Retinoide in der Therapie des metastasierten Nierenzellkarzinoms : Untersuchungen am Modell multizellulärer Tumorsphäroide
The special problem of metastatic renal cell cancer is the extensive resistance against common oncological treatment strategies like radiation and chemotherapy. Through means of cytokine immunotherapy, by which the interactions between the organism and tumor cells are to be modified by the therapeutically administration of intercellular messenger agents, the progression of disease can be positively influenced in some patients with metastatic renal cell cancer. Just like the cytokine therapy, the therapeutic use of retinoids in oncological indications is based on the concept of specific interference with tumor biology. Retinoids possess complex properties in regulation of growth and differentiation of cells. In the present paper the effects of two retinoid isomers tretinoin and isotretinoin on micrometastases of renal cell cancer are examined by using a model of multicellular tumor spheroids. In the therapy schemes introduced here the retinoid treatment is combined with following application of IFN-alfa or 5-FU. Success of therapy was measured by comparing the mean spheroid volume with the untreated control. Tretinoin as well as isotretinoin showed a dose-dependent inhibition of spheroid growth. In the same molar concentrations stronger antiproliferative effects were obtained by tretinoin than by isotretinoin. For combination therapy such concentrations were used, which could be obtained in vivo after therapeutical application of each substance. IFN-alfa monotherapy was not effective in such concentrations whereas by combination of IFN with tretinoin or isotretinoin the antiproliferative effects of the retinoids were improved slightly, referring to a synergistic effect. Using 5-FU antiproliferative effects were achieved at concentrations near to plasma peak concentrations measured in vivo. The present therapy scheme gave no indication of an improved retionid effect by the additional application of 5-FU. To summarize, in the present study and in a number of other in vitro studies and clinical trials the retinoid therapy of metastatic renal cell cancer in combination with IFN-alfa showed only slight antiproliferative effects.
info:eu-repo/classification/ddc/610, Medizin, multizelluläre Tumorsphäroide, Nierenzellkarzinom, Retinoide, Interferon-alfa, 5-Fluorouracil
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