Development of three vaccines intended to prevent cervical cancer (CC) caused by oncogenic human papillomaviruses (HPV) appears to be principal result of research into papillomaviral carcinogenesis. Two of these vaccines efficient in prophylaxis of about 70 % of new CC cases have been recommended for application in Russia. Up till now preventive HPV-vaccinations are not included into the Russian National Vaccination Shedule. In addition to CC HPV are known as etiological agents of some other anogenital as well as certain head and neck tumors. The overall cancer statistics data are found to vary owing to socioeconomic inequalities extremely dramatically for the most preventable cancers. The review is dedicated to major achievements and certain challenges in the field of oncogenic HPV studies.

This review presents technological approaches to 4-D printing, which are modifications of additive technologies. Showing the distinctive features of this technology from the three-dimensional printing. The use of four-dimensional printing in pharmaceutical technology and advantages over traditional methods of creating dosage forms are described. Demonstrated classification of adaptive materials, the principles of their application and features of printing equipment. Examples of adaptive materials are presented, including smart polymers and stimuli sensitive hydrogels. The advantages of this type of production, its development prospects and technological features of the production of microcapsules, hydrogels and mucoadhesive films of smart polymers by additive printing technology are given.

The review is dedicated to results of investigations of steroid conjugates published predominantly over the past decade. It consists of three parts in which the data concerning biological activity of steroid conjugates with known drugs, steroid dimers, and steroid conjugates with some natural compounds, their fragments and related derivatives and analogs, are discussed. The structures of 231 steroid conjugates and their anti-cancer properties are presented.

The aim of this investigation was to evaluate the expression of LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) β₂ integrins on blood cells in CBA mice in ontogenesis as well as under the dry extract of multifitoadaptogen administration during the first month of postnatal development.

Materials and methods. The study was carried out on CBA male mice (CBA/LacY). The experimental mice received 0.3 % dry multiphytoadaptogene extract water-solution during the first month of life (preventive administration). Preparation was produced by a desiccation technology of forty medical herbs (including Panax ginseng, Eleutherococcus senticosus, Rhodiola rosea) water-ethanol extracts components. The CD11a and CD11b antigens expressions on peripheral blood cells were analyzed by indirect immunofluorescence reaction at the age of 4, 8, 22 months. Statistical analysis was performed with the program Statistica 6.0.

Results. The development of genetically predisposed hepatocarcinomas in CBA male-mice was accompanied by a decrease in the expression of СD11a and CD11b antigens on blood cells. Dry multiphytoadaptogene extract administration during the first month of postnatal ontogenesis revealed the CD11a and CD11b antigens up-regulated expression. The effect of the dry multiphytoadaptogene extract is comparable to that for the liquid form of multifitoadaptogen previously identified.

Conclusion. Up-regulated LFA-1 and Mac-1 β₂ integrins expression on blood cells using dry multiphytoadaptogene extract administration during the first month of postnatal development is essential for enhance the contact interactions of immune effectors and cancer cells.

The study was performed in accordance with ethical principles adopted by the European Convention for the protection of vertebrate animals used for experimental and other scientific purposes.

Introduction. Special attention has been recently paid to photosensitizers that absorb and fluoresce in the near infrared region of the spectrum. One of the most promising photosensitizers is bacteriosens, a synthetic bacteriochlorin derivative. Objective. To conduct a preclinical study of the biodistribution and pharmacokinetics of bacteriosens in animals.

Materials and methods. The active ingredient of bacteriosens is (meso-tetra(3-pyridyl)bacteriochlorin) with of λ_max 747 nm). The biodistribution and pharmacokinetics of the agent were studied in mice and rabbits. It was administered intravenously once at three doses: 1.0; 2.5 and 6.25 mg/kg for the mice and 0.236; 0.59 and 1.475 mg/kg for the rabbits. Local fluorescence spectroscopy was used for the quantitative determination of the pharmacokinetic parameters of bacteriosens.

Results. Bacteriosens was removed quickly from the mouse bloodstream at 1 and 4 days after using minimal (1.0 mg/kg) and maximal (6.25 mg/kg) doses, respectively. When given at doses of 6.25 mg/kg and 1.0 mg/kg, bacteriosens was recorded in the skin, muscle, and spleen for 4 days and 24 h, respectively. The agent most intensively accumulated and long persisted in the omentum, liver, and kidneys for more than 6 days (6.25 mg/kg) and 2 days (1.0 mg/kg). A similar pattern was observed in the rabbits. Bacteriosens was rapidly removed from the rabbit bloodstream at 1 and 3 days after using at doses of 0.236 and 1.475 mg/kg, respectively. The agent was recorded in the skin, muscle, and spleen up to 4 days (1.475 mg/kg) and 3 days (0.236 mg/kg). It most intensively accumulated and long persisted in the omentum, liver, and kidneys for more than 6 days (1.475 mg/kg) and 4 days (0.236 mg/kg).

Conclusion. Bacteriosens was removed from the animal bloodstream within 3–4 days after administration of the maximum dose that was 2.5 times higher than therapeutic one. The half-life of bacteriosens for mice was directly proportional to the dose and increased from 8 to 24 min; the half-life for rabbits was 20 min, irrespective of the dose. The drug was recorded in the skin for no more than 4 days. The main routes of bacteriosens elimination from the body of animals were the kidneys and liver.

The study was performed in accordance with ethical principles adopted by the European Convention for the protection of vertebrate animals used for experimental and other scientific purposes.

Introduction. The use of polymeric biodegradable nanoparticles (NP) as drug delivery systems is a promising approach to overcome histohematomatic barriers. Thus, poloxamer 188-coated poly (lactide-co-glycolide) (PLGA) NP are able to overcome blood-brain barrier and to deliver therapeutic agents, in particular doxorubicin, into intracranial tumour upon intravenous administration. It is important to evaluate NP interaction with blood components in preclinical studies.

The objective of the study was to investigate cytotoxicity and hemocompatibility of doxorubicin-loaded PLGA NP (Dox-PLGA NP), to essess NP uptake by glioblastoma cells.

Materials and methods. The influence of NP on coagulation cascade was evaluated by prothrombin time measuring before and after plasma incubation with NP. To assess NP thrombogenicity the platelet activation level was determined by flow cytometry. The NP hemolytic activity (released hemoglobin concentration) was measured spectrophotometrically. NP cytotoxicity was determined by MTS assay. NP uptake by human glioblastoma cells was evaluated by flow cytometry.

Results. Dox-PLGA NP did not influence blood coagulation time and thrombocyte activity at concentrations up to 100 mcg/mL: PT values were 12–15 s for all tested samples, and P-selectin expression level did not exceed 15 %. All samples were not hemolytic after 3 h of incubation. Cytotoxicity of doxorubicin released from PLGA NP on glioma U87MG cells was comparable to that of free doxorubicin. As shown by flow cytometry Dox-PLGA NP were efficiently internalized into the cells.

Conclusion. The study of hemocompatibility confirmed the safety of Dox-PLGA NP: NP did not influence blood coagulation system and did not induce hemolysis. NP were efficiently internalized into the human glioblastoma cells and produced considerable antitumor effect in vitro.

Introduction. Age is considered as an important clinical and pathological factor in cancer patients. Malignant tumors are more likely to develop in older people, but the disease is less aggressive than in young patients. According to various authors, the influence of age on the development of tumors largely depends on the age-related features of the immune system.

The aim of the present study was to determine the relationship of indicators of systemic antitumor immune response with the age of patients with primary operable breast cancer and cancer of the oral mucosa.

Materials and methods. The study included patients with all subtypes of primary-operable breast cancer (n = 145) and patients with cancer of the oral mucosa (n = 29). Immunophenotyping of peripheral blood lymphocytes was performed using a wide panel of monoclonal antibodies to markers of adaptive and innate immunity cells.

Results. In elder patients (40 years and older) with primary-operable breast cancer, the percentage of activated CD25⁺ lymphocytes and CD4⁺CD25⁺ and CD3⁺CD4⁺ T cells, NKT cells, activated HLA-DR+ lymphocytes, including activated CD3⁺HLA^-DR⁺ T cells before treatment, was statistically significantly higher than in patients younger than 40 years. Patients of this group showed increase of CD8⁺CD - 11b⁺CD28^– CTLs and a decrease in the number of naive lymphocytes (CD4 – CD62L+ and CD8⁺CD11b ^– CD28⁺) in comparison with control percentage, and the downward trend in CD4⁺CD25⁺CD127^– T_reg, with increased numbers of CD4⁺CD25⁺ T cells. In patients with cancer of the oral mucosa, an increase in the number of cells of some populations of the immune effector link and a decrease in the number of suppressor lymphocytes were revealed with age.

Conclusion. The results suggest that age-related differences in the state of systemic antitumor immune response contribute to a more favorable course of breast cancer and some other malignancies in older persons. It is obvious that the features of age differences in the immune response to the tumor should be taken into account when prescribing systemic therapy, including immunotherapy.

All patients gave written informed consent to participate in the study

Introduction. Acute lymphoblastic leukemia (ALL) is diagnosed mainly in children (2/3 of diseases) making this type of leukemia one of the most common oncological diseases among children. Oncogenes are involved in the development of ALL, in particular the product of chromosomes 1 and 19 translocation, the oncogene E2A-PBX1 that codes for E2A-PBX1 chimeric oncoprotein with strong transcription activation properties as well as oncogenes of HOX family, mainly HOXA and HOXB cluster genes. E2A-PBX1 chimeric oncoprotein and НОХА proteins are associated in vivo with factors participating in epigenetic regulation of gene expression such as chromatin modifying and remodeling enzymes that partially determines their oncogenic properties. In previous studies we obtained data indicating genetic interactions of E2A-PBX1 and НОХ genes participating in leukemia development.

The aim of this research was to confirm the role of Е2А – РВХ1 oncogene in the activation of the expression of НОХА cluster genes coding for the proteins with high oncogenic potential.

Materials and methods. The objects of the study were four B cell progenitor (pre-B) leukemia cell lines: RCH-ACV, KASUMI-2, 697 and NALM-6. Standard polymerase chain reaction (PCR) was used for the identification of chromosome 1 and 19 translocation product, E2A-PBX1 oncogene and its expression. Method of reverse transcription coupled with quantitative polymerase chain reaction (Q-RT-PCR) was used for the analysis of 11 HOXA cluster genes expression.

Results. It is demonstrated that E2A-PBX1 oncogene is present and expressed in three studied human pre-B leukemia cell lines, RCH-ACV, KASUMI-2 and 697, while its expression is absent in NALM-6 cell line. High expression of 7 from 11 HOXА cluster genes is revealed in RCH-ACV, KASUMI-2 and 697 cell lines expressing E2A-PBX1 oncogene, whereas NALM-6 cell line, that does not express E2A-PBX1 oncogene, also does not express HOXA genes except low expression of two genes from this cluster.

Conclusions. The data obtained in this study demonstrate that RCH-ACV, KASUMI-2 and 697 human leukemia pre-B cell lines, containing and expressing Е2А-РВХ1 oncogene, also express most of HOXA genes (7 genes of 11 genes) at high level in contrast to control NALM-6 cell line that does not comprise Е2А-РВХ1 oncogene and almost does not express НОХА genes. Therefore, the results of this study suggest the participation of strong transcriptional activator, chimeric oncoprotein Е2А-РВХ1, associated with chromatin modifying and remodeling enzymes, in the expression activation of HOXA cluster genes that also possess high oncogenic potential.

Introduction. Tumor necrosis factor α (TNF-α) is a natural cytokine, characterized by pronounced antitumor properties. A wide range of side effects serves as an obstacle for the use of TNF-α in clinical practice. One of the ways to improve its therapeutic properties is to increase the tropism of the cytokine to the tumor tissue by incorporating it into the targeted delivery system.

The aim of the study was to evaluate the antitumor activity of the preparation containing TNF-α as part of the artificial “virus-like particle” (VLP-TNF-α), developed in SRC VB “Vector” as a transport system for delivering proteins to target cells.

Materials and methods. The antitumor effect of VLP-TNF-α preparation was evaluated in experimental B16F10 melanoma model by the change of dynamics of tumor growth (volume, mass) and its morphological structure (presence of necrotic processes, blood vessel destruction). The number of the effector immune cells (CD3⁺, CD11b⁺) in the tumor tissue was determined by immunohistochemical method.

Results. It has been shown that VLP-TNF-α administered intravenously at the doses of 5 × 10⁴ and 1 × 10⁵ IU/mouse inhibits the growth of the primary tumor. The most pronounced and stable effect was observed with a five-fold administration at the dose of 1 × 10⁵ IU/mouse every other day: tumor growth inhibition was 40 % on the 1st day, and 47 % on the 7 th day upon the treatment. Injections of the preparation resulted in the increase of necrosis number, destruction level of the tumor tissue, development of damage and destruction of the tumor blood vessels and its infiltration with immunocompetent cells.

Conclusion. The obtained data indicates that TNF-α within the delivery system exerts antitumor activity, which suggests the possibility of its further use for the treatment of malignant neoplasms, in particular, melanoma.

The study was performed in accordance with ethical principles adopted by the European Convention for the protection of vertebrate animals used for experimental and other scientific purposes.