Pharmacology and Pharmacokinetics of Traditional Systemic Antifungal Agents

Barriere, Steven L.

doi:10.1002/j.1875-9114.1990.tb02598.x

Cited by 15 publications

References 49 publications

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Transduction of cytosine deaminase gene makes rat glioma cells highly sensitive to 5-fluorocytosine

Zheng

et al. 1997

Int. J. Cancer

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To investigate the potential use of E. coli cytosine deaminase (CD) gene instead of the commonly used HSV-TK gene in the gene therapy of brain tumors, we constructed a retrovirus vector carrying the CD gene. We then transduced a rat glioma cell line C6 with CD gene by the retrovirus vector. Transduction of the CD gene made C6 cells become highly sensitive to the anti-fungi drug 5-fluorocytosine (5FC). IC 50 for 5FC was 6,000 µM in CD-negative cells, while it was 3 mM in CD -positive cells. Mixed cellular assay showed that CDpositive cells had a strong ''bystander effect'' on CD-negative cells when exposed to 5FC. Significant anti-tumor effects were observed in nude mice bearing s.c. tumors derived from CD-positive cells when these animals were given 250 mg/kg 5FC twice a day for 20 consecutive days. A marked decrease in tumor weight occurred when a mixture containing 50% CD-positive and 50% CD-negative C6 cells was injected s.c., followed by 5FC treatment, suggesting the bystander effect in vivo. Concerning the pharmacokinetics of 5FC, especially its high oral bio-availability and good penetration into cerebrospinal fluid, we suppose that the combination of CD-gene transfer and 5FC oral administration may have potential use in the gene therapy of brain tumors. Int.

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Transduction of cytosine deaminase gene makes rat glioma cells highly sensitive to 5-fluorocytosine

Zheng

et al. 1997

Int. J. Cancer

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Antibiotics in intensive care unit patients

Lalla¹,

Cruciani²

1998

Critical Care Nephrology

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Increased sensitivity of glioma cells to 5-fluorocytosine following photo-chemical internalization enhanced nonviral transfection of the cytosine deaminase suicide gene

et al. 2014

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Despite advances in surgery, chemotherapy and radiotherapy, the outcomes of patients with GBM have not significantly improved. Tumor recurrence in the resection margins occurs in more than 80 % of cases indicating aggressive treatment modalities, such as gene therapy are warranted. We have examined photochemical internalization (PCI) as a method for the non-viral transfection of the cytosine deaminase (CD) suicide gene into glioma cells. The CD gene encodes an enzyme that can convert the nontoxic antifungal agent, 5-fluorocytosine, into the chemotherapeutic drug, 5-fluorouracil. Multicell tumor spheroids derived from established rat and human glioma cell lines were used as in vitro tumor models. Plasmids containing either the CD gene alone or together with the uracil phosphoribosyl transferase (UPRT) gene combined with the gene carrier protamine sulfate were employed in all experiments. PCI was performed with the photosensitizer AlPcS2a and 670 nm laser irradiance. Protamine sulfate/CD DNA polyplexes proved nontoxic but inefficient transfection agents due to endosomal entrapment. In contrast, PCI mediated CD gene transfection resulted in a significant inhibition of spheroid growth in the presence of, but not in the absence of, 5-FC. Repetitive PCI induced transfection was more efficient at low CD plasmid concentration than single treatment. The results clearly indicate that AlPcS2a-mediated PCI can be used to enhance transfection of a tumor suicide gene such as CD, in malignant glioma cells and cells transfected with both the CD and UPRT genes had a pronounced bystander effect.

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Pharmacology and Pharmacokinetics of Traditional Systemic Antifungal Agents

Cited by 15 publications

References 49 publications

Transduction of cytosine deaminase gene makes rat glioma cells highly sensitive to 5-fluorocytosine

Transduction of cytosine deaminase gene makes rat glioma cells highly sensitive to 5-fluorocytosine

Antibiotics in intensive care unit patients

Increased sensitivity of glioma cells to 5-fluorocytosine following photo-chemical internalization enhanced nonviral transfection of the cytosine deaminase suicide gene

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