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 concentrations of 16 to 21 enzymes, representing various metabolic pathways, have been determined in human adult, fetal, and neoplastic lung. At midgestation, 12 enzymes (among them, several that metabolize amino acids) were above their adult values while 3 other enzymes were still at low concentrations. These signs of biochemical immaturity are contrasted and compared with those in fetal human liver and rat lung. The enzymic composition of the 11 human pulmonary tumors studied resembled that of the normal fetal lungs closely; the same 12 enzymes were elevated and the same 2 were decreased (compared to nonneoplastic adult lung) in both. The characteristic abnormality in the overall pattern of enzymes, in the concentrations of individual ones, and in the quality of pyrroline-5-carboxylate reductase was clearly evident in both primary and metastatic tumors. The mean concentrations of 10 enzymes in the tumors were significantly different (higher or lower) from those in the control lungs (p less than 0.001 to less than 0.05). The best markers of neoplasticity were thymidine kinase, peptidyl proline hydroxylase, phosphoserine phosphatase, hexokinase, and pyrroline-5-carboxylate reductase. The results demonstrate that quantification of a small battery of enzymes, none of them tissue specific, can distinguish adult human lung from its neoplasms.
Cancer Res 1977 Mar
PMID:The undifferentiated enzymic composition of human fetal lung and pulmonary tumors. 18 17

In samples of colonic adenocarcinomas, the mean activities of thymidine kinase, glucose-6-phosphate dehydrogenase, phosphoserine phosphatase and pyrroline-5-carboxylate reductase were several fold higher than those of nonneoplastic colon. The presence of considerable, cold labile pyrroline-5-carboxylate reductase activity provided an additional criterion for distinguishing tumors from the control tissue. Deviations from the pattern of enzymes in normal colon were much more pronounced in the five moderately well-differentiated than in the single well-differentiated adenocarcinoma.
Cancer 1978 Sep
PMID:Human colon tumors: enzymic and histological characteristics. 21 73

To investigate chromosomal site(s) of integration of the herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) gene in biochemically transformed [HeLa(BU25)/KOS 8-1] cells, these human cells which had been transformed by ultraviolet light-irradiated HSV-1 were fused with TK-negative mouse LM(TK-) cells, human-mouse somatic cell hybrid clones (LH81 clones 1-20) were isolated by HATG-ouabain selection and their chromosomes and isozymes were analyzed. Electrophoretic and serological analyses showed that all 20 clones expressed type-specific HSV-1 TK. Isozyme analyses on 29 gene-enzyme systems representing 22 human chromosomes revealed that all of the HSV-1 TK-positive clones expressed human aminoacylase-1 (ACY-1) and esterase D (ESD), which have been mapped to human chromosomes 3 and 13, respectively. Other human isozymes were detected in only one to four clones or in none of the clones. Chromosome analyses showed that: (1) the hybrid clones retained only a few human chromosomes; (2) a marker chromosome, designated M7, consisting of a chromosome 17 translocated to the short arm of chromosome 3, occurred in 36 out of the 41 metaphases examined of LH81-4 clones 1 to 4 and in 31 out of the 33 metaphases examined of LH81-12 clone 10; (3) a modified M7 chromosome, (M7/m), in which the distal 2/3 of the long arm of M7 was translocated to a small acrocentric mouse chromosome, was the only human chromosome found in metaphases of LH81-13 clone 17; and (4) an intact human chromosome 13 was not present in LH81-12 clone 10 or LH81-13 clone 17 cells. Counterselection with BrdUrd resulted in the isolation of subclones lacking HSV-1 TK, human ACY-1 and ESD, and the human marker M7 chromosomes. The experiments indicate that the HSV-1 TK gene is probably associated in HeLa (BU25)/KOS 8-1 cells with marker chromosome M7, but the possibility is not excluded that the segment of human chromosome 13 which codes for ESD is involved.
Int J Cancer 1979 Dec 15
PMID:Isozyme studies on the association of the herpes simplex virus type 1 thymidine kinase gene with human chromosomes in somatic cell hybrids. 23 92

Malignant cells have enhanced sensitivity to inhibition of growth by thymidine. Cell growth of the permanent lymphoid cell line CCRF-CEM, originating from a patient with acute lymphoblastic leukemia, is inhibited by 3 x 10(-5) M thymidine, compared to 1 to 5 x 10(-3) M thymidine required to inhibit growth of normal lymphoid lines. Thymidine-resistant cells were isolated at a frequency of approximately 1/100,000 cells after cloning CCRF-CEM cells in medium containing 5 x 10(-4) M thymidine. The resistant cells lacked the enzyme thymidine kinase, had a 20-fold decrease of thymidine uptake, and were resistant to 1 x 10(-4) M 5-bromo-2-deoxyuridine. The cells were sensitive to 1 x 10(-5) M methotrexate, even in the presence of exogenously added thymidine and hypoxanthine. The data indicate that a small fraction of malignant cells may escape the toxic effect of high thymidine therapy and therefore, require additional chemotherapy for their control.
Cancer Res 1979 Sep
PMID:Isolation of thymidine-resistant cells from a thymidine-sensitive acute lymphoblastic leukemia cell line. 28 39

I have reviewed the current status of microinjection based on fusion of red blood cells and tissue culture cells. Macromolecules are introduced into red blood cells during hypotonic hemolysis, and the resealed red cells are then fused to tissue culture cells with Sendai virus. The procedure has been used to inject ferritin, thymidine kinase, bovine serum albumin, and transfer RNA molecules into large numbers of tissue culture cells. Physiologically significant amounts of various macromolecules can be transferred, and preliminary studies show that [125I]bovine serum albumin and transfer RNA are stable within recipient culture cells. Tissue culture cells remain viable following microinjection. Red cell-mediated microinjection should facilitate the study of various processes, such as macromolecular turnover and genetic regulation, that are not easily studied with conventional biochemical techniques.
Natl Cancer Inst Monogr 1978 May
PMID:Red cell-mediated microinjection. 37 19

We have examined the interaction of dexamethasone with the ZR75-1 human breast cancer cell line to determine if glucocorticoids might directly inhibit growth of breast cancer cells. Growth of these cells in serum-free medium was stimulated significantly by physiological concentrations of insulin (0.1 to 1.0 nM). Pharmacological concentrations of dexamethasone (10 nM) reduced cell number below that found in controls and nearly abolished the effect of insulin after several days in culture. Thymidine and uridine, but not leucine, incorporation into macromolecules or acetate incorporation into fatty acids were similarly inhibited by dexamethasone in the presence of absence of insulin. Dexamethasone did not inhibit insulin effects by altering insulin receptor affinity or concentration, as determined by Scatchard analyses of insulin binding. Net thymidine uptake into the trichloroacetic acid-soluble fraction of the cell was stimulated by insulin and inhibited by dexamethasone also inhibited thymidine kinase activity multiple potential sites of glucocorticoid action that directly oppose the effects of insulin. They also suggest that glucocorticoids have a direct inhibitory effect on proliferation of human breast cancer cells, which may help explain breast tumor regression following pharmacological glucocorticoid therapy.
Cancer Res 1979 Jul
PMID:Direct inhibition of growth and antagonism of insulin action by glucocorticoids in human breast cancer cells in culture. 44 41

A solid lymphoma implanted into normal inbred Kx rats and one partner of parabiotic pairs caused appreciable decreases in hepatic ornithine aminotransferase and arginase about a week earlier (4-6 days after implantation) in single hosts than in parabiotic hosts. By 18-21 days significant decreases in both enzymes were apparent in the host partner also. The hepatic thymidine kinase showed a fivefold elevation in single hosts 4 days after implantation; by 14 days in its levels were about 200 times above normal and had also risen in the parabiotic hosts (20-fold) and host partners (fourfold). Implantation of fibrosarcoma caused qualititatively similar but generally less pronounced changes in these three enzymes in livers of single hosts, parabiotic hosts, and host partners. The splenic thymidine kinase 14 days after implantation was increased from control levels of about 3 U/g to 50.6, 44.8, and 13.5 U/g in single hosts, parabiotic hosts, and host partners, respectively. At later stages, 17-20 days after implantation of the lymphoma, appreciable amounts of thymidine kinase appeared in the plasma: The units of activity per milliliter were 6.2 in single hosts, 0.79 in parabiotic hosts, and 0.55 in host partners (control less than 0.05). Our observations on the changes in hepatic and splenic enzymes in parabiotic rats suggest that effects of neoplasms on distant host tissues are mediated by humoral factors. The less pronounced responses in parabiotic than in single hosts indicate that the tumor-free partner affords some "protection" against these systemic effects.
J Natl Cancer Inst 1978 Apr
PMID:Tissue enzyme changes in parabiotic rats with subcutaneous lymphoma or fibrosarcoma. 63 92

Epithelial cells from colons of adult Sprague-Dawley rats were fractionated on a discontinuous Ficoll gradient at low centrifugal forces (170 x g) for approximately 60 minutes. Epithelial cells were separated into three distinct zones, whereas cell debris, yeast, and bacteria remained at the top of the gradient. The percentage of cells in each zone was inversely related to the density of the gradient. More than 95% of the cells were morphologically intact and viable (excluded trypan blue). Cells sedimenting at higher densities of Ficoll exhibited higher thymidine kinase activity and DNA synthesis, suggestive of active cell division. The cells sedimenting at lower densities of Ficoll showed the least thymidine kinase activity and DNA synthesis, properties that are compatible with those of mature absorptive cells. Tall columnar cells with vesicular nuclei were predominant in the fraction sedimenting at the lowest density (top fraction). At higher densities (middle and lower fractions), most of the cells were short and columnar with basally located condensed dark-staining nuclei.
J Natl Cancer Inst 1978 Apr
PMID:DNA synthesis and thymidine kinase activity of rat colon epithelial cells fractionated by discontinuous Ficoll gradient. 63 99

Rats were entrained to a 12 h dark/12 h light cycle with food (60% protein +/- 0.5% butylated hydroxytoluene or 0.05% phenobarbital) available only during the first 2 h of the dark period. Under these conditions liver ornithine decarboxylase (ODC) activity in control animals displayed a characteristic diurnal oscillation. In livers of rats fed butylated hydroxytoluene or phenobarbital ODC activity was not increased whereas thymidine kinase (TK) activity was stimulated 4--10 fold at 3 days. In lungs from the same animals ODC and TK activities were unchanged. In rats fed butylated hydroxytoluene for 3 days [3H]thymidine incorporation into DNA was increased in liver but decreased in lung.
Cancer Lett 1978 Sep
PMID:Effects of dietary butylated hydroxytoluene and phenobarbital on the activities of ornithine decarboxylase and thymidine kinase in rat liver and lung. 68 94

Thymidine kinase activity in rat C6 glioma cells is inhibited by 50 to 70% after 4 hr incubation with 20 mM D-glucosamine. The inhibition is uncompetitive with respect to thymidine, reducing both the apparent Km and Vmax of the enzyme. The inhibition does not appear to be caused by the reversible combination of the enzyme with a cytoplasmic inhibitor, including D-glucosamine and its metabolites. The addition of D-glucosamine or its metabolites to cell-free thymidine kinase produced an inhibition which differed quantitatively and qualitatively from that which resulted from treatment of intact cells with D-glucosamine. The presence of a reversible cytoplasmic inhibitor of the enzyme was also excluded by mixing experiments. D-Glucosamine inhibited the incorporation of labeled uridine and amino acids into acid-precipitable material. The magnitude of inhibition of thymidine kinase activity and amino acid incorporation by D-glucosamine was comparable to that produced by cycloheximide, suggesting that the inhibition might arise from interference with enzyme synthesis. However, whereas the kinetics of recovery of amino acid incorporation from inhibition was rapid, thymidine kinase activity was depressed for at least 6 hr after drug washout. The results presented are best explained by assuming either that two forms of thymidine kinase are present in rat C6 cells and are differently affected by D-glucosamine or that D-glucosamine acts by two separate mechanisms to inhibit a single form of the enzyme.
Cancer Res 1977 Apr
PMID:The inhibition of thymidine kinase in glial tumor cells by an amino sugar, D-glucosamine. 84 39


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