• To investigate the in vitro effects of suicide gene therapy system of herpes simplex virus thymidine kinase gene (HSV-TK) in combination with the treatment of nucleotide analog-ganciclovir (GCV) on human pancreatic cancer, and to provide a novel clinical therapeutic method for human pancreatic cancer. (wjgnet.com)
  • The potential for treatment of liver tumors was analyzed using L nanoparticles containing the herpes simplex virus thymidine kinase gene, in conjunction with ganciclovir pro-drug administration. (elsevierpure.com)
  • FOSCAVIR does not require activation (phosphorylation) by thymidine kinase or other kinases and therefore is active in vitro against HSV TK deficient mutants and CMV UL97 mutants. (nih.gov)
  • Phosphorylation of human choline kinase beta by protein kinase A: Its impact on activity and inhibition. (mpg.de)
  • This allows for greater concentration of ganciclovir in virus-infected cells, possibly because of preferential phosphorylation of this agent in infected cells. (medscape.com)
  • Ganciclovir The pharmacokinetics of foscarnet and ganciclovir were not altered in 13 patients receiving either concomitant therapy or daily alternating therapy for maintenance of CMV disease. (druglib.com)
  • Evidence is presented for PI3P-dependent signalling in which transgenic expression of an additional kinase confers resistance. (nature.com)
  • In this model, the senescence-sensitive promoter from the cyclin-dependent kinase inhibitor 2A ( Cdkn2a ) gene, also known as p16 INK4a , drives expression of 3MR, a fusion protein that is composed of luciferase and red fluorescent protein (RFP) reporters and herpes simplex virus-1 thymidine kinase, which converts ganciclovir (GCV) into an apoptosis inducer. (jax.org)
  • It phosphorylates first to monophosphate form by a viral-encoded protein kinase homologue, and then to diphosphate and triphosphate forms by cellular kinases. (medscape.com)
  • However, acyclovir or ganciclovir resistant mutants with alterations in the viral DNA polymerase may be resistant to FOSCAVIR and may not respond to therapy with FOSCAVIR. (nih.gov)
  • Ganciclovir is thought to inhibit HSV replication by competitive inhibition of viral DNA polymerases and by incorporating itself into viral DNA, causing termination of viral DNA elongation. (medscape.com)
  • The Herpes Simplex Virus thymidine kinase/ganciclovir (HSV-TK + GCV) system is currently one of the best-studied tumor suicide gene therapy systems [ 9 - 11 ]. (biomedcentral.com)
  • In clinical trials, a herpes simplex gene encoding the enzyme thymidine kinase (TK) is delivered, via a retrovirus vector, to dividing brain cancer (glioma) cells. (the-scientist.com)
  • Although the combination of herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) with ganciclovir (GCV) has been shown as a promising suicide gene treatment strategy for glioma, the almost immunodepressive dose of GCV required for its adequate in vivo efficacy has hampered its further clinical application. (hindawi.com)
  • Herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) in combination with ganciclovir (GCV) has been shown as one of the most promising suicide gene systems for tumor treatment in laboratory studies and is currently being tested in several clinical trials. (hindawi.com)
  • A colorectal cancer model was used to decipher the molecular mechanism of BF-rTK + GCV (bifidobacterial recombination thymidine kinase/ganciclovir) using a human apoptosis antibody array kit in a murine cancer model in vivo . (biomedcentral.com)
  • Here we provide biochemical and cellular evidence that artemisinins are potent inhibitors of Plasmodium falciparum phosphatidylinositol-3-kinase (PfPI3K), revealing an unexpected mechanism of action. (nature.com)
  • The patient's myalgia and weakness worsened, his serum creatine kinase level increased ( Appendix Figure 1), and watery diarrhea developed. (cdc.gov)
  • Bifidobacterium (BF) or BF-rTK was injected intratumorally with or without ganciclovir in a human colo320 intestinal xenograft tumor model. (biomedcentral.com)
  • Human herpesvirus 8 open reading frame 21 is a thymidine and thymidylate kinase of narrow substrate specificity that efficiently phosphorylates zidovudine but not ganciclovir. (umassmed.edu)
  • Solution structure and functional investigation of human guanylate kinase reveals allosteric networking and a crucial role for the enzyme in cancer. (mpg.de)
  • 1 H, 13 C and 15 N resonance assignment of human guanylate kinase. (mpg.de)
  • Insights into open/closed conformations of the catalytically active human guanylate kinase as investigated by small-angle X-ray scattering. (mpg.de)
  • Given the lack of effective treatments, we constructed a bifidobacterial recombinant thymidine kinase (BF-rTK) -ganciclovir (GCV) targeting system (BKV) to meet this requirement and to explore antitumor mechanisms. (biomedcentral.com)
  • A designed equine herpes thymidine kinase (EHV4 TK) variant improves ganciclovir-induced cell-killing. (mpg.de)
  • Polyubiquitination of PfPI3K and its binding to PfKelch13 were reduced by the PfKelch13 mutation, which limited proteolysis of PfPI3K and thus increased levels of the kinase, as well as its lipid product phosphatidylinositol-3-phosphate (PI3P). (nature.com)
  • The infected cells produce TK, which kills them when the patient takes the anti-herpes drug ganciclovir. (the-scientist.com)
  • Although immunosuppressant drugs were tapered dramatically, and broad-spectrum antimicrobial drugs and ganciclovir were added, the patient remained febrile ( Figure 1 ). (cdc.gov)
  • Herpes simplex virus thymidine kinase (HSV-tk) converts ganciclovir (GCV) into an active compound, which can be incorporated into DNA molecules and terminate DNA synthesis. (nih.gov)
  • Herpes simplex virus thymidine kinase and ganciclovir suicide gene therapy for human pancreatic cancer. (wjgnet.com)
  • 1. Synergy between the herpes simplex virus tk/ganciclovir prodrug suicide system and the topoisomerase I inhibitor topotecan. (nih.gov)
  • 2. Enzyme prodrug gene therapy: synergistic use of the herpes simplex virus-cellular thymidine kinase/ganciclovir system and thymidylate synthase inhibitors for the treatment of colon cancer. (nih.gov)
  • 3. Therapy of colon cancer with oncolytic adenovirus is enhanced by the addition of herpes simplex virus-thymidine kinase. (nih.gov)
  • 4. Retrovirus-mediated herpes simplex virus thymidine kinase gene transduction renders human thyroid carcinoma cell lines sensitive to ganciclovir and radiation in vitro and in vivo. (nih.gov)
  • 8. Adenovirus-mediated gene transfer of enhanced Herpes simplex virus thymidine kinase mutants improves prodrug-mediated tumor cell killing. (nih.gov)
  • 9. Temozolomide enhances herpes simplex virus thymidine kinase/ganciclovir therapy of malignant glioma. (nih.gov)
  • 12. Treatment of malignant gliomas with a replicating adenoviral vector expressing herpes simplex virus-thymidine kinase. (nih.gov)
  • 14. Intravenous RMP-7 increases delivery of ganciclovir into rat brain tumors and enhances the effects of herpes simplex virus thymidine kinase gene therapy. (nih.gov)
  • 16. [Bystander effect mediated by herpes simplex virus-thymidine kinase/ganciclovir approach on prostatic cancer cells and its regulation]. (nih.gov)
  • 17. (E)-5-(2-bromovinyl)-2'-deoxyuridine potentiates ganciclovir-mediated cytotoxicity on herpes simplex virus-thymidine kinase--expressing cells. (nih.gov)
  • 18. Enhanced anti-tumor effects of herpes simplex virus thymidine kinase/ganciclovir system by codelivering monocyte chemoattractant protein-1 in hepatocellular carcinoma. (nih.gov)
  • 19. [Recombinant adenovirus vector-mediated herpes simplex virus thymidine kinase gene transfer followed by ganiciclovir administration effectively inhibits growth of human small-cell lung cancer in a murine xenotransplant model]. (nih.gov)
  • Background: To explore a new combination of thermal treatment and gene therapy for hepatoma, a heat-inducible herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) gene therapy system was developed in which thermal energy generated by Mn0.5Zn0.5Fe2O4 nanoparticles (MZF-NPs) under an alternating magnetic field was used to activate gene expression. (mendeley.com)
  • To investigate contributions made by CE and CGRP-expressing cells to epithelial renewal, CE cells were ablated through acute administration of ganciclovir to transgenic mice expressing herpes simplex virus thymidine kinase under the regulatory control of the mouse CCSP promoter. (nih.gov)
  • For example, emergence of thymidine kinase deficient mutants of herpes simplex virus in immunocompromised patients renders the three acyclic nucleosides for herpes simplex infections ineffective for the treatment of these infected patients. (nih.gov)
  • One of the more well-known reporter genes is herpes simplex virus type 1 thymidine kinase (HSV1-tk). (diagnosticimaging.com)
  • To study the infection of herpes simplex virus, Conti and others in the field attached a radioactive tracer to drugs such as ganciclovir, which was commonly used to treat viral infection. (diagnosticimaging.com)
  • Mesnil M, Yamasaki H. Bystander effect in herpes simplex virus-thymidine kinase/ganciclovir cancer gene therapy : role of gap-junctional intercellular communication. (medecinesciences.org)
  • ZIRGAN contains the active ingredient, ganciclovir, which is a guanosine derivative that, upon phosphorylation, inhibits DNA replication by herpes simplex viruses (HSV). (mdtodate.com)
  • Reference: Co-expression of herpes simplex virus thymidine kinase and Escherichia coli nitroreductase by an hTERT-driven adenovirus vector in breast cancer cells results in additive anti-tumor effects. (neb.com)
  • Previous studies suggested that combining herpes simplex virus thymidine kinase (HSV-TK) and ganciclovir (GCV) with Escherichia coli nitroreductase (Coli.NTR) and 5-(azaridin-1-yl)-2, 4-dinitrobenzamide (CB1954) by a recombinant retrovirus delivery system resulted in a co-operative killing effect in vitro. (neb.com)
  • LIVTENCITY may antagonize the antiviral activity of ganciclovir and valganciclovir. (nih.gov)
  • Thus,HCMVUL97 kinase is involved in the antiviral action of these MCPNs, but the in vitro selection of UL97-defective viruses suggests that their activity against more typical ganciclovir-resistant growth-competent UL97 mutants may be relatively preserved. (elsevierpure.com)
  • ZIRGAN (ganciclovir ophthalmic gel) 0.15% contains a sterile, topical antiviral for ophthalmic use. (mdtodate.com)
  • Ganciclovir is transformed by viral and cellular thymidine kinases (TK) to ganciclovir triphosphate, which works as an antiviral agent by inhibiting the synthesis of viral DNA in 2 ways: competitive inhibition of viral DNA-polymerase and direct incorporation into viral primer strand DNA, resulting in DNA chain termination and prevention of replication. (mdtodate.com)
  • Maribavir is an antiviral that elicits its activity by competitive inhibition of the protein kinase activity of human cytomegalovirus (CMV) enzyme pUL97, which inhibits protein phosphorylation. (medscape.com)
  • Some maribavir pUL97 resistance-associated substitutions confer cross-resistance to ganciclovir and valganciclovir. (nih.gov)
  • When transferred to baseline laboratoryHCMVstrains, these mutations individually conferred resistance to all of the tested MCPNs, ganciclovir, and maribavir. (elsevierpure.com)
  • Use of Maribavir in conjunction with medicine valganciclovir or ganciclovir is not recommended. (indianpharmanetwork.in)
  • Livtencity is a Cytomegalovirus pUL97 kinase inhibitor approved for both adults and pediatric patients (aged 12 years and older and weighing at least 35 kg) to treat post-transplant CMV infection/disease, refractory to treatment (with or without genotypic resistance) with drugs valganciclovir, ganciclovir, cidofovir or foscarnet. (indianpharmanetwork.in)
  • The pharmacokinetics of valganciclovir and ganciclovir after administration of valganciclovir tablets have been evaluated in HIV- and CMV-seropositive patients, patients with AIDS and CMV retinitis, and in solid organ transplant patients. (druglib.com)
  • Connexin 43 reverses the phenotype of transformed cells and alters their expression of cyclin/cyclin-dependent kinases. (medecinesciences.org)
  • Mutations in the gene that encode this kinase are associated with X-LINKED AGAMMAGLOBULINEMIA. (nih.gov)
  • 10. Long-circulating liposome-encapsulated ganciclovir enhances the efficacy of HSV-TK suicide gene therapy. (nih.gov)
  • 15. Enzyme/prodrug gene therapy: comparison of cytosine deaminase/5-fluorocytosine versus thymidine kinase/ganciclovir enzyme/prodrug systems in a human colorectal carcinoma cell line. (nih.gov)
  • But when gene therapy hit the presses, it was immediately obvious that a radioactively labeled version of ganciclovir could also be used as a reporter probe. (diagnosticimaging.com)
  • Preliminary data previously presented suggests that PDA cells can be selectively targeted and killed using the rat insulin promoter (RIP) driving the suicide gene thymidine kinase (tk) in vitro , and that the presence of the transcription factor PDX-1 in these PDA cells is vital for insulin promoter activation. (ssat.com)
  • 13. Human amniotic fluid-derived stem cells expressing cytosine deaminase and thymidine kinase inhibits the growth of breast cancer cells in cellular and xenograft mouse models. (nih.gov)
  • to Rho GTPases represents a significant mechanism where EphA kinase activation inhibits HGF-induced MDCK branching morphogenesis. (researchhunt.com)
  • Cells that express HSV-TK undergo programmed death when exposed to a molecule called ganciclovir. (nih.gov)
  • BX795 is known to block a molecule called TANK-binding kinase 1 (TBK1), which cells produce to protect themselves after an infection. (nih.gov)
  • Although a number of different enzyme/prodrug systems have been utilized in relevant studies, HSV-thymidine kinase (HSV-tk)/ deoxyguanosine analog ganciclovir (GCV) has been the most commonly tested in animal and in vitro models. (sanguinebio.com)
  • Eph kinases and their ephrin ligands are widely expressed in epithelial cells in vitro and in vivo. (researchhunt.com)
  • Subsequently, the monophosphate form is further phosphorylated into the active triphosphate form, aciclo-GTP, by cellular kinases . (wikidoc.org)
  • Once translated, HSV1-tk specifically phosphorylates thymidine analogs, such as the drugs ganciclovir and penciclovir, and traps them in the cell. (diagnosticimaging.com)
  • When tested against a kinase-inactive UL97 K355M virus, a moderate 5- to 7-fold increase in 50% effective concentration (EC 50 ) was observed, in comparison to a 13- to 25-fold increase for either cyclopropavir or ganciclovir. (elsevierpure.com)
  • The combination of these elements permits stopping neurogenesis at any time point in development by selectively providing ganciclovir to mice or rats expressing HSV-TK in neuronal precursor cells. (nih.gov)
  • Ganciclovir is a synthetic guanine derivative active against CMV. (druglib.com)
  • Monitor renal function during therapy with Ganciclovir for Injection, particularly in elderly patients and in patients taking other nephrotoxic drugs, and reduce dosage in patients with renal impairment. (nih.gov)
  • Because the major elimination pathway for ganciclovir is renal, dosage reductions according to creatinine clearance are required for Valcyte tablets and Valcyte for oral solution [see Dosage and Administration ] . (druglib.com)
  • The role of theHCMVUL97 kinase in the mechanism of action of these derivatives was examined. (elsevierpure.com)
  • These highlights do not include all the information needed to use GANCICLOVIR FOR INJECTION safely and effectively. (nih.gov)
  • See full prescribing information for GANCICLOVIR FOR INJECTION. (nih.gov)
  • Hematologic Toxicity: Granulocytopenia, anemia, thrombocytopenia, and pancytopenia have been reported in patients treated with Ganciclovir for Injection. (nih.gov)
  • Impairment of Fertility: Based on animal data and limited human data, Ganciclovir for Injection may cause temporary or permanent inhibition of spermatogenesis in males and suppression of fertility in females. (nih.gov)
  • Fetal Toxicity: Based on animal data, Ganciclovir for Injection has the potential to cause birth defects in humans. (nih.gov)
  • Mutagenesis and Carcinogenesis: Based on animal data, Ganciclovir for Injection has the potential to cause cancer in humans. (nih.gov)
  • Ganciclovir for Injection is administered only intravenously. (nih.gov)
  • For injection: 500 mg of ganciclovir as lyophilized powder in a single-dose vial for reconstitution. (nih.gov)
  • Renal Impairment: Increased serum creatinine levels have been observed with the use of Ganciclovir for Injection, particularly in elderly patients and transplant recipients receiving concomitant nephrotoxic drugs. (nih.gov)
  • Mycophenolate mofetil (MMF): When coadministered with ganciclovir, the risk of hematological and renal toxicity may be increased. (nih.gov)
  • However, the engineered strains also demonstrated severe growth defects and abnormal cytopathic effects similar to the kinase-inactive mutant. (elsevierpure.com)
  • For this reason, it is often used in the second-line setting to treat strains of HSV and CMV that have mutated their viral kinases. (pixorize.com)
  • Other drugs associated with myelosuppression or nephrotoxicity: Due to potential for increased toxicity, such drugs should be considered for concomitant use with ganciclovir only if the potential benefits are judged to outweigh the risks. (nih.gov)
  • Cyclosporine or amphotericin B: When coadministered with ganciclovir, the risk of nephrotoxicity may be increased. (nih.gov)
  • Imipenem-cilastatin: Seizures were reported in patients receiving ganciclovir and imipenem-cilastatin. (nih.gov)
  • Although immunosuppressant drugs were tapered dramatically, and broad-spectrum antimicrobial drugs and ganciclovir were added, the patient remained febrile ( Figure 1 ). (cdc.gov)