scholarly journals Predictor of Liver Biochemistry Improvement in Patients with Cytomegalovirus Cholestasis after Ganciclovir Treatment

2022 ◽  
Vol 25 (1) ◽  
pp. 70
Author(s):  
Gina Puspita ◽  
Titis Widowati ◽  
Agung Triono
1993 ◽  
Vol 79 (5) ◽  
pp. 729-735 ◽  
Author(s):  
David Barba ◽  
Joseph Hardin ◽  
Jasodhara Ray ◽  
Fred H. Gage

✓ Gene therapy has many potential applications in central nervous system (CNS) disorders, including the selective killing of tumor cells in the brain. A rat brain tumor model was used to test the herpes simplex virus (HSV)-thymidine kinase (TK) gene for its ability to selectively kill C6 and 9L tumor cells in the brain following systemic administration of the nucleoside analog ganciclovir. The HSV-TK gene was introduced in vitro into tumor cells (C6-TK and 9L-TK), then these modified tumor cells were evaluated for their sensitivity to cell killing by ganciclovir. In a dose-response assay, both C6-TK and 9L-TK cells were 100 times more sensitive to killing by ganciclovir (median lethal dose: C6-TK, 0.1 µg ganciclovir/ml; C6, 5.0 µg ganciclovir/ml) than unmodified wild-type tumor cells or cultured fibroblasts. In vivo studies confirmed the ability of intraperitoneal ganciclovir administration to kill established brain tumors in rats as quantified by both stereological assessment of brain tumor volumes and studies of animal survival over 90 days. Rats with brain tumors established by intracerebral injection of wild-type or HSV-TK modified tumor cells or by a combination of wild-type and HSV-TK-modified cells were studied with and without ganciclovir treatments. Stereological methods determined that ganciclovir treatment eliminated tumors composed of HSV-TK-modified cells while control tumors grew as expected (p < 0.001). In survival studies, all 10 rats with 9L-TK tumors treated with ganciclovir survived 90 days while all untreated rats died within 25 days. Curiously, tumors composed of combinations of 9L and 9L-TK cells could be eliminated by ganciclovir treatments even when only one-half of the tumor cells carried the HSV-TK gene. While not completely understood, this additional tumor cell killing appears to be both tumor selective and local in nature. It is concluded that HSV-TK gene therapy with ganciclovir treatment does selectively kill tumor cells in the brain and has many potential applications in CNS disorders, including the treatment of cancer.


2001 ◽  
Vol 2 (3) ◽  
pp. 271-273 ◽  
Author(s):  
Natalie Dehtiar ◽  
Matityahu Eherlichman ◽  
Elie Picard ◽  
David Kleid ◽  
Joram Glaser ◽  
...  

1999 ◽  
Vol 3 (6) ◽  
pp. A75
Author(s):  
D. Dunin-Wasowicz ◽  
B. Milewska-Bobula ◽  
M. Idzik ◽  
A. Szmytkowska ◽  
K. Kozlowski ◽  
...  

1993 ◽  
Vol 167 (2) ◽  
pp. 278-282 ◽  
Author(s):  
Douglas T. Dieterich ◽  
Donald P. Kotler ◽  
David F. Busch ◽  
Clyde Crumpacker ◽  
Charles Du Mond ◽  
...  

Blood ◽  
1997 ◽  
Vol 89 (12) ◽  
pp. 4636-4645 ◽  
Author(s):  
José L. Cohen ◽  
Olivier Boyer ◽  
Benoı̂t Salomon ◽  
Rosine Onclercq ◽  
Frédéric Charlotte ◽  
...  

Abstract Alloreactive T cells present in a bone marrow transplant are responsible for graft-versus-host disease (GVHD), but their depletion is associated with impaired engraftment, immunosuppression, and loss of the graft-versus-leukemia effect. We developed a therapeutic strategy against GVHD based on the selective destruction of these alloreactive T cells, while preserving a competent T-cell pool of donor origin. We generated transgenic mice expressing in their T lymphocytes the Herpes simplex type 1 thymidine kinase (TK) suicide gene that allows the destruction of dividing T cells by a ganciclovir treatment. T cells expressing the TK transgene were used to generate GVHD in irradiated bone marrow grafted mice. We show that a short 7-day ganciclovir treatment, initiated at the time of bone marrow transplantation, efficiently prevented GVHD in mice receiving TK-expressing T cells. These mice were healthy and had a normal survival. They maintained a T-cell pool of donor origin that responded normally to in vitro stimulation with mitogens or third party alloantigens, but were tolerant to recipient alloantigens. Our experimental system provides the proof of concept for a therapeutic strategy of GVHD prevention using genetically engineered T cells.


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