ABSTRACT
The review summarizes literature data on the development of drugs based on natural and synthetic high-polymeric double-stranded RNA, and their antiviral, immunoadjuvant and antitumor properties. Special attention is paid to cell receptors responding to exogenous dsRNA, the paths of dsRNA-dependent antiviral reaction, ability of dsRNA to inhibit growth and induce apoptosis ofmalignant cells. It has been shown that enhancing the innate immune response with dsRNA can be an effective component in improving methods for treating and preventing infectious and cancer diseases. The further use of dsRNA for the correction of pathological processes of different origin is discussed.
Subject(s)
Antineoplastic Agents , Antiviral Agents , Drug Development , Immunity, Innate , RNA, Double-Stranded/pharmacology , HumansABSTRACT
Abstract-The review summarizes literature data on the development of drugs based on natural and synthetic high-polymeric double-stranded RNA (dsRNA), their antiviral, immunoadjuvant, and antitumor properties. Special attention is paid to cell receptors responding to exogenous dsRNA, pathways of dsRNA-dependent antiviral reaction, ability of dsRNA to inhibit growth and induce apoptosis of malignant cells. It has been shown that enhancing the innate immune response with dsRNA can be an effective component in improving methods for treating and preventing infectious and cancer diseases. The further use of dsRNA for the correction of pathological processes of different origin is discussed.
ABSTRACT
The author name M. V. Edeeva should read M. V. Edeleva.
ABSTRACT
Effect of alkoxyamines on normal and tumor cells was studied in vitro and in vivo. In vitro experiments showed that alkoxyamines produce a dose-dependent toxic effect on cells of human breast tumor MCF7 line. Transplantation of Krebs-2 ascites carcinoma cells preincubated with alkoxyamines to mice did not induce tumor growth. An opposite effect was observed in normal mouse cells: functional activity of peritoneal macrophages increased. The possibility of using alkoxyamines as theranostic agents is discussed.
Subject(s)
Antineoplastic Agents/pharmacology , Hydroxylamines/pharmacology , Animals , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Humans , Inhibitory Concentration 50 , MCF-7 Cells , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/physiology , Male , Mice , Mice, Inbred CBA , Neoplasm Transplantation , Phagocytosis/drug effectsABSTRACT
AIM: Evaluation of composite formulation of yeast double stranded RNA with polyglucinum (dsRNA-PG) effect on non-specific antiviral resistance factors in mice in comparison with commercial formulation Ridostin. MATERIALS AND METHODS: dsRNA and Ridostin formulations were injected intramuscularly once at the dose of 5 mg/ml, polyglucinum--at the dose of 3.75 mg/ml. 3, 5, 24, 48 and 72 hours after the injection serum interferon levels, neutrophil oxidation-reduction activity parameters, peritoneal macrophage phagocyte activity levels were analyzed in mice blood samples. RESULTS: New dsRNA and polyglucinum containing composite formulation is a non-specific resistance system stimulator. dsRNA-PG effect on interferon synthesis and mice phagocyte activity was higher than with Ridostin and developed earlier. Neutrophil function activation by the formulation had a prolonged effect. A possible explanation for increased activity of dsRNA and polyglucinum composite formulation is a modulating effect by the polysaccharide component. CONCLUSION: The new formulation may have a more intensive and prolonged protective effect against influenza virus in comparison with Ridostin.
Subject(s)
Antiviral Agents/administration & dosage , Dextrans/administration & dosage , Interferon Inducers/administration & dosage , Interferons/blood , RNA, Double-Stranded/administration & dosage , Animals , Mice , Neutrophils/drug effects , Neutrophils/immunology , Orthomyxoviridae/drug effects , RNA, Fungal/administration & dosageABSTRACT
Antitumor activity of TNF-α incorporated in nanoparticles (VLP-TNF-α) and dynamics of its accumulation and elimination from the blood and tumor tissue were studied in ICR mice. The VLP-TNF-α preparation exhibited higher antitumor activity compared to free TNF-α, presumably due to longer circulation of the cytokine in the blood and its more intensive accumulation by tumor tissue.
Subject(s)
Antineoplastic Agents/pharmacology , Antineoplastic Agents/pharmacokinetics , Carcinoma, Ehrlich Tumor/drug therapy , Nanoparticles , Tumor Necrosis Factor-alpha/pharmacology , Tumor Necrosis Factor-alpha/pharmacokinetics , Animals , Antineoplastic Agents/administration & dosage , Injections, Intramuscular , Mice , Mice, Inbred ICR , Time Factors , Tumor Necrosis Factor-alpha/administration & dosageABSTRACT
A six-member HLDF6 peptide, fragment of HL-60 cell differentiation factor, exhibited antimetastatic and immunomodulating effects.
Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Lewis Lung , Interleukin-6/pharmacology , Macrophages, Peritoneal/drug effects , Neoplasm Proteins/chemistry , Peptides/pharmacology , Animals , Cell Proliferation/drug effects , Cells, Cultured , Macrophages, Peritoneal/metabolism , Mice , Mice, Inbred C57BL , Peptides/chemistry , Spleen/cytologyABSTRACT
A study of antitumor properties of HLDF-6 was carried out in DBA/2 mice with transplantable ascites lympholeukemia P-388 as well as in tumor cell culture. Immunomodulating characteristics were evaluated. Five-fold administration of HLDF-6 peptide to tumor-bearing mice inhibited tumor growth thus extending survival. As a result metabolic activity decreased which was followed by longer survival of lympholeukemia P-388 cells and enhanced cytological effect of peritoneal macrophages on tumor cells of the same strain.
Subject(s)
Antineoplastic Agents/pharmacology , Hematologic Neoplasms/drug therapy , Oligopeptides/pharmacology , Animals , Hematologic Neoplasms/physiopathology , Male , Mice , Mice, Inbred DBA , Treatment OutcomeABSTRACT
The methods of treatment by using the stimulators of the non-specific resistance system have been growing even more topical. Drugs based on interferon (INF) and its inducers belong to the group. IFN is of key importance in the regulation of antiviral immunity. The use of IFN inducers can be referred to as the most promising approach to enhancing and activating the body resistance mechanisms. The advantages of IFN inducers before IFN drugs, a wide spectrum of antiviral effects, compatibility with many pharmaceuticals, good tolerability by patients and effectiveness in different administration modes served as a basis for designing a new class of antiviral drugs--IFN inducers. A lot of experimental medical-and-biological research was made to evaluate the efficiency of IFN inducers in influenza. They were shown to possess a pronounced therapeutic-and-preventive action in experiment and clinical trials. Synthetic and natural dsRNA belong to IFN inducers. Multiple research made in cell culture and with experimental animals demonstrated a high interferon-inducing and antiviral activity of double-stranded RNA against influenza virus. A number of dsRNA-based IFN inducers are permitted for clinical use. Data obtained in clinical trials of such inducers are indicative of their pronounced therapeutic-and-clinical effect. Hence, the IFN inducers having different structures and origins can be regarded as promising in the treatment and prevention of influenza and acute respiratory viral diseases.
Subject(s)
Interferon Inducers/therapeutic use , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/virology , Acute Disease , Humans , Influenza, Human/drug therapy , Influenza, Human/prevention & control , Respiratory Tract Infections/prevention & controlABSTRACT
Recombinant tumor necrosis factor-beta potentiated the inhibitory effect of cisplatin on intramuscularly transplanted GA-1 tumor and liver metastasis in mice. The antitumor effect was related to cytotoxic and cytostatic activities of the test preparations rather than to initiation of apoptosis.
Subject(s)
Antineoplastic Agents/therapeutic use , Cisplatin/therapeutic use , Liver Neoplasms/drug therapy , Lymphotoxin-alpha/therapeutic use , Muscle Neoplasms/drug therapy , Animals , Apoptosis , Drug Synergism , Liver Neoplasms/secondary , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/immunology , Male , Mice , Mice, Inbred A , Mitosis , Muscle Neoplasms/chemically induced , Muscle Neoplasms/pathology , Neoplasm Transplantation , Neutrophils/drug effects , Neutrophils/metabolism , Peroxides/metabolism , Phagocytosis/drug effects , Reactive Oxygen Species/metabolismABSTRACT
The effect of 10(3)-10(5) E/20 g doses of the recombinant factor of human beta tumor necrosis (rFNT-beta) on formation of the immune response and macrophage functional activity was studied in CBA and C57Bl/6 mice that differ in genetically determined level of the immune response to an antigen (sheep erythrocytes). The rFNT-beta was found to cause a modulating effect on the cell and humoral links of the immune response. The effect of the agent depended on the dose and the genotype of the experimental animals. It is suggested that the interlinear differences in the intensity of the humoral immune response in rFNT-beta administration may be connected with the different sensitivity to the agent of the peritoneal macrophages of mice of the used lines.
Subject(s)
Adjuvants, Immunologic/pharmacology , Antigen-Antibody Reactions/drug effects , Lymphotoxin-alpha/pharmacology , Animals , Antibody Formation/drug effects , Antibody-Producing Cells/drug effects , Antibody-Producing Cells/immunology , Antigen-Antibody Reactions/immunology , Dose-Response Relationship, Drug , Humans , Immunity, Cellular/drug effects , Immunization/methods , Male , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Phagocytosis/drug effects , Recombinant Proteins/pharmacology , Species SpecificityABSTRACT
Influence of dsRNA isolated from killer yeast of S. cerevisiae on humoral and cellular immune responses in mice CBA/CaY and C57Bl/6Y with opposing reaction to the antigen was studied. It was shown that after administration of the yeast dsRNA preparation to the animals simultaneously with the antigen there was an increase in the number of the antibody forming cells in the spleen and the titer of hemolytic antibodies in blood serum of the animals with high and low reactions to the antigen. After sensitization with different doses of sheep red blood cells (10(7) and 10(8)) the preparation had immunomodulating action on development of DTH in mice CBA/CaY. The effect of the dsRNA preparation on the immunity system depended on the preparation dose, antigen loading and animal genotype and was the most marked in mice CBA/CaY with interferon levels in blood serum 2-3 times higher than those in mice C57Bl/6Y.
Subject(s)
Antigens/immunology , Erythrocytes/immunology , Immunization , Interferon Inducers/pharmacology , Interferon Type I/biosynthesis , RNA, Double-Stranded/pharmacology , RNA, Fungal/pharmacology , Saccharomyces cerevisiae , Adjuvants, Immunologic , Animals , Antibody-Producing Cells/cytology , Interferon Inducers/immunology , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , RNA, Double-Stranded/immunology , RNA, Fungal/immunology , Sheep , Spleen/cytologyABSTRACT
The studies showed that yeast dsRNA in a dose of 2.5 mg/kg had a stimulating effect on the humoral immune response. When the preparation was administered soon after sensitization of experimental animals by the thymus-dependent antigen (sheep red blood cells, SRBC), there were observed a more than two-fold increase in the AFC count in the spleen and increased titers of hemolysins in blood serum. With the use of higher doses of the preparation (up to 10 mg/kg) the level of the immunostimulating effect remained unchanged. The efficacy of the preparation in CBA and C57BL/6 mice with high and low reactivity to the antigen was the same. Delayed-type hypersensitivity in the animals sensitized by SRBC was inhibited by yeast dsRNA in a dose of 10 mg/kg.
