Diagnosis, treatment and designing an adequate strategy of neuroblastoma (NB) therapy in children is still a complicated tasks for pediatric oncology and hematology. One of the key aspects of NB control is detection and monitoring of minimal residual disease.

The authors make a concise review of the up-to-date methods, such as immunocytochemistry, fluorescent in situ hybridization (FISH), flow cytometry, the methods of qualitative and quantitative polymerase chain reaction (PCR) to estimate mRNA (RT-PCR and QRT-PCR), which are currently used for minimal residual disease detection in patients with NB. Disialoganglioside GD2, a specific NB marker, is traditionally determined by immunocytochemistry with fluorochromes that enhance its specificity, and by flow cytometry, as well. At present, FISH test is a gold standard for evaluation of the MYCN gen status in NB. A widely used multicolor flow cytometry method allows achieving high specificity of the analysis for NB diagnosis. RT-PCR may search for various targets to reveal NB cells, however, at the moment the only accepted immune target is tyrosine hydroxylase mRNA. Moreover, the studies established that quantitative QRT-PCR has more advantages than traditional qualitative RT-PCR, since this method allows a more accurate and quantitative detection of one or several mRNAs in clinical samples. The review discusses advantages and disadvantages of the main methods currently used for minimal residual disease evaluation of NB cells, such as RT-PCR, flow cytometry, FISH, etc. Comparative studies included multicolor flow cytometry with various combinations of CD9/CD81/CD56/CD45/GD2 monoclonal antibodies, conventional RT-PCR and quantitative QRT-PCR to reveal circulating/disseminated NB cells in the clinical samples of cancer patients and healthy volunteers.

The authors analyze the results of various studies that compared accuracy and sensitivity of diagnostic methods such as RT-PCR, flow cytometry, FISH and some others. Despite the advantages of each method, the authors emphasize that multicolor flow cytometry is the optimal approach for the rapid and reliable detection of minimal residual disease and micrometastases of NB. 

The review presents the concept the key mechanism of the tumor process is a violation of adhesion interactions involving local and central mechanisms. Local features of adhesive dysregulation are demonstrated in the first part. The lack of histospecific adhesion molecules expression resulting from stress or genetic mutation damages an important mechanism of antitumor protection of the tissue disrupting the processes of proliferation and differentiation. The deficiency of histone-specific homotypic adhesion molecules which occurs later exacerbates the disorders. This leads to a decrease in the expression of leukocyte integrins (LFA-1, Mac-1) ligands of the β2 family on the surface of immune effectors and to an increase also in the expression of adhesion molecules to the substrate-antigens VLA (very late activation) family of β1 -integrins on tumor cells. The first restricts the interaction of ICAM family molecules with their contra-receptors from the β2 -integrin family reducing the elimination of target cells by immune effectors which contributes to the screening of the tumor from antitumor surveillance. The second promotes the invasion of the tumor into the surrounding tissues, the formation of blood vessels as well as its heterotypic adhesion with other tissues which further stimulates the proliferation and suppression processes of tumor cells apoptosis. So, the adhesion molecules can be compared to the Phoenix bird: disappearing at the beginning of the process (between the similar cells), they reappear in a new quality (increasing adhesion to cells of other tissues), increasing the totalysm of the tumor. It should be taken into account that tumor cells due to adhesion dysregulation “isolate themselves from society”, lose their differentiation, their maturity and “fall into childhood”, being unable to perform specific, “adult” functions. So, cancer can be considered as a manifestation of the cells aging. Therefore, the anti-stress, endogenous geroprotective mechanisms activation based on the adhesion correction can be effective for preventing and treatment the oncological process. 

Introduction. Breast cancer (BC) is an immunogenic tumor. Immune cells infiltration of tumor tissue can affect the clinical course of the disease. The immunogenicity of breast cancer varies depending on the molecular subtype.

The aim of this work was to study the main indicators of systemic and local immunity before patient’s treatment and to determine their relationship with the immediate neoadjuvant chemotherapy results.

Materials and methods. Patients with stage II–III BC received standard neoadjuvant chemotherapy in accordance with the molecular subtypes. The percentage of the main effector and regulatory lymphocytes populations of systemic and local immunity was determined by flow cytometry.

Results. A decrease in the level of effector CD8 and CD4 lymphocyte populations and an increase in the level suppressor populations in tumor tissue in comparison with peripheral blood indicate an immunosuppressive state of local immunity in BC patients. In tumor tissue, a high level of CD8⁺ PD-1⁺ and CD4⁺ PD-1⁺ cells were associated with a high level of regulatory CD4⁺ CD25^highCD127^–/low and CD8⁺ CD11b^– CD28^– lymphocytes. Differences were found in the significance of individual lymphocyte populations for the immediate results of treatment between patients with different subtypes of breast cancer.

Conclusion. Determination of lymphocyte subpopulations correlating with the level of PD-1 cells, and the results of treatment in patients with different molecular BC subtypes, will help a clearer understanding of the antitumor immune response in this pathology, and will also serve as a basis for identifying immune biomarkers that can be used as additional predictive factors in various treatment options for BC patients. 

Introduction. The SeDeM-ODT method is a relatively new method based on expert judgment and pie charts, which reflect 15 main parameters of the suitability of a dosage form for direct compression and dispersibility in the oral cavity.

The purpose of the research presented in this article is to study the pharmaceutical substance (API) GK-2 (bis- (N-monosuccinyl-L-glutamyl-L-lysine)hexamethyleneamide) using the SeDeM-method, to determine the direction for the correction of technological properties using excipients and to develop using the presented methods of the composition of tablets GK-2, dispersible in the oral cavity.

Materials and methods. Preparation of tablets – manual hydraulic press PRG-50; method for determining flowability (GPM.1.4.2.0016.15, GP XIV, volume 2) – bulk density analyzer (ERWEKA SVM 221), GTB flowability tester (ERWEKA, Germany); crushing strength of tablets (GPM.1.4.1.0011.15, GP XIV, volume 2) – strength analyzer TBF 1000 CopleyScientific® (Great Britain); method for determining disintegration (GPM.1.4.2.0013.15, GP XIV edition, volume 2) – PTZ-S disintegration tester (Pharma Test, Germany); weight loss on drying (GPM.1.2.1.0010.15, GP XIV edition, volume 1) – moisture analyzer Sartorius MA-35 (Sartorius AG, Germany); determination of fractional composition – a vibrating sieve with pore sizes: 850, 600, 425, 300 and 250 microns, is used to determine the particle size distribution; tablet abrasion tester (GPM.1.4.2.0004.15, GP XIV edition, volume 2) – tablet abrasion tester PTF 30 ERA (Pharma Test, Germany); Optical microscopy (GPM.1.2.1.0009.15, GP XIV edition, volume I) – microscope Nicon, Eclipse E 200; digital camera Nicon Ds-Ri2. The data were processed using the SeDeM and SeDeM-ODT methods.

Results. Model formulations have been developed containing various types of co-process fillers and a sliding excipient, which have been studied using the main pharmaceutical-technological methods and optical microscopy. Based on the data obtained, SeDeM-ODT diagrams were constructed, in which the parameters were converted into “radii”, reflecting the degree of acceptability for each technological characteristic. In addition, the following factors were calculated from the pie charts: volumetric parameter, compressibility coefficient, flowability parameter, stability coefficient, dosage coefficient, dispersibility coefficient, as well as the index of good pressing, the parametric index and the parametric index of the profile.

Conclusion. As a result of the data obtained, the most optimal composition was selected that was acceptable for all the factors under consideration and had the highest values of the parametric index. 

Introduction. Nowadays, the development of delivery systems based on micro- and nanoparticles is being actively pursued to increase the selectivity and efficiency of photosensitizers in photodynamic therapy. Such microparticles could increase the effectiveness of the already used chemotherapeutic drugs due to their accumulation in the tumor and help to overcome the drug resistance of tumor cells.

The aim of this research was to obtain microparticles based on a biocompatible block copolymer of lactic and glycolic acids with the inclusion of the photosensitizer radachlorin, magnetic nanoparticles, and perfluorodecalin and their subsequent evaluation as therapeutic agents for photodynamic therapy.

Materials and methods. Microparticles were obtained using the double emulsion method, described using of electron microscopy. Evaluation of their photodynamic properties was carried out using spectrophotometry and MTTtest on cell culture.

Results. Spherical microparticles with a size of less than 1 μm were obtained. The release of the active substance from microparticles occurred gradually over two weeks, and in the case of the presence of magnetic nanoparticles, the concentration of radachlorin remained practically unchanged for a month. Exposure of microparticles to the light of LED is accompanied by the formation ofsinglet oxygen. Electron microscopy indicated intracellular position of microparticlesin tumor cells. The MTT test revealed a significant inhibition of cell viability in the presence of microparticles.

Conclusion. The research results allow us to consider the obtained biocompatible polymer microparticles with the inclusion of radachlorin as a depot of radachlorin for local use in photodynamic therapy of tumors. 

Introduction. Increasing of poorly soluble pharmaceutical substances bioavailability is one of important problems of pharmaceutical technology. Resveratrol is a plant origin polyphenol with a broad spectrum of biological effects. However, due to poor solubility and, as a result, low bioavailability, it is not promising for the development of oral drugs. Thus, today resveratrol is presented only as a biologically active substance that is component of biologically active food supplements.

The objective of the research is selection of the optimal solubilizer to increase the solubility of resveratrol by determining the solubilization parameters.

Materials and methods. The spectrophotometric characteristics of resveratrol were studied using three groups of solubilizers: poloxamers, polysorbates and cyclodextrins. Studies were carried out in 50 mM hydrochloric acid buffer(pH 1.2) and 50 mM phosphate buffer(pH 6.8). Spectrophotometric measurements were carried out on a spectrophotometer UV/VIS-3600 Shimadzu (Japan) in the wavelength range of 220–380 nm. The effect of solubilizers on the spectrophotometric characteristics of resveratrol was determined in buffer solutions containing the solubilizer and resveratrol in significantly less concentration of its own solubility in water. The used multiple excess of the solubilizer ensured the finding of all resveratrol in a solubilized form. During the determining parameters of solubilization, buffer solutions containing from 2 to 10 mM solubilizers were added to the obviously excess of resveratrol. The indicated amount of resveratrol ensured the presence of its precipitate in all experimentsto determine the completeness of solubilization of the studied polyphenol.

Results. Based on the obtained spectrophotometric characteristics of solubilizers solutions with resveratrol, the most effective for the further development of solid dosage forms for oral administration are poloxamer 407, polysorbate 80 and modified methyl-beta-cyclodextrin, which ensure complete dissolution of resveratrol when its content in the composition with a solubilizer is about 10 %.

Conclusion. Based on the data obtained on the spectrophotometric characteristics of resveratrol using solubilizers, it can be argued that it is possible to create drugs with improved solubility of the studied polyphenol. On the basis of its compositions with poloxamer 407, polysorbate 80 and modified methyl-beta-cyclodextrin, with the selection of appropriate excipients, solid dosage forms for oral intake can be developed. 

Introduction. Suppression of activation of an alternative immune response is promising approach of tumor immunotherapy. In this study we evaluated antitumor and antimetastatic activity of SNK-411.

Objective. Evaluation of antitumor and antimetastatic activity of 5-hydroxypyrimidine derivative SNK-411 in mouse melanoma B16 model.

Materials and methods. Antitumor and antimetastatic activity of the SNK-411 were studied in tests on male C57BL/6 mice using the B16-F10 melanoma model. SNK-411 was injected intraperitoneally at doses of 10 and 25 mg/kg from day 2 to day 15 of melanoma development. Doxorubicin was injected at dose of 4 mg/kg on day 2 of tumor development to act as positive control. Antitumor and antimetastatic activity were studied by calculation of tumor growth inhibition and metastasis inhibition index (MII).

Results. SNK-411 at doses of 10 and 25 mg/kg and in combination with single injection of doxorubicin in dose of 4 mg/kg showed antimetastatic activity. MII in SNK-411 at 10 mg/kg dose was 72 %, at dose of 25 mg/kg was 82,9 %. The combination of 14-day course of intraperitoneal injections of SNK-411 at dose of 10 mg/kg and injection of doxorubicin 4 mg/kg revealed MII 97,1 %, in half of mice in this group metastasis were not observed on 21st day of melanoma development. All results are statistically significant. There was no significant inhibition of tumor growth in all groups.

Conclusion. SNK-411 has antimetastatic activity in tests on melanoma B16 model. Further investigation is required.