PURPOSE To determine whether trifluorothymidine (TFT) and ganciclovir (GCV) are synergistic against herpes simplex virus type 1 (HSV-1). METHODS TFT and GCV activity against 12 strains of HSV-1 (including an acyclovir-resistant strain) was measured by plaque-forming unit (PFU) inhibition. Cellular toxicity was assessed with an MTT dye reduction assay. Synergism was determined by calculating f...

The efficacy of suicide herpes simplex virus-1 thymidine kinase (HSVtk)/ganciclovir (GCV) gene therapy is often limited by intrinsic resistance of tumor cells. Here we show that repair of GCV incorporated in DNA is a factor involved in GCV resistance. A protective role of DNA repair in GCV-induced cell killing is supported by the following findings: (a) GCV-exposed Chinese hamster ovary-HSVtk c...

Ganciclovir (GCV) is an essential part of the Herpes simplex virus thymidine kinase (HSV-tk) gene therapy of malignant gliomas. The purpose of this study was to investigate the brain pharmacokinetics and tumor uptake of GCV in the BT4C rat gliomamodel. GCV’s brain and tumor uptakes were investigated by in vivo microdialysis in rats with orthotopic BT4C glioma. In addition, the ability of GCV to...

BACKGROUND Poisson regression modeling has been widely used to estimate influenza-associated disease burden, as it has the advantage of adjusting for multiple seasonal confounders. However, few studies have discussed how to judge the adequacy of confounding adjustment. This study aims to compare the performance of commonly adopted model selection criteria in terms of providing a reliable and va...

Ganciclovir (GCV) is the first therapeutic choice for prevention and treatment of active cytomegalovirus (CMV) infection in solid organ transplant recipients in Bahia state, Brazil. Prolonged and repeated GCV therapy may result in drug-resistant virus, associated with progressive and disseminated disease. We present a case report of a young male kidney recipient, who was CMV-seronegative with a...

We have previously demonstrated (L. Z. Rubsam et al., Cancer Res., 59: 669-675, 1999) that low ganciclovir (GCV) triphosphate (TP) levels similar to cellular deoxynucleotide concentrations can induce multilog killing in cells stably expressing herpes simplex virus thymidine kinase (HSV-TK). In this study, we evaluated whether reducing the endogenous competitor of GCV-TP, dGTP, enhanced GCV-medi...

Transfer of the herpes simplex thymidine kinase (HSV-TK) gene into tumor cells confers sensitivity to the cells to the viral drug ganciclovir (GCV). Although the efficacy of the HSV-TK/GCV approach is well studied, the mechanisms for the resistance of HSV-TK-transduced tumor cells to GCV are poorly understood. Here, we examined the mechanisms for GCV resistance in HSV-TK-transduced gastrointest...

[1] Estimating CO2 fluxes from the pattern of atmospheric CO2 concentrations with atmospheric transport models is an ill-posed inverse problem, whose solution is stabilized using prior information. Weights assigned to prior information and to CO2 concentrations at different locations are quantified by parameters that are not well known, and differences in the choice of these parameters contribu...

Ganciclovir (GCV) is a nucleoside analogue with antiviral activity against herpes viral infections, and the most widely used antiviral to treat cytomegalovirus infections. However, the low bioavailability and short half-life of GCV necessitate the development of a carrier for sustained delivery. In this study, guanosine-based GCV was used as the initiator directly in ring-opening polymerization...

New treatment strategies are required for renal cell carcinoma (RCC) due to its relative insensitivity to conventional radio- and chemotherapies. The promising strategy of tumor inhibition using human telomerase reverse transcriptase (hTERT)-controlled herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) in the hTERT promoter-driven HSV-TK/GCV suicide gene system was investigated. Tum...