Summary The 50% survival time for low grade astrocytomas is 50 months and for high grade astrocytomas it is 13 months, underlining the need for new therapies. Several reports show that in vivo histamine antagonists cause retardation of tumour growth in some animal models and prolonged survival in cancer patients. Therefore we have tested the growth modulating effects of histamine and histamine antagonists on human glioma cultures.Twelve freshly excised human gliomas were cultured and tested for their in vitro sensitivity to histamine and histamine antagonists. Four continuous glioma cell lines were used to confirm the glioma-specificity of the effects observed in the primary cell lines. In low serum concentration (0 or 1%) the growth of 5/9 primary glioma-derived cultures could be stimulated with 0.2 mm histamine, and in 4/5 cases with 0.2 tLM histamine. One mm of the histamine H2-receptor antagonist cimetidine could inhibit the growth of 4/5 primary glioma cultures when tested in 1% human AB serum, and of 6/13 cases when tested in 1% FCS. Lower concentrations (down to I fLM) were less effective. The histamine HI-receptor antagonist pyrilamine gave variable results.The specificity of the effects is indicated by the absence of a generalised toxic effect, by the observation that the antagonist-induced inhibition could be reversed with histamine, and by the correlation of the obtained cimetidine-induced growth inhibition with the maximal growth rate of the primary cell lines in 10% FCS.The observed cimetidine-induced inhibition of the in vitro proliferation of gliomas suggests that cimetidine is a relevant candidate for the in vivo growth inhibition of these tumours.
Two malignant fibrous histiocytoma (MFH) cell lines were established: one from a storiform‐pleomorph subtype and the other from a myxoid one (codes, MFH‐3 and MFH‐4). Light microscopic examination revealed large rounded cells, growing mostly separately, in both cell lines. Their ultrastructure was different in various aspects. The MFH‐3 cells showed abundant lysosomal activity, a well‐developed Golgi apparatus, and a few desmosome‐like cell contacts. The MFH‐4 cells had a well‐developed rough endoplasmic reticulum, delicate bundles of tonofilaments, the formation of pseudoacini, and the presence of small completely developed desmosomes. Based on immunostaining and immunoblotting assays of cultured cells, both cell lines expressed immunoreactivity for vimentin; cytokeratins 7, 8, and 18; desmin; and laminin, but they lacked reactivity for cytokeratins 10 and 19, neurofilament, α‐smooth muscle actin, S‐100 protein, collagen type IV, carcinoembryonic antigen, and antigens specific for macrophages. Fibronectin and, to a variable extent, glial fibrillary acid protein and epithelial membrane antigen (EMA) were detectable in MFH‐3 cells only. Furthermore, a 60‐kilodalton band was present in both cell lines which was reactive for cytokeratins 8 and 18. The MFH‐3 cells had the capacity to grow as xenografts with a carcinoma‐like pattern. The cells retained their immunoreactivity for vimentin and cytokeratin 8 and showed the presence of desmosomes. Several of these immunophenotypic features also were noticed in established sarcoma cell lines and in short‐term cultures of fibroblasts, smooth muscle cells, and endothelial cells. However, experimental data on the two MFH cell lines show that the MFH cell line may express some immunophenotypic and ultrastructural features considered to be specific for epithelial cells. The MFH cells may originate from multipotential mesenchymal cells with a capacity to differentiate to fibroblast‐like cells, and less frequently, to epithelial cells, smooth muscle cells, and Schwannian cells. Such a differentiation became evident when these cells were adapted to culture conditions or grew in nude mice.
The expression of insulin‐like growth factor‐1 (IGF‐1) was studied in normal tissues, in eight benign lesions and in 50 sarcomas. In palmar fibromatosis the spindle cells in cell‐dense areas exhibited a strong immunoreactivity. IGF‐1 was variably found in leiomyosarcomas (7/8), malignant schwannomas (7/9), synovial sarcomas (2/3), liposarcomas (3/6), fibrosarcomas (1/3), malignant fibrous histiocytomas (10/18) and in one angiosarcoma. Two rhabdomyosarcomas failed to express IGF‐1 and only the spindle cell component of synovial sarcomas was positive. Immunoreactivity for IGF‐1 in 10 malignant filrous histiocytomas (MFH) appeared to be related to co‐expression of smooth muscle actin. These findings imply that MFHs can be subdivided into a group of tumours which are devoid of morphological and immunophenotypic evidence of differentiation and a group which manifest immunophenotypic differentiation.
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