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)

Molecular imaging is broadly defined as the characterization and measurement of biological processes in living animals, model systems, and humans at the cellular and molecular level using remote imaging detectors. One underlying premise of molecular imaging is that this emerging field is not defined by the imaging technologies that underpin acquisition of the final image per se, but rather is driven by the underlying biological questions. In practice, the choice of imaging modality and probe is usually reduced to choosing between high spatial resolution and high sensitivity to address a given biological system. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) inherently use image-enhancing agents (radiopharmaceuticals) that are synthesized at sufficiently high specific activity to enable use of tracer concentrations of the compound (picomolar to nanomolar) for detecting molecular signals while providing the desired levels of image contrast. The tracer technologies strategically provide high sensitivity for imaging small-capacity molecular systems in vivo (receptors, enzymes, transporters) at a cost of lower spatial resolution than other technologies. We review several significant PET and SPECT advances in imaging receptors (somatostatin receptor subtypes, neurotensin receptor subtypes, alpha(v)beta(3) integrin), enzymes (hexokinase, thymidine kinase), transporters (MDR1 P-glycoprotein, sodium-iodide symporter), and permeation peptides (human immunodeficiency virus type 1 (HIV-1) Tat conjugates), as well as innovative reporter gene constructs (herpes simplex virus 1 thymidine kinase, somatostatin receptor subtype 2, cytosine deaminase) for imaging gene promoter activation and repression, signal transduction pathways, and protein-protein interactions in vivo.
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PMID:Molecular imaging of gene expression and protein function in vivo with PET and SPECT. 1235 50

Despite multimodality treatment for thyroid cancer, including surgical resection, radioiodine therapy, thyrotropin (TSH)-suppressive thyroxine treatment, and chemotherapy/radiotherapy, survival rates have not improved over the last decades. Therefore, development and evaluation of novel treatment strategies, including gene therapy, are urgently needed. A variety of gene therapy approaches have been evaluated for the treatment of follicular cell-derived and medullary thyroid cancer, including corrective gene therapy (p53 restoration, expression of a dominant negative RET mutant), cytoreductive gene therapy (suicide gene/prodrug strategy herpes simplex virus-thymidine kinase [HSV-tk]/ganciclovir, antiangiogenic therapy with endostatin) and immunomodulatory gene therapy (expression of interleukin (IL)-2 and IL-12). Furthermore, cloning of the sodium iodide symporter (NIS) gene has paved the way for the development of a novel cytoreductive gene therapy strategy based on NIS gene transfer followed by the application of radioiodine therapy ((131)I). NIS gene delivery into medullary and follicular cell-derived thyroid cancer cells has been shown to be capable of establishing or restoring radioiodine accumulation and might therefore represent an effective therapy for medullary and dedifferentiated thyroid tumors that lack iodide accumulating activity. The data summarized in this review article clearly demonstrate that the currently available strategies represent potentially curative novel therapeutic approaches for future gene therapy of thyroid cancer. The combination of different therapeutic genes has been demonstrated to be very useful to enhance therapeutic efficacy and seems to have a promising role at least as part of a multimodality approach for advanced thyroid cancer.
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PMID:Gene therapy for thyroid cancer: current status and future prospects. 1524 69

The sodium iodine symporter (NIS) or mutant Herpes-simplex virus type1 sr39 thymidine kinase (HSV1-sr39tk) gene is used for in vivo imaging and cancer therapy. Transfection of both NIS and HSV1-sr39tk genes to hepatocellular carcinoma cells (Huh-7/NTG) could enhance intracellular accumulation of therapeutic radionuclides and guanosine nucleoside analogue prodrugs to produce better outcomes than single gene therapy. Non-invasive imaging with I-124, F-18 FHBG and combination therapy with I-131 and GCV were performed in hepatocellular carcinoma cells transfected with NIS, HSV1-sr39tk and GFP. Our results show that: (1) all three genes are stably expressed in Huh-7/NTG cells, (2) I-125 and H3-PCV uptake were markedly increased in the Huh-7/NTG cells in vitro, (3) cellular survival and tumor growth of Huh-7/NTG was inhibited by I-131 or GCV both in vitro and in vivo, and was much prominent with combination therapy, (4) in vivo imaging with I-124 and F-18 FHBG revealed increased uptake in the Huh-7/NTG tumor. Our results demonstrated the potential of combination gene therapy using NIS and HSV1-sr39tk followed by radioiodine treatment and chemotherapy in human hepatocellular carcinoma cells.
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PMID:Combined radionuclide-chemotherapy and in vivo imaging of hepatocellular carcinoma cells after transfection of a triple-gene construct, NIS, HSV1-sr39tk, and EGFP. 1981 65