Oncology
Kase et al.' investigated the modulating effect of folinic acid (leucovorin) on the antitumour action of 5-fluorouracil (5-FU) against C-1 human colonic carcinoma cells in oitro and c o -4 human colonic cancer xenografts in nude mice. The modulating effect of folinic acid on 5-FU was optimal at a concentration of 40-80pg/ml in vitro as determined by a colorimetric 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay. An optimal dose of 200 mg/kg was observed in the nude mouse system. The modulating effect of folinic acid increased according to the extent of thymidylate synthetase inhibition in uiuo. Since the pharmacodynamics of folinic acid in nude mice given the drug at 200 mg/kg were similar to those in patients treated at a dose of 100mg/m2, this method of administration was thought to be adequate for modulating the antitumour activity of 5-FU in clinical practice.
Oka et a/.' studied the natural killer ( N K ) activity of peripheral blood mononuclear cells and serum immunosuppressive acidic protein (IAP) levels in patients with oesophageal or gastric cancer before and after surgery. Patients with stage IV oesophageal or gastric cancer had significantly lower NK cell activity (mean(s.d.) 3 9 3 14.8) and 37.0( 11.6) per cent respectively) and higher serum IAP levels (mean( s.d.) 778( 264) and 633( 156) pg/ml respectively) than corresponding controls (50.0( 5.6) per cent and 375(26) pg/ml). Patients with oesophageal or gastric cancer who underwent curative resection had high NK cell activity (mean(s.d.) 54.8(11.6) and 54.8(8.0) per cent respectively) and low IAP levels (mean(s.d.) 471( 116) and 490(42) pg/ml) compared with those undergoing palliative resection, and this effect was seen 1 month after surgery. Mononuclear cells in the regional lymph nodes and tumour specimens showed significantly lower N K cell activity than those in the peripheral blood and spleen. Thus, N K cell activity and IAP level reflected the immunocompetence, clinical course and surgical curability of these patients. NK cells appeared not to have significant antitumour activity in the regional lymph nodes or in the tumour itself, although they were still active in the peripheral blood.
Toge et aL3 investigated the role of lymphocyte surface binding sites for wheat germ agglutinin (WGA) in the negative regulation of disease in patients with malignancy. The number of WGA binding sites on the surface of each lymphocyte ranged from 10' to lo8. Fluorescein isothiocyanate-conjugated WGA bound to the majority of peripheral blood lymphocytes with two peaks of fluorescent intensity (dim and bright). The increase in the proportion of lymphocytes with bright fluorescence ('WGA-bright' lymphocytes) correlated significantly with the number of WGA binding sites. The suppression of lymphocyte proliferation mediated by purified soluble suppressor factor correlated significantly with an increase in the size of the OtW7-1323/93/121517-02