Obtaining preclinical models of malignant growth in a variety of xenografts (heterotransplantation), usually the subcutaneous, is the most important area for the use of nude mice in oncology. In a review paper describes the characteristics of Balb/c nude mice obtained from Buffalo (USA) and introduced to the Federal State Budgetary Scientific Institution “N.N. Blokhin Russian Cancer Research Center» of the Russian Ministry of Health of the Russian Federation and systematized their application. There are various variants «palentology» models of tumor growth, allowing you to personalize the forecast performance of selected impacts for a particular patient. Detailed modeling of metastases of various human cancers: colon cancer, pancreas, esophagus, lung, breast and prostate glands, testicles and ovaries, tumors of the head and neck. The characteristic of orthotopic (“MetaMouse” model) and experimental confirmation of the value of the hypothesis of Paget’s “seed and soil”, postulating a paired part of the process of metastasis of cell and tissue components of the tumor. Describes the use of the subcutaneous xenografts as control cell lines in the study of oncogenic potencies of the various drugs that are recommended for cellular immunotherapy of human. Examples and main thematic literature in recent years.

In 2012 the new, iron-dependent form of cell death - ferroptosis - distinct from apoptosis, autophagy and programmed necrosis at morphological, biochemical, and genetic levels has been described. In this review we will discuss the iron metabolism in physiological and pathological processes in humans, the molecular characteristics of ferroptosis and therapeutic options of cancer patients in the light of new data.

Multipotent mesenchymal stromal/stem cells (MSCs) are regarded as a stable, safe and easily available source of precursor cells for purposes of regenerative medicine. However, under repeated replication in tissue reparation processes and action of inflammatory mediators, aged MSCs may be transformed and obtain certain tumor-cell characteristics. The present review deals with the MSCs role in pathogenesis of rheumatoid arthritis. High proliferation speed, lack of contact inhibition and invasive growth of transformed MSCs is an important mechanism of cartilage destruction in rheumatoid arthritis.

The prognosis of breast cancer in the elderly is associated with increased risk of various complications. Recommendations for the treatment of breast cancer in this group of patients are controversial and range from radical surgery to conservative therapy. There are no specific clinical recommendations for this age group. It makes this problem relevant.

In this review we discuss some biological activities of quinazolinon derivatives. The derivatives of quinazolinon possess their activity by binding to some proteins important for the survival, proliferation and metastasis of tumor cells. There are grounds to initiate clinical trials of these substances to create new treatment protocols for a wide range of cancer diseases, several parasitic diseases, and certain neurodegenerative diseases.

Background. Multiple primary malignant tumors (MPMT) - 2 or more tumors, arising during patient life - are an important risk factor of cutaneous melanoma (CM). The frequency of MPMT in Russia ranges from 2 to 20 % with the incidence increasing. This tendency is linked mainly with the increasing life expectancy of the patients, with use of a potentially carcinogenic treatment methods, with the influence of adverse environmental factors and genetic predisposition In 15 patients with MPMT, including CM, has revealed a trend towards more frequent family history in male patients. In female patients MPMT included breast, ovarian and renal malignant tumors. CM relapses were observed shortly after surgical removal of the primary tumors. Objective. Clinical and genetic characteristics of patients with MK in MPMT structure. Materials and methods. Disease histories, MPMT structure and CM mutational status (PCR followed by direct sequencing of amplions) were analyzed in 8 male and 7 female patients with MPMT included metastatic CM. Results. A preliminary analysis of 15 patients with metastatic CM in MPMT structure has revealed some gender features. In female patients MPMT more often included breast, ovaries or kidney tumors. Excess body weight or obesity was detected in female patients (5/7) more often than in male patients (4/8). There is a tendency to more frequent family cancer histories in male patients compared to female ones - 3/8 vs. 1/7 in 3/8 male patients somatic mutations in BRAF gene (2) and PDGF gene (1) were identified in CM. The frequency of mutations of BRAF and NRAS genes in CM of female patients was 2 times higher than that of male patients. The combination of CM with bowel cancer was prevalent in male patients. In 2/7 male patients CM was the last tumor in MPMT structure, in 5/7 - the first, with the exception of the patient with primary multiple melanomas, while CM as the first tumor was revealed in 4/7 female patients and last CM - in 1/7 ones. Conclusions. Various combinations of tumors in MPMT structure were characterized in male and female patients. In female patients MPMT included breast, ovarian and renal malignant tumors/were the most frequent, while the combination CM with bowel tumors were prevalent in male ones. In male patients CM was diagnosed as the first tumor more frequently than the last one. The frequency of mutations in BRAF and NRAS genes in MK tumors in female patients with MPMT was 2 times higher than that in male patients. In 15 patients with MPMT, including CM, a trend towards more frequent family cancer history in male patients was revealed. CM relases were observed shortly after surgical removal of the primary tumor.

Introduction. Chemotherapy is an extremely ineffective and unsatisfactory means of treating malignant melanoma due to drug resistance, which is characteristic of this disease. A number of studies have shown that liposomal forms of anticancer drugs are able to overcome the multidrug resistance, but the mechanism by which this occurs is still remained to be elucidated. Aranoza (DNA-alkylating agent, a derivative of nitrosourea) has been approved for the treatment of patients with metastatic melanoma. Objective: to examine the influence of liposomal aranoza as well as the empty liposomes and “liophilisate for the preparation of solution for injections” (aranoza-lio) on the expression of mRNA of p53, MDM2, NFkB1, NFkB2, MyD88. Materials and methods. The study was performed with 10 melanoma cell lines, 4 of which carried the BRAF mutation. The level of p53, MDM2, NFkB1, NFkB2, MyD88 mRNA was investigated by quantitative polymerase chain reaction in real time. Results. Aranoza-lio increased slightly the expression of p53 mRNA in BRAF-mutated cells. We have observed also the increased expression of MDM2 mRNA (p = 0.0013). The expression of NFkB2, MyD88 mRNA did not change significantly as compared to control. Liposomal aranoza increased the expression of NFkB1 mRNA. Conclusion. Based on the data obtained we conclude that the liposomal aranoza triggers the mechanisms that contribute to sensitivity of cells toward anticancer drugs while aranoza-lio favored the enhancing of the expression of MDM2 mRNA and increase the resistance to chemotherapy.

Introduction. High indices of prostate cancer (PC) incidence and mortality as well as high speed of growth of these figures testify to urgency of research into PC origin as well as means of its prophylaxis. The problem of possible PC association with oncogenic human papillomaviruses (HPV) is still being disputable. Objective: to test whether surgical materials from PC patients in Russia harbour E7 oncogene of HPV type 16 (HPV16), the main HPV type responsible for cervical cancer. Materials and methods. Prostate tissues excised in the course of radical prostatectomy from 17 PC patients were tested by polymerase chain reaction. For better DNA preservation cryopreserved tumor specimens not treated with either formalin or paraffin were used. The PC typical multifocal type of growth was taken into account by microdissecting of cryostate cuts to accumulate homogeneous cells (cancerous, dysplastic or normal). Results. HPV16 E7 was registered in prostate tissues of 7 patients out of 17 examined including all those 5 cases for which DNA had been isolated from homogeneous sites of cancer cells. Conclusion. The result obtained enables one to admit that HPV16 may be harbored in prostates of Russian PC patients not infrequently.

Background. The purpose of this investigation is the search of new compounds with high selectivity of antitumor action on the tumor of the gastrointestinal tract (GIT) in the series of analogues of the peptide hormone gastrin. Objective: synthesis of 2 analogues of gastrin, 1 of which contains the cytotoxic group, the study of their cytotoxic and antitumor activity. Materials and methods. Synthesis of peptides was carried out by classical methods of peptide chemistry. Cytotoxic activity was studied on the cell culture НСТ116. Antitumor activity of analogues of gastrin were studied on transplanted tumors of the GIT of mice AKATOL and AKATON. Results. Two analogues of gastrin (octapeptide) were synthesized, 1 of which contains a cytotoxic group. Analogue containing cytotoxic group revealed the cytotoxic activity. Antitumor activity of two analogues of gastrin were studied on transplanted tumors of the GIT of mice AKATOL and AKATON. The cytotoxic and non-cytotoxic analogues of gastrin showed antitumor activity only on AKATON. Inhibition of tumor growth is 74 and 84 %, respectively. Conclusions. The therapeutic effect of two analogues of gastrin on adenocarcinome AKATON, probably, is associated with the expression of gastrin receptors ССК2 in this tumor.

Introduction. Oxidation-reduction dendrimers can produce anion-radicals, that is singlet oxygen and hydrogen peroxide. In this study toxicity of newly synthesized REDOX-dendrimer (RD) in mammalian cells in vitro and in vivo were preliminary evaluated. Objective: toxicity assessment of new RD for mammalian cells in vitro and in vivo. Materials and methods. Cytotoxicity studies of RD was made with MTT and direct living cells counting methods in Syrian hamster embryonic fibroblasts, modified with Src gene (HETR-SR); Syrian hamster embryonic fibroblasts, modified with NRAS gene (HEТR-NRAS); Chinese hamster ovary cancer cell line CHO-K1; erythroid human leukosis K562 and it’s subclone K562/iS9. In vivo toxicity was evaluated in healthy BDF mice using single intraperitoneal injection. Results. RD studies showed that it effectively influences cell lines with different catalase activity. 50 % growth inhibition (1C_%) was observed at concentration of RD: 6,871E-09- 7,031E-09 М - for HEТR-NRAS; 1,64E-08-1,78E-08 М - for HETR-SR; 2,92E-08- 3,06E-08 M-for СНО-К1 strain. For K562/iS9 and К562 IC₅₀ value was within the range from 1,698Е-005 to 2,606Е-005 М and from 1,288Е-005 to 1,722Е-005 М, respectively. Acute toxicity studies in mice showed that LD₁₀ = 948 + 4 mg/kg and LD₅₀ = 1000 + 21 (958 - 1043) mg/kg. Conclusion. New RD was studied in this research both in vitro and in vivo. It’s toxic parameters were determined in mammalian cells with different catalase strength. Obtained values of IC₅₀ ≤10^-4 М show that studied RD is cytotoxic. Acute toxicity studies in mice showed that RD influence on animals is dose dependant.

Objective: to study the cytotoxic activity of the zinc (II) and cadmium (II) iodide complexes with antipyrine (AP), caffeine (caf) and 1,10-phenantroline (phen) in comparison with that of free ligands, zinc (II) and cadmium (II) iodides in vitro. Materials and methods. The cytotoxic activity of the zinc (II) and cadmium (II) iodide complexes with AP, caf and phen in comparison with that of free ligands, zinc (II) and cadmium (II) iodides was investigated by methylthiazole tetrazolium assay using 5 human tumor cell lines. Results. It has been found that all 3 cadmium complexes demonstrate cytotoxic activity towards all 5 cell lines with concentration of inhibition of 50 % cell growth 5.5-84.0 mkM. Cytotoxicity of the most active diiodo(1,10-phenantroline)cadmium was slightly above than that of the respective ligand. One zinc-containing complex (diiodo(1,10-phenantroline)zinc) demonstrated significant activity towards 3 cell lines. The Jurkat cells were the most sensitive to studied compounds. Conclusion. It seems that zinc (II) and cadmium (II) iodide complexes with organic ligands are promising ones as potential antitumor drugs for further investigations both in vitro and in vivo.

Introduction. As a rule, pharmacotherapy of neoplastic diseases is associated with side effects varying degrees of severity. This is determined by the insufficient selective action of antitumor agents and, as a result, high nonspecific toxicity. One way to solve this problem is the development of the targeted drugs, delivered the active agent to the tumor cells. Over the past decades many experimental and clinical studies were undertake, but only few of them have demonstrated clinical efficacy of targeted drugs. This determines the necessity of further search in this direction. Objective: to investigate the toxicity of aimpila, its correlation with dose and reversibility. Materials and methods. Toxicological study of aimpila, developed by Pharmaceutical Scientific Center “PharmAccess” Ltd. (Moscow), was performed in male and female outbred rats. Aimpila is atractyloside alpha-fetoprotein noncovalent complex. Capsule mass of the drug in starch gel was administrated per os at the 1 and 10 therapeutic dose (30 x 0.1 mg/kg or 30 x 1 mg/kg with 24-h interval). Dynamics of body weight, hematological parameters, blood biochemical parameters, electrocardiography and urinalysis were performed for all animals. 5 animals in each group were sacrificed 1 and 30 days post treatment. Results. The results of the study demonstrate that the treatment with aimpila does not produce any changes in examined clinical-labora- tory parameters. Liver, renal, cardio, pancreatic and gastrointestinal toxicity of aimpila have been documented by microscopic pathology observation only in groups of rats, treated with high dose of drug. Histopathological findings of hepatotoxicity were supported by the results of clinical chemistry. Marked elevation of aspartate aminotransferase in serum was found after high dose aimpila treatment. These abnormalities were reversible during a month. Conclusion. The overall result of this study suggests the aimpila formulation has favorable toxicological profiles. Dose dependence and reversibility of toxic effects allows us to recommend it to further advance.

Introduction. The use of standardized model is required at preclinical researches of drug safety and efficiency. Apart of veterinary control the leading laboratories of the world use genetic monitoring of animals. Objective: to develop the method for detecting genetic contamination of laboratory mouse based on microsatellite DNA markers analysis. Materials and methods. We tested two lines of mice C57BL/6J and BALB/cJLac. We used 5 primers: (GAG)6C, (CTC)6C, (CTC)6A, AG9-1, AG9-2. We weighted the results of рolymerase chain reaction using 1.5 % agarous gel. Results. Three of tested primers allowed to distinguish 2 lines of mice statistically reliably. Two mice lines were bred to control the results. Our data shows track of every line gives a boots in assortment of alleles in locuses. We composed a table of alleles assortment in locuses for every line based of results. Conclusion. Our results prove that this method provides fast, reliable and cost-effective way of genetic monitoring.

Background. Some natural carotenoids have anti-carcinogenic, anti-mutagenic, and immunomodifying activity and may be considered as potential agents for chemoprevention of cancer. Objective: to study pharmacokinetics of beta-carotene, cantaxantene, lycopene, and carotene-containing compounds created on the base of the mentioned substances. Materials and methods. The study used carotene-containing drugs, which we previously created, such as Betask, Kaskatol, Tomatol, natural carotene-tocopherol complex derived from cankerberry. The research was conducted on mice, rats, rabbits, dogs, piglets, monkeys (Javanese macaque); the observations also involved healthy donors and patients with colorectal cancer before surgery. Carotenoid and retinoid detection was made by high performance liquid chromatography in blood plasma and liver tissue. Results. Comparative analysis of pharmacokinetics of the studied carotenoids demonstrates their relatively low absorption in animals. Bioavailability varies significantly among species; and it increases in the following order: dogs, rabbits, mice, rat, piglets, humans. Pharmacokinetics of carotenoids and carotene-containing compounds was studied with single and multiple administration per os. Cantaxantene and lycopene have a better bioavailability as compared to synthetic beta-carotene. Pharmacokinetics of synthetic carotenes and carotenoids of carotene-containing compounds has no significant differences. Beta-carotene in natural carotene-tocopherol complex has higher bioavailability (2-4 fold higher) as compared to synthetic beta-carotene. Regular complex administration into monkeys results in enhanced beta-carotene levels in blood serum of the animals and inhibits chemically induced carcinogenesis. The patients’ intake of beta-carotene in the pre-operational period was associated with the enhanced pro-vitamin levels in blood serum and stimulation of a number of cellular immune parameters. Conclusions. The studied carotenoids and carotene-containing compounds may be used in combined antitumor therapy and as treatment and prophylactics agents in cancer risk groups.