In experiments designed to study effect of taxan-containing agents on the progeny of Wistar rats, one of the parents was given a single intravenous injection of the antineoplastic drug paclitaxel 1, 3 and 6 months before crossing with the untreated partner. The number of systemic pathological changes in the off-springs of paclitaxel-treated females was significantly greater and their spectrum wider than in those of the treated males. Severity of toxic effects depended on the time of crossing after drug administration. The optimal time for obtaining less affected off-springs of treated females and males was 3 and 6 months after administration of paclitaxel.

This article is devoted to classical and alternative macrophage activation, and intracellular transmission of external signals onto genes. It presents data on postreceptor events resulting in the formation of classical or alternative properties of macrophages. The role of some molecules of intracellular signaling pathways (STAT1, NF-kappaB, IRAK, TRAF6, Jak1, Tyk2, STAT3, c-Maf, Sp1, C/EBP, CREB, STAT6, MAP-kinase, PI3-kinase, c P) in the development of proinflammatory and anti-inflammatory activities of macrophages is discussed.

The influence of various antineoplastic preparations (farmorubicin, paclitaxel, etoposide, platidiam) on morphological and functional status of the liver in experimental animals was studied. It is shown, that all these antineoplastic drugs possess strong hepatotoxic activity and thereby cause toxic hepatitis and increase activity of hepatic enzymes. Biochemical parameters were normalized within 30 days after treatment whereas morphological changes persisted somewhat longer.

Fusion gene consisting of dextran-binding domain from Leuconostoc mesenteroides subsp. Mesenteroides (DBD) and human recombinant interferon-beta (IFN-beta) incorporated between the nucleotide sequence encoding for the recognition site of human enteropeptidase (DDDDK) was installed and constructed in Escherichia coli. The overproducing strain of the chimeric protein DBD-IFN-beta consisting of the IFN-beta, spacer including 10 GS-repeats, human enteropeptidase recognition site, and dextran-binding domain from Leuconostoc mesenteroides was constructed. Free human recombinant interferon-beta was obtained as a result of treatment of the chimeric protein DBD-IFN-beta immobilized on sephadex G-25 with human enteropeptidase. The ability of free and immobilized protein to protect human cells from viral infection was demonstrated. The developed approach can be used for purification of the recombinant proteins with different biological activity and possible construction of new immunostimulating and antiviral drugs, growth factors, anti-cancer drugs, etc.

The study was concerned with antitumor action of internalized peptide incorporating a fragment of p161INK4a using a model of short-lived human tumor cultures sampled from resected material. Renal cancer sample showed the greatest therapeutic interval.

The efficiency of the chemotherapeutic agent methotrexate (MTX) in tumor cells is limited by the frequent development of the drug resistance of tumor cells. We had previously shown in vitro using human acute leukemia cells with various sensitivity to MTX (T-lymphoblastic CCRF-CEM line and resistant CEM/MTX subline) that MTX incorporation into liposomes as a lipophilic prodrug, diglyceride conjugate (MTX-DG), allows for the overcoming of cell resistance due to the impaired active transmembrane transport. In this work, we have studied the profile of binding with carbohydrates of the cell lines mentioned using carbohydrate fluorescent probes (poly(acryl amide) conjugates). Lipophilic conjugates of tetrasaccharide SiaLe(x), 6'-HSO3LacNAc, and also inactive pentaol for incorporation into liposomes, have been synthesized. The cytotoxicity of MTX-DG liposomes equipped with the SiaLe(x) ligand toward the sensitive CCRF-CEM cell culture was demonstrated to be 3.5 times higher than that of MTX-DG liposomes bearing the control inactive pentaol. The activity of MTX liposomes bearing 6'-HSO3LacNAc toward resistant CEM/MTX was 1.6-fold increased. The use of carbohydrate ligands as molecular addresses for drug-carrying liposomes as a potential method of treating heterogeneous tumor tissue is discussed.

The time course of changes in the content of lipid-soluble antioxidants in the sera of male Wistar rats with transplantable Walker-256 carcinosarcoma in the application of controlled systemic hyperthermia, cyclophosphan, and melatonin were studied. When controlled systemic hyperthermia and cyclophosphan were used, the rat serum levels of alpha-tocopherol and retinol reduced whereas the addition of melatonin to therapy unchanged their content. Therefore, one of the promising ways of increasing the efficiency of treatment for malignancies may be to maintain the high activity of the antioxidant regulation system in nonneoplastic cells and tissues.

The putative causative relationship between mutator nature of carcinogenesis and positive results of empirical application of supermutagens for anticancer therapy is discussed. Part 1 of the review is devoted to the substantiation of the mutator theory of carcinogenesis. Part 2 provides an explanation of positive results of empirical application of supermutagens for anticancer therapy in the framework of this theory.

The authors analysed the findings concerning thromboses of sirolimus- and paclitaxel-eluting stents over the time period from 2004 to 2007, having singled out the following causes of a stent's thrombosis: 1 - an anatomical cause (bifurcation stenosis, a prolonged atherosclerotic plaque, and in-stent restenosis; 2 - the stent's failure to fit snugly to the arterial wall; 3 - dissection of coronary arteries during stenting; 4 - cocaine dependence; 5 - resistance to aspirin and clopidogrel therapy; 6 - discontinuation of anti-platelet therapy.

To analyse resistance to imatinib therapy, efficacy and safety of dasatinib.

To ascertain individual sensitivity to velkeid in patients with resistant and recurrent multiple myeloma (MM) by determination of free light chains (FLC) of serum immunoglobulins.

The aim of chemotherapy of acute leukemia in pregnant women is to save two lives. Abortion is not mandatory in acute leukemia as this disease is curable by chemotherapy. Effective treatment of pregnant women with acute leukemia diagnosis is now practiced not only by large clinics, it is also provided by regional centers. Overall 5-year actual survival for acute myeloid leukemia is 64%, for APL and ALL - 25%. All the children born by the patients during chemotherapy are healthy at maximal follow-up of 19 years, minimal - 11 months.

Effect of dexamethasone on differentiation of multipotent stromal cells from human adipose tissue was evaluated. Addition of dexamethasone to growth medium resulted in active adipogenesis. Addition of dexamethasone to the osteogenic medium (containing active vitamin D3 form as the main inductor) led to simultaneous realization of the adipogenic and osteogenic potencies of multipotent stromal cells of the adipose tissue. Hence, the quality of the transplant on the basis of predifferentiated multipotent stromal cells from the adipose tissue for bone tissue repair can be deteriorated by dexamethasone directing some cells to adipogenic development.

Exogenous NO donor 3,3-bis-(nitroxymethyl)oxetane (NMO) was synthesized at the Institute for Problems of Chemical Physics (Russian Academy of Sciences). This compound was shown to inhibit cell death (apoptosis and necrosis) in cyclophosphamide-sensitive and cyclophosphamide-resistant P388 murine tumor. p53 protein was expressed in both lines of tumor cells. NO donor NMO had little effect on p53 protein expression in cells of both stains. Our results suggest that the proapoptotic effect of NMO is mediated by the p53-independent molecular mechanisms.

Clinical and experimental effects of neoadjuvant treatment of endometrial cancer patients with non-steroidal aromatase inhibitors: letrozole (femara, n=10, 2.5 mg/day, 14 days), anastrozole (arimidex, n=15,1 mg/day, 28 days) and exemestane (aromazine, n=13, 25 mg/day, 14 days) were compared. Administration of anastrozole was mostly frequently followed by pain relief in the lower abdomen and/or decreased rates of uterine discharge. Endometrial wall thickness (M-echo signal) decreased significantly in 60% of patients receiving anastrozole, exemestane - 58.3% and letrozole - 40%. Substantial drop in intratumoral aromatase and blood estradiol levels occurred more frequently after anastrozole and letrozole while progesterone receptor levels in tumor were markedly lower after exemestane administration. Assay of blood LH (except letrozole), FSH and cholesterol appeared to be of less relevance. On the contrary, significance of assessment of marker Ki-67 expression, which, in the case of anastrozole, dropped in 6 out of 12 patients after a 28-day course, could hardly be underestimated.

Our study involved 247 patients with histologically verified breast tumors, aged 48-89, who had received hormones - tamoxifen as first-line therapy, exemestan (second-line) for 12 months. FACT-B and FACT-G questionnaires were used to assess quality of life. Worse results were reported in tamoxifen-treated patients older than 60 years. Indices of emotional and social security in the two groups: 60-70 year-olds (10.8+/-0.96% and 14.3+/-1.27% vis-à-vis 14.8+/-1.31% and 15.6+/-1.42%, respectively) and over 70 year-olds (15.2+/-1.46% and 15.8+/-1.48%, respectively). Our evidence suggested that a large-seale complex of effective psychological rehabilitation be given, particularly, to those under 60, married andlor with minors, right from the very beginning of treatment.