Increased plasminogen level in tear fluid was found within 28 days and increased plasmin activity in 1-3 and 21 days after alkali burn of cornea, this is the time of cornel ulcers development. Increased plasminogen level and plasmin activity in cornea, conjunctiva and intraocular fluid was found in three days after trauma. Subconjunctival injections of angiostatin K1-4,5 (a product of plasminogen metabolism) during 3 weeks resulted in significant suppression of corneal neovascularization within 14 days and of active branching of the vessels in the following. The use of angiostatin reduced depth and area of corneal ulcers. Obtained data shows the promising potential of development of medications based on angiostatin K1-4,5 for suppression of corneal neovascularization and for treatment of diseases associated with corneal ulceration.

SHR mice with intracranial transplanted lymphosarcoma LIO-1 received a single intraperitoneal gemcitabine injection in maximal tolerated dose of 25 mg/kg or single maximal tolerated oral dose of lomustine, 50 mg/kg. Compared to control group gemcitabine injection increased the mice lifespan 1.4-fold (p < 0,01) and oral lomustine 1.6-fold (p < 0,01). The median lifespan of the mice receiving both gemcitabine and lomustine in maximal dose underwent a significant 3.3-fold increase (p < 0,01) compared to controls (2.4-fold compared to gemcitabine and 2.1-fold compared to lomustine group). Combined therapy didn't cause an increase of toxicity.

In the presented work antitumor effects of thermo- and phagelysates of Ps.aeruginosa and E.coli on Ehrlich carcinoma growth in mice have been studied. The treatment efficacy was evaluated according to the dynamic changes in volume of cancer tissue, cancer growth inhibition percent and calculations using Semi-empirical mathematical model describing cancer volume variations in relation to time passed after carcinoma inoculation. It was shown that at the early stage of cancer growth all tested bacterial preparations significantly inhibit cancer growth. Antitumor treatment effects were better expressed in animal studies using bacterial pagelysates in comparison to that of thermolysates. Comparative analysis of anticancer treatment efficacy of Ps.aeruginosa and E.coli phagelysates have shown that E.coli phagelysates reveal stronger and more prolonged anticancer treatment properties than phagelysates of Ps.aeruginosa.

The antimitotic agent combretastatin A4 (CA-4) has been suggested as an antivascular agent for anticancer therapy relatively recently. To reduce systemic toxicity by means of administration in liposome formulations, in this study new lipophilic prodrugs, oleic derivatives of CA-4 and its 4-arylcoumarin analog (CA4-Ole and ArC-Ole, respectively), have been synthesized: Liposomes of 100 nm mean diameter prepared on the basis of egg phosphatidylcholine and phosphatidylinositol from bakers yeast have been shown to include completely up to 10 mol. % of CA4-Ole, or 7 mol. % of ArC-Ole. Also, prodrug bearing liposomes decorated with tetrasaccharide selectin ligand Sialyl Lewis X (SiaLe(x)) have been constructed to achieve targeting to endothelium under neovascularization. The antitumor activity in vivo was studied in the model of slowly growing mouse breast cancer. Under the used dose (22 mg/kg) as well as the regimen of treatment (four injections, one per a week, starting from the appearance of palpable tumors) cytostatic CA-4 did not reveal any anticancer effect, and oppositely even stimulated tumor growth. Liposome formulations of CA4-Ole did not show such stimulation. However, to achieve pronounced antitumor effect, number of injections of liposomes should be apparently elevated. New antimitotic agent ArC revealed cytotoxic activity of only one tenth value obtained for CA-4 in vitro in the culture of human breast carcinoma cells. Nevertheless, in vivo in the mouse model of breast cancer this compound showed antitumor effect under double CA-4 equivalent dose. The results demonstrate availability of SiaLe(x)-liposomes loaded with ArC-Ole: this preparation began to inhibit tumor growth already after the second injection. It is necessary further to choose doses and regimens of administration both for ArC and liposome formulations bearing ArC-Ole.

Mechanisms of suppression of carcinogenesis promotion/progression by plant polyphenols have been considered. They can decrease cyclins and cycline dependent kinases and activate inhibitor proteins in tumor cells that results in cell cycle arrest. Plant polyphenols can induce apoptosis by modulating anti/proapoptotic proteins and also can inhibit tumor metastasis and angiogenesis. Polyphenols act through the regulation of cell signal transduction and gene expression.

Hemostasis disorders are the part of multiple organ failure (mOF) in sepsis. This work objective is to evaluate the system parameters in septic patients.

The efficiency of using high-density lipoproteins (HDLPs) as the transport form of an antineoplastic drug daunorubicin (rubomycin hydrochloride, daunoxome) has been shown on the culture of HA-1 hepatoma cells of mice. The use of HDLPs in a complex with daunorubicin led to an increase in the efficiency of drug transport and cytotoxic action with respect to tumor cells in comparison with hepatocytes of healthy animals.

The effects of copper nanoparticles on the structure and function of the immune system organs (thymus and spleen) and intensity of free radical processes in the spleens of rats with sarcoma 45 were studied. A relationship between morphological and biochemical changes and antitumor efficiency of copper nanoparticles was demonstrated.

Antitumor resistance decreased in mice 24 h after injection of cyclophosphamide in a dose of 100 mg/kg. This was seen from more rapid growth of Ehrlich's ascitic carcinoma transplanted intraperitoneally 24 h after cyclophosphamide injection and 17% reduction of the lifespan of mice with tumors. Three, 7, 10, 14, and 22 days after cyclophosphamide injection, the antitumor resistance increased and the lifespan of animals with Ehrlich's ascitic carcinoma transplanted at the corresponding periods increased by 20, 14, 42, 29, and 36%, respectively, in comparison with mice with transplanted tumor not injected with the drug. Injection of cyclophosphamide 1 day after tumor transplantation prolonged of the lifespan of animals with tumors by 76%.

Pigment epithelium-derived factor (PEDF), a 50 kDa secreted glycoprotein, is among the most potent endogenous inhibitors of angiogenesis. PEDF-derived fragment (44-77) possesses antiangiogenic properties of the full-sized protein and is a potential drug candidate for the treatment of ocular neovascular diseases. In this study we propose an efficient scalable biotechnological method for the production of PEDF (44-77) as part of a fusion protein with SspDnaB intein. The fusion protein was obtained in bacterial E. coli cells in the form of inclusion bodies, solubilized and subjected to autocatalytic cleavage with the release of PEDF (44-77) (yield, 77%). The target peptide was separated from the intein using tangential ultrafiltration. The final purification of PEDF (44-77) was performed by reversed-phase HPLC. The yield of the target peptide (purity, 99%) was 65 mg per 1 liter of culture. Antiangiogenic activity of the obtained peptide was studied in vitro using murine endothelial cells SVEC-4-10. PEDF (44-77) suppressed proliferation of endothelial cells by 53% and inhibited endothelial cell tube formation at the concentration of 1 nM. The ability of the recombinant PEDF (44-77) to block initial stages of angiogenesis was demonstrated using the model of rabbit corneal neovascularization.

Influence of bioginseng (biotechnological pharmaceutical drug from ginseng radix culture) on radiation-induced carcinogenesis has been studied. LIO female rats were divided into 3 groups. Rats of the first group (n=25) were used as intact control and weren't exposed to any influence. Rats of the second (n=50) and third (n=50) groups were exposed to single total body gamma-irradiation at a dose of 4 Gy. Animals of the 2nd group weren't exposed to any influence after irradiation, while animals of the 3rd group were given bioginseng with tap water (20 ml/l) until the end of study (438 days). In the control group 22,7% of animals developed tumors. In the 2nd group (irradiated control) 70% of animals were bearing multiple tumors one third of which were malignant. Mammary gland tumors were most frequent. Compared to the 2nd group the 3rd group receiving irradiation and bioginseng demonstrated the decrease in tumor incidence by 24.5% and 2,4 rate of decrease in tumors number. For the malign tumors was observed the decrease by 26.8% and 2,9 times, accordingly. For the mammary tumors the decrease was by 23.0% and 2,0 times, for mammary adenocarcinomas by 23.4% and 3,5 times, accordingly. The incidence and number of endocrine and reproductive organs tumors was 20,9% and 5,6 times, accordingly. Therefore, bioginseng effectively inhibits carcinogenesis induced by ionizing radiation in female rats.

10 months old mice receiving SSH&H with daily food increased the lifespan in comparison to the control group. The maximal lifespan was increased by 1,6 months. For the long-living 10% group the mean lifespan increased by 8,7% compared to the control group (p<0,05). The mammary gland neoplasia rate was the same in both groups. The mean latent tumor development period duration, number and size of the tumors were also similar. There was a tendency to lower lung metastases rate in the experimental group. The cumulative neoplastic frequency curve for the experimental group was shifted to the right in comparison to the control group curve giving evidence to the inhibitory effect of SSH&H on the neoplastic rate in transgenic mice with HER-2/neu mutation.

Mechanisms of anti-cancer effects of polyphenols, found in fruits, vegetables, spices and representing parts of daily nutrition, have been considered. These compounds may be the basis for development of cancer preventive preparations. They can block carcinogenesis initiation by inactivation of exogenous or endogenous genotoxic molecules including reactive oxygen species. Another mechanism consists in inhibition of activity and synthesis of carcinogen-metabolizing enzymes. Plant polyphenols also induce expression of antioxidant and detoxification enzymes genes.

Liposomes quite recently have turned from a model of biological membranes into an object of extensive research and practical use. The versatile traits of liposomal formulation allow its' universal implementation, especially in cancer chemotherapy. The advantages of liposomal use as a carrier of an anticancer drug for its targeted selective accumulation are discussed in this article. This article contains description of new types of liposomes, differing in contents and use, such as: simple, sterically stabilized, targeted (immunoliposomes),cationic, sensitive to physical and chemical stimuli. The characteristics of liposomal systems of anticancer drug delivery designed at Blokhin Russian Oncological Scientific Centre is given in the article.

It was shown recently, that high affinity Cu(I) importer eukaryotic protein CTR1 can also transport in vitro abiogenic Ag(I) ions and anticancer drug cisplatin. At present there is no rational explanation how CTR1 can transfer platinum group, which is different by coordination properties from highly similar Cu(I) and Ag(I). To understand this phenomenon we analyzed 25 sequences of chordate CTR1 proteins, and found out conserved patterns of organization of N-terminal extracellular part of CTR1 which correspond to initial metal binding. Extracellular copper-binding motifs were qualified by their coordination properties. It was shown that relative position of Met- and His-rich copper-binding motifs in CTR1 predisposes the extracellular CTR1 part to binding of copper, silver and cisplatin. Relation between tissue-specific expression of CTR1 gene, steady-state copper concentration, and silver and platinum accumulation in organs of mice in vivo was analyzed. Significant positive but incomplete correlation exists between these variables. Basing on structural and functional peculiarities of N-terminal part of CTR1 a hypothesis of coupled transport of copper and cisplatin has been suggested, which avoids the disagreement between CTR1-mediated cisplatin transport in vitro, and irreversible binding of platinum to Met-rich peptides.

Antineoplastic effect of hydrogel dextran phosphate, hydrogel prospidin, and prospidin in an injectable preparation has been assessed using Seidel ascites hepatoma as a model. Injectable and hydrogel prospidin in doses from 250, 500 to 1000 mg/kg and hydrogel phosphate dextran in doses of 500 and 1000 mg/kg were administered to rats intraperitoneally in a single dose in a volume of 1 or 2 ml per each 100 g of animal body weight. The study has shown that irrespective of rats with Seidel ascites hepatoma and significantly increase in the dosage of prospidin preparations and hydrogel dextran phosphate results in a longer average life expectancy of rats Compared with its injectable variant, hydrogel prospidin appears to produce more than twice as high antineoplastic effect, and is found to provide prolonged therapeutic effects, as well as cure of animals in more than 60 % of cases.

In experiment conducted on male mice of C57B1/6 line quercetin (80-100 mg/kg injected 60 minutes before carboplatin) or an emergency radioprotector indralin B-190 (50-100 mg/kg injected 5 minutes after carboplatin) decreased the mortality of animals from toxic carboplatin dose of 100 mg/kg from 40% to 10-11% (p < 0.05). In mice receiving both quercetin and B-190 the reduction of carboplatin toxicity evaluated by blood WBC level was even more prominent (p < 0.05). The results were confirmed in rat experiment. In animals receiving both quercetin and B-190 with 50 mg/kg of carboplatin the WBC level was higher (p < 0.05). Quercetin alone had no effect on hematologic toxicity in those settings. Besides, quercetin and B-190 didn't have any effect on RBC level changes.