Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on biochemical tumour markers beta 2-microglobulin (beta 2m), thymidine kinase (TK) and lactate dehydrogenase (LDH) were studied in eight patients with chronic lymphocytic leukaemia (CLL). The serum concentration of beta 2m rose by a median of 30% (range 8-50%) and serum TK by 101% (range 30-1414%). Serum LDH concentration, on the other hand, significantly decreased in all patients. The significant increases of beta 2m and TK could not be explained by progression of the disease or impaired renal function. Treatment with GM-CSF reduces the value of serum beta 2m and TK in assessment of tumour mass and disease activity.
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PMID:GM-CSF raises serum levels of beta 2-microglobulin and thymidine kinase in patients with chronic lymphocytic leukaemia. 875 22

Cytoplasmic fractions from species of the Mollicutes genera Entomoplasma, Mesoplasma, Mycoplasma, and Acholeplasma were assayed for NADH oxidase (NADH ox), ATP- and PPi-dependent phosphofructokinase (PFK), ATP- and PPi-dependent deoxyguanosine kinase (dGUOK), thymidine kinase (TK), TMP kinase (TMPK), glucose-6-phosphate dehydrogenase (G6Pde), lactate dehydrogenase (LDH), malate dehydrogenase (MDH), phosphoenolpyruvate carboxylase, hypoxanthine-guanine phosphoribosyl transferase, dUTPase, and uracil-DNA glycosylase (UNG) activities. Membrane fractions were also examined for NADH ox activity. These activities were used as indicators of the presence and relative activities of major Mollicutes metabolic and DNA repair pathways. This was the first study to determine the presence of these enzymes in members of the genera Entomoplasma and Mesoplasma. Using the data obtained, we constructed a preliminary scheme for distinguishing genera of the class Mollicutes on the basis of the results of signature functional enzyme assays. This scheme includes phylogenetic relationships deduced from rRNA analyses, but is more informative with respect to metabolic potential. The criteria used include the presence of PPi-dependent PFK, urease, dUTPase, and dGUOK activities. Entomoplasma ellychniae ELCN-1T (T = type strain), Entomoplasma melaleucae M-1T, Mesoplasma seiffertii F7T, Mesoplasma entomophilum TACT, Mesoplasma florum L1T, Mycoplasma fermentans PG18T, and Acholeplasma multilocale PN525T were similar in most respects. NADH ox activity was localized in the cytoplasm of these organisms. These strains had ATP-dependent PFK, MDH, LDH, ATP- and PPi-dependent dGUOK, and UNG activities, but not dUTPase or G6Pde activities. In contrast, Acholeplasma equifetale C112T, Acholeplasma oculi 19LT, Acholeplasma hippikon C1T, Acholeplasma modicum PG49T, and Acholeplasma morum 72-043T had membrane-localized NADH ox activity, PPi-dependent PFK, G6Pde, and dUTPase activities, and significantly lower MDH and LDH activities and exhibited a faster rate with PPi than with ATP in the dGUOK reaction. All of the members of the Mollicutes tested had hypoxanthine-guanine phosphoribosyl transferase, phosphoenolpyruvate carboxylase, and (except for Mesoplasma entomophilum TAC(T)) UNG activities. All of the Acholeplasma strains except Acholeplasma multilocale PN525T had TK, TMPK, and UNG activities. Mesoplasma entomophilum TAC(T) was distinguished by having no detectable dUTPase, UNG, TK, and TMPK activities, indicating that there is a severe restriction in or an absence of a synthetic route to dTTP. Our data also suggest that A. multilocale PN525T is a member of an unrecognized metabolic subgroup of the genus Acholeplasma or is not an Acholeplasma strain.
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PMID:Comparative metabolism of Mesoplasma, Entomoplasma, Mycoplasma, and Acholeplasma. 886 14

As the clinical manifestations of adult T-cell leukemia (ATL) can be quite diverse, useful indicators for the therapy and prognosis are required for the disease. In this review, the clinical and biological significance of serum tumor markers at diagnosis in ATL patients is described. Serum lactic dehydrogenase (S-LDH), serum thymidine kinase (S-TK) and serum parathyroid hormone-related protein (S-PTHrP) at diagnosis of ATL showed a correlation with among leukocyte count, absolute number of abnormal lymphocytes with polymorphic nuclei, platelet count, serum calcium and the length of survival after the initial diagnosis. Serum beta 2-microglobulin (S-beta 2M) correlated with age, platelet count and survival. A statistical correlation existed between these four serum tumor markers. Other serum tumor markers such as immunosuppressive acidic protein (S-IAP), ferritin (S-Ft) and tissue polypeptide antigen (S-TPA) showed no correlation with clinical and histological data in ATL patients.
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PMID:Clinical and biological significance of serum tumor markers in adult T-cell leukemia. 888 54

Chronic lymphocytic leukemia (CLL) and immunocytoma (IC) are remarkably heterogeneous with regard to their clinical course. The current staging systems can distinguish prognostic subgroups, but do not seem to predict the risk of disease progression of an individual patient with sufficient accuracy. Given the increase of treatment options for CLL and IC, additional parameters are needed to decide which patients may benefit from early or intensified treatment. It has been shown that two biochemical markers, serum beta 2-microglobulin (s-beta 2M) and serum thymidine kinase (s-TK), might identify CLL and IC patients at high risk of disease progression. Therefore, the prognostic value of these two serum parameters was compared with a panel of several established prognostic factors in a prospective clinical trial. 113 patients with CLL and 41 patients with IC (mean age +/- SD 63.9 +/- 10.7 years) were included. The following parameters were determined: histopathological diagnosis (IC vs. CLL), age, sex, performance status (Karnofsky index), B symptoms, peripheral blood lymphocyte count, platelet count, blood hemoglobin, serum lactate dehydrogenase (s-LDH), s-beta 2M, s-TK, serum creatinine, number of lymph node areas involved, prior therapy, and the time from diagnosis to inclusion in the study. Univariate analyses showed that nine parameters (Karnofsky index, peripheral blood lymphocytosis, platelet count, blood hemoglobin, lymph node areas involved, pretreatment, s-LDH, s-beta 2M, and s-TK) significantly predicted progression-free survival. In a Cox regression model, only four of these parameters provided independent prognostic information on progression-free survival: 1. s-beta 2M, 2. Karnofsky index, 3. platelet count, and 4. s-TK. The results show that s-beta 2M and s-TK independently predict progression-free survival in patients with CLL and IC, and suggest that these prognostic factors may allow an improved prediction of progression-free survival, particularly in early disease stages.
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PMID:Serum beta(2)-microglobulin and serum thymidine kinase are independent predictors of progression-free survival in chronic lymphocytic leukemia and immunocytoma. 888 57

Soluble isoforms of various adhesion molecules have recently been observed in the blood circulation, but the physiological effects of such molecules remain unsettled. Our earlier results indicate that soluble CD44 can be detected in sera of healthy individuals and that significantly higher levels of serum CD44 (s-CD44) can be found in lymphoma patients. The serum level of the standard form of CD44 parallels the clinical treatment response in patients with lymphoma. In the present study, we have investigated the clinical significance of s-CD44 in non-Hodgkin's lymphoma measured at the time of the diagnosis. S-CD44 was measured from the sera of 123 patients with non-Hodgkin's lymphoma by dot blotting high levels of s-CD44 were associated with high serum levels of lactate dehydrogenase and thymidine kinase, high histological grade of malignancy and poor overall survival. However, s-CD44 level did not have independent prognostic value in a multivariate analysis. In conclusion, a high s-CD44 level at the time of diagnosis was associated with poor survival and several other adverse prognostic factors. Our previous and present studies taken together suggest that measurement of s-CD44 is a valuable tool to monitor treatment response in lymphoma patients. However, it may not be an improved prognostic marker.
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PMID:Clinical significance of circulating CD44 in non-Hodgkin's lymphoma. 964 41

The present study is the first to report elevated serum levels of soluble (s)VCAM-1 in B-cell chronic lymphocytic leukaemia (B-CLL). A large cohort of 106 untreated patients was studied. sVCAM-1 was compared to known prognostic serum markers (soluble (s)ICAM-1; lactate dehydrogenase, LDH; sCD23; thymidine kinase, TK; beta2microglobulin, beta2m). The serum levels of sVCAM-1 reflected tumour burden as expressed by Binet/Rai stages more closely than any other marker. sVCAM-1 also reflected the kinetics of the disease as revealed by lymphocyte doubling time. sVCAM-1 was the only one of the studied markers which showed elevated levels in smouldering disease compared to controls. sVCAM-1, sICAM-1 and sCD23 (but not LDH, TK, beta2m) separated smouldering from non-smouldering B-CLL. Only sICAM-1, sCD23 and TK added independent prognostic information for survival to that of stage and lymphocyte doubling time. The expression of both adhesion molecules was examined in lymph node and splenic specimens. VCAM-1 and ICAM-1 were overexpressed by vascular endothelium and stroma, but the intensity of expression correlated poorly with serum levels of the soluble molecules. In conclusion, serum levels of sVCAM-1 correlated with tumour burden and other prognostic markers in B-CLL. VCAM-1 was overexpressed in tumour tissue as was ICAM-1. sVCAM-1 could prove a valuable marker in younger early-stage patients eligible for therapeutic trials.
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PMID:Elevated serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) closely reflect tumour burden in chronic B-lymphocytic leukaemia. 988 31

The authors present the characteristics of a group of 23 patients with mantle cell lymphoma. In the group only a slight predominance of men over women was found (1.1:1), the median age was 63 years. Twenty-one (91%) of the patients were diagnosed in stage IV (Ann Arbor). In all these patients the bone marrow was affected. In 19 of them immunoflowcytometric analysis revealed the typical clone of B lymphocytes (CD5 positive)/CD 23 negative). The majority of patients had at the time of diagnosis a large tumourous mass with massive splenomegaly (61%), hepatomegaly (57%) and bulky disease (52%). The node was excised in 17 patients, but in four patients (24%) during the first session the diagnosis was not assessed correctly. In the laboratory findings an inclination to anaemia, thrombocytopenia, lymphocytosis and in particular to high levels of serological indicators of activity of the disease dominated--lactate dehydrogenase, beta-2-microglobulin and serum thymidine kinase. All patients were treated by chemotherapy. Complete remission was achieved by the date of evaluation in one patient (4%), partial remission in seven patients (30%) but 48% patients did not respond to first line treatment. Nine patients of the group died, their median of survival was 14 months (0-24), the median of the follow up of the remaining patients was 133 months (2-31). Two female patients had large-dose treatment with subsequent administration of autologous stem cells. The first one is after 370 days of treatment in complete remission, the second one developed a relapse 100 days after the procedure. From the results and analysis of the literature ensues that mantle cell lymphoma is one of the aggressive malignant B-lymphoproliferations with a very adverse prognosis and it deserves therefore special diagnostic and intense therapeutic attention.
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PMID:[Mantle cell lymphoma as a diagnostic and therapeutic problem]. 1042 28

In a group of 85 patients with multiple myeloma (MM) incl. 50 patients examined at the time when the diagnosis was established the relationship of the values of the propidium-iodide index (PI index) of myeloma plasmocytes of the patients were examined by flow cytometry using the double staining method, and selected laboratory parameters of the disease were analyzed. It was revealed that the values of the PI index examined with the aid of different "identification" monoclonal antibodies did not differ significantly. The median and average value of the PI index was in the whole group for PI/CD38 2.3 and 2.3%, for PI "UHKT" 1.8 and 1.8% and for PI/B-B4(CD138) 2.2 and 2.4%. In the group of patients examined at the time when the diagnosis of MM was established before chemotherapy the median and average value of the PI/CD38 index was 2.0 and 2.2%, PI/"UHKT" was 1.5 and 1.6%, PI/B-B4 (CD138) 2.6 and 2.5%. In the two analyzed groups no statistically significant correlations of PI/CD38,/"UHKT" and B-B4(CD138) index were found with the number of granulocytes, thrombocytes, immunochemical type and the value of the serum M-component, and levels of S-beta 2 microglobulin, S-urea, S-creatinine, S-calcium, and S-lactic dehydrogenase. A significant positive correlation was found in both groups with the level of S-thymidine kinase, in the whole group of indexes PI/CD38 and PI/B-B4(CD138) with the severity of anaemia, index PI/CD38 correlated with S-albumin and index PI/B-B4(CD138) with the percentage ratio of plasmocytes in bone marrow. It was revealed that examination of the propidium-iodide index is a suitable and prompt method for evaluation of proliferative properties of the myeloma population.
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PMID:[Importance of determining the propidium-iodide index of plasmacytes in multiple myeloma. I. Relation to selected laboratory indicators of the disease]. 1104 67

Adult T-cell leukemia (ATL) is usually defined as a malignant disease of T cells infected by human T-lymphotropic virus type I (HTLV-I). In the present study, we describe a 49-year-old woman with an acute type ATL, whose leukemic cells do not contain the HTLV-I genome. Laboratory tests revealed an increase in abnormal lymphocytes with convoluted nuclei, elevated serum lactate dehydrogenase levels, increased thymidine kinase activity and soluble interleukin-2 receptor-alpha levels. Serum examination demonstrated positive anti-HTLV-I antibody, but Southern blot analysis using the whole HTLV-I genome as a probe did not detect any integration of the viral genome. In contrast, PCR detected the HTLV-I pX region in the same DNA samples as used for Southern blot analysis. These findings suggest two possibilities. One possibility is that ATL in this patient is generated by other pathogens than HTLV-I virus. She is also an HTLV-I carrier. The other possibility is that her leukemic T cell clone derived its malignant phenotype from HTLV-I infection, and once this malignant phenotype was obtained, partial deletions of viral genome repeated until the whole viral genome was deleted. Although there is no direct evidence, the former possibility is more likely in the present case.
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PMID:Adult T-cell leukemia with anti-HTLV-I antibody but no HTLV-I DNA in tumor cells. 1140 14

Non-Hodgkin's lymphoma (NHL) forms a heterogeneous group of diseases. Tumor markers may help to identify high-risk patients who might benefit from more aggressive therapy. Serum soluble CD27 (sCD27) and thymidine kinase (TK) are potentially valuable markers, since sCD27 has previously been shown to be related to tumor load and TK to proliferation of malignant cells. We determined serum sCD27, TK, beta-2-microglobulin (beta(2)M) and lactic dehydrogenase (LD) levels at diagnosis in 79 lymphoma patients and correlated these parameters with the stage of disease, the International Prognostic Index (IPI) score and survival. Receiver operator characteristic (ROC) curve analysis showed an excellent ability for sCD27 to discriminate between low- and high-stage disease (p < 0.001), especially in indolent lymphomas. No discriminative value for TK, beta(2)M or LD was found. For aggressive NHL, sCD27, TK, beta(2)M and LD did predict survival in the univariate analyses. However, LD was found to be the most independent prognostic factor in a multivariate Cox regression model. In indolent lymphomas, sCD27 proved to be a powerful marker to predict progression-free survival (p = 0.008). Taken together, the results of the ROC curve and survival analysis suggest that substitution of LD by sCD27 in the IPI may be considered for indolent lymphomas to enhance the prognostic value. A study in a larger cohort of patients is required to validate this approach.
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PMID:Serum soluble CD27, but not thymidine kinase, is an independent prognostic factor for outcome in indolent non-Hodgkin's lymphoma. 1274 27


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