Keiko Matsunaga

Augmentation of in vitro cytotoxicity and in vivo tumor-inhibition by combined use of lymphotoxin-containing supernatants and antitumor drugs

The cytotoxicity of combined antitumor drugs and lymphotoxin (LT)-containing supernatants was studied on target cells. Marked reduction of L cells was observed after combined use of LT-containing supernatants with actinomycin D, adriamycin or aclacinomycin A but not with mitomycin C or vincristine sulphate. Similar effects were observed in Sarcoma 180 cells and Ehrlich ascites tumor cells in vitro. The survival of mice injected i.p. with Ehrlich ascites tumor cells was prolonged by the combined use of LT-containing supernatants and actinomycin D (0.1 or 0.3 microgram/mouse). The mechanisms of the synergistic effect are discussed in regard to the mode of action of antitumor drugs.

Enhancement of radiosensitizing effect of the nitroimidazole derivative RK28 on the proliferation of MethA tumor cells in combined use with diethyldithiocarbamate.

The radiosensitizing effect of the nitroimidazole derivative RK28 and diethyldithiocarbamate (DDC), which is an inhibitor of superoxide dismutase activity, was examined in vitro by using Meth A tumor cells. The radiosensitizing effect of 0.5 mM RK28 was observed in both of 10 Gy and 15 Gy irradiated groups. The addition of 5 x 10(-7) M DDC also enhanced the radiation-induced proliferation inhibition. Marked enhancement of the antiproliferative effect was observed in combined use of 0.2 mM or 0.5 mM RK28 with 2 x 10(-7) M or 5 x 10(-7) M DDC. These results suggest that enhanced oxygen effect could be expected through combined use of the ionizing irradiation with both of these agents.

Lymphotoxin production by regional lymph node lymphocytes in patients with uterine cervical cancer

The cytotoxin production by regional lymph node cells was examined in 25 patients with uterine cervical cancer and 10 patients with uterine myoma. The patients in stage I had significantly increased spontaneous release of cytotoxins compared with that in stages II, III, and IV. The spontaneous release in stages III and IV was markedly reduced. There was no difference in the release of cytotoxins from peripheral blood lymphocytes between cancer patients and patients with myoma or healthy controls. The cytotoxin production by lymph node cells was increased in stage III by stimulating with formalin-fixed QG-K cells derived from uterine cervical cancer, but not in stages I and II. Almost all of the cytotoxic activity of cytotoxin was abrogated by antilymphotoxin antibody. However, the cytotoxin activity was partially inhibited by anti-tumor necrosis factor antibody. These results suggest that cytotoxins released from the regional lymph node cells of uterine cancer patients are derived from, most of all, lymphotoxin.

Augmentation of antitumor activities in hamster macrophages by yeast cell walls treated with lymphokines in vitro

The effect of the treatment of yeast cell walls (YCW) with PPD-induced lymphokines (LK) was studied. The rate of macrophage spreading increased 1 h and 24 h after incubation with YCW treated with 16-fold or 64-fold diluted LK. Phagocytosis was slightly enhanced after 1 h incubation. Cytostatic activity was obtained when incubated with YCW treated with 16-fold or 64-fold diluted LK, but not with LK of higher or lower dilution. Tumor-inhibitory effect was observed when lymphoma cells were mixed with LK-treated YCW and inoculated s.c.