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

Of 102 patients suffering from prostatic carcinoma, complete data on the serum concentration of 7 tumour markers were available from 90 patients, together with tumour grade, local stage and the presence or absence of skeletal metastases. The serum content of prostatic acid phosphatase, prostate specific antigen, neopterin, thymidine kinase, osteocalcin, C-reactive protein and tissue polypeptide antigen was measured. By means of Cox's regression and multivariate analysis the ability of these variables to predict prognosis, i.e. death from prostatic cancer, was studied. Neopterin appeared to be the most efficient marker, followed by tumour grade, thymidine kinase and prostate specific antigen. No other variable provided information of statistical significance. In multivariate analysis thymidine kinase performed best, followed by neopterin, tumour grade and prostate specific antigen. Several serum tumour markers reflect the biological activity of human prostate cancers and their value should be further explored. They may become useful in the management of individual patients.
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PMID:Tumour markers as prognostic aids in prostatic carcinoma. 169 4

Serum from 102 patients was analysed with regard to its content of prostatic acid phosphatase (PAP), prostate specific antigen (PSA), neopterin, osteocalcin, thymidine kinase, C-reactive protein, and of tissue polypeptide antigen (TPA). The levels were related to the short-term survival (death from cancer within 3 years) and compared by statistical means. A comparison was also made with tumour grade and stage and the presence or not of metastatic lesions. In this study neopterin was found to be most closely related to the clinical course followed by tumour grade, thymidine kinase and PSA. When all these four variables were in the equation no other parameter added any information of statistical significance. The importance of selecting appropriate cut off values ('normal' vs 'elevated') when using the serum marker as a prognostic indicator is also discussed.
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PMID:Serum tumour markers in human prostatic carcinoma. The value of a marker panel for prognostic information. 202 1

Seven tumour markers, i.e. squamous cell carcinoma antigen (SCC), cancer antigen 125 (CA 125), tissue polypeptide antigen (TPA), neopterin, C-reactive protein (CRP), carcinoembryonic antigen (CEA) and deoxythymidine kinase (TK) were analysed in sera from 104 women with benign and 61 women with malignant gynecologic diseases, in order to create tumour marker panels for various gynecologic malignancies, for monitoring and prediction of disease development. The incidence of elevated tumour marker levels, in cervical carcinoma was 78% when SCC, CA 125 and CEA were used. In ovarian carcinoma one of the markers CA 125, TPA and CEA was elevated in 91% and for endometrial carcinoma the best combination of markers was SCC, CA 125 and CEA (57%). No individual marker was superior to the above combinations. However, in patients with a fatal outcome of their malignant gynecologic disease (mean survival time from serum sampling was 16 months), the incidence of death was highest among those who had TPA elevated (91%) followed by neopterin (86%) and CRP (76%). Although intercurrent diseases affected tumour marker levels the markers picked up a majority of patients with a poor prognosis. This demonstrates the importance of interpreting tumour marker results against a background of detailed clinical information.
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PMID:Evaluation of seven different tumour markers for the establishment of tumour marker panels in gynecologic malignancies. 262 71

High serum level of bioactive interleukin-6 (IL-6) is regarded as a predictor of poor prognosis in multiple myeloma (MM). On the other hand, the reported levels of immunoreactive IL-6 have been highly variable, and the prognostic value of immunoreactive IL-6 in MM is not clear. We have analyzed the prognostic significance of serum immunoreactive IL-6, as measured by a sensitive immunosorbent assay, in 210 patients with newly diagnosed MM subsequently treated with intermittent melphalan and prednisone. The serum levels of acute phase proteins C-reactive protein (CRP), alpha 1-antitrypsin (alpha 1AT), and acid alpha 1-glycoprotein (orosomucoid; OM) were evaluated as surrogates for IL-6. Serum IL-6, CRP, alpha 1AT, and OM levels were raised in 42%, 40%, 41%, and 24% of the patients, respectively. There was a significant correlation between the clinical stage of the patients and serum IL-6 (P = .006), alpha 1AT (P = .001), and OM (P = .004) levels at diagnosis. At 3 years, 52% of the patients were alive. Univariate logistic regression analysis showed that high levels of IL-6 (P = .002), CRP (P = .02), alpha 1AT (P < .001), OM (P = .007), beta 2-microglobulin (beta 2M; P < .001), and thymidine kinase (P < .05) were all associated with 3-year mortality. In multivariate regression analysis, beta 2M (P < .0001) and alpha 1AT (P = .01) had independent prognostic significance. The patients with high levels of both beta 2M and alpha 1AT or IL-6 were at very high risk of dying within 3 years from diagnosis (16% and 21% of the patients in these groups were alive, respectively). When the patients were stratified according to the clinical stage, the prognostic significance of serum IL-6 and alpha 1AT was especially evident in stage II patients. When the patients were divided into two groups according to normal or raised serum IL-6 levels, the patients with high IL-6 levels had more frequent osteolytic bone lesions (P = .03) and a more aggressive disease. We conclude that serum immunoreactive IL-6 is a significant prognostic marker in MM.
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PMID:Immunoreactive interleukin-6 and acute phase proteins as prognostic factors in multiple myeloma. Finnish Leukemia Group. 753 May 7

Biochemical markers of multiple myeloma (MM) including beta 2-microglobulin (beta 2MG), C-reactive protein, neopterin, fibronectin, lactate dehydrogenase (LDH), thymidine kinase, connective tissue components, osteocalcin, amylase, etc. are reviewed. To date, no reliable biochemical markers have been reported for the diagnosis of MM. beta 2MG and LDH are widely used to predict the prognosis of the patients with MM. The value of other parameters is however, controversial. The cytochemical diagnosis of MM, using acid phosphatase, beta-glucronidase and lysozyme are also mentioned. Furthermore, the significance of the assay of various hormones, ammonia, cobalamin and electrolytes in MM are discussed.
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PMID:[Biochemical markers of multiple myeloma]. 769 95

The clinical significance of plasma cell acid phosphatase (PCAP) was evaluated in 143 patients with monoclonal gammapathies, using a semiquantitative cytological scoring method. Significantly higher PCAP scores were measured in overt myelomas than in MGUS or in smouldering myelomas, during the phases of activity (diagnosis, progression, relapse), and in patients with extended disease. Among various clinical and laboratory parameters, PCAP was significantly related to the percentage of bone marrow plasma cells, the neoplastic growth fraction, as determined by Ki67 monoclonal antibody, and to serum levels of C-reactive protein. An inverse relationship was also found between PCAP and hemoglobin levels. Although the patients with "flaming" plasma cells exhibited low PCAP scores and poor prognosis, on the whole, myeloma patients with PCAP scores < 200 showed a significantly longer median overall survival than those with PCAP > 200 (46 vs 20 months, p < 0.003). However, in the multivariate analysis, beta 2-microglobulin, growth fraction, performance status, and serum levels of thymidine kinase and C-reactive protein, but not PCAP, maintained a significant prognostic relevance. In conclusion, although PCAP may be considered a marker of disease activity, other parameters provide better prognostic information in myeloma patients.
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PMID:Plasma cell acid phosphatase and prognosis in multiple myeloma. 781 11

The plasma cell labeling index (PCLI) and serum beta 2-microglobulin (beta 2M) are independent prognostic factors in multiple myeloma (MM). Recently, levels of thymidine kinase (TK) and C-reactive protein (CRP) have been shown to have prognostic value. We studied 107 patients with newly diagnosed myeloma to determine whether TK and CRP values added prognostic information not already available using the PCLI and beta 2M. Univariate survival analysis showed prognostic significance for the PCLI, TK, beta 2M, age, serum albumin, and CRP. Multivariate analysis showed that only PCLI and beta 2M have independent prognostic significance. The survival curves were better separated using the PCLI and beta 2M than with other combinations of variables. Among nine patients under age 65 with low PCLI and low beta 2M, eight were alive almost 6 years after starting chemotherapy. These good-risk patients could not be identified by standard clinical features. Although creatinine and calcium were normal, other features such as bone lesions, osteoporosis, fracture, and anemia were present and stage distribution was similar to other patients in the study. In conclusion, PCLI and beta 2M measured at diagnosis are independent prognostic factors. They must be considered when interpreting the results of clinical trials and should be helpful in counseling patients and in designing new trials. When the PCLI and beta 2M values are known, the TK and CRP values do not add useful additional prognostic information.
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PMID:Plasma cell labeling index and beta 2-microglobulin predict survival independent of thymidine kinase and C-reactive protein in multiple myeloma. 824 20

The median duration of survival for patients with multiple myeloma ranges from 2.5 to 3 years. However, there is considerable variability from one patient to another. Renal function as determined from blood urea nitrogen or serum creatinine values, hemoglobin value, calcium level and performance status have been recognized as prognostic factors for more than 20 years. A study of 107 patients with newly diagnosed multiple myeloma at the Mayo Clinic showed that plasma cell labeling index (PCLI); levels of thymidine kinase, beta 2-microglobulin (beta 2-M), serum albumin, and C-reactive protein; and age were all significant univariate prognostic factors. Only PCLI and beta 2-M levels had independent prognostic significance. Among nine patients younger than 65 years with low PCLI and low beta 2-M levels, eight were alive almost six years after starting chemotherapy. Interleukin 6 (IL-6) is a significant univariate predictor of survival in myeloma. An elevated lactate dehydrogenase content is associated with a poor prognosis. An elevated soluble IL-6 receptor (sIL-6R) level is an independent factor associated with shorter survival. In one study, the addition of sIL-6R to PCLI and beta 2-M to the analysis doubled the proportion of patients identified as high-risk. In this study, the two-year survival was 41% at two years if the PCLI was > or = 2%, beta 2-M was > or = 4.0 micrograms/dl, or sIL-6R was > 300 ng/ml. When none of these three factors were increased, the estimated two-year survival was 83%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prognostic factors in multiple myeloma. 852 May 13

Interleukin-6 (IL-6) is the major cytokine inducing transcription of human C-reactive protein (CRP) during the acute phase response. STAT (signal transducers and activators of transcription) family members, recently shown to be important mediators of the effects of many cytokines including IL-6, generally induce their effects by binding to palindromic sequences with TT(N)5AA motifs. We report an IL-6 responsive element in the proximal region of the human CRP 5'-flanking region that bears a TT(N)4AA motif, which we have termed CRP acute phase response element (CRP-APRE). In Hep3B cells, IL-6 but not interferon-gamma was capable of activating CAT constructs driven by the CRP promoter containing CRP-APRE. Overexpressed STAT3 was able to transactivate CRP-chloramphenicol acetyltransferase constructs through the CRP-APRE and was able to enhance endogenous CRP mRNA accumulation in response to IL-6. STAT3 (or an antigenically related molecule) bound to the CRP-APRE in response to IL-6. Overexpression of STAT3 in the presence of IL-6 was capable of inducing expression of a construct consisting of the CRP-APRE and a minimal thymidine kinase promoter lacking a C/EBP site. Taken together, these findings indicate that STAT3 participates in the transcriptional activation of CRP in response to IL-6.
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PMID:STAT3 participates in transcriptional activation of the C-reactive protein gene by interleukin-6. 862 22

Although Wilm's Tuomor gene (WT1) was first identified as a tumor suppressor gene for Wilm's tumor, WT1 overexpression has been detected in different malignant cell types including leukemia. Increased expression of WT1 in acute leukemia is potentially used as a marker of minimal residual disease. However, the significance of the gene for multiple myeloma is still not clear. To determine the clinical relevance of WT1 expression in multiple myeloma, we examined the association of clinical parameters and WT1 expression in bone marrow for 17 newly diagnosed multiple myeloma patients. WT1 was assessed by real-time quantitative polymerase chain reaction (RQ-PCR) and calculated standardized WT1 expression level per 100 plasma cells in the bone marrow specimen as "corrected WT1". The expression of standardized WT1 and corrected WT1 in myeloma was 59 to 1,600 copies/microg RNA and 0.05 to 406.3 copies/microg RNA/100 plasma cells, respectively, lower than in leukemia. WT1 transcripts increased when clinical factors worsen, including the stage, amount of M protein, Hb, platelet count, blood urea nitrogen (BUN), creatinine, serum alkaline phosphatase (ALP), calcium, beta2-microglobulin, thymidine kinase activity (TK), and C-reactive protein (CRP). In conclusion, the expression level of WT1 could be an additional marker to the standard parameters considered in risk assessment for multiple myeloma.
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PMID:WT1 expression level and clinical factors in multiple myeloma. 1647 22


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