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)

The serum levels of soluble ICAM-1 (sICAM-1, sCD54) were significantly elevated (p = .0006) in patients with Hodgkin's disease (HD) (n = 101) compared to healthy controls (n = 31). Serum levels of sICAM-1 in HD correlated significantly with the presence of B-symptoms, histology and tumour burden as reflected in the Ann Arbor staging system, but not to bulky disease. sICAM-1 was compared to other serum factors claimed to be of prognostic significance in HD, including erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), deoxythymidine kinase (TK), soluble interleukin-2 receptor (sIL-2R, sCD25) and soluble CD30 (sCD30, sKi-1-antigen). Serum levels of sICAM-1 correlated positively with all of these markers. In univariate regression analyses, all but ESR correlated with disease-free survival but only sICAM-1, sIL-2R and sCD30 correlated with overall survival. In multivariate analyses only sIL-2R (as a continuous variable) added independent prognostic information in addition to age, stage and B-symptoms. sICAM-1 and sCD30 approached significance (p = 0.07 and p = 0.08, respectively) for disease-free survival. sCD30 correlated with overall survival (p = 0.03) while sICAM-1 did not. When dichotomised at optimal cut-off levels, sICAM-1 as well as sIL-2R and sCD30 added independent prognostic information for both disease-free and overall survival. Based on the present observations, it appears that sICAM-1 may be a predictor for relapse and survival in HD. Determination of serum levels of sICAM-1 (in addition to sIL-2R and sCD30) may thus be of potential value when selecting HD patients eligible for intensive therapy in clinical trials.
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PMID:Soluble ICAM-1 in Hodgkin's disease: a promising independent predictive marker for survival. 853 15

The serum levels of soluble ICAM-1 (CD54) were significantly elevated in patients with non-Hodgkin's lymphomas (NHL, n=127) and hairy cell leukaemia (HCL, n=15) compared with healthy controls (n=31). In high-grade malignant NHL (n=79) the sICAM-1 levels correlated with the tumour mass as reflected in the Ann Arbor staging system but not with bulky disease. Further, the sICAM-1 levels correlated with disease activity as reflected by the presence of B symptoms and with other known prognostic markers. In particular serum thymidine kinase (sTK). In patients with low-grade malignant NHL (n=48) a trend towards higher serum levels of sICAM-1 was found in patients with advanced stage and B symptoms. In both low and high-grade malignant NHL, elevated levels of sICAM-1 were associated with poorer overall and disease-free survival. The present results indicated that sICAM-1 levels have a prognostic power equal to that of other serum markers claimed to be of prognostic value in NHL, namely serum lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), beta-2-microglobulin (beta2m), serum thymidine kinase (sTK), albumin and orosomucoid. The cellular origin and the possible interactions between soluble and surface ICAM-1 and its ligands needs further exploration.
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PMID:Elevated serum levels of soluble ICAM-1 in non-Hodgkin's lymphomas correlate with tumour burden, disease activity and other prognostic markers. 879 Jan 63

The herpes simplex virus thymidine kinase gene (HSV-TK) in combination with ganciclovir (GCV), is currently being used in gene therapy-based clinical trials for cancer treatment. Its therapeutic effect is based on a "bystander effect" whereby HSV-TK gene-modified tumor cells are toxic to nearby unmodified tumor cells when exposed to the antiviral drug GCV. We have recently hypothesized that the in vivo mechanism of this bystander effect is due to alterations in the tumor microenvironment in response to release of cytokines and an infiltration of leukocytes after treatment with HSV-TK gene-modified tumor cells and GCV, which results in tumor regression. Expression of B7, a recently identified costimulatory molecule that is important for T-cell stimulation, has been shown to be modulated by stimulatory cytokines interferon-gamma, tumor necrosis factor-alpha, and inhibited by interleukin-10. In the present study, we investigated whether the cytokines released after HSV-TK and GCV treatment could include the expression of the costimulatory molecules B7-1 and B7-2 and the adhesion molecule (ICAM)-1 in the tumor. Furthermore, we investigated whether this altered environment affected the antitumor properties of host lymphocytes. An in vitro model was developed to establish the effects of HSV-TK gene-modified tumor cells and GCV on tumor infiltrating cells. The murine macrophage cell line (IC21) was exposed to either supernatants or cell lysates collected from a mixture of HSV-TK-transduced (KBALB-STK) and non-transduced (KBALB) murine fibrosarcoma tumor cells previously exposed to GCV (experimental). Immunohistochemical analysis showed a significant expression (P < .0001) of B7-1 and B7-2 post exposure of IC21 cells to either supernatant or lysate. In contrast, the level of expression in IC21 cells exposed to the control lysate or supernatant remained unchanged for B7-1 and B7-2. In vivo analysis for B7-1 and B7-2 expression by immunohistochemistry in tumor tissues from experimental mice receiving HSV-TK gene-modified tumor cells and GCV treatment showed a significant expression of B7.1 (35%, P < .0001) and B7.2 (38.2%, P < .0001) on tumor-infiltrating mononuclear cells. In contrast, tumor-bearing control animals showed low levels of B7-2 expression (5.8%), whereas B7-1 was undetectable, as confirmed by reverse-transcriptase polymerase chain reaction. In addition, a significant up-regulation of ICAM expression (50%) on tumor tissues was observed in the experimental group (P = .0317) as compared with the control group (25%). Furthermore, T cells isolated from experimental mice showed a significant in vitro proliferative response (p = .0202) when exposed to syngeneic tumor cells as compared with the control group. These data demonstrated that the use of HSV-TK gene-modified tumor cells and GCV as a suicide gene in the treatment of an intraperitoneal tumor resulted in the expression of the B7 costimulatory molecules and ICAM-1 adhesion molecule and enhanced proliferative response of host T cells. These findings help to understand the mechanism of tumor cell killing in vivo using HSV-TK gene-modified tumor cells.
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PMID:Expression of costimulatory molecules: B7 and ICAM up-regulation after treatment with a suicide gene. 898 40

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

Hitherto conducted studies concerned with the problem of cytoadhesive molecules (CAM) dealt only in a very limited way with the problem of multiple myeloma (MM). The subject of the submitted paper was evaluation of the relationship of soluble forms of "vascular cell adhesive molecule-1" (sVCAM-1) and "intercellular cell adhesion molecule-1" (sICAM-1) in serum from the peripheral bloodstream (PBS) and serum from a bone marrow aspirate (BMA) with selected clinical and laboratory indicators of MM (beta 2-microglobulin, thymidine kinase, immunochemical type of MM, S-creatinine, S-monoclonal immunoglobulin, S-albumin, Hb, percentage ratio of plasmocytes in bone marrow, age, performance status, stage and substage of MM and activity of disease) and proliferation characteristics of myeloma plasmocytes. The authors analyzed two groups of patients with MM, a group of 64 examined in different stages of MM and a group of 39 examined when the diagnosis of MM was established (median age 63 and 64 years, male/female ratio 1.6 and 1.3:1). The sVCAM-1 and sICAM-1 levels were examined by the ELISA method. Elevated values of sVCAM-1 in PBS were recorded in both groups in 87.5% and 87% patients, medians of sVCAM-1 exceeded the upper range of normal values (714 ng/ml) almost twice (1180 and 1295 ng/ml) whereby median values in BMA (1347 and 1546 ng/ml) were always somewhat higher than in PBS. Elevated sICAM-1 values in PBS were found in 35 and 33% patients, median levels of sICAM-1 in PBS and in BMA did not exceed the upper normal range (691 ng/ml) and did not differ substantially (518 vs. 476 and 518 vs. 500 ng/ml). Correlation analysis (Pearson's correlation coefficient and Mann-Whitney's test, p0.05) revealed in both groups a significant relationship of both CAM assessed in PBS and BMA (sVCAM-1 p-0.0000 and p-0.012, sICAM-1 p-0.0000 and p-0.0011). No relationship was found between sVCAM-1 and s-ICAM-1 levels assessed in PBS and BMA with proliferation indexes of myeloma plasmocytes, i.e. values of the propidium-iodide index PI/CD38 and PI/B-B4 (CD138). In the whole group of 64 patients a relationship was found between sVCAM-1 in PBS and values of S-creatinine (p - 0.004), Hb (p - 0.033), S-albumin (p - 0.035), S-beta 2-microglobulin (S-B2M) (p - 0.0000) and S-thymidine kinase (S-TK)(p-0.0000), when evaluating BMA, a relationship with B2M (p -0.011). In the group of 39 patients examined when the diagnosis of MM was made a relationship was found of sVCAM-1 in PBS to S-B2M) (p - 0.0000), S-TK (p-0.0000) and to S-creatinine (p -0.005), in BMA there was only a relationship with B2M (p - 0.020). In the whole group of 64 patients there was no relationship between s-ICAM levels in PBS with any of the examined indicators, when evaluating BMA only a relationship with B2M (p - 0.038) and TK (p - 0.022). In the group of 39 patients examined during the diagnosis of MM a relationship was found of sICAM-1 only with B2M in BMA (p - 0.013). In the total group of 64 a relationship was found between sVCAM-1 in PBS with the patient's age (p - 0.032) and the substage of MM(p-0.024), in the group of 39 patients a relationship between sVCAM on PBS and the substage of MM (p -0.031). On analysis of sICAM-1 a relationship was found between levels in BMA only with the patient's age (p -0.015). From the investigation ensued that despite evidence of a number of correlations between sVCAM and sICAM-1 levels and clinical and laboratory indicators of MM no relationship was found which could be applied under conditions of clinical practice. Assessment of levels of different indicators in serum of bone marrow aspirate did not reveal any advantages over examination in peripheral blood serum.
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PMID:[Relation of the soluble cytoadhesion molecules VCAM-1 and ICAM-1 to selected clinical and laboratory indicators in multiple myeloma]. 1095 65