The physicochemical, catalytic, and antiproliferative activity of a recombinant L-asparaginase from Yersinia pseudotuberculosis (YpA) have been studied. The following results were obtained: the K(M) value for L-asparagine is 17 +/- 0.9 microM, the optimal temperature is 60 degrees C, pH is 8.0, pI is 5.4 +/- 0.3, the L-glutaminase activity is no more than 5-6% of the L-asparaginase activity, and the antiproliferative activity on the Fisher L5178y lymphadenosis cell line comprised T/C = 136% (p < 0.001) at a 15% recovery rate. The described characteristic allows one to regard YpA as an antitumor enzyme with biological features similar to the L-asparaginase of E. coli.

Double-stranded DNA is a one of the most important intracellular anticancer agent targets. Disturbance of DNA functions as well as DNA structure lead to disorder of such processes as transcription and/or translation thus inducing tumor cells death. Complex formation between novel dimeric bisbenzimidazole DB(7) and poly(dA-dT) duplex in comparison with known monomeric bisbenzimidazole MB(Ac) was investigated in this study. DB(7)-poly(dA-dT) binding constant was determined by fluorescence spectroscopy using Scatchard plot and it values 1.18 x 10(8) M(-1) that is two orders of magnitude larger than MB(Ac) one (2.06 x 10(6) M(-1)). Thus, from findings mentioned above it could be concluded that the presence of two bisbenzimidazole moieties in the ligand structure significantly increases its affinity to the polynucleotide which motivates the synthesis of new potential anticancer drugs based on dimeric bisbenzimidazoles.

The new sulfated polyhydroxysteroid has been isolated from the Pacific starfish Mithrodia clavigera, collected from Maldives Islands and named as mitrotriol (I, Na-salt of (20S)-3beta,6alpha,20-trihydroxy-5alpha-cholest-9(11)-ene 3-O-sulfate). In addition six previously known compounds, including glycosides: echinasteroside B, granulatoside A, linckoside K, forbeside L and thornasterol sulfate A and cholesterol sulfate were isolated and identified. The structure of mitrotriol was elucidated by spectroscopic methods (mainly 2D NMR: 1H, 13C, DEPT, COSY-45, NOESY, HSQC and HMBC) and mass-spectrometry. For selected compounds, concentrations that showed cytotoxic activity against melanoma cells SK-MEL-28, SK-MEL-5 and RPMI-7951 were determined.

Microspheres were obtained on the basis of poly(3-oxibutyrate) (POB) with the inclusion of the Chlorambucil and Etoposide cytostatic drugs in a polymer matrix, and the morphology, kinetics of drug release from microspheres, and the interaction between microspheres and tumor cells in vitro were studied. Data on the kinetics of drug release suggests that a prolonged release occurs by drug diffusion from the polymer matrix at the initial stage and at the expense of hydrolytic degradation of the polymer at a later stage. A study of the biocompatibility and biological activity of biopolymeric microspheres showed that chlorambucil operates actively and strongly inhibits the growth of cultured cells for a short time (24 h). Etoposide acts weaker (the percentage of cell growth suppression during 48 h does not exceed 50%), but subsequently it has a basis for the creation of new dosage forms with prolonged action of Etoposide and chlorambucil for cancer therapy.

Cytotoxic effect of anti-cancer drug, doxorubicin (DR), has been examined on human embryonic stem cells (ESC) C910 and fibroblasts spontaneously differentiated from these cells. The fibroblasts retained diploid karyotype. It was found that ESC are more sensitive to DR than fibroblasts: DR dose killing 20% cells was 0.01 and 0.1 microg/ml, respectively. DR induced ESC apoptotic death and reduced both ESC and fibroblast proliferation. Unlike fibroblasts DR reversibly inhibited ESC proliferation. Thus, we have demonstrated that ESC and their differentiated derivates differ their sensitivity and response to the genotoxic agent.

A highly effective and simple microbial test system for screening inhibitors of sterol biosynthesis (ISB) is described. The system is based on cultivation of the bacterial strain Halobacterium salinarum (former Halobacterium halobium), that possesses mevalonate pathway of sterol biosynthesis and is much similar in the biosynthesis to cholesterol formation in humans. In the H. salinarum test system the ISB were found as compounds that inhibited the test culture growth. Mevalonate which is one of the crucial intermediates of sterol biosynthesis dismissed the inhibitory effect of many microbial metabolites thus being evident of their action at the early stages of the sterol biosynthesis, including the HMG-CoA reductase stage. The H. salinarum test system was developed as a micromethod and could be easily mechanized by miniaturization of the microbiological procedures, cultivation in sterile 96-well plates and using automatic micropipettes and dispensers. The H. salinarum test system was effective in testing crude extracts of the culture broths and advantageous at early stage of screening. The use of the H. salinarum test system was shown possible for screening antitumor antibiotics.

The microbial test-system based on cultivation of Halobacterium salinarum developed earlier for screening inhibitors of sterol biosynthesis and proposed for screening anticancer antibiotics, proved to be efficient in revealing anticancer compounds among derivatives of tris(1-alkylindol-3-yl)methylium, synthetic analogues of antibiotic turbomycin A. Most of the methane sulfonate and chloride salts of such compounds, investigated with the help of the H. salinarum test-system, showed no activity (MIC>32 mcM), while several derivatives, containing N-butyl or N-pentyl substituents were rather active against the bacterial strain. The MICs of them against H. salinarum were 8 mcM for total and 1 mcM for partial inhibition of the bacterial growth. The results of the study correlated with the results of other investigations that revealed anticancer activity of such compounds in tumor cell cultures. Therefore, the H. salinarum test-system demonstrated its availability for screening compounds with anticancer activity.

The data on the mechanism of action, efficacy and safety of the drug fingolimod are presented. Further study of the molecular, biochemical and cellular mechanisms of action of pharmacological regulators of phospholipid mediators' signal transduction is an important basis for developing new immunomodulators and antitumor agents.

Due to biochemical characteristics of toxic action of fluoroacetate on energetics and metabolism of cells, including tumor cells, it was interesting to testify sodium fluoroacetate (SFA) for its antitumor activity in vivo. We have estimated that SFA significantly inhibits growth of Ehrlich tumor carcinoma. In experiments with autochthonous induced by benzo[a]pyrene subcutaneous tumors, SFA was not active in monotherapy regime, though potentiated antitumor effect of cyclophosphamide, significantly increasing the relative number of mice with stabilized or decreased tumor volume as well as the duration of this effect. The data obtained render basis for additional studies of mechanism of antitumor effect of SFA.

A study of the functional state of peritoneal macrophages was conducted of white outbred mice (W/o) which were resistant to cancer pathology as well as the mice of the A/sn line prone to development of cancer diseases. It was reveald that due to induction of aseptic inflammation ( induced by starch administration), chemotaxis of macrophages of the oncological line was 2.5-3 times reduced and capacity to adhesion was 1.5-2 times lower than capacity of macrophages of the control group (W/o). The paint on F-actin of cytoskeleton in cells showed that cells of the control group form filopodia as a result of adhesion to the substrate, during intercellular contacts as well as during macrophage incubation with retinoic acid. Macrophages A/sn can form pseudopodia when exposed to retinoic acid. Macrophages of both groups of mice were shown to be producer of endonucleases. The same activity of these enzymes was provided by the number of cells which was 1.5-2 times fewer in mice of the A/sn line.

Metformin (MF) belongs to the most popular andidiabetic medicines and is considered to possess a selective antineoplastic action. This selectivity at least partly may be explained by the certain features of MF pharmacogenetics. More than 150 postmenopausal females divided into 4 groups (cancer +diabetes type 2 (DM2); cancer without DM2; DM2 without cancer, and healthy) were studied. Genetic polymorphisms of the two groups of genes--entitled on the basis of the relation to potential MF effect as a 'standard' (S) or 'associated' (A)--were under investigation. Among S-markers a most informative in regard of MF response prediction appeared to be polymorphisms of OCT1-R61C organic cation transporter protein 1 gene and serin/threonine kinase STK11. In the group of A-polymorphisms the GC genotype of oxidized lipoprotein receptor OLR1_G501C demonstrated tendency to the combination with 'MF-positive' variant of OCT1_R61C. The carriers of the latter were characterized with insulin resistance while carriers of STK11 variants--with lower blood estradiol level. Postmenopausal diabetics with as well as without cancer, differ in genetic markers of potential response to metformin less than they differ from cancer patients without DM2.

The effect of root extract of Baikal skullcap (Scutellaria baicalensis) cultivated in vitro, on the gene structure of CBA/CaLac mice bone marrow cells damaged by anticancer drugs paclitaxel and cisplatin has been studied. It is established that the root extract exhibits gene protective property upon both single and chronic administration.

The paper presents a detailed review of the data available in the literature on the treatment of cryoglobulinemic vasculitis and some forms of B-cell non-Hodgkin lymphoma caused by hepatitis C virus. It shows treatment successes associated with the use of current combined antiviral therapy (interferon-alpha and ribavirin) and its combination with anti-CD20 monoclonal antibodies (rituximab). The combined therapy with rituximab and antiviral drugs allows a radical improvement of prognosis in nearly 50% of patients. Remaining treatment problems and new drug prospects are discussed.

The objective of this study was to investigate in vivo the dose response of radiation induced chromosomal aberrations in human blood lymphocytes of lung cancer patients given non-uniform fractional exposures to high doses of therapeutic 60Co gamma-rays delivered synchronously with polychemotherapy. The chromosome aberration analysis was carried out in peripheral blood lymphocytes of 13 lung cancer patients who manifested II to IV developmental clinical stage. During the course of radiotherapy they received the accumulated tumor dose ranged 47.5 to 70 Gy. The yield ofdicentrics, centric rings and fragments was measured in the blood samples taken before treatment, after the first day and after the complete course of radiotherapy. Based on cytogenetic measurements of 3 patients, the average tumor dose after the first day was estimated to be 2.1 to 3.0 Gy given that the corresponding physical dose was (1.0 Gy + 1.5 Gy). The quotient of the individual dose estimated by the frequency of aberrations to the physical dose after the complete course of radiotherapy was calculated for all 13 patients. The mean quotient was shown to be equal to 93 +/- 9% ranged 50 to 154%.

This article provides information about development and introduction of regional standard of specialized medical care for patients with neovascular age-related macular degeneration in medical practice in Tumen region. It discovered new opportunities for improvement of ophthalmologic care in the region.

Viability, histology and ultrastructure of normal cells and cells of different degrees of malignancy after interaction with dopamine as well as the ability of these cells and isolated G-actin in model experiments to stain by Falck technique were studied. It is shown that dopamine, virtually having no effect on the viability of the "normal" non-tumorigenic transformed cells, noticeably reduces cell viability of slightly tumorigenic cells, causes a significant reduction in viability of attachable cancerous cells and a very significant decrease in cell viability of cancerous cells growing in suspension. The intensity of fluorescence of the cytosole in cells treated with dopamine, has been very high and varied in different cultures, and that of isolated actin directly depended on its concentration. Common to all cell morphological feature of damage from the action of dopamine and the putative substrate of fluorescence was actodopamine filaments network strands (identified on the structure and size), which appears in the cytosole loci, where they were absent in control. The data show that dopamine can be used as an oncotherapeutic remedy and diagnostic tool interacting with G-actin as a cellular target.

Influence of alpha-difluoromethylornithine (DFMO) and tincture of Siberian ginseng root (TSGR) on radiation carcinogenesis and life span in rats has been studied. The results of the study demonstrate that DFMO as well as TSGR significantly improved survival and decreased incidence and multiplicity of malignant and benign tumors in rats subjected to ionizing radiation. Beneficial effect on the rat survival rate and anticarcinogenic action of DFMO were more expressed compared with TSGR.

The aim of the study was to investigate the effectiveness of combined long-term therapy by cytostatics and steroid hormones in older patients with membranoproliferative glomerulonephritis to halt renal failure progression. 27 patients older than 60 years with morphologically proved membranoproliferative glomerulonephritis have been treated. Nephrosclerosis was detected in 40% of studied patients according to results of kidney biopsies. The mean age of the patients was 65.8 +/- 1.5 years. The activity of the disease depended on presence and severity of nephrotic syndrome. 17 (62.9%) patients had coronary heart disease, 7 (25.9%) patients had chronic bronchitis, 7 (25.9%) patients had peptic ulcer disease in a remission phase. Patients received therapy by cyclophosphamide in a dose of 2 mg/kg daily and prednisolone in a dose of 1 mg/kg daily during 2 years. Tolerability of assigned treatment was satisfactory. The main clinical and laboratory signs of nephrotic syndrome were significantly reduced and the proof remission was reached after 8-12 months of combined therapy. During the observation (24 month) the glomerular filtration rate in studied patients didn't decreased over 30-59 mL/min/1.73 m2 and corresponded to stage 3 of chronic kidney disease.

We studied the expression of genes encoding vascular endothelial growth factors VEGF-A, VEGF-C, VEGF-D and their receptors in cell cultures of human multiple myeloma IM9, RPMI 1640, RPMI 8226. The studied cells did not differ by the expression of growth factors. Expression of VEGFR1 receptor was detected only in IM9 cells and VEGFR2 and VEGFR3 receptors were not expressed in multiple myeloma cells. A dependence between the aberrant CD45/CD56 phenotype of human multiple myeloma cells and VEGFR1 expression in them was revealed. The only VEGFR1-positive IM9 cell culture was most resistant to Velcade (bortezomib).

We studied the expression of peroxiredoxin genes (PRDX1, PRDX2, PRDX3, and PRDX6) in human erythroleukemia K652, human breast carcinoma MCF-7, and human ovarian carcinoma SKOV-3 cells during cisplatin resistance development. It was found that drug resistance formation was accompanied by a significant increase in the expression of PRDX1, PRDX2, PRDX3, PRDX6 genes in all cancer cell strains, which confirms the important contribution of redox-dependent mechanisms into the development of cisplatin resistance of cancer cells.