Antineoplastic drugs, especially those on the basis of platinum, used for chemotherapy of cancer can also affect various normal tissues and organs including kidneys. Cisplatin occupies one of the leading places and possesses the greatest nephrotoxisity. For many years nephrotoxicity has been evaluated at the level of serum creatinine and of blood urea nitrogen. However these markers have a number of essential shortcomings and do not provide early detection of AKI. To identify early AKI stages new more informative markers are needed, which could make evidence of emerging initial signs of disorders at the earliest and irrespective of filtrational function of kidneys. Characteristics of modern perspective markers of early disoeders of kidneys are presented in the review. Special attention is paid to the panel of markers of potential nephrotoxicity of drugs - candidates for clinical trials, which are recommended for preclinical study. The review presents data of investigations of the role of biomarkers in early diagnostics of AKI caused by cisplatin and its analogues. Use of the ROC analysis in these studies showed that new markers are more sensitive and specific than serum creatinine and blood urea nitrogen and can be used for diagnostics and monitoring of kidney disorders caused by chemotherapeutic drugs.

The review presents analysis of the papers that discuss mechanisms of antitumor immunity. The role of innate and adaptive immune reactions as well as local and systemic is considered in terms of immune defense in clinical and experimental studies. The article discusses characteristics and role tumor-associated antigens for clinical practice. Various types of immune effector cells, including T-cells, NK-cell, DC, tumor associated macrophages, etc., and cytokines, are discussed regarding their contribution into antitumor immune response. The authors also refer to the hypothesis of “immunoediting” and its part in antitumor immunity.

Tumor antigens recognized by CTLs have been identified several years ago and are major targets for creating anticancer vaccines. PRAME is an antigen which is highly expressed in various malignant tumors including melanomas and hematopoietic malignancies such as acute and chronic leukemias (AML, CML). Technology for producing recombinant antigen PRAME is based on creating a bacterial producer strain containing cDNA of human PRAME gene. We have obtained two producers of recombinant PRAME protein and its N-half, the synthesis of the target protein in the producers occurs in the inclusion bodies. The schemes of isolation and purification of soluble proteins have been developed. The protein purity was approximately 95-96%. The monoclonal antibodies raised against truncated recombinant PRAME were used for PRAME protein analysis by Western blot on the various tumor cells. Specific monoclonal antibodies recognized the native PRAME protein in tumor cell lines as well as in tumor samples from patients. Our findings support the suggestion that this recombinant antigen may be further used as a target for diagnostic and therapeutic approaches. The monoclonal antibodies can be used for immunoassays of tumor samples from patients with hematologic malignancies to reveal clinical features and to monitor tumor progression.

Monoclonal antibody (mAb) against CD133 antigen is a stem marker of human tumor cells. Strain ICO-401 was prepared by cell fusion of murine myeloma NS-1 cells with splenocytes of BALB/ C mice, pre-immunized three times with an interval of two weeks with the cells of human melanoma mel IbrEE34RMCR. Merging was conducted with solution PEG/DMSO. Screening of mAb ICO-401 was performed on human melanoma cell lines from FSBI «N.N. Blokhin RCRC» collection which differ in the expression of CD133 antigen. Antigen expression was evaluated in immunofluorescence reaction by flow cytometer BD FACSCanto^TMII. ICO-401 was compared with commercial mAb against CD133 antigen. The results indicated that both mAb recognize the same antigen, but bind to different epitops.

The report presents the results of preclinical study of N-glycoside indolocarbazole derivative LCS-1208 antitumor activity in epidermoid LLC; mechanisms of antitumor action were studied as well. Therapeutic index TI₅₀ equal to 2.8 was calculated during evaluation of LCS-1208 antitumor selective action on LLC. The assessment of LCS-1208 effect on metastasis in lungs in doses 125 mg/kg and 150 mg/kg shows that the agent is more effective as adjuvant chemotherapy (MGI=45% and 44%, respectively) than neoadjuvant chemotherapy (MGI=33% and 31%, respectively). LCS-1208 had the proved advantage of antitumor effect duration compared to irinotecan: TGI was 95% - 52% and 94% -27%, respectively, for 20 days after completed therapy. Combination of LCS-1208 with irinotecan in half doses of those combined agents (75 mg/kg and 33 mg/kg, respectively) resulted in synergic antitumor effect. Mechanism of antitumor action is determined by LCS-1208 intercalation in the two-stranded DNA and inhibition of topoisomerase I function.

The laboratory for development of drug forms, N.N. Blokhin Russian Cancer Research Center developed a lyophilized liposomal dosage form (LLDF) of a new infrared photosensitizer phthalocyanine derivative - Thiosens. Previous studies determined optimal composition of the dosage form, technology of its production and methods of analysis; a number of biological experiments were performed. The next step of preclinical research is studying "acute" toxicity of LLDF, which is presented in this paper. The study of "acute" toxicity of LLDF Thiosens was carried out in the laboratory of Pharmacology and Toxicology. "Acute" toxicity of LLDF Thiosens was studied in the experiments on mice hybrids F1 (CBA » C57Bl / 6J) male and female and weinbrener outbred male rats. In the first series of experiments LLDF Thiosens was administered to male mice in the dose range of 5; 10; 20 and 30 mg/kg. In the second series of experiments, male and female mice were injected with LLDF Thiosens in the dosage range 6; 12 and 24 mg/kg. Male mice were treated by LLDF Thiosens intravenously; no symptoms of toxicity were registered at the doses of 5 and 10 mg/kg; death was observed in all experimental animals after administration at the doses of 20 and 30 mg/kg on the first day in the result of inactivity and piloerection. In the second series of experiments no sex differences were found in single intravenous injection of LLDF Thiosens. The results of the studies of "acute" toxicity in rats demon strated that when LLDF Thiosens was administered in doses 3, 6 and 9 mg/kg animal deaths were reported. A single intravenous LLDF Thiosens administration in rats in the excess of the expected dose for human in 1.5-4.5 times was well tolerated by the animals: animal mortality, clinical signs of toxicity and changes in behavioral responses were absent.

Effectiveness of a new photosensitizer (PS) liposomal amidoaminchlorine for PDT was studied on a tumor model of rat sarcoma М-1. The research objective: to define parameters of PS minimum effective dose and laser irradiation to achieve complete regression of the tumor. Dynamics of PS accumulation in tumor and healthy tissue was studied to define the PDT time course and antitumor efficiency of different PS doses and various parameters of laser irradiation. The study results defined the optimum term for PDT and minimally effective PS dose and established the parameters for laser irradiation.

A large part of basic research including medical area studies transportation and delivery of drugs directly to the organs, tissues and cells. This interest has been caused by many reasons, and above all, by huge medical and economic benefits of directed transport, reduced side effects and significant reduction of therapeutic drug doses. LLC «KOLETEX» designs and manufactures therapeutic gels for targeted drug delivery - gels «Kolegel» with various drugs, with the aim to improve effectiveness of radiotherapy and prevent radiation reactions. These gels are widely used in major oncology clinics, they have proven to be highly effective in the treatment of cancer. Their application allows to enhance the effectiveness of radiation exposure due to the introduced modifiers (sensitizers), to protect healthy tissue in the irradiation zone, speed up recovery of mucous membranes, resulting in enhanced treatment efficacy, shorten hospital stay and improve patient’s quality of life.

The paper presents the results of the study of dielectric blood characteristics - 20% solution of human albumin, 40% solution of glucose and 0,9% solution of NaCl, at the temperature ranging from 30 to 42 °C and the frequency of 0,6 GHz. At 37 °C the blood and albumin showed an abrupt increase in absorption. The hysteresis of temperature - absorption of blood and albumin in the heating-cooling cycles has been revealed. Addition of nanoparticles of iron oxide and carbon to albumin solution leads to the change of temperature dependence as compared to the nanoparticle-free albumin solution.