast cancer had serial thymidine kinase levels measured 2-monthly during the first 6 months of primary hormone therapy. The serum values fell in all five responders (mean 9.12-4.78 pmol ml-1 h-1) and rose in all five progressors (mean 8.62-38.5 pmol ml-1 h-1). Serum thymidine kinase reflects stage of disease in breast cancer. Serial thymidine kinase levels in patients with systemic breast cancer reflected response to systemic therapy.
Br J Cancer 1990 Oct
PMID:Thymidine kinase in breast cancer. 222 87

We have measured by a radioenzymatic assay the thymidine kinase in the cytosol of 182 primary infiltrating breast cancers. Maximal follow-up is 95 months. Thymidine kinase was found to be related to SBR grade, tumour size and absence of oestradiol receptors (RE). Univariate analysis has pointed out a significant linkage between overall or metastase free survival and thymidine kinase, using a cut-off level of 80 mU/mg protein which is the most discriminating value. Thymidine kinase appeared to be particularly useful in lymph-node-positive, RE-negative and grade 3 patients. Multivariate analysis of the overall survival and of the metastase free survival (Cox model) revealed that they were strongly related to thymidine kinase status.
Bull Cancer 1990
PMID:[Prognostic value of thymidine kinase in cancer of the breast]. 224 17


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