Data on long-term interferon-alpha (reaferon) therapy in 6 patients with CML (5 in chronic phase, 1 in acceleration phase) are presented. Clinicohematological remission was achieved in all the patients in a chronic phase irrespective of their group of risk. Cytogenetic improvement occurred only in one patient from a low-risk group. Reaferon had no effect in the patient in the acceleration phase. Tumor necrosis factor neither influenced viability of mononuclear bone marrow cells of patients before treatment nor suppressed proliferation. Dose independent reduction of cell viability was revealed in a patient in remission after reaferon therapy. There were no cases of apoptosis induction. Mechanisms of CML pathogenesis and interferon action in CML chronic phase are discussed.

Both intact mice and those with transplantable adenocarcinoma 755 were used in the investigation. The nitroxyl radical Tempol was shown to cut down the toxicity of 6-mercaptopurine and potentiate its antitumor effect to a certain degree. The study results suggest on the basis of an investigation of cytochrome P450 and some other evidence that said effect of Tempol might be due, at least, in part to antioxidant activity.

Before starting treatment of chronic glomerulonephritis it is desirable to determine the patient's drug sensitivity in vitro because in the absence of such sensitivity chemotherapy should be preceded by immunomodulation with tactivin or thymalin and 3-5 sessions of plasmapheresis to stimulate drug sensitivity. Further measures include prednisolone or cyclophosphamide intravenously for 3-5 days in a dose 300-500 followed by oral administration. Active treatment lasts for 4-8 weeks. After that the patients receive maintenance for 1-2 years.

The influence of cytotoxic agents adriamycine (AD) and ethydium bromide (EB) on Ca(2+)-dependent K+ channels of erythrocytes was investigated. The incubation of erythrocytes with agliconic part of AD (without aminosugar residue) increased Ca(2+)-dependent K+ efflux induced by low concentration of propranolol, while EB suppressed the activating effect of propranolol. EB, verapamil and triphluoroperazine inhibited Ca(2+)-dependent K+ efflux induced by high doses of propranolol. The incubation of erythrocytes with AD took off the inhibitory action of EB and verapamil but did not influence the blocking effect of triphluoroperazine. Both AD and EB did not influence Ca(2+)-dependent K+ channels induced by Ca(2+)-ionophore A23187, and Pb(2+)-dependent K+ efflux from erythrocytes. It is suggested that opposite effects of AD and EB on Ca(2+)-dependent K+ channels are due to activation by AD and inhibition by EB of system of Ca2+ transport into cells, but not on their action directly on K+ channel.

A cell differentiating agent N-methylformamide (MF) was studied for its antitumor activity against a murine ascitic hepatoma 22A. After a 48 hour NMF administration (i/p) the tumor cell number was monitored; the distribution of these cells in the cell cycle was registered by flow cytometry, ultrastructural changes were studied by electron microscope. The polar solvent MF inhibited tumor growth, reduced mitotic activity, and nuclear/cytoplasmic ratio, led to structural complication of endoplasmic reticulum and mitochondria. The analysis of these events is suggestive that in consequence of MF effect on tumor cells, proportion of G0/G1 and M cells was decreased, while the proportion of S and G2 cells was increased.

The results of experimental studies of three drugs from aziridinyltriazine group, dioxadet, trisadet, and furizil, are presented. These drugs exhibit a pronounced therapeutic effect against a broaden spectrum of tumors grafted in mice and rats. Toxic effect of the drugs is exhibited mainly in suppression of blood formation. Other side-effects are slightly pronounced. One of the drugs, dioxadet passed the I and II stages of clinical trials and is recommended for application in chemotherapy of malignant tumors.

A third series of randomized tests was undertaken to evaluate the efficacy of postoperative adjuvant hormone therapy (tamoxifen, diethylstilbestrol, orimethen amino glutethymide) in breast cancer patients. Tamoxifen was studied in 176 patients with T1-2N0M0 tumors. Five-year recurrence-free survival was registered in 85.2% of menopausal patients treated with tamoxifen versus 71.1% in control (P < 0.05). Five-year recurrence-free survival in menopausal females with breast tumors, stage IIb, was 71.1% among those treated with diethylstilbestrol and as low as 57.4% in the tamoxifen group (P < 0.05). Untoward side-effect incidence was much higher in the diethylstilbestrol group (30.4%) as compared with tamoxifen (3.5%). No significant difference was found for the relationship between orimethen and tamoxifen treatment with respect to 5-year survival and recurrence-free survival.

The effects of the antitumor drug tiazofurin on development of sea urchins Sphaerechinus granularis, Paracentrotus lividus, Strongylocentrotus intermedius, and Arbacia lixula were studied. When 0.01-200 microM tiazofurin (TAF) was introduced in the incubation medium (artificial sea water) just after fertilization or at the midblastula stage, the development proceeded quite normally until the beginning of gastrulation. But later TAF blocked gastrulation and induced formation of mobile ball-shaped larvae with normal pigment cells but devoid of the nervous system, skeletal spicules and digestive tract. The threshold TAF concentrations varied from 0.05 microM (S. granularis) to 2-5 microM (all other species). When TAF was introduced during gastrulation and just after gastrulation, the larvae had defective nervous system and skeleton and suppressed expression of gangliosides. The nonhydrolyzable analog of GTP, GTP-gamma-S (5-20 microM), introduced in artificial sea water no later than at the midblastula stage prevented all above mentioned developmental defects.

Several retinoids with modified polar group were synthesized. Biological screening using HL-60 promyelocyte leukemia cells showed that the free carboxyl in the retinoid molecules is not the only group responsible for exhibiting the differentiating activity.

Doxorubicin and 14-hydroxycarminomycin 14-O-hemiadipates and 14-O-hemipimelates, synthesized from 14-bromo derivatives of daunorubicin and carminomycin and monosodium adipate and pimelate, were converted to the corresponding N-trifluoroacetylated compounds. 13-(4-Methylpiperazine-1-yl)imino derivatives of the anthracycline antibiotics were also obtained. The cytostatic activity of the compounds synthesized was studied using a panel of human and animal tumor cell lines sensitive or resistant to doxorubicin. N-Trifluoroacetylation of the antibiotics resulted in a decrease in the cytostatic activity. The activity of the water-soluble 13-(4-methylpiperazine-l-yl)imino derivatives is close to that of the corresponding parent antibiotics.

The authors consider fundamentals of hormone therapy in prostate cancer, mechanism of long-term androgenic stimulation, detail mechanism of action of antiandrogen (ciproteron acetate-androcur) on the basis of discovered key role of cellular receptor in endocrine regulation of physiological functions in metabolism. Monotherapy with androcur-depo (300 mg once a week) was given to 24 patients with prostatic cancer stage T2-T4. Eight patients had metastases to the bones. The age of the patients ranged from 58 to 80 years. Alleviation of pain, reduction of the prostate size and density, positive uroflowmetric changes (maximal urination rate increased from 2-5 to 10-15 ml/s), residual urine fall occurred as early as treatment week 5-7. There was also a decrease in the activity of acid phosphotase from 5-10 to 0.3-0.8 units according to Bodansky. Serum level of prostate-specific antigen (PSA) dropped from 388-23 to 116-4 ng/ml. Androcur-depo monotherapy demonstrated high efficacy in the treatment of local prostatic cancer.

The study of bone marrow hemopoiesis, the count of hemopoietic precursor cells, bone marrow structural and functional organization, the level of humoral stimulators and secretion by hemopoiesis-inducing microenvironment (HIM) cells following a single injection of 5-fluorouracil, cyclophosphamide or adriamycin has found out that cytostatic-related changes in hemopoiesis recovery depend primarily on relationships between proliferation and differentiation of hemopoietic cells. These relationships are dictated by the state of HIM cells. Enhanced functional activity of HIM elements in response to hemopoietic tissue damage caused by adriamycin or cyclophosphamide promotes rapid hemopoiesis regeneration. At the same time, 5-fluorouracil gave rise to prolonged bone marrow hypoplasia, severe disorder of microenvironment cell function.