Effects of adriamycin and cyclophosphamide treatment on induction of macrophage cytotoxic function in mice.

The effects of i.p. and s.c. Adriamycin and cyclophosphamide treatment of BALB/c x DBA/2F1 mice were studied alone and in combination with immunotherapeutic agents, pyran copolymer and Bacillus Calmette-Guérin, on macrophage cytotoxic ability, As assessed by direct viable cell counts of MBL-2 leukemia cells, both Adriamycin and cyclophosphamide produced growth-inhibitory macrophages. This function after s.c. cytostatic treatment peaked at Day 1 and decreased progressively, attaining normal control values by Day 6. When adjuvants, such as pyran and B. Calmette-Guérin, were administered i.p. simultaneously with s.c. Adriamycin or cyclophosphamide, adjuvant-induced cytotoxic function was not markedly affected. A better knowledge of the influence of cytostatic agents alone or combined with immunoadjuvants on macrophage cytotoxic ability may be useful in designing more effective chemoimmunotherapy protocols.

The effects of the anti-enteroviral agent PTU-23 on immune response in normal mice.

The anti-enteroviral agent PTU-23 (N-phenyl-N'-3-hydroxyphenyl carbamide) was tested for an effect on humoral and cellular immune response in normal BD2F1 hybrid mice. Humoral immune response was assessed by hemolytic plaque technique and cellular immunity--by the delayed type hypersensitivity reaction and by the rate of activated lymphocytes in the mesenteric lymph nodes. PTU-23 was administered subcutaneously in doses of 200, 400 and 800 mg/kg body weight during 6 consecutive days. The immune response was recorded on day 1, 7 and 14 after the treatment. The changes observed in humoral and cellular immunity were found to be dependent on the time interval between the administration of the drug and of the antigen (sheep red blood cells), as well as dose-dependent. On day 1 a considerable suppression of humoral and cellular immune response was recorded at the three dose levels used. On day 7 the inhibition of humoral and cellular immunity was less. On day 14 the immune response in the animals treated with 400 and 800 mg/kg of the tested substance approached the control values, whereas it was observed that the dose of 200 mg/kg results in a certain stimulation of humoral and cellular immune response.

Combined therapy of L1210 leukemia with cyclophosphamide and lycurim.

The authors treated DBA/2 mice with L1210 leukemia with cyclophosphamide (CY) plus lycurim (LY), both alkylating agents. There was established a dose-dependent antitumor effect after early single treatment with CY and LY. Sequentional combined treatment with CY and LY induced an enhancement or synergism in therapeutic effect of drugs, more related to the doses used than to the sequence of drug administration. The optimal synergistic effect, as well as "cure" of treated animals were observed when both drugs were used in doses close to LD10.

Synthesis, toxicity and immunomodulating activity of Co(II), Ni(II), Cu(II) and Zn(II) complexes of L(-)-2,3,5,6-tetrahydro-6-phenylimidazo[2,1-b]thiazole (levamisole).

Co(II), Ni(II), Cu(II) and Zn(II) complexes of levamisole (LMS) were prepared and characterized by elemental analyses, IR spectroscopy, 1H and 13C NMR and mass spectrometry. The following general formula was derived: M(LMS)2Cl2, where M = Co, Ni, Cu, Zn. It was established that LMS behaved as a monodentate ligand and the coordination was accomplished through the N-7 atom. The toxicity and the immunomodulating activity of the complexes on mice and rats in comparison with uncomplexed LMS was assayed. The metals in the complexes exerted different changes in the toxicity of LMS. The complex containing Zn(II) was less toxic and manifested higher immunomodulating activity than LMS.

Inhibition of spontaneous pulmonary metastases of Lewis lung carcinoma by oral treatment with Respivax and Broncho-Vaxom.

The antimetastatic activity of orally administered polybacterial vaccines, Broncho-Vaxom (BV) and Respivax (RV) was examined in C57BL/6 mice, bearing implants of Lewis lung carcinoma (3LL) in the footpad. The oral administration of BV or RV for 10 consecutive days before or after surgery caused significant reduction of the number and volume of lung metastases. In addition, the therapeutic potential of BV and RV was examined in combination with chemotherapy to determine if there is additive activity. In animals bearing pulmonary micrometastases, treatment with a combination of cyclophosphamide at 50-150 mg/kg with BV or RV was found to be more effective than each of these treatments alone. In immune function studies it was established that the oral administration of BV and RV induced an increase in the number of cells, recovered by broncho-alveolar lavage, and alveolar macrophages were dominant in these cell populations. Furthermore, oral treatment of mice with these vaccines rendered their alveolar macrophages tumoricidal for syngeneic metastatic 3LL cells in vitro. These results show that pulmonary macrophages induced by oral administration of BV and RV played a key role in the inhibition of metastasis in 3LL-bearing mice.

Testing of 2,3-dihydro-1,3-6H-oxazine-dione (3-oxauracil) in mouse L1210 leukemia and 37 sarcoma.

The antimetabolite 2,3-dihydro-1,3-6H-oxazine-dione (3-oxauracil) has been investigated in an attempt to elucidate its effects on survival time of DBA/2 and B6D2F1 mice with L1210 leukemia and of outbred albino mice with 37 sarcoma. A significant increase in survival time was observed in mice with 37 sarcoma and slight effects were observed in mice with L1210 leukemia when treated with 3 x 12.5 or 3 x 25 mg/kg of 3-oxauracil. No toxic side effects were observed when large therapeutic doses of the drug were given.

Enhancement of antitumor effect of cyclophosphamide by thaliblastine in Lewis lung carcinoma and L1210 leukemia in mice.

Cyclophosphamide (CY) was tested in combination with the thalictrum alkaloid named thaliblastine (TBL) for therapeutic activity against early Lewis lung carcinoma and early L1210 leukemia in mice. TBL alone had no activity whereas therapy with CY and TBL was significantly better than with CY alone. The therapeutic potentiation resulting from the combination of CY and TBL is apparently due to the different mechanisms of action and the pharmacological behavior of the two agents.