A culture of Streptomyces sp., producing an antibiotic named galtamycin was isolated from a soil sample collected in the Gorno-Altai Autonomous Region. The antibiotic belongs to anthracyclines. Biosynthesis, isolation, physico-chemical and biological properties of the antibiotic are described. The studies showed that galtamycin consisting of a chromophore and three unidentified sugars is a new compound differing from the known anthracyclines except trypanomycin by the absence of the UV absorption maximum at 230-240 nm. Galtamycin differs from trypanomycin by the molecular weight of the chromophore. Galtamycin showed low antitumor activity and was inactive against grampositive and gramnegative organisms and fungi.

The authors described a procedure of the instrumental neutron activation analysis of biomedical material on reactor and 14 MeV neutrons for determination of the platinum, silicon, chlorine, phosphorus, sodium and zinc content using the anticompton system of detection together with a programmed analyser and an automatic sample changer. The procedure was tested on rat small intestinal samples within the interval of 10 min-30 days after a single i. v. administration of oxoplatinum (15 mg per 1 kg of the animal body mass). Platinum redistribution with relative concentration maximum on the 15th day was noted. Changes in the phosphorus, chlorine, sodium and silicon content within the interval of 3-30 days were suggestive of a possible toxic effect of oxoplatinum metabolites during this period. In a clinical application of oxoplatinum one should take into account a possible toxic effect of metabolites in a long-term period after repeated administration of the agent.

Myelosuppressive effects of cis-dichlorodiamminoplatinum (DDP) and oxoplatinum have been revealed. The administration of these drugs leads to early and deep depletion of CFU compartment. The most rapid rate of reduction was registered during 24-48 hours after DDP administration and within first three hours after oxoplatinum administration. Reduction of the total bone marrow cellularity caused mainly by a decrease of erythroid cells and, to a less extent, by a decrease of lymphoid and myeloid cells is observed. Leukopenia and anemia have developed during the treatment. Myelosuppressive effects are more pronounced with the oxoplatinum administration. A strict correlation is established between the haemopoietic tissues damage and the level of platinum content in the animal organism.

The dimetinur effect upon chromosomes of the Ehrlich ascite carcinoma and bone marrow cell populations was analyzed by the cytogenetic method for 10 days after i.p. and i. v. drug administration in doses from 50 to 150 mg/kg. Kinetic regularities of changes in a fraction of cells with chromosome breakages and in the number of broken chromosomes per cell as well as "dose-effect" relations are determined. A linear correlation is established between the level of residual chromosome damages in a population of tumour cells and the coefficient of activity chi* characterizing the antitumour effect of dimetinur. Selectivity of the dimetinur mutagenic action expressed as a more deep and prolonged damage of the genetic system of tumour cells as compared to bone marrow cells of tumour-bearing animals is shown under conditions of a pronounced therapeutic activity.

The authors describe the experience gained with 19 allogenic and autologous transplantations of the bone marrow, peripheral blood leukocytes, embryonal liver cells of man and syngeneic transplantation of the bone marrow to 15 patients with hemoblastoses and aplastic anemia. Non-medullary toxicity of the pretransplantation conditioning of the patients was moderate and could be successfully corrected. The clinical analysis of the complications and causes of the patients' death demonstrated an evident reduction of organ lesions as a result of the use of the common methods of preventing exo- and endogenous infections and early treatment of the complications. The authors describe an acute secondary disease as the main reason for death during the latest allogenic transplantations of the bone marrow and support the conclusion about the necessity of transplantation only in the cases with a satisfactory prognosis.

The action of drugs of plant origin and of alkylating compounds (sarcolysine, prospidin) was accompanied by hormonal changes in rats with inoculated Pliss' lymphosarcoma. After the use of polyphenol plant drugs the secretion of pituitary FSH was inhibited, the blood concentration of testosterone was reduced and the cortisol secretion was substantially increased. The alkylating compounds stimulated the production of FSH, increased the secretion of testosterone, and clearly lowered the cortisol level.

The inhibitory effect of difluoromethylornithine (DFMO) synthesized by the authors on the activity of the ornithine decarboxylase (ODC) and proliferation of microbial and mammalian cells in vitro was studied. The in vivo growth of ascite plasmocytoma of solid melanoma B-16 cells in mice was also effectively inhibited by DFMO. But the antiproliferative activity of DFMO in solid tumours was substantially lower. Such a decrease in the antitumour activity may be associated with polyamines released from necrotic areas of solid tumours. As the tumour cells "catch" the vitally important metabolites, their effect inside solid tumours is turned against the tumour cells themselves. The second reason of the decrease in the DFMO activity is adsorption of polyamines on the erythrocyte surface.

Aclarubicin (ACR) has a selective inhibitory effect on the synthesis of RNA in the cells. The time of the antibiotic contact with the cells is an important factor in realization of its cytotoxic activity. As compared to adriamycin, ACR has a low specific activity in lymphoid leukemia P388, melanoma B16 and lung cancer LL. The therapeutic efficacy of ACR depended on the scheme of its use: in treatment of rapidly proliferating tumors such as P388 the highest effect is attained with the daily use of the antibiotic for 9 days, in treatment of slowly developing melanoma B16 the results were more satisfactory with intermittent use of the drug on days 1, 5 and 9 after the strain transplantation. The new antibiotic was highly effective on its use either intravenously or orally.

The effect of the polysaccharides tagetan, palustran, and zymosan injections to BALB/c mice on the formation of cytotoxic T-lymphocytes in allogenic mixed culture has been studied. Lymphocytes from a 5-day-old mixed culture were characterized by the greatest cytotoxic activity, with spleenocytes serving as reacting cells in mice injected 12-50 mg/kg of tagetan, 20 mg/kg of zymosan and 10-100 mg/kg of palustran, 7, 3 and 5 days, respectively, before the beginning of allogeneic stimulation in vitro. To determine correlation between immunostimulating and antitumor activity 25 mg/kg of tagetan every 14 days, 20 mg/kg of zymosan every 6 days, and 10 mg/kg of palustran every 6 days, were injected to BALB/c and BALB/c nu/nu mice prior to and following subcutaneous implantation of Crocker sarcoma cells. By the end of the first month of immunotherapy the tumour size in mice on tagetan or zymosan was 2-2,5 times smaller than in control animals. Tumour growth inhibition with palustran was about 30%. Polysaccharide administration to BALB/c nu/nu mice was not accompanied by tumour growth inhibition. The data obtained suggest that inhibition of Crocker sarcoma growth in mice injected the above polysaccharides is mediated by stimulation of antitumour T-cell activity.

Dynamic behavior of stem cells population of the "critical" tissue (normal population) and tumor cell population under periodic treatment with a phase-specific cytotoxic agent was considered. The results were used for optimization of anticancer chemotherapy. The schedules of treatment were found which provide a maximum rate of tumor-cell elimination for any given rate of the normal population size decrease. If the mean generation times of normal and tumor populations differ (which was stated for many tumors), usage of the optimal period markedly increases the selectivity of therapy, while application of other periods can result in selective elimination of the normal population. Problems concerned with practical realization of the proposed regimes are discussed.

Along with complement activation by the classical pathway, blastolysin, an antitumor and adjuvant preparation of Lactobacillus bulgaricus peptidoglycans, effectively inhibits the transformation of C3 in to C5 convertase. Values of inhibition maximum and dissociation constants of the reversible C3b-acceptor complex for blastolysin and main immunological active structural moieties of peptidoglycans (GMDP, MDP) and their inactive carbohydrate components (N-acetylglucosaminyl-N-acetylmuramic acid, N-acetylglucosamine, and N-acetylmuramic acid) have been determined. Immunostimulator concentrations for blastolysin, GMDP, and MDP in inhibition of the C5 convertase formation (C3b binding) correlate with their doses in vivo (animal blood), displaying antitumor activity.

Clinical trials of bleomycetin and platidiam combination were carried out in 13 patients with disseminated melanoma of the skin. Two regimens of the treatment were used. Regimen I included intravenous administration of platidiam in a dose of 20 mg/m2 with a water load on days 2, 3, 4, 5 and 6 of the treatment course and intravenous administration of bleomycetin in a dose of 30 mg/m2 on days 1 and 7. The intervals between the courses consisted of 4 weeks. Regimen II included the use of platidiam in a dose of 20 mg/m2 administered as 6-hour intravenous infusions in 1.2 1 of isotonic sodium chloride solution daily for 5 days. On the first day of this cycle bleomycetin was administered intravenously in a dose of 30 mg/m2. The cycles were performed during the 1st and the 3rd weeks of the treatment course. During the 2nd and the 4th weeks platidiam was administered in a dose of 40 mg/m2 once a week and bleomycetin was administered intramuscularly in a dose of 6 mg/m2 daily for 5 days. A more than 50 per cent decrease in the tumor formation was observed in 38 per cent of the patients. The combination had no toxic effect on hemopoiesis and may be used in new programs on chemotherapy of disseminated melanoma of the skin.

Stability is one of the most important indices of the quality of antibiotic microbiological standards. At present the expiry date of the mycoheptin standard (a specially purified preparation) is 1 year when stored in sealed ampoules in an inert gas at a temperature of -20 degrees C. To prolong the expiry date of the standard the effect of various antiohidants and complexons on its stability was studied with the method of "accelerated aging". Sodium hexametaphosphate and Trilon B were tested as complexing agents and propyl gallate, ionol, N-phenyl-2-napththyl amine, mannitol and their mixtures were tested as antioxidants. The substances were applied in an amount of 3 per cent of the antibiotic weight. The favourable effect of the complexons on mycoheptin stability was shown. Their stabilizing effect was potentiated by addition of certain antioxidants.

The cytogenetic analysis was performed in the bone marrow cells of Wistar rats treated with a therapeutic dose of thaliblastine (250 mg/kg) and exposed to gamma-rays (2 Gy). Thaliblastine alone induced chromosome aberrations and polyploid cells. The latter were the result of the stathmokinetic effect of the drug. In contrast to gamma-radiation of 2 Gy thaliblastine elicited a minor mutagenic effect. The cytogenetic effect of the combined treatment is greater than the sum of the two agents delivered separately, the maximum effect of radiation and thaliblastine being exhibited on the 8th and the 12th hour, respectively. The difference between the sum of aberrations after separate treatments and the yield of aberrations after the combined treatment is due to chromatid fragments.