25 patients with diabetic macula edema (DME) treated with 0,5 mg intravitreal ranibizumab (Lucentis) were studied. Mean number of intravitreal injections was 1.7 (1-5 injections). Visual acuity improved from 0.29 +/- 0.03 to 0.36 +/- 0.04 after the 1st injection and to 0.38 +/- 0.04 after the last one (p < 0.001). Central retinal thickness reduced from 469 +/- 36.3 to 353 +/- 31.5 microm in a month after the 1st injection and was 346 +/- 30.3 microm after the last one (p < 0.05). No systemic or ocular adverse effects were observed. Intravitreal ranibitumab (Lucentis) leads to stabilization and improvement of visual acuity and reduction of DME. The procedure is a safe treatment option for DME.

Two new asterosaponins, diplasteriosides A and B, with the same oligosaccharide chains beta-D-Fucp-(1-->2)-beta-D-Galp-(1-->4)-[beta-D-Quip-(1-->2)]-beta-D-Quip-(1-->3)-beta-D-Quip-(1-->, linked to C6 of known genins, 3-O-sulfates of thornasterols A and B, respectively, were isolated along with the previously known asteriidoside A from the Antarctic starfish Diplasterias brucei. The structures of new compounds were elucidated by spectroscopic methods (mainly 2D NMR and mass spectrometry). The cytotoxicity of isolated asterosaponins against human colon cancer cell line HCT-116, human breast cancer cell line T-47D, and human melanoma cancer cell line RPMI-7951 was investigated.

Mutagenic activity of non-phosphorous cationic alkyl glycerolipid rac-N-{4-[(2-Methoxy-3-octadecyloxy)propyl]oxycarbonylbutyl}-N,N-dimethyl-N-(2-hydroxyethyl) ammonium iodide was evaluated. According performed Ames assay results indicated on non-mutagenic properties tested compound. Resulting data open the possibility to carry out biological study in vivo for class of ether cationic glycerolipids and further applications as a potential agent of anticancer therapy.

Induced apoptosis in urinary bladder cancer tumor cells of patients was studied using TUNEL reaction. It was shown that increase in induced apoptosis value had a definite correlation between corresponding features of tumor reaction as a response on Gemcitabine-Cisplatin neoadjuvant chemotherapy application. It was found that evaluation of induced apoptosis in urinary bladder cancer tumor cells using TUNEL method allows forecasting the effectiveness of chemotherapy on the cellular level in patients with this type of cancer.

Regulatory T-cells (Tregs) are important components of the complex adaptive system of the body responsive to environmental challenges. Tregs ensure peripheral tolerance and play an important role in control of inflammatory reactions. Several subsets of Tregs have been described. Naturally occurring CD4+CD25+ Tregs are recognized as a major subset of immune cells responsible for peripheral immune self-tolerance. Another subtype of Tregs is inducible. Such Tregs are generated in the periphery and realize their suppressive potential largely in the form of anti-inflammatory activity. The latter plays an important role in cooperation of three principal anti-inflammatory mechanisms that developed in the course of evolution: macrophages possessed of suppressive activity, Tregs, and stress hormones. Normally, all the three mechanisms of inflammation control are in equilibrium. However, the balance may be disturbed with ageing due to repeated episodes of stress and HPA axis activation. As a result, secretion of stress hormones coupled to antigen overload leads to Treg accumulation. In the course of time activation of the HPA axis is replaced by its inhibition manifested both as a decrease of the baseline cortisol level and a reduction of stress-induced cortisol response. Cortisol present in blood at low concentrations is no longer capable of controlling inflammation and Tregs become a principal mechanism of anti-inflammatory machinery. Superfluous Treg accumulation results in the development of functional somatic syndromes, such as chronic fatigue syndrome, and (in some patients) in the growth of tumours resulting from the suppression of anticancer immunity. On the other hand, the lack of adequate antigen loading in the childhood may delay Treg maturation. Allergy and asthma manifestations may be a consequence of such Treg insufficiency. Thus, both excess and deficiency of Tregs may be at the bottom of morbid conditions. The advances in modern pharmacology open up opportunities for developing new methods to control the Treg level.

The synthesis of aminopropoxy derivatives of betulin, erythrodiol, uvaol and oleantriol via cyanoethylation of triterpenoids hydroxyl groups and subsequent reduction of cyanoethyl fragments is described. High and specific in vitro antitumor activity (cytotoxicity) of 3beta,28-di-O-[3-(aminopropoxy)]lupa-20(29)-ene and 3beta-O-hydroxy-28-O-[3-(aminopropoxy)]olean-12-ene towards a wide range of human tumor cell lines is discovered. The aminopropoxy group is shown to be a new perspective pharmacophor group for design of anticancer agents on the basis of triterpenoids.

For a series of 1,10-phenantroline tris-beta-diketonate europium complexes (EuC), cytotoxic activity on the HBL-100 human breast carcinoma cells was determined. Liposomal preparation of the most active EuC, V12, was also tested for cytotoxicity. Testing of this preparation in vivo on starting lethal murine model of T cell leukemic lymphoma ASF-LL showed that the inclusion of V12 in liposomes did not increase its antitumour activity in a local mode of administration.

Treatment with low doses (1/10 of LD50) of cisplatin and platinum (IV)-nitroxyl complex VS118 [e-ammin-d-(4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl)-a,f-bi s(acetate)-b,c-dichlorplatinum (IV)] was followed by a synergistic therapeutic effect (a 100% cure of animals) as compared with monotherapy with either drug. There was no synergistic increase in toxicity. The rates of resistance development decreased in the following order: P388/cPt+VS118, P388/cPt, P388/VS118. Resistant strains P388/cPt+VS18 and P388/VS118 were highly sensitive to doxorubicin, etoposide and cyclophoshamide. Further research in cPt+VS 118 combinations should be continued.

In this literature review we present analysis of various aspects of the problem of cardiotoxicity of antracyclines used for the treatment of the breast cancer. We consider mechanisms of their cardiotoxic action, role of risk factors, clinical manifestations of acute and chronic cardiotoxicity, and dependence of their severity on treatment duration and drug dose. We give data on contemporary methods of diagnostics of early toxic cardiac effects of antracyclines from the side of cardiovascular system. We also conducted assessment of possibility of prevention of toxic action of antracyclines with the use of combination of different methods including dose sparing regimens and schemes of treatment, combinations of drugs, use of cardioprotectors as well as novel preparations from the antracycline group, possessing lesser cardiotoxicity. Clinical and experimental data on the treatment of manifestations of cardiotoxicity with consideration of pathogenetic mechanisms of their development are given.

Development of systems of medicines with sustained action on the basis of biodegradable polymers is a promising trend in modem pharmacology. Polyhydroxyalkanoates (POA) attract increasing attention due to their biodegradability and high biocompatibility, which make them suitable for development of novel drug dosage forms. We obtained microspheres on the basis of poly(3-hydroxybutyrate) (PHB) loaded with the antitumor drug paclitaxel. Morphology, drug release kinetics and effect on tumor cells in vitro of microspheres were studied. The data on the kinetics of drug release, biocompatibility and biological activity of the biopolymer microspheres in vitro showed that the studied system of prolonged drug release had lower toxicity and higher efficiency compared to the traditional dosage forms of paclitaxel.

The drug composition based on the plant phospholipids and the antitumor drug doxorubicin (particle size <30 nm) was obtained using original technology elaborated in the Institute of Biomedical Chemistry (Russian Academy of Medical Sciences). In in vitro experiments demonstrated decreased drug association with blood cells for this nanophospholipid form as compared with free doxorubicin. This was accompanied by a with corresponding increase in its plasma level ans also by drug redistribution from plasma protein fraction to high density lipoproteins. Significance of these changes for doxorubicin biodistributon and antitumor activity is discussed.

The applicability of alkaline comet assay to studying the organ specificity of the genotoxic effects of drugs has been estimated using cells from four organs of mice (the liver, lungs, spleen, and brain). It has been found that cyclophosphamide damages DNA in all the four organs; and dioxidine, in all organs except the brain. It is concluded that this method can be used for studying the organ specificity of the DNA-damaging effects of various substances.

Effectiveness and safety of regional chemoinfusion in combination with radiation therapy in patients with breast cancer with metastases to the brain was clinically assessed. Cerebral angiography with chemoinfusion was fulfilled in six patients. The procedure could not be fulfilled completely in one patient because of transient vascular and neurological disorders. In the other five patients the regional superselective chemoinfusion was fulfilled successfully to the arteries feeding the metastatic foci in the brain with Carmustin in dosage 100 mg in combination with radiation therapy that was fulfilled in all six patients before the planned total focal dose. The incomplete response (n=5) to the treatment and stabilization of the process (n=l) were noted in six observations.

Despite its side-effects, most of which are reversible, effectiveness of hormonal therapy in prostate cancer has been demonstrated. Advantages of intermittent hormonal therapy have been evaluated in a number of phase II clinical tests. As a result, side-effects were shown to decrease and quality of life improved. Preliminary phase III tests failed to detect any negative effect of intermittent hormonal therapy on tumor progression-free survival as compared with continuous hormonal therapy.

Efficiency of gemcitabine plus lomustine treatment of transplantable lymphosarcoma LIO-1 in mice was significantly higher than that of monotherapy. According to the area under the kinetic curve for tumor growth, antitumor action, for single maximum tolerable dose of gemcitabine 25 mg/kg body, rose 4.6 times (p < or = 0.001), for lomustine 50 mg/kg body,--2.9 times (p < or = 0.01). The combination involved moderately increased toxicity. Lethality rate for gemcitabine+lomustine, 50 mg/kg body each, was as low as one and a half times as compared with gemcitabine therapy alone, 50 mg/kg body, (30 and 20%, respectively). The antitumor action of the combination (50 mg/kg body), was 32 times that of gemcitabine 50 mg/kg body (p < or = 0.001) and lomustine 50 mg/kg body--30 times (p < or = 0.001).

An experimental model of solid tumor of Ehrlich failed to reveal any influence of the hepatoprotector Metrop GP on tumor growth or affect antitumor action of doxorubicin.

While the most frequent, surgery for colorectal cancer is avoided in patients with metastases to the regional lymph nodes (stage III) or distant ones (stage IV). Hence, it is being increasingly substituted with neoadjuvant treatment. Our investigation is concerned with prospective evaluation of the efficacy and toxicity profile of capecitabine (XELODA) in combination with oxaliplatin (XELOX) and adjuvant Mayo treatment (stage IIb-III). Patients had undergone radical surgery (somatic status < or = 2-ECOG). The prospective group (166) received 8 courses of adjuvant polychemotherapy (XELOX); the retrospective (2001-2005) one (152)--6 (Mayo). The groups matched one another as far as number, gender, age and primary tumor localization are concerned. Regional lymph node involvement in group 1 was 64.5%; group 2--59.8%. Lympho-vascular invasion by tumor was typical of group 1; gastrointestinal toxicity - 9.2% (Mayo) vs. 7.2% in group 1. Hematological complications were 5.4% (XELOX) and 5.3% (Mayo); neutropenia-- 5.0% (Mayo) and 3.0% (XELOX); polyneutropenia-- 3.6% (XELOX); capecitabine-related Papillon-Lefevre syndrome-- 8.4%. Three-year relapse-free survival was 53.0% (XELOX) and 47.5 % (Mayo). After adjuvant treatment, toxicity profile with XELOX was lower than that after Mayo, with the survival tending to improve.

Neoadjuvant treatment should not be given to grave cases of rectal cancer with concomitant perifocal inflammation, anemia and advanced age. To improve results, intraoperative intrapelvic chemotherapy in combination with hyperthermia was carried out at the Center's Clinic. Pre-clinical studies involved working out optimal cryo-temporal regimens to maximize cytotoxic effects of drugs and hyperthermia as well as establishing systemic influence of local hyperthermia and chemotherapy on the intraoperative intrapelvic one. Our optimal cryo-temporal regimens and intraoperative intrapelvic chemotherapy proved highly effective.