The effect of agroclavine, a compound belonging to the group of ergot alkaloids, on the active and passive avoidance habit learning and retrieval in mice was studied. It was found that agroclavine violated the retention of both habit types, while changing neither the learning rate nor the retrieval efficacy. The drug effect was retained for three weeks after administration. It was suggested that agroclavine probably disturbs the short- to long-term memory transformation.

The investigation was concerned with the influence of preliminary injections of Olipiphat, irrigation of operative wound and combination of both procedures on healing and relapse processes, following resection of Pliss lymphosarcoma at different stages after transplantation into rats. The physical condition of the animals after tumor resection on days 12, 10 or 7 of tumor growth was better than in controls, as a result of irrigation of the operative wound with Olipiphat or in combination with preliminary injections of the drug: they came out from anesthesia quicker, tidied themselves up and moved about the cage. Irrigation of the wound with Olipiphat or in combination with preliminary injections followed by longer survival after surgery performed at all stages of tumor growth. Moreover, one animal out of 16 in each of the 4 Olipiphat-treated groups survived 60 days recurrence-free. The drug proved more effective in stimulating the healing of larger wounds but contributed to healing by first intention in all cases.

The influence of platinum derivatives, cisplatin (cis-diamminedichloroplatinum) and imidazolplatin (cis-diimidazoledichloroplatinum) on the activity of rat liver microsomal NADPH-oxidoreductases was investigated in vitro using spectrophotometrical and chemiluminometrical methods. In the range of concentrations from 1 to 12 microM cisplatin inhibited NADPH-cytochrome c-reductase activity and NADPH/lucigenin-dependent chemiluminescence of microsomes. The 3 microM cisplatin decreased the NADPH-dependent reductase activity by 50%. At concentrations less than 2.5 mM sanazole (drug AK-2123) did not prevent the inhibiting influence of cisplatin on microsomal NADPH-dependent reductases. Imidazolplatin insignificantly inhibited NADPH-reductases. It is concluded that negligible inhibiting effect of imidazolplatin on microsomal NADPH-oxidoreductase allows us to consider this platinum derivative as a promising compound for further experimental trials as anticancer drug with low toxic action on the normal tissues of an organism.

Various epiphyseal neuropeptides, participating in regulation of the secretory processes, are capable of inducing systemic changes. This circumstance determines both pharmacological and therapeutic properties. The drug elitalamine, representing a polypeptide extract, ensures effective treatment of the immune system and brain disorders and tumors and allows a prophylaxis of tissue aging.

Radiosensitizating abilities of taxol have been investigated in vitro using L929 cells and in vivo Geren carcinoma (T-8 cell line). Radiosensitizating effect of taxol was detected for the both cell lines. Pathologic mitoses have been also analyzed and increasing of abnormal mitosis total level was observed. It is supposed that this phenomenon could determine radiosensitizating abilities of taxol.

By using histological morphometric stereological and quantitative enzyme histochemical methods, structural and metabolic changes in thyroid gland after short-term treatment with high doses of cyclophosphamide (GY) were studied. Mice were treated with 400 mg/kg of GY every 48 h for up to 7 days(1-4 i.p. injections). To assess the effect of CY and its reversibility thyroids were studied on the day following each injection and 5-15 days after three injections. CY treatment caused significant dose-dependent structural and metabolic changes in thyroid gland which included vacuolization and destruction of thyrocyte apical cytoplasm, focal follicular wall destruction leading to the fusion of some follicles, reduction in volume fractions of epithelium with the condominant increase in volume fraction of colloid and stroma, decrease in follicular cell height, decline in both thyrocyte cytoplasmic NAD-H-diaphorase activity and vascular alkaline phosphatase activity. These changes were not completely reversible by day 15 after the last injection of CY.

Gene MDR1 coding for P-glycoprotein belongs to a group of genes responsible for cell defense. Overexpression of this gene determines the resistance of tumor cells to a series of chemotherapeutic drugs known as multidrug resistance. Many chemotherapeuticals induce both apoptosis and transcriptional activity of the MDR1 gene in tumor cells. It is not known, however, how these two processes are associated with each other. In order to elucidate a possible link between them, we have studied the sphyngomyelinic pathway of signal transduction. This pathway is activated in response to various stress factors and includes the hydrolysis of sphyngomyelin of cytoplasmic membrane resulting in an accumulation of intracellular ceramide, which activates cascades of enzymatic reactions leading to various cell responses, including apoptosis. C2 ceramide (N-acetyl-D-sphyngosine) and cytosar (1 beta-D-arabinosylcytosine, or ara C) were used to induce the sphyngomyelinic pathway. Their effects on human hemoblastosis cell lines (K562 and H9 cell lines) were examined. C2 ceramide and ara C induced apoptosis in both cell lines over an 18-h incubation. C2 ceramide also induced an increase in the expression of the gene MDR1 in both cell lines, while ara C increased the activity of the gene MDR1 only in H9 cells. The results obtained provide evidence for the contribution of ceramide-mediated signal pathway to the control of MDR1 activity.

Examined in treating rats with Guerin's carcinoma with doxorubicin was the possibility that the polyenzymic drug preparation wobe-mugos E had hepatoprotective, cardioprotective and myeloprotective effects. In intramuscular administration wobe-mugos E has not been found to stimulate the tumour growth, it exhibited a manifest hepatoprotective and myeloprotective actions with respect to adverse reactions of doxorubicin but failed to diminish cardiotoxicity of the latter. The protective effect of the above polyenzymic drug was of a dose-dependent character.

A natural avermectin complex, aversectin C, was shown to be capable of exerting selective cytostatic effect. It killed proliferating neuroblastoma B 103 cells but was non-toxic for differentiated cells of this culture. The activity of aversectin C was related neither to activation of the GABA alpha-receptors nor to their blocking and was at a large extent due to the action of avermectin A1, a component of aversectin C.

The radio-sensitizing capacity of cultured HeLa cells was investigated by using a number of compounds, which are analogues of purine and pyrimidine bases. Agents (5-fluorouracil, ftorafur, mercaptopyrine) used in chemotherapy for tumors for many years and some compounds (allopurinol and theophylline) that are sterically close to purine and pyrimidine bases and clinically used for various purposes, but have no cytotoxic activity against tumors cells were tested. Fluorouracil was shown to potentiate the action of gamma-radiation when the agent was given used before radiation or used in the concentrations producing no cytotoxic effect. Allopurinol and theophylline do not possess a radio-sensitizing effect. There was a more pronounced radiosensitization in the concurrent use of a double combination of agents and radiation and the greatest cell death rates were observed in the concurrent use of three agents (5-fluorouracil, ftorafur, and methylcytosine) and gamma-radiation.

Gluthoxim--bis(g-L-gluthamyl)-L-cystenyl-bis-glycin disodium salt (C20H32O16N6S2)--is an analog of oxidized gluthation with a stable disulfide bond. It is a drug of a new class of thiopoetins which regulate thiol disulfide metabolism. Gluthoxim is used as a support substance in chemotherapy of cancer. The present investigation deals with feasibility of gluthoxim-induced apoptosis in tumor cell cultures, including human myeloleukema cells HL60 which lack protein p53 gene, so crucial for apoptosis. Also, gluthoxim effect was studied with respect to transformed murine fibroblasts C8 and A4, carrying the plasmide structure with Ras and E1A genes which boost Ras-gene expression. This in turn makes fibroblasts ready to start apoptosis. Gluthoxim induction of cell death was demonstrated in both cell lines; however, apoptosis in cells C8 (with intact gene p53) was much more pronounced than in cells A4 without this gene. It is suggested that apoptosis can be triggered by both imbalance of redox potential typical of tumor cells, induction of p53 synthesis and an impact on the phosphoproteinase cascade of Ras-signal pathway.

Tumor process development in rats inoculated with cellular suspension of transplantable Walker's carcinosarcoma-256 involved enhanced thickening of blood on day 7. Treatment with 20 mg/kg cyclophosphamide, thrice a day, every other day, retarded tumor process and brought hemorheologic indices further down, at the same time. Similar treatment of intact rats with cyclophosphamide caused hemorheologic disorders too.

A synthesized analog of myelopeptide HP-2-->M[symbol: see text]-2 (Leu-Val-Val-Tyr-Pro-Trp) caused a significant (60-80%) and prolonged inhibition of s.c. grafted tumors P388, Ca-755, B-16 and sarcoma 180 in isogenic mice but did not affect the growth of tumor B-16 in nude mice. Nor did it influence proliferative activity or viability of cultured human tumor cells. The best results were obtained with s.c. injections of 0.5-2 mg/kg HP-2-->M[symbol: see text]-2, twice or trice a day, at 96 hr intervals. No symptoms of severe poisoning were registered at doses of HP-2-->M[symbol: see text]-2 100 times the therapeutic one. A pharmacokinetic study in mice revealed prolonged circulation of HP-2-->M[symbol: see text]-2 in blood and a high affinity for the bone marrow (t 1/2 (130.1 hr and 431.6 hr, respectively). HP-2-->M[symbol: see text]-2 restored in vitro the ascites P388-suppressed cytotoxicity of murine T-lymphocytes. HP-2-->M[symbol: see text]-2 is regarded as a candidate for clinical studies of its potential of immunocorrection in cancer patients suffering T-lymphocyte immunity disturbances.

Superoxide-removing activity, the number of sulfo-hydryl NH2-groups and groups, mean mass molecular concentration, free and antioxidant activity of albumin were determined in blood serum and its albumin fraction in 20 patients with breast cancer T3-4N1-2Mo, before and after incubation with cyclophosphamide, adriablastin, methotrexate and vincristine at concentrations used in clinic. Our data suggested that, following incubation with blood plasma, chemotherapeutic drugs bound to albumin fraction and protein fragmentation took place. Preincubation of blood plasma with the drugs and their immobilization on albumin molecules caused protein fragmentation to occur. Fragments having pro-oxidant properties might have been absorbed and fixed by both tumor tissues and any others thus creating a pool of fast-dividing cells and organs. Therefore, cytostatic drugs can exert enhanced antitumor action and, at the same time, a highly toxic effect when administered with autoplasma during chemotherapy.

Xeloda (capecetabine) has been tested for efficacy and toxicity in treating disseminated breast cancer after the potential of anthracycline (group 1) chemotherapy, anthracyclines plus taxanes (group 2) was exhausted. The patients included into the study (54) were divided into groups 1 (33) and 2 (21). Apparent response was in 24 and 21%, respectively. The drug may be used both in out-patients and those refractory to anthracycline chemotherapy and anthracyclines plus taxanes due to moderate toxicity, slight myelodepression and absence of alopecia which seldom makes treatment useless.

The list of sanitary standards with the mark "absent" should include antitumor cytostatics as the drugs satisfying the following criteria: extreme hazard and toxicity, late adverse effects, primarily mutagenic and carcinogenic properties; lack of highly sensitive methods for their determination in water; lack of 100%-efficiency methods for sewage purification. A complex of protective measures is justified and sanitary recommendations are given to protect the aqueous environment during cytostatic production.

Two diketopiperazine alkaloids, rugulosuvines A and B (tryptophan and phenylalanine are precursors), were isolated and purified from the culture liquid of Penicillium rugulosum VKM F-352 and Penicillium piscarium VKM F-325 fungi. Physical and physicochemical studies showed the absolute structure of rugulosuvine A. The absolute structure of rugulosuvine B was demonstrated to be similar to that of rugulosuvine A.

The anticancer activity of Trypanosoma cruzi has been confirmed by the example of seven strains. Five virulent strains induced the infection, which inhibited sarcoma-180 growth 1.5-22.0 times. The parasites featured tumortropism; i.e., the successfully developed in cancer cells and even preferred them to normal cells. This taxis-based phenomenon was particularly pronounced at cocultivation of the normal and cancer cells. Cultures of the seven (avirulent and virulent) strains can produce an anticancer agent that selectively damages human cancer cells in vitro. The long-term anticancer effect of T. cruzi or preparations from it, as well as possible its cancer preventing effect, has been demonstrated. Three problems are discussed on the basis of the obtained and recently published data: (1) the mechanism of T. cruzi anticancer effect; (2) the nature of the anticancer agent; and (3) the distribution of the considered phenomenon among trypanosomatides. The anticancer activity of T. cruzi may be due to a combination of surface cellular antigens and an inhibiting or lysing factor.

The influence of the number of differentiating agents on sensitivity of human erythroleukemic cells K562 to human leukocyte-mediated non-MHC-restricted lysis was studied. It has been shown that a 4-day treatment of cells K562 by dexamethasone (1 microM) or phorbol-12-myristate-13-acetate (100 nM) leads to a significant decrease in sensitivity of the treated cells to non-specific lysis mediated by human leukocytes. On the contrary, the treatment of cells K562 by a combination of dexamethasone and thymidine (2 mM) leads to an increased sensitivity of the treated cancer cells to non-specific lysis mediated by the above effector cells, compared with the situation when these cells were treated by dexamethasone only. The treatment of cells K562 by a combination of thymidine and phorbol-12-myristate-13-acetate demonstrates a tendency (P < 0.1) to increase the sensitivity to non-specific lysis mediated by human leukocytes, as compared with the cases, when these cells were treated by phorbol ester only. It has been shown that the changes in K562 cell sensitivity to lytic action of leukocytes, under the chosen incubation time and doses of the used agents, well compare with the changes of erythroid differentiation of the cancer cells in the same conditions.