Growth inhibition of human Tenon's capsule fibroblasts and rabbit dermal fibroblasts with non-carcinogenic N-alkylated anthracyclines
Autor: | Edward P. Chen, Sharon F. Freedman, Diane L. Hatchell, Ulrich H. Steinhorst, Robert Machemer |
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Rok vydání: | 1994 |
Předmět: |
Pathology
medicine.medical_specialty Proliferative vitreoretinopathy Biology Eye Cellular and Molecular Neuroscience chemistry.chemical_compound Dermis Tenon's capsule Fibrosis medicine Animals Humans Fascia Fibroblast Cells Cultured Skin Cell Death Dose-Response Relationship Drug Daunorubicin Infant Intravitreal administration Fibroblasts medicine.disease eye diseases Sensory Systems Ophthalmology medicine.anatomical_structure chemistry Aminosugar Child Preschool Cancer research Rabbits Growth inhibition Cell Division |
Zdroj: | Graefe's Archive for Clinical and Experimental Ophthalmology. 232:347-354 |
ISSN: | 1435-702X 0721-832X |
Popis: | Bleb fibrosis after glaucoma filtering surgery and proliferative vitreoretinopathy after retinal detachment surgery are complications caused by proliferation of fibroblasts or fibroblastlike cells. The anthracycline daunomycin (DNM) has been used for treatment of those proliferative processes in humans. However, complications such as conjunctival necrosis and corneal or scleral ulcerations have been reported after administration of DNM to glaucoma patients. Intravitreal administration of DNM in rabbit eyes resulted in morphological and functional retinal damage. DNM also has the undesired general effect of carcinogenicity. N-Alkylation of the aminosugar moiety of DNM results in reduction or loss of carcinogenicity. We evaluated the inhibitory effect of the new non-carcinogenic N-alkylated analogues aclacinomycin A (ACA), N,N-dimethyladriamycin (AD280), and N-trifluoroacetyladriamycin-14-O-hemiadipate (AD143) on the growth of cultured human Tenon's capsule fibroblasts and rabbit dermal fibroblasts. Using DNM as a positive control, we conducted proliferation assays that demonstrated that ACA and AD280 inhibited fibroblast growth as effectively as DNM. AD143 was less efficacious. The magnitude of cellular growth inhibition was concentration dependent for all drugs tested. Extension of exposure times resulted in increased rates of cell death. Our in vitro studies suggest that further evaluation of ACA and AD280 should be carried out in animal models of ocular proliferative disorders. |
Databáze: | OpenAIRE |
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