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 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.
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PMID:Clinical and serologic markers of stage and prognosis in small cell lung cancer. A multivariate analysis. 216 41

Using a neural transplantation model, we have studied the effect of polyoma virus middle T antigen and of the viral src oncogene on the developing rat brain. For this purpose, single-cell suspensions of fetal rat brain were prepared on day 14 of gestation (E14), infected with a replication-defective retroviral vector which carries the middle T oncogene driven by an internal thymidine kinase promoter, and stereotaxically injected into the caudoputamen of adult host rats. With mock-infected donor cells, the transplants developed into an organotypically differentiated population of neurons, astrocytes, oligodendrocytes and other central nervous system cell types and expressed marker proteins of mature neuroectodermal cells, including neuron-specific enolase, synaptophysin, neurofilament protein, glial fibrillary acidic protein and S-100 protein. A high percentage of rats carrying transplants infected with the middle T-encoding vector died within two to six weeks from massive haemorrhage into the transplant. Upon microscopic examination, gross abnormalities of the microvasculature were seen, with formation of large blood-filled spaces lined by a thin layer of proliferating endothelial cells. This effect of middle T was apparently cell type-specific, since the differentiation of neuroectodermal cells within the graft proceeded in a regular fashion. In order to assess further the cell-specificity of the oncogene, analogous experiments were carried out with a retroviral construct in which the middle T cDNA had been replaced by the viral src gene (v-src). Transplants infected with the v-src vector developed astrocytomas, but no vascular abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumour induction in fetal brain transplants exposed to the viral oncogenes polyoma middle T and v-src. 280 88

We analyzed serum lactate dehydrogenase (LDH), neuron-specific enolase (NSE) and thymidine kinase (TK) levels in 22 patients with small cell lung cancer. Tumor proliferation was expressed as the proportion of S-phase cells (SPF), determined by DNA flow cytometry, from concomitantly taken biopsy samples. A positive correlation between serum NSE (r = 0.41) or LDH (r = 0.65, p = 0.05) levels and tumor SPF was noted, but was not found between serum TK levels and the SPF. The correlation between NSE and SPF was even more pronounced if only patients with extensive disease were considered (r = 0.77). The serum NSE and LDH, but not TK levels, were significantly greater in the patients with extensive disease (NSE 50.4 ng/ml, LDH 621 U/ml) compared to the patients with limited disease (NSE 21.0 ng/ml, LDH 272 U/ml, p = 0.05). Our results suggest that the combined determination of serum LDH and NSE levels gives valuable data on the primary tumor mass and its proliferative activity in small cell lung cancer.
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PMID:Correlation between serum tumor marker levels and tumor proliferation in small cell lung cancer. 284 99

Herpes simplex virus type 1 (HSV-1) can transduce genes into non-proliferating cells such as neurons that are refractory to other means of gene transfer. We have been interested to examine the potential usefulness of HSV-1 as a gene transfer vehicle to analyze neuron-specific regulatory sequences. In this study, we have used a replication-defective HSV-1-based vector deleted for the essential immediate early gene 3 (IE3) to transduce a 1.8 kb promoter fragment from the rat neuron-specific enolase gene (nse) linked to the firefly luciferase reporter gene (luc). It has previously been shown that the same promoter fragment is capable of directing neuron-specific expression of a linked reporter gene in transgenic mice. As an internal control for infection and gene expression, we also inserted the chloramphenicol acetyltransferase (cat) gene driven by the SV40 early promoter/enhancer into the thymidine kinase locus of the same vector. We infected (i) non-neuronal BHK-C13 cells which do not express the endogenous nse gene, (ii) differentiated and non-differentiated pheochromocytoma PC12 cells as well as (iii) N1E-115 neuroblastoma cells, all of which do express endogenous nse. All three cell types produced luciferase upon infection, indicating that the same nse promoter fragment that has previously been shown to be regulated in a cell-specific manner in transgenic mice, was not regulated cell type-specifically in the context of the HSV-1 genome.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transduction of foreign regulatory sequences by a replication-defective herpes simplex virus type 1: the rat neuron-specific enolase promoter. 775 77

Serological tumor markers may become widely used as inexpensive and non-invasive methods of cancer detection. Markers of current interest for small cell lung cancer (SCLC) comprise enzymes, peptides, proteins, and carbohydrates. None of the serological markers for SCLC have yet proven to be of diagnostic value and at present their use is limited to monitoring disease and indicating prognosis. However, whilst serological markers related to the metabolic state of SCLC cells, such as neuron-specific enolase, serum thymidine kinase and tissue polypeptide antigen, may only be used for monitoring patients and for estimating prognosis, the other serological markers under current investigation may be used to indicate new treatment forms. Several novel approaches, including interference in the autocrine growth-regulating loop of SCLC by either peptides or antibodies, have been tried, SCLC is a highly heterogeneous tumor with respect to antigen expression, regulation of growth, and differentiation state. It is therefore important that new interventions are directed against both antigen-positive and antigen-negative tumor cells. For instance, radioisotopes or enzymes coupled to antibodies may be effective by exerting toxicity at some distance from the target. Antigens expressed on SCLC cells, such as peptide receptors involved in growth regulation, carbohydrate antigens like Lewis antigens, carcinoembryonic antigen and the ganglioside fucosylGM1, provide potential targets for antibody-conjugated therapy.
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PMID:Serological tumor markers for small cell lung cancer and their therapeutic implications. 794 58

1. Herpesvirus infection with genetically engineered vectors is a way to deliver foreign gene products to various cell populations in culture and in vivo. Selective neuronal gene expression can be achieved using the neuron-specific enolase (NSE) promoter regulating expression of a transgene placed in and delivered by a herpesvirus vector. 2. We sought to determine the anatomical specificity and efficiency of herpesvirus-mediated gene transfer into the rat brain following placement of virus particles carrying a transgene (lacZ) under control of the NSE promoter. The virus utilized was thymidine kinase (TK) deficient and therefore replication deficient in the brain. 3. Infusion of 10(6) plaque-forming units of virus into the striatum caused a limited number of striatal neurons to express the lacZ transgene mRNA and protein product 7 days postinfection. In addition, small numbers of neurons expressing the transgene mRNA and protein were found ipsilateral to the viral injection in the frontal cortex, substantia nigra pars compacta, and thalamus. Neurons at these anatomic loci project directly to the striatal injection site. No other cells within the brains of injected animals expressed the lacZ gene. 4. While this herpesvirus NSE vector was capable of introducing novel functional genetic information into postmitotic neurons within defined neuroanatomic constraints, the numbers of neurons expressing detectable levels of beta-galactosidase was minimal. The calculated efficiency of delivery and transgene expression at 7 days postinfection was 1 transgenic neuron per 10(4) virus particles infused. 5. We conclude that NSE probably is not an optimal promoter for use in gene delivery to CNS neurons in herpesvirus vectors and that the efficacy of gene delivery using other neuron-specific promoters placed at various sites in the herpes viral genome needs to be explored.
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PMID:Herpesvirus-mediated gene delivery into the rat brain: specificity and efficiency of the neuron-specific enolase promoter. 811 22

The clinical usefulness of neuron-specific enolase (NSE), thymidine kinase (TK), and tissue polypeptide-specific antigen (TPS) was investigated in 41 patients (53-80 years old) with recently discovered small-cell lung cancer (SCLC). Eleven patients exhibited limited disease (LD) and 30 extensive disease (ED). Serum samples for NSE, TPS (immunoradiometric assay), and TK (radioenzymatic assay) evaluations were drawn from all patients at the time of diagnosis and before each cycle of chemotherapy in the treated patients. Therapy consisted of i.v. carboplatin 300 mg/m2 on the first day and i.v. etoposide 120 mg/m2 from the first to the third day every 3 weeks. Nine patients refused or were not eligible for chemotherapy. Five patients received only one course and showed no response (NR); 9 patients received two courses; 18 patients received three or more courses. In the last group, complete remission (CR) was obtained in 9 cases, partial remission (PR) in 18 cases. The tumor markers studied did not show any significant difference in distinguishing LD from ED. NSE and TPS were significantly more often abnormal than TK, either at the time of diagnosis (p < 0.05) or in PR or NR patients (p < 0.05). In relation to chemotherapy response, NSE and TPS serum patterns were shown to be more reliable than TK in PR (p < 0.05) and NR patients (computed error between 10% and 15%). No significant difference was observed between serum NSE and TPS patterns. Serum NSE and TPS seem to be more useful in the diagnosis and follow-up of SCLC patients undergoing chemotherapy. Further trials are necessary to ascertain whether the associated assessment of NSE and TPS can add useful information to that provided by the assessment of NSE alone.
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PMID:Neuron-specific enolase, thymidine kinase, and tissue polypeptide-specific antigen in diagnosis and response to chemotherapy of small-cell lung cancer. 1040 2

The present study examines the clinical significance of serum neuron-specific enolase (NSE) in patients with adult T cell-leukemia (ATL). Serum NSE values were measured using a radioimmunoassay in 35 patients (acute type, n = 15; lymphoma type, n = 10; chronic type, n = 10) and in 7 controls carrying T lymphotropic virus type-1 (HTLV-1). Serum NSE values >10 ng/mL were detected in 9 of 15 patients with acute type (60%), 5 of 10 with lymphoma type (50%), and in one of 10 patients with chronic type (10%) ATL, but in none of the HTLV-1 carriers. Contrary to previous findings demonstrating that 20% of patients with non-Hodgkin's lymphoma (NHL) had positive serum NSE, the frequency of a high NSE value in patients with acute and lymphoma type ATL was much higher (60% and 50%, respectively). The serum NSE value positively correlated with serum thymidine kinase activity (TK) and serum soluble interleukin-2 receptor (sIL-2R) levels (P < 0.04 and P < 0.01, respectively). Serum NSE values at the initial diagnosis were adversely related to overall survival time according to the log-rank test (P < 0.02). Pathological examinations demonstrated that both patients with anaplastic large cell lymphoma type ATL had cytoplasmic NSE and CD30 markers on cell membranes. These findings suggest that serum NSE is partially produced by ATL cells and that ATL tumor cells seem preferentially produce NSE compared with other NHL cells. Serum NSE may be a novel marker of disease aggressiveness as well as a prognostic factor for ATL.
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PMID:Clinical significance of serum neuron-specific enolase in patients with adult T-cell leukemia. 1235 4

In this study, selective expression of therapeutic transgenes was evaluated in neuroblastoma cells. Promoter fragments of the genes for neuron-specific enolase (NSEp), tyrosine hydroxylase (THp), and dopamine-beta-hydroxylase (DBHp) were studied in neuroblastoma and nonneuronal cell lines by transient transfection experiments using fluorescence-activated cell sorting (FACS) analysis of enhanced green fluorescent protein (egfp) and luciferase (luc+) assay. Both reporter gene assays revealed a neuroblastoma-selective expression mediated by NSEp and THp, whereas DBHp was active only in a murine neuroblastoma cell line. Reporter gene expression by NSEp in neuroblastoma cells was markedly higher than expression by THp, but NSEp also showed considerable background activity in nonneuronal cells. THp-driven expression of egfp was 35-fold higher in human neuroblastoma MHH-NB11 compared with nonneuronal HeLa cells. Thus, THp was chosen for a neuroblastoma-selective suicide gene therapy approach using the herpes simplex virus type 1 thymidine kinase (HSV-tk)/ganciclovir (GCV) system. A retrovirus vector that contained an expression cassette of a HSV-tk/egfp fusion gene and THp in antisense orientation was generated. Stably transduced human neuroblastoma cells and nonneuronal cell lines were generated, and HSV-tk/egfp expression was measured by FACS and GCV cytotoxicity assay. There was a 2.2-fold difference in green fluorescence and a 1.4-fold difference in cell killing between the human neuroblastoma MHH-NB11 and HeLa cells after HSV-tk/egfp gene transfer. The overall difference in THp-HSV-tk/egfp-mediated cell killing between neuroblastoma and nonneuronal tumor cell lines was statistically significant (P = 0.001). In conclusion, the present study demonstrated the feasibility of a neuroblastoma-selective gene therapy approach using the THp/HSV-tk/egfp expression cassette.
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PMID:A neuroblastoma-selective suicide gene therapy approach using the tyrosine hydroxylase promoter. 1518 Nov 82


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