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)

We have investigated the transcriptional activity of human cytomegalovirus, herpes thymidine kinase, human chorionic gonadotropin alpha, somatostatin, immunoglobulin kappa chain, alpha crystallin, albumin and interferon-beta promoters in the fission yeast Schizosaccharomyces pombe. Among these, the human cytomegalovirus, human chorionic gonadotropin alpha, and somatostatin promoters were found to be very active, approximately 11-, 9-, and 0.9-fold as active as the SV40 early promoter, respectively. The remainder of the promoters studied were weak, having only 10-20% of the SV40 promoter activity. Primer extension analysis showed that the strong promoters initiated transcription in S. pombe at the same sites as in mammalian cells, indicating the high similarity between both transcriptional systems.
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PMID:Human chorionic gonadotropin alpha and human cytomegalovirus promoters are extremely active in the fission yeast Schizosaccharomyces pombe. 197 20

The structural gene for Herpes simplex virus (HSV) thymidine kinase (Tk) was fused downstream of the 5'-flanking sequence (from -284 to +20; numbering relative to the putative transcription initiation site) of the cloned human interferon-beta 1 (IFN-beta 1) gene. The fusion gene was linked to the vector pSV2-Ecogpt and the recombinant plasmid was used to transform mouse FM3A cells. All cloned transformants in which the fusion gene was integrated in an intact form produced the Tk specific transcript with the distinct 5' terminus corresponding to that of the authentic IFN-beta 1 mRNA when they were exposed to Newcastle disease virus (NDV). Thus, the results reported here provide evidence for the presence of specific DNA sequences in the 5'-flanking region of the IFN-beta 1 gene required for the virus mediated activation of transcription.
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PMID:The 5'-flanking sequence of human interferon-beta 1 gene is responsible for viral induction of transcription. 631 Apr 98

Glucocorticoids bind to their receptors and trigger the transcriptional activation or repression of target genes by binding to DNA sequences, the glucocorticoid responsive element (GRE). The murine interferon-beta (Mu-IFN beta) gene in L929 cells can be induced by dexamethasone to give both transcription and translation products specific to murine IFN beta. The 3'-noncoding region of the Mu-IFN beta gene was found to contain a GRE very similar to the consensus GRE sequence involved in glucocorticoid-regulated genes. Gel retardation assays showed that the oligonucleotide corresponding to that GRE competed with the MMTV GRE oligonucleotide for glucocorticoid receptor binding and was supershifted by human antiglucocorticoid receptor antibodies. Transiently transfected murine cells (L929) with the GRE-IFN beta 3' sequence inserted upstream of the thymidine kinase promoter and the chloramphenicol acetyl transferase gene treated with dexamethasone with or without the antiglucocorticoid RU486 and their chloramphenicol acetyl transferase activity assayed, show that this GRE is efficient. We conclude that the Mu-IFN beta gene in L929 murine cells can be induced by dexamethasone, and that the hormone effect may be mediated by the 3'-GRE sequence.
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PMID:Induction of interferon-beta gene expression by dexamethasone in murine L929 cells. 777 70

Life sciences and computer technologies have begun to create new medical fields such as pharmacogenomics, nutrinogenomics, and genetic medicines (genetic diagnosis and gene therapy). In gene therapies for malignant brain tumors, suicide gene therapies using herpes simplex virus-thymidine kinase gene and ganciclovir, and immuno-gene therapies using cytokine genes have been developed. Recently, we made a gene therapy protocol of our own, which used cationic multilamellar liposomes entrapped with interferon-beta (IFN-beta) gene as a vector and we started clinical trial of IFN-beta gene therapy for patients with malignant glioma in April 2000. Until now, five patients received the treatment and then they are under evaluation on safety and usefulness. Here the authors introduce present and prospect of gene therapy for malignant brain tumors.
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PMID:[Gene therapy for malignant glioma]. 1577 47

The poor prognosis for patients with aggressive or metastatic tumors and the toxic side effects of currently available treatments necessitate the development of more effective tumor-selective therapies. Stem/progenitor cells display inherent tumor-tropic properties that can be exploited for targeted delivery of anticancer genes to invasive and metastatic tumors. Therapeutic genes that have been inserted into stem cells and delivered to tumors with high selectivity include prodrug-activating enzymes (cytosine deaminase, carboxylesterase, thymidine kinase), interleukins (IL-2, IL-4, IL-12, IL-23), interferon-beta, apoptosis-promoting genes (tumor necrosis factor-related apoptosis-inducing ligand) and metalloproteinases (PEX). We and others have demonstrated that neural and mesenchymal stem cells can deliver therapeutic genes to elicit a significant antitumor response in animal models of intracranial glioma, medulloblastoma, melanoma brain metastasis, disseminated neuroblastoma and breast cancer lung metastasis. Most studies reported reduction in tumor volume (up to 90%) and increased survival of tumor-bearing animals. Complete cures have also been achieved (90% disease-free survival for >1 year of mice bearing disseminated neuroblastoma tumors). As we learn more about the biology of stem cells and the molecular mechanisms that mediate their tumor-tropism and we identify efficacious gene products for specific tumor types, the clinical utility of cell-based delivery strategies becomes increasingly evident.
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PMID:Stem and progenitor cell-mediated tumor selective gene therapy. 1836 24

Current prostate cancer treatment, especially hormone refractory cancer, may create profound iatrogenic outcomes because of the adverse effects of cytotoxic agents. Suicide gene therapy has been investigated for the substitute modality for current chemotherapy because it enables the treatment targeting the cancer cells. However the classic suicide gene therapy has several profound side effects, including immune-compromised due to viral vector. Recently, stem cells have been regarded as a new upgraded cellular vehicle or vector because of its homing effects. Suicide gene therapy using genetically engineered mesenchymal stem cells or neural stem cells has the advantage of being safe, because prodrug administration not only eliminates tumor cells but consequently kills the more resistant therapeutic stem cells as well. The attractiveness of prodrug cancer gene therapy by stem cells targeted to tumors lies in activating the prodrug directly within the tumor mass, thus avoiding systemic toxicity. Therapeutic achievements using stem cells in prostate cancer include the cytosine deaminase/5-fluorocytosine prodrug system, herpes simplex virus thymidine kinase/ganciclovir, carboxyl esterase/CPT11, and interferon-beta. The aim of this study is to review the stem cell therapy in prostate cancer including its proven mechanisms and also limitations.
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PMID:Stem cell based gene therapy in prostate cancer. 2512 Nov 3