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)

A human primary lung carcinoma cell line (HPL-R1) established from the tumor biopsy of a lung cancer patient, lacking in cytochrome P1-450 [aryl hydrocarbon (benzo[a]pyrene) hydroxylase (AHH)], was cloned and used to obtain variants deficient in the expression of thymidine-kinase via treatment with 5-bromo-2'-deoxyuridine, and selection for drug resistance phenotype. The variant cell line, precharacterized for thymidine kinase negative phenotype, was transfected with the thymidine kinase gene bearing p R-tk and px1-tk plasmids. Transfections from both the plasmids, demonstrated a frequency of 5.5 X 10(-5). The transfectants showed a 76-100% retention of the transferred phenotype. These data suggest that transfection in variant human cells can approach significant levels of stability observed with rodent cell recipients.
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PMID:Plasmid DNA mediated transfer of the herpes simplex virus thymidine kinase gene to a new bromodeoxyuridine resistant variant of human primary lung carcinoma cells. 283 65

Post-transplant lymphoproliferative disorders (PTLD) are a heterogeneous group of potentially life-threatening complications that occur after solid organ and bone marrow transplantation. Risk factors for acquiring PTLD are type of organ transplanted, age, intensity of immunosuppression, viral infections such as Epstein-Barr virus (EBV) and time after transplantation. Due to a dearth of well designed prospective trials, treatment for PTLD is often empirical, with reduction in immunosuppression accepted as the first step. Rituximab, a monoclonal antibody directed against the CD20 antigen of immature B cells, is often used as monotherapy after reduction in immunosuppression, although this is associated with a high risk of relapse if patients have at least one of the following risk factors: age greater than 60 years, elevated lactate dehydrogenase levels and Eastern Cooperative Oncology Group Score between 2 and 4. For such patients, rituximab should be considered in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone), particularly if high-grade PTLD is present. Although widely prescribed, the use of ganciclovir for PTLD remains controversial as EBV-transformed cells lack the thymidine kinase necessary for ganciclovir activation. Newer antivirals that combine ganciclovir with activators of cellular thymidine kinase have shown promising results in preclinical studies. In the absence of controlled trials, surgery may be indicated for localized disease and radiotherapy for patients with impending spinal cord compression or disease localized to the central nervous system or orbit. Future interventions may include adoptive immunotherapy, intravenous immunoglobulin, mammalian target of rapamycin inhibitors, monoclonal antibodies to interleukin-6 and galectin-1, and even EBV vaccination. Although several trials are in progress, it is necessary to wait for the long-term outcome of these studies on risk of PTLD relapse.
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PMID:Managing post-transplant lymphoproliferative disorders in solid-organ transplant recipients: a review of immunosuppressant regimens. 2286 44