Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 9 de 9
Filtrar
1.
J Exp Med ; 180(3): 1047-57, 1994 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-8064224

RESUMEN

Transforming growth factor beta 1 (TGF-beta 1) and TGF-beta 2 can reversibly inhibit the proliferation of hematopoietic progenitor cells in vivo, leading us to hypothesize that such quiescent progenitors might be more resistant to high doses of cell cycle active chemotherapeutic drugs, thereby allowing dose intensification of such agents. Initial studies showed that whereas administration of TGF-beta 1 or TGF-beta 2 did not prevent death in normal mice treated with high doses of 5-fluorouracil (5-FU), those mice that received TGF-beta 2 did exhibit the beginning of a hematologic recovery by day 11 after administration of 5-FU, and were preferentially rescued by a suboptimal number of transplanted bone marrow cells. Subsequently, it was found that the administration of TGF-beta 2 protected recovering progenitor cells from high concentrations of 5-FU in vitro. This protection coincided with the finding that significantly more progenitors for colony-forming unit-culture (CFU-c) and CFU-granulocyte, erythroid, megakaryocyte, macrophage (GEMM) were removed from S-phase by TGF-beta in mice undergoing hematopoietic recovery than in normal mice. Further studies showed that the administration of TGF-beta protected up to 90% of these mice undergoing hematologic recovery from a rechallenge in vivo with high dose 5-FU, while survival in mice not given TGF-beta was < 40%. Pretreatment of mice with TGF-beta 1 or TGF-beta 2 also protected 70-80% of mice from lethal doses of the noncycle active chemotherapeutic drug, doxorubicin hydrochloride (DXR). These results demonstrate that TGF-beta can protect mice from both the lethal hematopoietic toxicity of 5-FU, as well as the nonhematopoietic toxicity of DXR. This report thus shows that a negative regulator of hematopoiesis can be successfully used systemically to mediate chemoprotection in vivo.


Asunto(s)
Doxorrubicina/toxicidad , Fluorouracilo/toxicidad , Factor de Crecimiento Transformador beta/farmacología , Animales , Médula Ósea/efectos de los fármacos , Trasplante de Médula Ósea , División Celular/efectos de los fármacos , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/fisiología , Ratones , Ratones Endogámicos BALB C , Proteínas Recombinantes/farmacología
2.
Anticancer Res ; 10(2A): 437-9, 1990.
Artículo en Inglés | MEDLINE | ID: mdl-2346316

RESUMEN

The pharmacokinetics of flavone acetic acid (FAA) were comparatively studied in Balb-c mice and in immunocompetent nude mice treated with i.v. doses of 100 and 300 mg/kg. In both strains of mice, FAA kinetics appear to be dose-dependent, since the AUC values increased disproportionally to the dose. FAA protein binding and the pattern of distribution were similar in Balb-c and nude mice, the highest drug concentrations being found in liver and small intestine and the lowest in brain. Renal excretion appears to be the major route of FAA elimination in both strains, accounting for about 75% of the total drug administered after a dose of 100 mg/kg and 50-60% after a dose of 300 mg/kg. We conclude that FAA pharmacokinetics are comparable in Balb-c and nude mice so that the previously investigated FAA dosage schedules in inbred mice can also be employed in nude mice bearing human tumors.


Asunto(s)
Flavonoides/farmacocinética , Animales , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Flavonoides/sangre , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Distribución Tisular
3.
Int J Cancer ; 43(6): 1091-7, 1989 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-2659542

RESUMEN

A novel murine tumor resistant to cis-diamminedichloroplatinum (cisplatin, DDP) was obtained (M5/DDP) after 22 passages in which mice bearing the ovarian reticular cell sarcoma M5076 (M5) were treated with DDP. Although DDP conserved some inhibitory activity on growth of M5/DDP, it was much less effective than on M5. Treatment with DDP did not prolong the survival time of mice with M5/DDP, whereas it markedly prolonged survival of M5-bearing mice. M5 and M5/DDP tumors shared many biological and biochemical features. They were similar histologically, they metastasized reproducibly to the liver and were poorly immunogenic. Their growth rates were comparable; their DNA index, percentage of cells in S phase and intra-cellular glutathione content were also similar. In both tumors, DDP caused an accumulation of cells in S late-G2-M within 24 hr after drug treatment. However, this was efficiently reversed in M5/DDP, whereas it worsened and persisted longer in M5. Cross-resistance was observed between DDP and its analogues carboplatin and iproplatin, but tetraplatin retained marginal activity on M5/DDP tumor. Several alkylating agents tested [L-phenyalanine mustard (L-PAM); cyclophosphamide (CTX); chlorambucil (CLB); 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and dacarbazine (DTIC)] were not totally cross-resistant to DDP, but showed greater activity on M5 than on M5/DDP. Other non-alkylating anti-neoplastic drugs showed a similar degree of activity on M5 and M5/DDP. 5-Aza-2'-deoxycytidine (Aza-d-Cyd) was very effective on both tumors, etoposide (VP-16) and cytosine arabinoside (Ara-C) had no activity and Adriamycin (ADR) was weakly effective.


Asunto(s)
Cisplatino/antagonistas & inhibidores , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Animales , Antineoplásicos/antagonistas & inhibidores , Línea Celular , Cisplatino/administración & dosificación , Evaluación Preclínica de Medicamentos , Resistencia a Medicamentos , Femenino , Citometría de Flujo , Glutatión/análisis , Linfoma de Células B Grandes Difuso/análisis , Linfoma de Células B Grandes Difuso/mortalidad , Ratones , Ratones Endogámicos C57BL , Trasplante de Neoplasias , Neoplasias Ováricas/análisis , Neoplasias Ováricas/mortalidad , Células Tumorales Cultivadas
4.
Surg Gynecol Obstet ; 163(1): 37-41, 1986 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-3088741

RESUMEN

Injured patients treated with fructose 1,6-diphosphate (1 millimole of phosphate per kilogram per day) together with parenteral nutrition had a better nitrogen balance than patients treated with isocaloric nutrition and an inorganic source of phosphate. Excretion of 3-methylhystidine was similar while tyrosine and alanine output from the extremities was lower in the group of patients given fructose 1,6-diphosphate. The data indicates that the protein sparing action of fructose 1,6-diphosphate is exerted through an increased protein synthesis.


Asunto(s)
Fructosadifosfatos/uso terapéutico , Hexosadifosfatos/uso terapéutico , Nitrógeno/metabolismo , Nutrición Parenteral Total , Compuestos de Potasio , Heridas y Lesiones/terapia , Traumatismos Abdominales/terapia , Adulto , Anciano , Aminoácidos/sangre , Evaluación de Medicamentos , Femenino , Fructosadifosfatos/metabolismo , Humanos , Masculino , Metilhistidinas/orina , Persona de Mediana Edad , Fosfatos/metabolismo , Fosfatos/uso terapéutico , Potasio/metabolismo , Potasio/uso terapéutico , Distribución Aleatoria
7.
Nouv Presse Med ; 6(26): 2315-7, 1977 Jun 25.
Artículo en Francés | MEDLINE | ID: mdl-560682

RESUMEN

The effectiveness of three plasma cleansing techniques (exchange transfusion, peritoneal dialysis and plasmapheresis) is studied in the treatment of phalloides intoxication. The severity of the latter is dependent upon the amount of toxin ingested, with can now be measured by radio-immunology, as well as the fixation of the toxin in the liver. Methods to ensure its elimination must be instituted as soon as possible. Thus in 43 patients who had consumed more than 50 g of fresh fungi, there were no deaths amongst those treated during the first 36 hours and 7 deaths out of 22 patients treated late. It is not yet possible to define the respective values of each method.


Asunto(s)
Agaricales , Amanita , Intoxicación por Setas/terapia , Oligopéptidos/envenenamiento , Faloidina/envenenamiento , Adolescente , Adulto , Anciano , Amanitinas/análisis , Transfusión Sanguínea , Peso Corporal , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intoxicación por Setas/mortalidad , Diálisis Peritoneal , Radioinmunoensayo , Factores de Tiempo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA