RESUMEN
The novel ideas of fundamental role of mitochondria in the maintenance of viability of malignant cells have been reviewed. The modern state of research is considered in detail, including: mitochondrial control of the cellular redox state, sites of reactive oxygen species (ROS) production in inner mitochondrial membrane and antioxidant protection systems. Specificities of the structural-functional mitochondrial remodelling in malignant tumors, the mechanisms of the energy metabolism reprogramming, enhancement of the ROS production and adaptation to the hypoxic conditions and metabolic stress are analyzed. The available data including our research on transplanted tumors indicate that cytotoxic action of sodium dichloroacetate (the inhibitor of pyruvate dehydrogenase kinase) depends on biological properties of tumors and intensity of structural-functional mitochondrial rearrangement. Dichloroacetate turned out to be effective for sarcoma 37, but not for Lewis lung carcinoma.
Asunto(s)
Carcinoma Pulmonar de Lewis/metabolismo , Metabolismo Energético/efectos de los fármacos , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sarcoma 37/metabolismo , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Carcinoma Pulmonar de Lewis/genética , Carcinoma Pulmonar de Lewis/patología , Catalasa/genética , Catalasa/metabolismo , Ácido Dicloroacético/farmacología , Metabolismo Energético/genética , Humanos , Ratones , Mitocondrias/genética , Mitocondrias/patología , Especificidad de Órganos , Estrés Oxidativo , Sarcoma 37/tratamiento farmacológico , Sarcoma 37/genética , Sarcoma 37/patología , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismoRESUMEN
It was shown for the first time that extracellular FBPase of B. subtilis 668 like the preparation obtained from culture liquid of B. subtilis B 7025 displays citotoxicity activity in respect of tumor cells of sarcoma 37 in vitro. It is shown that the preparations remove TA antigens from the surface of the tumor cell. It is supposed that the mechanisms of citotoxic effect of extracellular FBFase of B. subtilis 668 and preparation from the culture liquid of B. subtilis B 7025 in vitro on cells of sarcoma 37 is probably realized through the apoptosis.
Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Bacillus subtilis/enzimología , Medios de Cultivo/química , Líquido Extracelular/enzimología , Fructosa-Bifosfatasa/farmacología , Animales , Antineoplásicos/aislamiento & purificación , Línea Celular Tumoral , Fructosa-Bifosfatasa/aislamiento & purificación , Sarcoma 37/patologíaRESUMEN
This study examined the effect of mixed bacterial vaccine (MBV), a biological response modifier prepared from Streptococcus pyogenes and Serratia marcescens, on the immune system of mice and on the regression of a transplantable mouse tumor sarcoma 37. The study examined MBV's biological properties and analyzed its chemical composition. The chemical composition varied with the growth media. A typical centrifuged, dialyzed supernate of the serum-containing preparation was found to consist mainly of protein and minimal amounts of carbohydrate and endotoxin, while MBV made with synthetic medium contained similar amounts of all three. MBV was nontoxic for mice, which gained weight following the injection of 0.5-1.0 ml of MBV. MBV caused regression of 20-100% of well-established mouse tumors without appreciable toxicity. MBV also had a striking effect on the immune response of mice to sheep red blood cells. When administered simultaneously with antigen injection, MBV increased the number of antibody-secreting splenocytes measured by the plaque-forming assay threefold. Serum antibody levels also increased two- to threefold. MBV did not enhance the immune response to pneumococcal polysaccharide type III, a B-cell-dependent response. However, the in vivo administration of MBV increased the in vitro response to MBV and the B-cell mitogen lipopolysaccharide. MBV compares favorably with other biological response modifiers because of its enhancing effect on the immune response and its oncolytic properties at nontoxic levels.
Asunto(s)
Vacunas Bacterianas/uso terapéutico , Inmunoterapia , Sarcoma 37/terapia , Sarcoma Experimental/terapia , Serratia marcescens/inmunología , Streptococcus pyogenes/inmunología , Animales , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/toxicidad , Carbohidratos/análisis , Ciclofosfamida/uso terapéutico , Endotoxinas/análisis , Técnica de Placa Hemolítica , Células Asesinas Naturales/inmunología , Ratones , Ratones Endogámicos ICR , Mitógenos/farmacología , Trasplante de Neoplasias , Proteínas/análisis , Sarcoma 37/inmunología , Sarcoma 37/patologíaAsunto(s)
Reparación del ADN/efectos de los fármacos , ADN de Neoplasias/biosíntesis , Leucemia Experimental/radioterapia , Tolerancia a Radiación , Sarcoma 37/radioterapia , Sarcoma Experimental/radioterapia , Animales , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Células Cultivadas , Citarabina/farmacología , Reparación del ADN/efectos de la radiación , Femenino , Hidroxiurea/farmacología , Leucemia Experimental/metabolismo , Leucemia Experimental/patología , Ratones , Sarcoma 37/metabolismo , Sarcoma 37/patologíaRESUMEN
Present work is based on the data of experimental studies on the influence of inhalatory (ether, chloroform, halothane and methoxyfluorane) and intravenous anaesthesia (neurovegetative block and neuroleptoanalgesia) upon the tumour growth and metastasization as well as the level of corticosteronemia in surgical trauma. It has been revealed that the narcosis may change the course of the tumorous process both by means of its action on the endocrine part of the organism-tumour system and immediately (halothane) due to its cytostatic action. Obviously, anaesthesia may appear one of the factors influencing the results of multifactoral therapy of tumorous diseases.
Asunto(s)
Anestesia por Inhalación , Anestesia Intravenosa , Corticosterona/sangre , Neoplasias Pulmonares/secundario , Linfoma no Hodgkin/patología , Sarcoma 37/patología , Sarcoma Experimental/patología , Animales , ADN/biosíntesis , Éter/farmacología , Femenino , Halotano/farmacología , Ratones , Índice Mitótico/efectos de los fármacos , Neuroleptanalgesia , Ratas , Sarcoma 37/metabolismoRESUMEN
The modifying influence of anaestesia on tumourigenic process (its stimulative or inhibitory effect upon tumour and metastasis growth) was established. It may occur indirectly, i.e. through endocrine link of the host-tumour system, and due to cytostatic effect of the anaesthetic drug (fluothane in particular).
Asunto(s)
Anestesia por Inhalación , Linfoma no Hodgkin/patología , Sarcoma 37/patología , Sarcoma Experimental/patología , Animales , Cloroformo/farmacología , Éter/farmacología , Halotano/farmacología , Linfoma no Hodgkin/cirugía , Metoxiflurano/farmacología , Ratones , Ratones Pelados , Mitosis/efectos de los fármacos , Metástasis de la Neoplasia , Neuroleptanalgesia , Ratas , Sarcoma 37/cirugíaAsunto(s)
Transformación Celular Neoplásica/efectos de la radiación , Neoplasias Experimentales/radioterapia , Animales , Ciclo Celular/efectos de la radiación , Cinética , Melanoma/patología , Melanoma/radioterapia , Ratones , Neoplasias Experimentales/patología , Dosificación Radioterapéutica , Sarcoma 37/patología , Sarcoma 37/radioterapiaRESUMEN
The mitotic activity of the transplantable mouse tumors, Sarcoma 37, Krebs-2, and Ehrlich carcinomas, in the ascites form, were inhibited after treatment with a mixture of vitamins C and B12 with no apparent toxic side effects. These vitamins when administered alone, at the same dosage, did not seem to have any apparent effect on mitosis or the morphology of the cells studied. Microscopic examination of the stained ascites fluid taken from the mice treated with the vitamin mixture showed few tumor cells, and these in various stages of disintegration. Also, an increase in lymphocytes, monocytes and neutrophils were noticed; however, later in the experiment, no tumor cells could be found and monocytes and macrophages were abundant.
Asunto(s)
Ácido Ascórbico/farmacología , Carcinoma de Ehrlich/patología , Carcinoma Krebs 2/patología , Mitosis/efectos de los fármacos , Sarcoma 37/patología , Vitamina B 12/farmacología , Animales , Depresión Química , Femenino , Ratones , Factores de TiempoRESUMEN
D-Isoascorbic acid, an isomer of vitamin C, and betaine hydrate (quaternary amine) were found to inhibit mitoses of sarcoma 37, Ehrlich carcinoma, and L1210 leukemia cells in vitro. However, the combined effect of these compounds produced a greater inhibitory activity than when either was administered individually.
Asunto(s)
Ácido Ascórbico/farmacología , Betaína/farmacología , Mitosis/efectos de los fármacos , Neoplasias Experimentales/patología , Animales , Carcinoma de Ehrlich/patología , Línea Celular , Quimioterapia Combinada , Leucemia L1210/patología , Ratones , Sarcoma 37/patologíaRESUMEN
The use of spectrophotometric method of objective quantitative estimation of tumor cells growth in diffusion chambers and chemotherapeutic sarcolysin effect on them are described.
Asunto(s)
Ácidos Nucleicos/análisis , Sarcoma 37/patología , Animales , Técnicas de Cultivo/instrumentación , Melfalán/uso terapéutico , Ratones , Sarcoma 37/análisis , Sarcoma 37/tratamiento farmacológico , Espectrofotometría UltravioletaRESUMEN
There was revealed a correlation between the activity of erythropoiesis and the resistance of the mouse organism both to the induced carcinogenesis and to the growth of the transplanted tumour. By choosing animals with a weakened erythropoiesis into experiment it is apparently possible to decrease considerably the period of the examination of the carcinogenic activity of the preparations under study.