Effect of the tretionine (retinoid) and aluminum chloride (neurotoxin) on the growth and differentiation of neuroblastoma cells in culture after their introduction into the medium separately and in combination was studied. The introduction of these substances creates a new information field in the medium, which becomes apparent by the reactions of neuroblastoma found on the populational and cellular levels of its organization. The presence of tretionine stimulates proliferation and induces differentiation of the cells into astrocytes. Aluminum chloride inhibits cell proliferation and enhances the process of their destruction in the monolayer. The variety of the reactions of neuroblastoma cells to the presence of these substances in the medium indicates the existence and functioning of a mechanism that selects from the information introduced only the portion which may contribute to adaptation of neuroblastoma cells to the changed culture conditions.

Changes of visual fixation in patients with choroidal neovascularitation (CNV) associated with age macular degeneration (AMD) after bevacizumab are studied. 45 patients (45 eyes) with active CNV treated with intravitreal bevacizumab were enrolled into the study. Visual fixation was studied before and 3-6 months after treatment using original method that included fundus foto and fluorescein angiography. Fixation relative to fovea and lesion was evaluated. Foveal fixation beyond lesion was found in 9%, foveal fixation within lesion--in 47%, extrafoveal fixation beyond lesion--in 18%, extrafoveal fixation within lesion--in 26% of patients. Changes of fixation localization after treatment was found in 24% patients. Examination of visual fixation may be useful for prognosis of anti-VEGF treatment efficacy in patients with CNV.

The report discusses our experimental data in support of biotherapy which uses chemotherapy and antitumor immune treatment with in vivo xenogenic transfer-factor polypeptides (TFP) isolated from lymphocytes sensitized to antigens of given tumor. After excision of primary tumor--lung carcinoma of Lewis--mice C57BL/6 were injected intraperitoneally with xenogenic TFP (200 pg/body, twice) and a cytostaic dose of cyclophosphamide. Such adjuvant chemotherapy was found to prevent metastases from spreading to the lung in 100%. The marked anti-metastatic effect of the treatment correlated with recovery of splenic cell mass and its cellular structure, higher levels of large granular lymphocytes in peripheral blood and enhanced functional activity of cytotoxic cells in vitro. Our results point to a possibility of raising efficacy of treating solid malignancies with adjuvant chemotherapy in combination with adoptive immune therapy.

Alloferon-1 (AF) and allostatin-1 (AS) cytotoxic and growth modulating activities have been compared. AF is cationic oligopeptide isolated from the hemolymph of experimentally infected blow fly Calliphora vicina. AS is AF synthetic analog that differs from the parent molecule in two amino acids substituted. It has been shown that both AF and AS have no direct cytotoxic activity in concentrations ranging from 1 x 10(-1) to 10 microg/ml, however, the peptides demonstrated significant effect on tumor cells proliferation in vitro. Both peptides displayed growth modulating activity in mass cell cultures and boosted growth inhibiting activity of doxorubicin in the course of P388D1 cells cloning, although AS potentated doxorubicin cytostatic activity to a greater extent. Similarly, AS boosted anti-clonogenic activity of cyclophosphamide applied in a subthreshold concentration. Experiments with peptide-fluorescein complex have demonstrated that AF and AS belong to the group of cell-penetrating peptides. Moreover, the experiments displayed AF ability to bind with chromosomes.

The detoxifying efficacy of remaxol in the experimental model of cisplatin-induced toxicosis has been studied and the possibility of using this drug in cancer patients therapy is evaluated. Remaxol exhibited pronounced dose-dependent detoxifying effect in the model of toxicosis induced by cisplatin in a toxic dose (LD50). It reduced the death rate in test animals about three times when used at a 130 ml/kg dose, and prevented lethal outcome at a 500 ml/kg dose. Remaxol also normalized biochemical blood indices that characterized liver and kidney functions in survived animals. Remaxol did not stimulate growth of experimental carcinoma, sarcoma, melanoma, and lympholeukosis. The drug did not interfere with the anti-tumor efficacy of cisplatin in the schemes with combined treatment of animals bearing tumors of various histogenesis. Remaxol can be recommended for clinical study as a detoxifying preparation for cancer patients with various malignancies.

Paclitaxel-loaded poly(lactic-glycolic) copolymer nanoparticles have been prepared using a precipitation technique. The cytotoxic activity of nanosomal paclitaxel was studied on the model of highly resistant cell line Jurkat WT (human T-cell leukemia) using various biochemical assays. It is found that the inhibitory concentration (IC50) for the experimental formulation of paclitaxel falls within 10(-4)-10(-6) M. Accumulation of nanoparticles in the highly resistant Jurkat/WT cells was revealed by fluorescence microscopy.

The effects of the new chemical substance BIV-30 on bone marrow hemopoiesis has been studied in laboratory mices on the background of myelosupression induced by a single intraperitoneal injection of cyclophosphan in a dose 160 mg/kg. The injection of BIV-30 significantly accelerated lymphocyte, monocyte, granulocyte regeneration branches of bone-marrow hemopoiesis. These results showed evidence of the hemostimulating activity of BIV-30 on the model of bone-marrow hemopoiesis deficiency.

Part 2 of this review concerns the application of melatonin (Mt) to the treatment of aged patients with cardiovascular diseases and other pathology with reference to its genoprotective and anticarcinogenic action. Effects of Mt on the cardiovascular system are underlain by its antioxidative, vasodilating, and sedative activities, the ability to regulate the heart rate and inhibit platelet aggregation. Certain authors report negative correlation between Mt production and blood cholesterol level. Mt was shown to protect from cardiac lesions associated with ischemia and reperfusion. Mt inhibits carcinogenesis and is active at systemic, tissue, cellular and subcellular levels. At the systemic level, Mt decreases hormonal production, stimulates immune activity, and prevents the development of metabolic syndrome. It inhibits cell proliferation and promotes apoptosis of tumour cells but suppresses it the nervous tissue. Mt activates telomerase. It decreases expression of oncogens and interferes with the action of mutagens and clastogens at the genetic level. Extensive studies of Mt protective action in nervous diseases are underway with special reference to spinal cord, brain, neuron and glial cell lesions; experimental cerebral stroke, Parkinson's and Alzheimer's diseases. Similar studies concern the role of Mt in the protection against ionizing radiation, the development of renal pathology, and ophthalmology (glaucoma, cataract). Mt is shown to influence practically all organ systems by inhibiting mutagenesis and maintaining correlation between circadian rhythms of different biological processes throughout human evolution.

Doxorubicin-resistant MCF-7Dox line, which is a derivative of the drug-sensitive MCF-7 human breast carcinoma line, differs from the latter by a strongly reduced expression of the alpha2beta1 integrin and a highly increased expression of the alpha5beta1 receptor. Silencing of this integrin in the MCF-7Dox cells by transfection with alpha5-specific siRNA markedly stimulated anoikis and increased sensitivity of the cells to doxorubicin. Alpha5beta1 silencing also leads to significant inhibition of the activity of kinases Akt and Erk2 in MCF-7Dox cells. Our results suggest that integrins alpha5beta1-induced signals, controlling distinct aspects of cell behavior, are conducted through the common signal pathways.

In the current study a technique for microencapsulation of human breast adenocarcinoma cells MCF-7 in alginate-chitosan microcapsules is used. Microencapsulation is proposed to generate multicellular tumor spheroids (MTS) based on these cells and to test them further as an in vitro model for anti-tumor drug screening. Cytotoxicity of methotrexate (MTX) was studied on the obtained MTS. A set of MTS with mean size of 150, 200 and 300 m was prepared in function of a cultivation time. After incubation of MTS in cultivation medium containing MTX at concentrations of 1, 2, 10, 50 and 100 nM for 48 hs cell viability was evaluated. MTS were shown to be more resistant to MTX than the monolayer culture, and the resistance to MTX was increased with enhancing a spheroid size. At MTX concentration of 100 nM a number of viable cells in MTS with the size of 300 m was 2.5-fold bigger than that one in monolayer culture. It is suggested that the cells in microencapsulated MTS can better mimic cell behavior in a small size solid tumor than the cells in a monolayer culture. In future microencapsulated MTS can be proposed as a novel in vitro model for anticancer drug screening.

The ability of artificial ribonucleases to cause in the concentration-dependent manner death of cancer cells has been studied. The cytotoxic activity of artificial ribonucleases is observed at rather low concentration of these compounds (10(-5) M). Analysis of the mechanism of artificial ribonucleases cytotoxicity revealed that compounds under the study exhibit membranotropic activity in addition to ribonucleases activity found earlier. This activity is responsible for effective penetration of these compounds inside cells. The results obtained show that artificial ribonucleases induce cell death via damage of cells membrane, detachment of plasmalemma and derangement its macromolecular organization. In the case of short-term exposure of cells to the compounds, cells, even with damaged membrane, survive.

A convergent synthesis of biosynthetic precursors of brassinosteroids - secasterol and 24-episecasterol with Δ²-bond in cycle A is described. The key stages in the construction of the side chain of these compounds were Julia olefination of steroid 22-aldehyde followed by asymmetric Sharpless dihydroxylation of the intermediate Δ²²-olefin. Toxicity of synthesized compounds against breast carcinoma MCF-7 cells was studied.

Two main ways playing a cardinal role in the pathogenesis of metastatic renal cell carcinoma (mRCC) have been identified in recent years, they are following: 1) a way of the mutation of a gene suppressor VHL (Van-Hippel-Lindau), stimulating various types of tyrosine-kinases participating in the development of tumors; 2) mTOR way, where ramapycyn plays a leading role, which effect proliferation and angiogenesis of mRCC. This discovery enabled the development of a new generation of highly effective medications for target-therapy of mRCCC--tyrosine-kinases inhibitors (VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-alpha/PDGFR-beta, Raf-kinases, etc.) sunitimab, sorafenib, pazopanib, axitinib, etc. and mTOR inhibitors--everolimus and temsirolimus as well as monoclonal neutralising antibody VEGF (bevasizumab). The review is devoted to the analysis of antitumor activity, patient tolerance and side effect of these preparations in the system therapy of patients with mRCC.

The effect of L-lysine-alpha-oxidase from Trichoderma harzianum Rifai on the functional activity of T-lymphocytes was investigated. It was shown that in a dose of 35 units/kg administered parentally the enzyme had no suppressive effect on the T-lymphocyte functional activity. An inhibitory effect of L-lysine-a-oxidase on some indices of the macrophages functional activity was observed. L-Lyzine-alpha-oxidase had a selective lymphotropic action and showed no mytostatic activity, which is in favour of the enzyme vs. other antitumor agents.