Melphalan uptake, hyperthermic synergism and drug resistance in a human cell culture model for the isolated limb perfusion of melanoma.
Melanoma Res
; 4(6): 365-70, 1994 Dec.
Article
en En
| MEDLINE
| ID: mdl-7703715
Isolated limb perfusion with melphalan is a long-standing treatment for melanoma but the clinical conditions have not been subjected to a systematic evaluation. In order to establish optimal conditions for perfusion, three human melanoma cell lines were cultured with melphalan in vitro under conditions comparable to in vivo therapy. The most important findings were that: (a) 41.5 degrees C was synergistic for melphalan killing of three human melanoma cell lines; (b) prolonging the treatment time beyond 1 h had little additional toxicity; and (c) varying the initial pH of the culture medium had no effect. After 1 h of treatment, cells accumulated more melphalan at 41.5 degrees C than at 37 degrees C, relative to the extracellular concentration. A cell line (MM418) derived from a primary tumour was the most resistant of the three lines; pigmented or non-pigmented sublines were equally resistant. The A2058 line showed the lowest level of synergism with hyperthermia, and displayed a marked plateau at 10% of controls in the dose-response for survival, yet no melphalan-resistant subpopulation could be isolated. The implications of this work are that (a) enhanced cellular uptake of melphalan may account for hyperthermic synergism of melphalan; (b) varying conditions other than treatment time will be necessary to deal with the variation in resistance between tumours; and (c) repeated cycles of treatment may be needed for phenotypes such as A2058 where melphalan resistance appears to be based on an epigenetic mechanism.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Cutáneas
/
Quimioterapia del Cáncer por Perfusión Regional
/
Hipertermia Inducida
/
Melanoma
/
Melfalán
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Melanoma Res
Asunto de la revista:
NEOPLASIAS
Año:
1994
Tipo del documento:
Article
País de afiliación:
Australia
Pais de publicación:
Reino Unido