The action of Staphylococcus aureus, Escherichia coli and Herpes simplex virus on the hemopoiesis of mice with cytostatic myelosuppression was studied. The study revealed that the infection of the animals simultaneously with the action of cyclophosphamide considerably activated the processes leading to the restoration of hemopoiesis due to an increase in the mitotic activity of hemopoietic cells, the accelerated differentiation of hemopoietic precursor cells which could survive the cytostatic action and an increase in the functional activity of the hemopoiesis-producing microenvironment.

The bone marrow of hematological patients was studied as were effects of cytozar at different dilutions on the bone marrow cells. The analysis of the secured results showed the magnetic field to be a powerful biologically active factor capable of changing clonogenic properties, proliferative and differentiative potential of hemopoietic cells precursors. A long exposure brings about a decline in the colony-forming activity of bone-marrow cells, that is to say, with prolongation of time of the exposition the magnetic field becomes an unfavourable factor for the leukotic cell culture development. Similar results were obtained with cytozar in the culture while studying the colony-forming capability of bone-marrow cells. Hence it appears that action of magnetic field under long exposition to it, combined exposure to magnetic fields, are, in some cases, comparable to effects of cytozar. It is possible that concurrent prescription of cytozar together with magnetization of blood in patients with hemoblastoses should permit enhancing the efficacy of treatment. Employment of weak magnetic fields is a satisfactory and worth-while therapeutic attempt to be made in a multimodality treatment of patients with hemoblastoses.

It was demonstrated that radiosensitizer AK-2123 of the triazole group significantly enhanced the sensitivity of MDR-strains of P388 murine leukemia (reported by the authors earlier) to mitomycin C (MMC). There was a direct correlation between the modulating effect of AK-2123 and dose increase from 1 to 10 mg/kg. The effect depended on the initial sensitivity of the MMC-resistant strain which in turn correlated with the absence or presence of sorcin (cytosole low-molecular Ca(2+)-binding protein) gene coamplification in the mdr-amplicon. Since AK-2123 was reported earlier by us to disrupt active Ca(2+)-transport, it is suggested that the modulating effect of the radiosensitizer was at least partially due to said disruption. AK-2123 exerted no antitumor action of its own whatsoever. It could neither modify the sensitivity of parent strain P388 to MMC, nor overcome the cross resistance of one of the MDR-tumor strains under study to such drugs as etoposide and adriablastin.

The effectiveness of adjuvant therapy with adriablastin and doxorubicin for breast cancer has been compared to that of standard CMF. During 1985-1990, the study included 349 patients with T1-2N2M0 and T3N0-2M0 tumors; mean age--46 yrs; mean follow-up--96.7 months. Overall survival rate in the doxorubicin group was 73%, CMF--62%; relapse-free survival--62.1 and 55%, respectively. The absolute difference in overall survival rates (11%) proved barely significant (p = 0.056). However, the difference in overall survival (p < 0.05) after anthracyclines and CMF in patients with tumors T1-2N2M0 and T3N1M0 was significant and in favor of the former. As far as frequency and degree of side-effects is concerned, their patterns were practically identical in both groups, except for the significantly higher frequency of cardiotoxity and complete alopecia in doxorubicin therapy. Cardiotoxic complication rate was significantly reduced from 13.8 to 3.9% by cardioxane treatment.

The effect of phencarol, ranitidine, propranolol, atropine, and diethylstilbestrol (known as modulators of the tamoxifen-binding sites in plasma membranes) on the 3H-tamoxifen binding to the plasma membrane fraction of white rat uterine cells was studied by determining the amounts of estradiol and H1- and H2-receptors. The interaction of tamoxifen with various receptors of uterine cells may be significant for evaluation of the tumor activity of this compound.

The effect of reaferon (introduced at a dose of 1 x 10(6) IU/kg over six days prior to ischemia induction) on the levels of catecholamines and the activity of succinate dehydrogenase and NADH-dehydrogenase in various structures of kidney was studied in experiments on white rats. The ischemia was modeled by 90-min ligation of renal vessels. Reaferon retained the luminescence of catecholamines in all renal structures 24 h after circulation was restored on the level of intact kidney, except for the nerve trunks where the luminescence intensity decreased by 40%. Preliminary introduction of reaferon stimulated restoration of the enzymatic activity in the Krebs cycle and mitochondrial respiratory chain after 24- and 48-h revascularization, respectively.

The effect of antitumor medicine Brotheophine to insertion of the marked precursors into DNA (14[C]-timidine), RNA (3[H]-orotic acid) and proteins (14[C]-leucine) of tumor cells (Pliss lymphosarcoma) as the indices of biosynthetic processes was investigated. It has been shown that Brotheophine acts as an antimethabolite of purine exchange and inhibits the vertical genetic information transfer in tumor cell (DNA-RNA-protein). Namely, a significant inhibition of 14[C]-timide insertion to DNA has been observed. less distinct is the inhibition of 3[H]-orotic acid to RNA und 14[C]-leucine to proteins. The above revealed allows to assume that during Brotheophine treatment certain changes in DNA biosynthesis take place leading to synthesis of slightly transformed RNA with subsequent impairment of proteins synthesis.

Plasma-membrane-enriched particles isolated from the tissues of malignant tumors of different sites are shown to accumulate ATP under the influence of polypeptide growth factors and cytokines whose receptors have a tyrosine kinase activity. Polypeptide growth factors, such as EGF, FGF, NGF, TNF, insulin, and the cytokine IL-2, were studied on the accumulation of adenosine-5'-triphosphate (ATP) by the preparations of plasma-membrane-enriched particles isolated from the target tissues of human malignant tumors. The tumor (transformed) cell plasma membranes of the lung, bowel, stomach, pancreas, as well as the cells of neurinoma and a retroperitoneal extra-organ malignant tumor (leiomyosarcoma) are demonstrated to be able to synthesize ATP from inorganic phosphate and ADP under aerobic conditions human with the participation of the cyanide-insensitive proton phoric NADH-bound transversely oriented chain. Signal-stimulated accumulation of plasma membranous ATP was found to increase in the tissues in malignant transformation as compared to that in normal tissues. Experiments using selective inhibitors of tyrosine kinases (tyrphostin-25, quercetin) indicated the involvement of plasma membranous signal-transducing ATP in the activation of receptor tyrosine kinase growth factors.

The effect of some steroid hormones and their synthetic analogs--dexamethasone, estradiol, progesterone, testosterone, and cytostatics--on the fibroblast nuclei in a monolayer culture was studied. Their proliferation was studied at the same time by the radioindicator method. The method of computerized morphodensitometry with the use of the apparatus-programmer complex DiaMorf (Russia) showed that the compounds under study induce reorganization of interphase chromatin of fibroblast nuclei over the molecules, the amount of which may be recorded by means of the computer system of analysis of cell and tissue images.

A computer-assisted method of video imaging the adhesive, permeability and thrombogenic properties of microvessels was used to study the effect of dexamethasone on the functional activity of the mesenteric microvascular endothelium in rats with Pliss' lymphosarcoma. Dexamethasone-21 Na-phosphate (0.1 mg/ml) was supplied to the desired mesenteric area and the necessary measurements were carried out. The latter showed that tumor growth was associated with microcirculation disturbances, namely, raised leukocyte adhesion to the mesenteric microvascular endothelium, microvascular permeability and thrombogenicity. Enhanced microvascular sensitivity to dexamethasone pointed to the important role played by changes in the adhesive properties of the endothelium among general paraneoplastic disorders of microcirculation.

Tumor growth and proliferative activity of tumor cells were suppressed and the number of pulmonary metastases in C57B16 mice decreased 3.3-fold following seven injections of cycloferon (100 mg/kg body) to induce interferon production. Injections were carried out 1-16 days after subcutaneous transplantation of Lewis lung carcinoma. After mice were immunized with ovine red blood cells, cycloferon administration raised thymus-dependent humoral immune response. After eight injections of cycloferon (50 mg/kg body) into rats, from day of intravenous transplantation of rhabdomyosarcoma RA-23 until day 20, no significant effect on metastasizing into the lung was recorded. However, single injection of cyclophosphamide 50 mg/kg inhibited metastasis formation. The highest suppressor effect was registered with combination cycloferon-cyclophophamide treatment: mean weight of metastasis decreased by half, as compared with treatment with cyclophosphamide alone. Both drugs caused karyotypical abnormalities to occur in metastatic cells. Tumor growth and spreading suppression after cycloferon should be attributed to cytotoxic antitumor action, cell proliferation inhibition and immunomodulating effect.

In an experimental model of cardiomyopathy in Syrian hamsters, four principal phases were identified: lesion, reparation, compensation, and decompensation. Calcium overload seems to be a leading pathogenic factor in the 1st phase. If the action of damaging factor persists, the reparation phase is incomplete, and the compensation of the cardiac contractile function occurs due to an altered protein composition in the cells and extracellular matrix.

An experimental treatment with rose bengal showed that optimal effectiveness of photodynamic therapy of sarcoma M-1 was achieved 3-4 hr after intraperitoneal injection of 10 mg/kg body.

Glycyrramum was shown to potentiate the antitumor and antimetastatic effects of cyclophosphamide treatment in mice and rats with transplantable tumors. It also decreased its myelotoxicity. After primary Lewis lung carcinoma was removed glycyrramum treatment significantly inhibited metastacizing processes in mice.

To study pharmacokinetics of liposomal daunorubicine DaunoXome and daunorubicine (rubomycin) associated with red cells: to assess their effectiveness and toxicity in patients with acute leukemia.

The results of toxicological evaluation of the new plant preparation Phitomix-40 (PM-40) used in the treatment of cancer are presented. To prevent a patient's individual immunological responsiveness to some phytoadaptogens, the preparation comprises 40 plant extracts (Rhodiola r. L.; Juniperus C. L.; Helichrysum a. L; Viburnum o. L., etc.). Animal experiments demonstrated that PM-40 had a low toxicity; LD50 was more than 20 and 15 ml/kg for rats and mice, respectively.