RESUMEN
The aim of the study was to evaluate antitumor and antioxidant properties of water-soluble polysaccharides from submerged myceliumn of Flammulina velutipes grown under optimized conditions. The optimization of the nutrient medium composition allowed to increase the biomass yield by more than 2 times (up to 35 g/l) and to reduce the time of the cultivation process. The submerged mycelium of F.velutipes strain Fv-1 contained 14.8% of a water-soluble polysaccharides, 31.6% of proteins, 2.5% of total lipids, vitamins B (B1, B5, B6). The polysaccharides contained glucose, galactose, fucose, mannose, xylose, rhamnose. The proteins contained all the essential amino acids except for tryptophan. Dry powder of the submerged mycelium, water extract of the mycelium and total fraction of the water-soluble polysaccharides demonstrated the antitumor activity against murine lymphocytic leukemia P 388 in vivo. The antitumor activity of the substances was mainly due to the polysaccharides, since their purification increased the tumor growth inhibition. The maximum tumor growth inhibition by the water-soluble polysaccharides amounted to 94%. The total fraction of the water-soluble polysaccharides from F.velutipes strain Fv-1 demonstrated antioxidant activity. The antioxidant capacity (AOC) of the water-soluble fraction from F.velutipes was higher than that of the water-soluble polysaccharides from the sub- merged mycelium of Grifolafrondosa, but inferior to the AOC of the water-soluble polysaccharides from the submerged mycelium of Ganoderma luciduma.
Asunto(s)
Antineoplásicos , Antioxidantes , Flammulina/química , Polisacáridos Fúngicos , Micelio/química , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Línea Celular Tumoral , Flammulina/crecimiento & desarrollo , Polisacáridos Fúngicos/química , Polisacáridos Fúngicos/aislamiento & purificación , Polisacáridos Fúngicos/farmacología , Ratones , Micelio/crecimiento & desarrollo , Neoplasias/metabolismo , Neoplasias/patologíaRESUMEN
Ophiocordyceps sinensis and Cordyceps militaris metabolites showed a high potential in the treatment of tumors as well as some other diseases. Antitumor properties of O. sinensis and C. militaris submerged mycelium were investigated. It was found that the O. sinensis dry biomass in a dose of 50 mg/kg administered once a day to the mice with subcutaneously inoculated P388 lympholeucosis lowered the tumor growth by 65% vs. 54% for the C. militaris dry biomass. The water extract of O. sinensis submerged culture however accelerated the growth of the P388 lympholeucosis tumor node in the mice almost two times, compared to the control. A greater caution in using this fungus as a source of biologically active substances is required since unwanted tumor-stimulating effects can arise.
Asunto(s)
Antineoplásicos/farmacología , Cordyceps/química , Leucemia P388/terapia , Micelio/química , Saccharomycetales/química , Animales , Antineoplásicos/química , Peso Corporal/efectos de los fármacos , Quimera , Desecación , Esquema de Medicación , Leucemia P388/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Polvos , SuspensionesRESUMEN
The basidiomycetes Ganoderma lucidum, Hericium erinaceus, Lentinus edodes and Trametes versicolor were used for preparation of aqueous extracts. A polysaccharide preparation (VPG) was isolated from the G. lucidum aqueous extracts. The mycelium was grown under submerged conditions according to an original procedure. Preliminary exposure of mice with tumors to cyclosphosphamide in a low dose for prolonged elimination of T-suppressors and rapid recovery of T-killers induced an increase in the efficacy of the H. erinaceus and L. edodes extracts. Investigation of the aqueous extracts and VPG on different tumor strain lines for the potential Modifiers of Biological Response (Ca755, s/c P388, s-180) demonstrated antitumor activity and satisfactory tolerabily after oral administration. Inhibition of the tumor growth by the H. erinaceus and T. versicolor extracts and VPG amounted to 88-99% and that of s-180 treated with the L. edodes aqueous extract amounted to 66-75%. Compositions 1, 2, 4 amd 5 were significantly more active by the duration and value of the effect on the animal tumor nodes as compared to the aqueous extracts and VPG included to the compositions and composition 4. Composition 5 (T. versicolor + H. erinaceus + G. Lucidum) proved to be the most efficient by all the criteria. The results of the design of the technologies for cultivation of the mycelum of the medicinal basidiomycetes, investigation of the antumor properties of the extracts and polysaccharide fraction of the mycelium and development of efficient compositions on their basis are summarized. Composition 5 proved to be the most promising for the clinical trials.
Asunto(s)
Antibióticos Antineoplásicos/farmacología , Basidiomycota/química , Productos Biológicos/farmacología , Micelio/química , Animales , Antibióticos Antineoplásicos/química , Productos Biológicos/química , Línea Celular Tumoral , Masculino , Ratones , Ratones Endogámicos C57BL , Reishi/química , Agua , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Ascorbigen, a natural product, is an indole derivative of L-ascorbic acid. Its effect on postnatal development and antibacterial resistance of the small intestine was studied on newborn mice. Ascorbigen was administered to 3-5-day old mice in a dose of 100 mg/kg orally every day for 7-10 days. 30 minutes before the last administration of the drug clinical isolates of Staphylococcus aureus or Escherichia coli were administered intragastrically to the young mice. The animals were killed in 24 hours and the frequency of the isolation of the microbes from the blood, spleen, kidneys and liver was developed. The oral use of the drug normalized the intestinal microflora, provided a reliable decrease of the bacteria isolation from the blood, spleen, kidneys and liver and prevented the animal death. The morphological examination showed that ascorbigen significantly increased the number and activity of the Paneth cells in the gland crypts, the goblet cells in the villi and mononuclear cells in the selfplate of the intestine mucous membrane vs. the intact control.
Asunto(s)
Ácido Ascórbico/análogos & derivados , Indoles/farmacología , Mucosa Intestinal/citología , Mucosa Intestinal/microbiología , Intestino Delgado/efectos de los fármacos , Administración Oral , Animales , Animales Recién Nacidos , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/farmacología , Sangre/efectos de los fármacos , Sangre/microbiología , Enteritis/tratamiento farmacológico , Enteritis/microbiología , Escherichia coli/patogenicidad , Femenino , Indoles/administración & dosificación , Mucosa Intestinal/efectos de los fármacos , Intestino Delgado/microbiología , Riñón/efectos de los fármacos , Riñón/microbiología , Hígado/efectos de los fármacos , Hígado/microbiología , Ratones , Ratones Endogámicos , Bazo/efectos de los fármacos , Bazo/microbiología , Staphylococcus aureus/patogenicidadRESUMEN
It was shown that hen egg-white lysozyme (LM) in the dose 100 mg/kg under the daily intragastral use slightly inhibited tumor grown or did not influence significantly upon it and did not change antitumor activity of cyclophosphamide. When used at mice C57Bl/6J with the transplanted ascitic or solid T-cell lymphoma EL4 (syngeneic system). On model of the same tumors in ascitic form at mice-hybrids (C57Bl/6J x DBA2)F1 (semisingeneic system) LM significantly potentiates antitumor activity of cyclophosphamide, though it had no effect on the rate of tumor growth. Potentiation of the effect of cyclophosphamide revealed itself in more slow development of ascite, increased mean life-span and the overall survival, appearance of completely cured animals. Our clinic-laboratory studies have revealed a sharp deficit of endogenic lysozyme in the blood serum of leukemic patients and extremely low lysozyme content in lavage liquid, from leukemic patients, with pneumonia. These data suggest that LM can be useful as a food additive in the complex treatment of oncological patients for enhancing antineoplastic chemotherapy efficacy.
Asunto(s)
Antineoplásicos Alquilantes/farmacología , Ciclofosfamida/farmacología , Linfoma/patología , Muramidasa/farmacología , Animales , División Celular/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBARESUMEN
Olipifat is an antineoplastic drug containing pyrophosphate and a product of special lignin processing. Donor C57Bl/6J mice with syngeneic B16 melanoma received a single 5-day course of olipifat. Effect of olipifat on antitumor resistance was evaluated by local neutralization test [3]. In animals with rapid melanoma growth, splenic cells from intact donors stimulated tumor growth. Olipifat abolished this growth-stimulating effect of splenocytes. In animals with slow melanoma growth, splenocytes had no effect on the growth of melanoma or Lewis lung cancer. In this case, splenocytes from olipifat-treated donors completely arrested the growth of melanoma B16 and decelerated the growth of Lewis lung carcinoma.
Asunto(s)
Antineoplásicos/uso terapéutico , Lignina/análogos & derivados , Lignina/uso terapéutico , Animales , Carcinoma Pulmonar de Lewis , Ganglios Linfáticos/efectos de los fármacos , Metástasis Linfática , Melanoma Experimental , Ratones , Ratones Endogámicos C57BL , Bazo/efectos de los fármacos , Timo/efectos de los fármacos , Factores de TiempoRESUMEN
It was shown in vitro that high concentrations of lovastatin, a competitive inhibitor of hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibited human malignant cells MOLT-4. The activity of lovastatin in doses of 50-250 microM was dose-dependent. Addition of mevalonate in a concentration of 3 mM to the growth medium completely prevented the cytotoxic effect of 100 microM of lovastatin. At the same time, exogenous mevalonate did not decrease the cytotoxicity of the anthracycline antibiotic carminomycin. Moreover, in a high concentration (7 mM) mevalonate slowly but significantly inhibited the growth of the malignant target cells and the effect was added to the cytotoxic effect of carminomycin low concentrations (0.08 to 0.175 microgram/ml). The results and the literature data suggested that combination of mevalonate, HMG-CoA reductase inhibitors and anthracyclines could be useful in tumor chemotherapy. The suggestion needs further investigation.
Asunto(s)
Antibióticos Antineoplásicos/toxicidad , Antineoplásicos/toxicidad , Carubicina/toxicidad , Lovastatina/toxicidad , Ácido Mevalónico/toxicidad , Linfocitos T/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Depresión Química , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Humanos , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
Possible local application of a new dosage form of bleomycetin (bleomycin) with the prolonged action was studied in experimental in vivo models. When the ion exchange textile polymer with the immobilized bleomycetin was implanted subcutaneously to tumor-bearing mice, there was observed marked inhibition of the growth of the following tumors: lung carcinomatosis (LLC), melanoma B-16 and lympholeukemia (NK/Ly). The implants proved to be less toxic by comparison to bleomycetin solutions. The new bleomycetin dosage form is useful as a new delivery system increasing the antibiotic selective action.
Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Vendajes , Bleomicina/análogos & derivados , Adsorción , Animales , Bleomicina/administración & dosificación , Carcinoma/tratamiento farmacológico , Implantes de Medicamentos , Transporte Iónico/efectos de los fármacos , Leucemia Experimental/tratamiento farmacológico , Leucemia Linfoide/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Melanoma Experimental/tratamiento farmacológico , Ratones , Ratones Endogámicos C57BL , Trasplante de NeoplasiasRESUMEN
Bleomycetin, an antitumor antibiotic of the domestic origin, is component A5 of the bleomycin complex. Design of new drug delivery systems especially for local application is an important problem of antitumor chemotherapy. Bleomycetin immobilized on ion exchange medical gauze was studied with this purpose in an in vivo experimental model of murine lympholeukemia NK/Ly. Subcutaneous implantation of the new dosage form of bleomycetin with prolonged action provided a significant antitumor systemic effect evident from an increase in the mouse life-span. In vitro determination of the bleomycetin contents in the gauze revealed that the antibiotic was completely absorbed from the carrier within 72 hours. The bleomycetin half-life in the plasma after the antibiotic administration in the bound form on the ion exchange gauze was twice as long as that after the antibiotic injection with NaCl isotonic solution.
Asunto(s)
Antibióticos Antineoplásicos/farmacología , Bleomicina/farmacología , Resinas de Intercambio Iónico/química , Animales , Antibióticos Antineoplásicos/química , Bleomicina/química , Carcinoma de Ehrlich/tratamiento farmacológico , Difusión , Sistemas de Liberación de Medicamentos , Implantes de Medicamentos , Leucemia Linfoide/tratamiento farmacológico , Masculino , RatonesRESUMEN
Searches for the natural compounds that determine the anticarcinogenic properties of a cruciferous-vegetable diet, revealed the products of alkaloid glucobrassicin biotransformations; among these, ascorbigen, an indole-containing derivative of L-ascorbic acid, was found to be the most abundant. Study of chemical properties of ascorbigen showed that it is capable of different transformations in acidic (including gastric juice) and slightly alkaline (including blood) media. The stable and unstable products of ascorbigen transformation determine the biological properties of the compound. The most important product of ascorbigen transformation in gastric juice is 5,11-dihydroindolo[3,2-b]-carbazole, with a binding affinity to the Ah receptor only 3.7 x 10(-2) lower than that of tetrachlorodibenzodioxin. This compound may be responsible for modifying P450 enzyme activities. Ascorbigen and its analogs are available synthetically. Their biological evaluation showed that some of the compounds of these series are immunomodulators. The most active is N-methylascorbigen, which demonstrates therapeutic effects (inhibition of tumor growth, protection of animals from bacterial and viral infections). The immunomodulatory activity of natural ascorbigen may be an additional factor of importance for the anticarcinogenic properties of a cruciferous-vegetable diet.
Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Anticarcinógenos/uso terapéutico , Ácido Ascórbico/análogos & derivados , Brassica , Indoles/uso terapéutico , Neoplasias Experimentales/tratamiento farmacológico , Adyuvantes Inmunológicos/química , Adyuvantes Inmunológicos/aislamiento & purificación , Animales , Anticarcinógenos/química , Anticarcinógenos/aislamiento & purificación , Ácido Ascórbico/química , Ácido Ascórbico/farmacocinética , Ácido Ascórbico/uso terapéutico , Biotransformación , Brassica/química , Brassica/metabolismo , Glucosinolatos/química , Glucosinolatos/aislamiento & purificación , Glucosinolatos/farmacocinética , Humanos , Concentración de Iones de Hidrógeno , Indoles/química , Indoles/aislamiento & purificación , Indoles/farmacocinética , Datos de Secuencia MolecularRESUMEN
The efficacy of eremomycin, a new glycopeptide antibiotic, was studied on a model of antibiotic-associated colitis in golden hamsters. The colitis was induced by intraperitoneal or intragastric administration of lincomycin. In a dose of 100 mg/kg administered orally once a day for 5 days eremomycin protected the animals from the lincomycin-induced colitis: some animals survived, the others died in later periods. When the animals were infected with a pathogenetic strain of Clostridium difficile followed by exposure to lincomycin the use of eremomycin produced the similar effect.
Asunto(s)
Antibacterianos/uso terapéutico , Clostridioides difficile/patogenicidad , Modelos Animales de Enfermedad , Enterocolitis Seudomembranosa/tratamiento farmacológico , Lincomicina/efectos adversos , Administración Oral , Animales , Clostridioides difficile/efectos de los fármacos , Cricetinae , Enterocolitis Seudomembranosa/inducido químicamente , Enterocolitis Seudomembranosa/microbiología , Glicopéptidos/uso terapéutico , Inyecciones Intraperitoneales , Lincomicina/administración & dosificación , Masculino , Mesocricetus , Factores de TiempoRESUMEN
Activity of cytochrome P-450-dependent monooxygenase system is significantly lower in hepatoma H-2-73 and Lewis lung carcinoma-bearing mice as compared to that in control animals. An inhibition of the cytochrome P-450 system was observed after the injection of ftorafur. Treatment of the mice with perfluorodecalin markedly increased the antineoplastic activity of ftorafur determined by a loss of the leucocytes and of the weight hepatoma H-2-73- and Lewis lung carcinoma resistant to ftorafur alone.
Asunto(s)
Sistema Enzimático del Citocromo P-450/metabolismo , Fluorocarburos/uso terapéutico , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Microsomas/enzimología , Neoplasias Experimentales/tratamiento farmacológico , Oxidorreductasas/biosíntesis , Tegafur/uso terapéutico , Animales , Sustitutos Sanguíneos , Inducción Enzimática , Neoplasias Hepáticas Experimentales/enzimología , Neoplasias Pulmonares/enzimología , Masculino , Ratones , Ratones Endogámicos C57BL , Neoplasias Experimentales/enzimología , Sustitutos del PlasmaAsunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Ácido Ascórbico/análogos & derivados , Infecciones Bacterianas/prevención & control , Indoles/uso terapéutico , Animales , Ácido Ascórbico/inmunología , Ácido Ascórbico/farmacología , Ácido Ascórbico/uso terapéutico , Infecciones por Escherichia coli/prevención & control , Indoles/inmunología , Ratones , Infecciones Estafilocócicas/prevención & controlRESUMEN
Injection of cyclophosphamide in a dose of 100 mg/kg two or four times at 18- or 7-day intervals, respectively, prolonged the remission in EL-4-leukemia-bearing C57Bl/6j mice induced by cytosar under deoxycytidine protection. Injection of blastolysin in a dose of 25 mg/kg once a week at the same period had no effect. However, blastolysin potentiated the antirelapse effect of cyclophosphamide. It is suggested that the potentiation of the cyclophosphamide effect with blastolysin is mediated by activation of antitumor immunological reactivity.
Asunto(s)
Antibacterianos , Antibióticos Antineoplásicos/uso terapéutico , Ciclofosfamida/uso terapéutico , Recurrencia Local de Neoplasia/prevención & control , Timoma/tratamiento farmacológico , Neoplasias del Timo/tratamiento farmacológico , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Sinergismo Farmacológico , Glicopéptidos/uso terapéutico , Masculino , Ratones , Ratones Endogámicos C57BL , Trasplante de NeoplasiasRESUMEN
Undulatory changes in the ratio of proliferating to quiescent spleen cells of (C57BL/6j X DBA/2)F1 male mice were revealed in the course of Rauscher's leukemia development by means of nucleoprotein-celite chromatography. Administration of colloidal gold particles for the purpose of the functional loading of the mononuclear phagocyte system (MPS) induced a temporary diminution (for several hours) of the proliferating cell percentage and the DNA synthesis rate. Then the number of proliferating cells returned to normal (by 24 hours), with the DNA synthesis rate exceeding the basic level. The data obtained point to the dependence of tumor cell proliferation on the MPS in Rauscher's leukemia.
Asunto(s)
Leucemia Experimental/patología , Monocitos/fisiología , Fagocitosis , Bazo/patología , Animales , Coloides , Oro , Masculino , Ratones , Virus RauscherRESUMEN
The possibility of raising the efficacy of the treatment with lethal doses of 5-fluorouracil (FU) under body protection by allopurinol has been demonstrated in experimental blast leukemia (hemoblastosis) La. The protective effect was found to be dependent on dose-time correlations between FU and allopurinol. Oral administration of allopurinol in high doses of 150-200 mg/kg 30 minutes before intraperitoneal injection of FU provoked the development of CNS toxic lesions and death of part of mice in the next 72 hours. The data obtained provide evidence in favour of trying the efficacy of combined allopurinol and FU for non-lymphoid leukemias of man.
Asunto(s)
Alopurinol/administración & dosificación , Fluorouracilo/administración & dosificación , Leucemia Experimental/tratamiento farmacológico , Enfermedad Aguda , Administración Oral , Animales , Quimioterapia Combinada , Fluorouracilo/efectos adversos , Inyecciones Intraperitoneales , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
The growth of syngeneic hepatoma H-2-73 in adult (CBA x C57BL/6j) F1 mice leads to the development of leukemoid response that is manifested by leukocytosis, splenomegaly and a considerable increase in the content of lymphoid cells in the spleen. Meanwhile the newborn recipients of the tumor do not develop leukemoid response but manifest physiological changes in the hemopoietic tissue normally occurring within the first weeks after birth. The sensitized cells of the spleen of the adult tumor-bearing mice enhance tumor growth in the newborn recipients and inhibit it in the adult mice. Spleen cells of normal adult donors do not affect tumor growth in the newborn recipients. The data obtained suggest that the opposite effect of the transferred sensitized spleen cells from the adult animals on tumor growth in the newborn and adult mice is related to the age-associated features of the immune system of recipient mice.
Asunto(s)
Sistema Hematopoyético/fisiopatología , Neoplasias Hepáticas Experimentales/fisiopatología , Animales , Animales Recién Nacidos , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Trasplante de Neoplasias , Bazo/fisiopatología , Trasplante IsogénicoRESUMEN
The growth of syngeneic hemangiopericytoma in CBA X X C57BL/6j)F1 male mice was attended by the development of leukemoid reaction. The spleen showed an abrupt increase of the area taken by the red pulp with a remarkable activation of erythropoiesis in the pulp. The peripheral blood developed erythrocytosis 7 days after transplantation of pericytoma followed by anemia.
Asunto(s)
Médula Ósea/patología , Hemangiopericitoma/patología , Reacción Leucemoide/complicaciones , Bazo/patología , Animales , Hemangiopericitoma/complicaciones , Hibridación Genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Trasplante de Neoplasias , Neoplasias Experimentales/patologíaRESUMEN
The inducers of microsomal drug-metabolizing enzymes phenobarbital (PB) and 20-methylcholanthrene (MC) inhibited the lethargic effect of high doses of ftorafur in C57BL/6j mice, but stimulated the animal mortality at days 4-8 after the drug administration. The opposite effect has been obtained by the combination of ftorafur with the inhibitor of the microsomal enzymes SKF 525A. Animal pretreatment with PB or with PB + MC markedly enhanced the antineoplastic activity of ftorafur in Rauscher leukemia-, leukemia La-, or hemangiopericytoma-bearing mice but seemed unlikely to afford any therapeutic advantage over this drug because the lethal toxicity of ftorafur was increased.