Antitumor activity of a new highly active promising gestagen 17alpha-acetoxy-3beta-butanoyloxy-6-methyl-pregna-4,6-dien-20-one (butagest) was studied in mice with model cervical carcinoma (RShM-5). The reference drug was medroxyprogesteron acetate (MPA, Depo Provera) used in clinics. The new preparation introduced perorally in a dose of 1 mg per mice inhibited the model tumor growth by 73%, which was 18% (p < 0.01) more effective than the action of the reference drug MPA. The effect of the new gestagen was also studied in vitro with respect to human breast carcinoma of the MCF-7 line and human cervical carcinoma HeLa. The viability of the tumor cells was studied during a 6-day incubation with the drug at a concentration of 10(-7)-10(-5) M (MTT test). The reference compounds were progesterone and MPA. These drugs suppressed the growth of both MCF-7 and, in higher concentrations, of HeLa. Butagest inhibited the growth of HeLa in all concentrations. Thus, the new gestagen 17alpha-acetoxy-3beta-butanoyloxy-6-methyl-pregna-4,6-dien-20-one is capable of suppressing the viability of human breast carcinoma and human cervical carcinoma, being comparable or even more effective than the reference drugs.

A study was made of apoptotic cell shrinkage, which is generally believed to be a hallmark of apoptosis. The two conventional models of apoptosis were used for examination of changes in cell water balance--one is apoptosis caused in human lymphoma cell line U937 by staurosporine, and the other by etoposide. Intracellular water was determined by measuring buoyant density of cells in continuous Percoll gradient. Apoptosis was recognized by microscopy and flow cytometry. Apoptosis caused by staurosporine (1 microM, 4 h) was found to be associated with a decrease in cell water content by almost 24%. In contrast, no decrease in cell water content was observed in U937 cells incubated with etoposide (50 microM, 4 h), in spite of the number of features suggesting the presence of apoptosis, such as the appearance of apoptotic bodies, chromatin condensation and fragmentation and disappearance of S-phase cells in DNA histogram. It is concluded that definition of apoptosis as "shrinkage-necrosis" (Kerr, 1971) needs correcting: the distinction of apoptotic cells involves the absence of swelling, rather than cell shrinkage.

Cytostatic drugs used in the treatment of hemopoietic malignancies affect cells of other organs and systems, vascular endothelium, in particular. This leads to cardiovascular complications. We studied effects of some drugs and their combinations on cultured human endothelial cells (EC).

Comparative efficacy of moxifloxacin and ciprofloxacin as prophylactics of infection in cancer patients with severe neutropenia after the chemotherapy was studied. The study included 40 patients with malignant lymphomas and solid tumore who received 52 courses of the aggressive chemotherapy. Twenty four patients (30 courses) received oral moxifloxacin in a dose of 400 mg once a day from the first day of the neutrophil count decrease below 1.0 x 10(9)/l until its recovery to > 1.0 x 10(9)/l or when the signs of infection appeared. In the control group 16 patients (22 courses) received oral ciprofloxacin in a dose of 500 mg twice a day. The patients in both the groups were compatible by the diagnosis, age and neutropenia duration. The median of the days of the febrile neutropenia duration in the patients prophylactically treated with moxifloxacin was statistically lower (2.1 vs 3.6 in the control group, p < 0.05). The incidence of febrile neutropenia in the moxifloxacin group was significantly lower than that in the control group (73 and 100% respectively, p = 0.01). The incidence of bacteriologically confirmed infection in the moxifloxacin group was also lower (6% vs 27.2%, p = 0.04). Therefore, moxifloxacin proved to be a more efficient agent vs ciprofloxacin (standard prophylactic) in prevention of febrile neutropenia and neutropenic infection in cancer patients, which is likely due to its higher activity against grampositive organisms.

Most of anti-tumor factors are designed to kill selectively cancer cells; in most cases this action is related to the ability of the above substances to induce apoptosis. One of potent anti-apoptotic mechanisms is based on Hsp70 protein. Since the level of this protein is often higher in malignant tumors than in normal tissues, the aim of this study was to establish whether the elevated Hsp70 content may influence the process of apoptosis induced by anti-tumor drugs in cancer cells population. The increase of intracellular content of Hsp70 in human leukemia U-937 cells was attained by a mild heat stress or by transfection of cells with the human hsp70 gene. The elevation of Hsp70 quantity, irrespective of the way it was performed, leads to the inhibition of apoptosis in cells treated with two substances, etoposide or adriamycin. The inhibition of apoptosis was accompanied with the reducing of the share of cells with fragmented nuclei and with the delay in caspase activation. It is suggested that in addition to the previously discovered targets, whose activity is suppressed by the Hsp70 chaperone, this protein can inhibit the activity of caspase-3 and -7; this delays the onset of apoptosis in part of a cancer cell population.

E1A + c-Ha-ras-transformants overexpressing bcl-2 oncogene are able to be arrested at the G1/S boundary of the cell cycle after DNA damage and upon serum starvation, this cell cycle blockage being accompanied by a decrease in the activity of cyclin E--Cdk2 complexes. Roscovitine-induced inhibition of cyclin-dependent kinases (Cdks) activity does not result in the G1/S arrest of E1A + c-Ha-ras + bcl-2-transformants. Roscovitine treatment causes an accumulation of G2/M cells, mainly at the expense of mitotic cells. However, the expression of Bcl-2 oncoproducts does not re-establish the regulation of mitotic events broken by introduction of E1A and c-Ha-ras oncogenes in normal cells, as revealed by the treatment of E1A + c-Ha-ras + bcl-2-transformants with nocodazole inducing mitotic arrest in normal cells. In spite of the elevated expression of antiapoptotic bcl-2 gene in transformants, nocodazole treatment results in mass apoptotic death preceded by polyploidy. Roscovitine also induces apoptosis with no polyploid cell accumulation being observed. Inhibition of Cdks activity with Roscovitine, as well as violation of microtubule depolymerization with nocodazole result in the apoptotic death in the tested cell lines sensitive (E1A + c-Ha-ras) and resistant (E1A + c-Ha-ras + bcl-2) to damaging agents. Thus, the application of Roscovitine, a specific inhibitor of Cdks, suggests that the decrease in Cdks activity in E1A + c-Ha-ras + bcl-2-transformants is not likely to be responsible for G1/S cell cycle arrest realization after damaging influences. Moreover, an antiproliferative effect of Bcl-2 in E1A + c-Ha-ras-transformants is restricted by restoration of cell cycle events at G1/S and G2/M boundaries, and does not concern the program of mitotic events regulation.

Pregnant rats exhibited regenerative anemia development 3 months upon a single intravenous injection of carboplatin in a maximum tolerated dose; the effect increased by the end of pregnancy. The character of changes in parameters of the peripheral and central erythron parts (increased level of erythrocyte hemolysis, decrease in the amount of erythrocytes, increase in the number of reticulocytes, development of erythropoietic hyperplasia in bone marrow and spleen) was indicative of the hemolytic type of anemia.

In experiments on rats (290 animals) exposed to chronic gamma-radiation with the total dose of 10.0 Gy it was detected that prescription of synthetic pharmaceutical of the dihydropyridine class--glutapyrone--together with drinking water during 6 months reduced the rate of malignant neoplasms from 26.5% in the control group to 13% in the treated animals. In radiation-exposed rats that received glutapyrone there was a narrowing of spectrum of the emerged neoplasms (connectively-tissual tumors only) as compared to the animals of the radiated control group, where blastomas of epithelium and lymphoid origin were also revealed. Low toxicity of glutapyrone and its anticarcinogenic action show the potential for this preparation to be used in practice.

Preliminary results of treatment of 28 patients with cancer recti, in whom lymphatic chemotherapy was applied and operative intervention as well, were studied. The results of treatment in control group, consisting of 28 patients, to whom neoadjuvant systemic chemotherapy was conducted, are adduced. Comparative analysis performed have shown that general toxic signs occurred three times lesser in patients of the main group, than in a control one; the postoperative complications was two times lesser. In one-year follow-up in the main group the recurrences and metastases were absent, in a control group the tumor recurrence had occurred in 3 (10%) of patients.

The paper contains an analysis of research on designing drugs based on acridine derivatives. The discussed series of compounds is of essential value since acridines belong to the group of natural compounds with the pronounced antibacterial and anti-tumor activity. Improved chemical-synthesis techniques made it possible to synthesize both simple and complex compounds of the acridine series; they displayed a clear pharmacological activity as anti-proliferative, anti-tumor and antiparasitic preparations. The ability to induce interferons (INF), type 1, is an expected property of simple acridine derivatives. A variety of INF inducers, now used clinically, have been designed recently on the basis of the above compounds. The most well-known acridine derivatives, their pharmacological properties, action mechanisms and outlooks for practical application are described in the paper. The unique qualities of acridines are primarily attractive due to the possibility of using them for the purpose-oriented designing of drugs. Thus, acridines were used as a basis to create the specific regulatory HIV-1 elements, proliferation inhibitors of leukemia cells and new anti-tumor drugs. The elaboration of complexes of acridines derivatives combined with peptides intercalating specifically into the DNA big or small grooves is the most outstanding trend of acridines' research--it opens up prospects for using them in the synthesis of compounds regulating the gene expression.

The many-year use of interferons (IFN) and of their inducers in medical practice made the drugs a weighty component of a rational pharmacotherapy of infectious and oncological diseases. Their main advantage is a wide IFN efficiency spectrum preconditioned by their action mechanism and by the fact that IFNs are an important constituent element of the natural (congenital) immunity. The paper is a comprehensive survey of the antiviral IFN potentialities fit for the prevention and therapy of a huge variety of viral infections. Finally, it was proven that IFNs and some of their inducer are effective when used in the treatment of a number of autoimmune and allergic diseases.

Ultrastructural, morphometric and metabolic characteristics were studied in thyrocytes of 96 mice treated with immunosuppressing and cytostatic drug cyclophosphamide (CY), injected intraperitoneally every other day either for a short time (up to 6 days) in high doses (400 mg/kg) or for a long time (up to 70 days) in moderate doses (40 mg/kg). High doses of CY caused the reduction in thyrocyte height, NADH-diaphorase activity in their cytoplasm and protein content in the follicular colloid as compared to these parameters in a control group. The cisterns of rough endoplasmic reticulum (RER) underwent swelling and deformation with the loss of electron density of their contents. This was accompanied by mitochondrial swelling with matrix clarification and disorganization of cristae and an increase in the amount of cytoplasmic lipid droplets. Following long-term administration of CY in moderate doses the thyrocyte height exceeded that one in control group, while the NADH-diaphorase activity changed insignificantly and protein concentration in colloid increased. In the majority of thyrocytes the nucleus and major organelles retained their normal structure, while in some cells the cisterns of RER appeared dilated. Acid phosphatase activity was unchanged in both experimental groups. Thus, despite the approximately equivalent total CY dose in experimental groups, its damaging effect on thyrocytes was expressed much less in animals receiving the moderate doses of CY, that, probably, could be explained by the lack of CY cumulative effect and high rate of its metabolic degradation and clearance.

Hydroxymethyluracil (HMU) in a dose of 1.5-3 g/day produces a stimulant effect upon leukopoiesis and granulocytopoiesis in cases of toxic neutropenia caused by chemotherapy. In the same dose range, HMU produces immunostimulant action in patients with immune deficit caused by oncopathology and chemotherapy.