GROWTH OF CULTURED HUMAN GLIOMA TUMOR-CELLS CAN BE REGULATED WITH HISTAMINE AND HISTAMINE-ANTAGONISTS

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 cau se retardation of tumour growth in some animal models and prolonged su rvival in cancer patients. Therefore we have tested the growth modulat ing effects of histamine and histamine antagonists on human glioma cul tures. Twelve freshly excised human gliomas were cultured and tested f or their in vitro sensitivity to histamine and histamine antagonists. Four continuous glioma cell lines were used to confirm the glioma-spec ificity of the effects observed in the primary cell lines. In low seru m concentration (0 or 1%) the growth of 5/9 primary glioma-derived cul tures could be stimulated with 0.2 mm histamine, and in 4/5 cases with 0.2 muM histamine. One mm of the histamine H-2-receptor antagonist ci metidine 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 1 muM) were less effective. The histamin e H-1-receptor antagonist pyrilamine gave variable results. The specif icity of the effects is indicated by the absence of a generalised toxi c effect, by the observation that the antagonist-induced inhibition co uld 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 inh ibition of the in vitro proliferation of gliomas suggests that cimetid ine is a relevant candidate for the in vivo growth inhibition of these tumours.