[The drop in toxicity and the rise in the effectiveness of antineoplastic chemotherapy by correcting the activity of liver monooxygenases: from the experiment to the clinical practice]. / Snizhenie toksichnosti i povyshenie éffektivnosti protivoopukholevoi khimioterapii putem korrektsii aktivnosti monooksigenaz pecheni: ot éksperimenta -- v kliniku.

The paper reviews both the data available in the literature and the authors' own results of long-term experimental and clinical investigations of the involvement of hepatic monooxygenases (HMO) in the biological activity of antitumor drugs. It reports data of evaluation of HMO activity in pediatric and adult cancer patients, which has shown a decrease in HMO activity in one third of patients without clinical signs of hepatopathy and two thirds of those with toxic hepatic damages after prior chemotherapy. Decreased HMO activity has been found to be stimulated with the enzyme inductor zyxorin. Altered biochemical parameters, such as total bilirubin, ALT and AST, can be corrected with HNO, even if they show a 10-fold deviation from the normal physiological level. The efficacy of zyxorin was tested in patients with advanced cancer and concomitant toxic or viral hepatic disorders (grades II-IV by the WHO classification). Stimulation of inhibited HMO activity allows both decrease and prevention of the manifestations of hepatic toxicity due to anticancer chemotherapy providing a beneficial effect, the dose of cytostatics being not reduced. The authors concluded that the findings provide strong evidence for their assumption that the efficiency of antitumor chemotherapy can be enhanced in patients with concurrent hepatic abnormality by stimulating monooxygenases whose activity is diminished in the majority of these patients.

CD95 (FAS/APO-1) antigen is a new prognostic marker of blast cells of acute lymphoblastic leukaemia patients.

We analyzed CD95(Fas/APO-1) antigen expression on bone marrow blasts in 38 children with acute lymphoblastic leukemia (ALL) receiving a treatment in the Department of Leukaemias at the Cancer Research Center in 1987-1989 years (n = 22) and in 1994-1997 years (n = 16). CD95 antigen expression was studied by monoclonal antibodies (MoAbs) IPO-4 in indirect immunofluorescence analysis. CD95 antigen was expressed on 35.8 +/- 7.5% bone marrow blasts, most frequently (63.6%) in the clinically favourable Pre-B ALL. Only in this group CD95 antigen expression was correlated with CD10 antigen expression that has a positive influence to the time of complete remission in ALL patients. Our data showed that CD95 expression on blast cells is a favourable prognostic sign, associated with increased relapse-free and total survival. On the contrary, the absence of CD95 antigen on blasts is an unfavourable sign for disease evolution.

[Effect of calcium gluconate on the toxicity and antitumor of doxorubicin in mice]. / Vliianie gliukonata kaltsiia na toksichnost' i protivoopukholevuiu aktivnost' doksorubitsina u myshei.

The effect of calcium gluconate on the toxicity and specific activity of the anthracycline antibiotic doxorubicin was studied on mice with transplanted hemoblastosis La or plasmocytoma MOPS-406. In both cases after the animal exposure to nontoxic therapeutic doses of doxorubicin no influence of calcium gluconate on the antibiotic antitumor activity was observed. When doxorubicin was used in toxic (and even lethal) doses the antitoxic effect of calcium gluconate and an increase of the antibiotic therapeutic activity were stated. The combination of calcium gluconate and doxorubicin made it possible to significantly increase the maximum therapeutic effect of doxorubicin (higher levels of the animal survival and some cures) and to widen the ranges of the drug therapeutic doses at the account of decreasing the toxicity of the antibiotic and increasing its dose. The results suggested that the antitoxic modifier calcium gluconate could be used for increasing anticancer efficacy of doxorubicin which is given now at the total dose limit of 550 mg/m2 even in cases with preserved tumor sensitivity to the drug.

[The cytotoxicity of Chamaenerium angustifolium (L.) Scop. and Hippophae rhamnoides L. tannins and their effect on mitochondrial respiration]. / Tsitotoksichnost' tanninov Chamaenerium angustifolium (L.) Scop. i Hippophae rhamnodies L. i ikh vliianie na dykhanie mitokhondrii.

The cytotoxic activity of complexes of hydrolysable tannins of Chamaenerium angustifolium L. Scop. and Hippophae rhamnoides L. was compared with that of the antineoplastic drugs vinoblastin (VLB), methotrexate (MT), and 5-fluorouracil (5-FU). The tannins yield to VLB and MT in activity but resemble 5-Fu in their active concentration. They inhibited succinate oxidation by the rat liver mitochondria and their cytotoxicity was displayed in much lower concentrations than their inhibitory effect on mitochondrial respiration. It is concluded that tannins inhibit the respiratory chain at the third point of conjugation in the transfer of electrons from cytochrome c to oxygen.

[The effect of calcium gluconate on the acute and chronic toxicity of doxorubicin in mice]. / Vliianie gliukonata kal'tsiia na ostruiu i khronicheskuiu toksichnost' doksorubitsina u myshei.

The effect of calcium gluconate on the toxicity of the anthracycline antibiotic doxorubicin (DOX) in mice was studied. Calcium gluconate showed a significant protective action with respect to the DOX acute toxicity. When DOX was used in the lethal doses, up to the LD50s calcium gluconate protected all the mice from death. At the DOX LD100 or higher the antitoxic effect of calcium gluconate manifested itself in a lower death rate and/or in a higher lifespan of the animals (at least 2-fold). When DOX was used for the treatment course its chronic toxicity in the presence of calcium gluconate was 2 or more times lower by all the quantitative indices: the lifespan of the animals that died, the maximum and minimum total lethal doses of DOX, the latent period before the first mouse death, the overall duration of the DOX treatment course. The antitoxic effect of calcium gluconate also manifested itself in a lower DOX acute and chronic toxicity with respect to the gastrointestinal tract. Thus, calcium gluconate proved to be an effective DOX antitoxic modificator which provided the use of about 2 times higher single and courses doses of DOX in mice.

[The biochemical mechanisms of the action of N-alkyl-N-nitrosoureas. The possible reasons for drug resistance to these compounds]. / Biokhimicheskie mekhanizmy deistviia N-alkil-N-nitrozomochevin. Vozmozhnye prichiny lekarstvennoi ustoichivosti k étim soedineniiam.

N-alkyl-N-nitrosoureas exhibit a wide spectrum of antitumor activity. They react as alkylating agents at nucleophilic sites in purine and pyrimidine moieties of DNA. The predominant site of this alkylation is N7 of guanine, which is followed by the site N3 of adenine and 06 of guanine. The formation and persistence of 0(6)-alkylguanine (0(6)-AG) may be of primary importance in cytotoxicity of the nitrosoureas. 0(6)-AG adducts of DNA of the tumor cells are repaired by protein 0(6)-alkylguanine-DNA transferase (0(6)-AGT) which transfers the alkyl group to internal cysteine residue being the acceptor protein for the alkyl group in an irreversible transfer reaction. 0(6)-AGT can protect the tumor cells against 0(6)-AG adducts by the way of inhibiting the formation of the DNA interstrand cross-links 0(6)-AGT plays an important role in the drug resistance because it repairs the DNA alkyl adducts at the 0(6) position of guanine. The 0(6)-AGT activity inversely correlates with the cytotoxic effect of the nitrosoureas. The agents like 0(6)-methylguanosine, 0(6)-methyl-2'-deoxyguanosine, and some 0(6)-benzylated guanine derivatives are effective inactivators of 0(6)-AGT, and thus can be used to enhance the cytotoxicity of N-nitrosoureas. The activation of 0(6)-AGT and other repairing enzymes such as alpha and beta DNA-polymerases as well as an increase in the level of reduced glutathione may be used in developing the resistance to the nitrosoureas.

[ICO-166 monoclonal antibodies against the CD45RA antigen]. / Monoklonal'nye antitela ICO-166 protiv antigena CD45RA.

Monoclonal antibodies (MCA) ICO-166 against CD45RA antigen were generated and characterized. In the indirect IFA, MCA ICO-166 reacted with 54.1 +/- 1.9% lymphocytes of human peripheral blood and 15.2 +/- 2.3% monocytes but not with granulocytes or thrombocytes. The method of double labelling of cells demonstrated that MCA ICO-166 detected all B-lymphocytes, all NK-cells and 31% of mature T-lymphocytes but only 55% of CD8 suppressor cells and only 21% of CDA helper cells carried this antigen on the surface. Experiments were carried out to block binding of FITC-labeled MCA ALB11 against CD45RA antigen with human lymphocytes by pretreatment of cells with different concentrations of MCA ICO-166. Treatment of cells with MCA ALB11 blocked binding of MCA ALB11-FITC by 85% on the average. MCA ICO-166 blocked binding of MCA ALB11-FITC by 66% on the average. When different dilutions of MCA ICO-166 were used, the dose-dependent effect of blocking of MCA ALB11-FITC binding was observed. MCA ICO-166 immunoprecipitated a protein band of molecular weight 220 kDa from lysates of mononuclear cells of the human peripheral blood.

[Development of substances for active prevention of cancer based on vitamins and preventive-treatment products]. / Razrabotka sredstv aktivnoi profilaktiki raka na osnove vitaminnykh preparatov i lechebno-profilakticheskikh produktov.

The conception and program are described for development of drugs involved in active prophylaxis of malignant neoplasms. Development of prophylactic drugs and new treatment-prophylactic food-stuffs was shown to be possible and expedient to use toxic immunomodulators and natural anticarcinogens. Complex drugs are assumed to include carotenoids, tocopherols, water-soluble vitamins, polysaccharides and other biologically active substances exhibiting anticarcinogenic, antimutagenic and immunostimulating properties. New treatment-prophylactic food-stuffs are developed using milk protein concentrates, lyophylized cruciferous and vegetable juices and extracts of medicinal herbs. The work is realized in the research association involving academic, branch and educational institutions according to State priority programs.

[The trypanocidal action of fluorouracil on Crithidia oncopelti in the presence of lipid metabolic modifiers]. / Tripanotsidnoe deistvie ftoruratsila na Crithidia oncopelti v prisutstvii modifikatorov lipidnogo metabolizma.

Effect of fluorouracil in combination with ascorbate and L-valin, modifiers of lipid metabolism was studied in cultured protozoa Crithidia oncopelti. The inhibitory effect of preparation in a concentration of 100 mcg/ml gradually decreased in the course of cultivation. Its readdition to a 96-hour culture did not increase its effect on protozoa cells. Combined addition of fluorouracil and modifiers (100 mcg/ml each) resulted in insignificant decrease of the cell accumulation in the culture as compared with the effect of fluorouracil alone. When fluorouracil and modifiers were readded to the 96-hour culture, the trypanostatic effect of preparation was 2.5 times enhanced. This enhancement was confirmed by destructive alterations in cell morphology and by the culture lysis by 192 h of protozoa cultivation.

[The preclinical assessment of the activity and pharmacological action of native human interleukin-2]. / Predklinicheskaia otsenka aktivnosti i farmakologicheskogo deistviia nativnogo interleikina-2 cheloveka.

It was demonstrated in in vivo and in vitro experiments that interleukin-2, obtained by cultivation of donor lymphocytes and purified by gel filtration, induces the production of mouse and human killer lymphocytes possessing high cytolytic activity against tumor cells. Interleukin-2 does not cause irreversible changes of the physiological and morphologic indices of vital activity in mice.

[Dextran-ferrite distribution in the body of animals in a nonuniform permanent magnetic field]. / Raspredelenie dekstran-ferrita v organizme zhivotnykh v neodnorodnom postoiannom magnitnom pole.

Dextran-ferrite (DF) was injected via the femoral artery to the dogs and followed by local magnetization (induction 0.3 T, grade 0.024 T/cm). It has been shown that the local retention of the iron in some tissues of the leg was 3-5 times as high as the control. The magnetization did not increase the local retention of the iron after intravenous injection of DF to mice and rabbits.

[Antidotal and antineoplastic properties of copper sulfate]. / Antidotnye i protivoopukholevye svoistva sul'fata medi.

Copper sulfate in peroral administration to small experimental animals has an inhibitory effect on the growth of transplanted solid tumors and possesses antidote properties in respect to cisplatin. An antitumor effect of the compound was registered at doses ranging from 10 to 120 mg/kg. Antidote properties are manifested clearly when copper sulfate is applied at a single dose 10 mg/kg, 24 hours before cisplatin administration. It has been determined that copper sulfate decreases acute toxicity, nephro- and hemotoxicity of cisplatin, but fails to change its antitumor effect. The experimental data obtained give the ground for the clinical studies of copper sulfate.