The universal dependence of the synergistic interaction on the intensity of the acting agents was demonstrated. This dependence is not associated with the biological object, as well as the nature of the physical or chemical agents used in the combined exposures. In all cases, with a decrease in the intensity of one of the agents the intensity of the other factor should be also decreased to ensure the greatest synergistic effect. Such relationship of synergy and the intensity of the acting agents is of interest for radiation safety. This regularity indicates the principal possibility of synergistic interaction of harmful environmental factors actually occurring in the biosphere at their low intensities.

The dendritic polymers (dendrimers) are perspective nanocontainers for transportation of anticancer drugs into cells and a controlled release of the delivered substances. However, the combined effect of ionizing radiation and dendrimers loaded with anticancer drugs has been poorly studied and is the aim of this research. We used poliamidoamin (PAMAM) dendrimers of the second generation (G2) covalently conjugated with doxorubicin (Dox) via an acid labile linker, cis-aconitic anhydride. We compared the intracellular accumulation of Dox and growth rate of the MCF-7 cell culture under the single and combined action of ionizing radiation at a dose of 4 Gy, free Dox and G2-Dox. It was found that within 2 hours free Dox accumulated in cancer cells better than Dox connected with G2 dendrimers (p < 0.05 in the concentration range of 1-5 μmol/l). The intracellular accumulation of Dox was higher by 1.7 times for the free Dox than that connected with dendrimers (for concentration 0.5 μmol/l p = 0.02) after 26 hours of incubation. Like the intracellular accumulation of Dox, inhibition of the cell culture growth was more pronounced when using free Dox than G2-Dox in the case of both a single and combined action of these drugs. Subadditivity effects of the combined action of both drugs and ionizing radiation are shown in terms of reducing the number of tumor cells 24 hours after irradiation. The results indicate the need for further development of selective delivery systems for Doxin tumor cells, providing a more intense accumulation of anticancer drug in target cells.

The data on the pharmacoeconomic research of the use of Remaxol in treatment of drug-associated liver injury due to the chemotherapy in cancer patients are presented. The costs-efficiency method was applied to two groups of the patients with drug-associated liver injury treated according to different schemes. The research showed economical benefits of the Remaxol use.

Ophiocordyceps sinensis and Cordyceps militaris metabolites showed a high potential in the treatment of tumors as well as some other diseases. Antitumor properties of O. sinensis and C. militaris submerged mycelium were investigated. It was found that the O. sinensis dry biomass in a dose of 50 mg/kg administered once a day to the mice with subcutaneously inoculated P388 lympholeucosis lowered the tumor growth by 65% vs. 54% for the C. militaris dry biomass. The water extract of O. sinensis submerged culture however accelerated the growth of the P388 lympholeucosis tumor node in the mice almost two times, compared to the control. A greater caution in using this fungus as a source of biologically active substances is required since unwanted tumor-stimulating effects can arise.

Since the prognosis for visual acuity after polychemotherapy or superselective intra-arterial chemotherapy (SIACT) is doubtful, studying retinal function in children with retinoblastoma by means of clinical electroretinography (ERG) is a relevant issue. The latter enables objective post-treatment assessment of retinal function and evaluation of possible infusion-related retinal toxicity. This review analyzes ERG findings in children with retinoblastoma treated with chemotherapy, including SIACT.

As a new means of prevention and treatment of diabetes can be considered Embryonic antitumor modulator Mkrtchyan (EATM). According to our data on the STZ model of diabetes in rats EATM revealed hypoglycemic effect. Moreover, EATM prevented the development of oxidative stress. It is shown that EATM having immunomodulatory action, realizes its effect by regulating the Nox (NAPH oxidase) system. Inactivation of Nox, including the pancreas, is one of the factors determining the safety of the organ responsible for the development of diabetes. The release of the Nox is increased ex vivo and in the patients with type 1 and 2 diabetes. Mechanism for enhancing of the Nox isoforms release from erythrocyte membranes and blood serum exosomes in the presence of ferriHb in diabetes may be due to destabilizing of the cell membranes. It is established that the glucose at low concentrations bound to isoforms of Nox at the membrane surface due to increasing their stability, and at high concentrations, on the contrary, it lowers their stability. Thus, we have demonstrated a new mechanism of destabilization of cell membranes in diabetes mellitus. Suppression of the release of the pancreas Nox membrane cells in this pathology by means of EATM is perhaps a new mechanism of stabilization of these membranes, which explains the antidiabetic effect of the preparation.

Nausea and vomiting are among adverse effects of chemotherapy that significantly worsen quality of life of patients. 5-HT3 receptor antagonists have been used in recent decades to prevent and arrest these complications. Palonosetron is the most modern drug in this group. Palonosetron application during highly and moderately emetogenic chemotherapy showed its high effectiveness for nausea and vomiting prevention.

The study or antitumor effects of dioxadet, cisplatin, melphalan, paclitaxel, mitomycin C, cyclophosphamide and gemcitabine at intraperitoneal (i.p.) and intravenous (i.v.) administration as monochemotherapy and polychemotherapy in a rat model of ascitic ovarian cancer was carried out in 244 female Wistar rats. Ovarian cancer was transplanted i.p. at a number of 1 x 10(7) tumor cells. The drugs were administered once in 48 hours after ovarian cancer transplantation i.p. or i.v. for monotherapy--in maximum tolerated doses, for i.p. polychemotherapy--in half doses from maximum tolerated doses. Antitumor effects of the treatment were estimated in increase in median survival time (MST) compared to control rats who were administered saline i.p. At i.p. administration dioxadet, cisplatin and melphalan increased MST by 79%, 88% and 144%, respectively, while at i.v. administration these drugs didn't affect MST. Mitomycin C and paclitaxel had stronger antitumor action at i.v. administration increasing MST by 152% and 81%, respectively, while at i.p. administration these drugs increased MST by 35 and 45%, respectively. Combinations dioxadet + cisplatin, dioxadet + cyclophosphamide and dioxadet + paclitaxel at i.p. administration increased MST by 305%, 277% and 133%, respectively, and had additive antitumor action compared to mono-effects of these drugs. Gemcitabine and combination dioxadet + gemcitabine at i.p. administration didn't significantly affect survival of rats with ovarian cancer. Intraperitoneal monochemotherapy and polychemotherapy could be more effective in the treatment of peritoneal carcinomatosis from ovarian cancer compared to systemic administration of the drugs.

The article presents immediate results of neoadjuvant treatment of patients with locally advanced head and neck squamous cell cancer and an evaluation of the toxicity of cetuximab. Standard chemotherapy in combination with targeted therapy with cetuximab showed its high effectiveness and satisfactory tolerance.

A novel drug for treatment of bone metastases based on human recombinant tumor necrosis factor (TNF-alpha) has been designed. The drug is a molecular structure containing yeast double-stranded ribonucleic acid (dsRNA) covered by the conjugate of polyanion dextran with TNF-alpha and bisphosphonate, alendronic acid. The structure is characterized by the combination of substances possessing antitumor activity (TNF-alpha, dsRNA) and a vector molecule (bisphosphonate) providing tropism to hydroxyapatite, the main mineral component of the bone tissue matrix. The conjugation conditions were optimized and the conjugates of TNF-alpha and alendronic acid with dextran were synthesized. Molecular structures were obtained by self-assembly, and the resulting complexes were separated by gel filtration on Sepharose CL-6B. The electrophoretic analysis method revealed decreased mobility of dsRNA in the complex with the conjugate as compared to the mobility of the original dsRNA. This confirms formation of the designed structures. Transmission electron microscopy confirmed the presence of particles with sizes of 30-40 nm in the drug. Evaluation by the sorption/desorption method showed a higher affinity of TNF-alpha conjugates to hydroxyapatite as compared to the original TNF-alpha molecules (from 1.0 to 1.8 mol/L vs. 0.3 mol/L of potassium phosphate buffer for desorption, respectively).

Induced differentiation of leukemia cells is in the focus of basic and applied biomedical studies medicine and biology for more than 30 years. During this period specific regulatory molecules involved in the maturation process have been identified by biochemical and molecular biological methods. Recent developments of high-throughput transcriptomic and proteomic techniques made it possible to analyze large sets of mRNA and proteins; this resulted in identification of functionally important signal transduction pathways and networks of molecular interactions, and thus extent existing knowledge on the molecular mechanisms of induced differentiation. Despite significant advances in mechanisms of induced differentiation, many problems related to the molecular mechanism of cell maturation, a phenomenon of therapeutic resistance of leukemic cells need better understanding and thus require further detailed study. Transcriptomics and proteomics methods provide a suitable methodological platform for the implementation of such studies. This review highlights the use of transcriptomic and proteomic methods in studies aimed at various aspects of the induced differentiation. Special attention is paid to the employment of the systems approach for investigation of various aspects of cell maturation. The use of the systems approach in studies of induced differentiation is an important step for the transition from the formal data accumulation on expression of mRNA and proteins towards creating models of biological processes in silico.

Although several years have passed since the determination of the human papilloma virus (HPV) as the causative agent for cervical cancer, a definitive treatment has not yet been found. Interferon-alpha (IFN-α) immunotherapy is one of the promising methods for tumor treatment, although numerous side effects were observed in clinical trials. Recently, a new type of interferon, lambda-interferon (IFN-λ), has been discovered with fewer side effects than IFN-α since its receptor repertoire is limited. IFN-λ has a series of activities including antiviral, anti-proliferative and anti-tumor actions. In the present study, the effects of IFN-α and IFN-λ on the TC1 papilloma tumor model in C57BL/6 mice were evaluated. TC1 cells were injected into the mice subcutaneously. Upon tumor formation, murine IFN, mIFN-α and mIFN-λ, expression plasmids were injected intratumorally in combination or alone. The survival time and tumor size as well as apoptosis in tumors and NK cytoxicity were measured after three injections. As compared with the control group, the remarkable results especially in the group which received mIFN-α and mIFN-λ together were obtained for all of the measured parameters. Although IFN-λ is a new member of the interferon family and its properties should be studied in detail, the data obtained suggests that the use of IFN-λ especially in combination with IFN-α could be considered as an effective strategy for papilloma cervical cancer immunotherapy.

Synthesis of lupane C28-imidazolides, contained 3-oxo-, 3-oximino- and 2-cyano-2,3-seco-4(23)-en-frag ments in cycle A was carried out. The most antitumor activity at. in vitro testing showed 3-oximino-lup- 20(29)-en-28-yl-1H-imidazole-1-carboxylate; which inhibited the growth or induced apoptosis of non-small lung cancer, colon cancer, breast cancer, CNS cancer, ovarian cancer, prostate cancer, leucosis, melanoma cells. In experiments in mice its moderate antitumor activity against grafted breast adenocarcinoma Ca 755 and adenocarcinima of colon was observed.

to assess the dynamics of macular morphofunctional parameters in wet age-related macular degeneration after three injections of ranibizumab.

The aim of work was to study the effect of anticancer drugs on the process of CD 95 mediated apoptosis in BL-41 and DG-75 infected with Epstein-Barr virus. Studies of the effect of anticancer drugs "Doxorubicin" "Ebewe" and "Vepesid" (Etoposide) on the apoptosis in EBV infected cells using cytomorphological methods, spectrophotometry and PCR carried out. The influence of the tested drugs in cell culture was assessed by calculating the CC50. It was shown that it was 20 μg ml both for Etoposide and for Doxorubicin in the case of cell line DG-75. BL-41 cells were more sensitive to the tested drugs. CC50 was 5 μg/mI. PCR method showed that in the studied cell lines active accumulation of EBV DNA took place. In 24 hours after infection in the DG 75 + EBV system 20 μg/ml Doxorubicin provoked apoptosis in 89% of cells, and Etoposide-induced apoptosis was 35%. Cell culture BL-41 was equally sensitive to both drugs. At the same time, in the EBV super infected cells + Doxorubicin only 10% of apoptotic cells were detected. The obtained data prove the impact of viral infection on the sensitivity of lymphoma cells BL-41 and DG-75 to tested anticancer drugs.

The antitumor effect of L-lysine-α-oxidase from the culture fluid of Trichoderma harzianum Rifai F-180 was investigated for the first time. The in vitro studies revealed its high activity on a model of the forest-spring encephalitis virus and no activity against the Sindbis, Western Nile, Tyaginya and Dhori viruses.

Carnosine is an endogenous dipeptide with antiproliferative properties. Here we show that carnosine selectively inhibits proliferation of human glioblastoma cells (U-118-MG) compared to breast (MB231) and oral (Cal27 and FaDu) cancer cells. Carnosine-induced inhibition of U-118-MG proliferation is associated with a significant: decrease in cellular reactive oxygen species levels, increase in manganese superoxide dismutase (MnSOD) and increase in cyclin B1 expression resulting in G2-block. We conclude that the antiproliferative property of carnosine is due to its ability to enhance MnSOD and cyclin B1 expression. These results will be of significance to the potential application of carnosine in brain cancer therapy.

The impact of a number of synthetic nucleoside derivatives on the growth and survival of cultured human ovarian tumor cells (line SKOV-3) and normal human lung fibroblasts was investigated. It was shown that the dialdehyde derivatives of uridine, 1-β-D-eritrofuranozyl uracil and 3'-O-β-D-ribofuranosyl-2'-deoxythymidine, in contrast to their unoxidized counterparts, exert marked toxic effect on SKOV-3 cells. Cultured human fibroblasts were less susceptible to the damaging effect of the dialdehyde nucleosides. The dialdehyde derivative of 1-β-D-eritrofuranozyl uracil demonstrated greatest differences in the cytotoxic effect on these cultures: inhibition of tumor SKOV-3 cells growth on 50% or more was achieved at the concentrations of this compound ten times lower than in the case of normal fibroblasts.

The anticancer antibiotic doxorubicine (DOX) is highly toxic and induces functional complications in vital organs. The effect of DOX on normal cells has not been examined in sufficient detail, and the search for compounds reducing DOX toxicity did not lead to success so far. It has been suggested that DOX induces death of cancer cells via p53-dependent apoptosis, however, the information regarding the role of p73 protein, a member of p53 tumor suppressor family, is scanty. Cytomegalovirus (CMV) induces an antiapoptosis program that allows its replication until death of the target cell. Our objectives were to examine the effect of DOX on normal cells (human fibroblasts), analyze the ability of CMV-induced antiapoptosis program to reduce DOX toxicity, and to evaluate the involvement of p73 protein and its isoforms in the regulation of death of CMV-infected and DOX-treated cells. Within a 24-h time period DOX caused death of about 70% human embryonic lung fibroblasts (HELF) in cell culture, this parameter decreased significantly in CMV-infected DOX-treated HELF cells. TUNEL has shown that the number of cells with DNA fragmentation decreases from 5.2% under the effect of DOX to 3.2% (P < 0.05) after combined CMV-DOX treatment. Analysis of mitotic figures revealed that DOX causes accumulation of mitotic cells, which was not observed in CMV-infected DOX-treated cells. PCR analysis of mRNA of two p73 protein isoforms (TAp73 and dNp73) has shown that in uninfected cells the expression of TAp73 isoform was low, while in CMV-infected cells level of TAp73 was significant and expression of dNp73 was demonstrated for the first time. Expression of TAp73 associated with lack of mitosis block. The activation of caspases 8, 9 and 3 in CMV-infected cells was registered but cell death was not, however, as massive as that caused by DOX. From these findings it can be concluded that CMV attenuates DOX-related damage to normal cells. It can be suggested that induction of TAp73 and dNp73 isoforms provides conditions for reduction of DOX effect which leads to DNA damage and death of normal cells.

to evaluate the efficacy of anti-VEGF therapy in patients with exudative age-related macular degeneration (AMD) and glaucoma.