Search PubMed⌕ Search

Biomedical subjects

J Hildebrand

Publications and source records attributed to J Hildebrand.

At least 109 records · Page 6Linked to original sources
PubMed1983

Chemotherapeutic efficacy of Nocodazole encapsulated in liposomes on L1210 murine leukemia.

The use of sonicated phospholipid vesicles (liposomes) as carriers of methyl [5-(2-thienylcarbonyl)-1H-benzimidazol-2-yl] carbamate (Nocodazole), a water insoluble antimitotic compound active on mouse L1210 leukemia was investigated. Nocodazole was incorporated in dipalmitoyl-phosphatidylcholine: cholesterol: stearylamine (4:3:1) liposomes that were stable at room temperature for at least 48 hr. No drug leakage nor lipid exchange occurred after a 4 hr incubation at 37 degrees C with RPMI 1640 medium supplemented with 10% fetal calf serum. L1210 cells preincubated (2 x 10(6) cells/ml) at 37 degrees C for 3 hr with various concentrations of micronized Nocodazole or liposome-entrapped Nocodazole were injected i.p. into normal CDF1 mice (10(5) cells/mouse). Longest mean survival times and long-time survivors were observed in the group inoculated with L1210 cells preincubated with liposomes containing Nocodazole. CDF1 mice bearing i.p. or i.v. L1210 leukemia were treated i.p. on days 1, 5 and 9 with micronized or liposome-entrapped Nocodazole. Administration of this latter preparation induced a 50% increase in animal life span at the dosage (25 mg/kg/day) half the one required with the free compound (50 mg/kg/day). The present data indicate that enclosing Nocodazole, a water insoluble antimitotic compound, in liposomes results in an enhanced therapeutic activity against L1210 murine leukemia.

Animals↗
PubMed1983

Iv administration of a water-insoluble antimitotic compound entrapped in liposomes. Preliminary report on infusion of large volumes of liposomes to man.

Five patients with advanced multiresistant neoplasms were infused with NSC-251635 (a water-insoluble antimitotic agent) entrapped in egg yolk lecithin, cholesterol, and stearylamine liposomes. The maximum volume injected was 400 ml containing 8 g of lipids, ie, a dose of 135 mg/kg of body weight. Overall tolerance of the treatment was excellent. This study indicates that liposomes may be used safely as carriers for the iv administration of water-insoluble drugs to humans.

Adenocarcinoma↗
PubMed1983

Antitumor activity of a water-insoluble compound entrapped in liposomes on L1210 leukemia in mice.

The use of sonicated phospholipid vesicles (liposomes) as carriers of 2-[3'-(methoxycarbonylamino)-phenyl]-3-phenyl-6-methoxycarbonylamino-4-(3H)- quinazolone (NSC-251635), a water-insoluble antimitotic compound, was investigated in mice. NSC-251635 was incorporated in egg yolk lecithin, cholesterol, and stearylamine (4:3:1) liposomes. In vitro, NSC-251635 in suspension or entrapped in liposomes was not toxic for L1210 cells. In vivo, after ip or iv injections to CDF1 mice bearing intraperitoneal or intravenous L1210 leukemia, NSC-251635 was active only when it was incorporated in the liposomes and not when it was given as a suspension in Klucel or in saline. The NSC-251635 liposome preparation induced significantly prolonged survival of the treated animals.

Animals↗
PubMed1981

A review of studies of the EORTC brain tumor group.

The results of three randomized trials performed by the EORTC Brain Tumor Group in patients with histologically proven brain gliomas are presented. CCNU (130 mg/m2 every 6 weeks) in combination with dexamethazone (4-20 mg daily) prolonged total survival compared to a group of patients treated only with corticosteroids. CCNU (130 mg/m2 every 6 weeks) either alone or one day after VM-26 (100 mg/m2) produced an objective remission in less than 30% of treated patients. However, the two treatment modalities did not prolong the interval between surgical removal of the tumor and relapse (recurrence). None of 12 patients with signs of brain tumor recurrence previously treated with VM-26 plus CCNU responded to procarbazine (3-week courses of 150 mg/m2/day).

Antineoplastic Agents↗
PubMed1981

Nocodazole entrapped into liposomes: no more effect on human CFU-C than free nocodazole.

Nocodazole, a water insoluble antimitotic drug active on L1210 leukemia was incorporated into liposomes, to investigate whether this procedure could increase cellular uptake. The effects of micronized nocodazole and liposome-entrapped nocodazole were compared on human marrow cells in vitro using a myeloid progenitor cell assay (CFU-C). The human CFU-C were sensitive to the micronized drug in a dose-related fashion. However, contrasting with a previous report on L 1210 leukemia, entrapping of nocodazole into liposomes did not increase its activity of CFU-C of either normal or leukemic subjects.

Antineoplastic Agents↗
PubMed1980

Treatment of brain giomas with high dose of CCNU and autologous bone marrow transplantation.

Seven patients with recurrent brain gliomas were treated by a single dose of CCNU 390 mg per m2. In five cases, chemotherapy was followed by autologous bone marrow transfusion containing 1.5 to 3 X 10(8) nucleated cells, 2.8 to 18 X 10(4) clusters plus colonies and 0.4 to 5 X 10(4) colonies forming cells per kg of body weight. Two patients were not grafted. None of these patients showed a clear cut response to the treatment as judged by clinical improvement and changes of the brain CT-scan. In 3 patients blood toxicity occurred early and was severe. In 4 others, it was milder and delayed. The duration and the severity of blood toxicity were modified by bone marrow transfusion but only slightly.

Bone Marrow Transplantation↗
PubMed1980

Inhibition of RNA synthesis in murine ependymoblastoma by the combination of amphotericin B and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea.

The aim of this study was to clarify the mechanism of the potentiation by amphotericin B (AMB) of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) antineoplastic effects on s.c. murine ependymoblastoma. The effect of AMB on tumor cell permeability to CCNU labeled on the cyclohexyl moiety was studied. The radioactivity measured in ependymoblastoma 1, 6, 14, and 25 hr after i.m. injection of 10.4 microCi of 1-(2-chlorethyl)-3-[cyclohexyl-1-14C]cyclohexyl-1-nitrosourea per mouse was significantly higher (p less than 0.001) in the tumors of animals treated with AMB (25 mg/kg 10 hr prior to [14C]CCNU) as compared to controls. The effects of AMB and CCNU given separately or in combination on RNA and protein synthesis were studied by measuring the incorporation of [3H]uridine and [14C]leucine, respectively, into RNA and proteins. The administration of AMB (25 mg/kg) or CCNU (10 mg/kg) did not affect the incorporation of [3H]uridine measured 2 hr after the i.p. injection of 40 microCi of labeled precursor per mouse. On the other hand, the incorporation of [3H]uridine was significantly (p less than 0.001) inhibited in animals treated with AMB (25 mg/kg) followed 10 hr later by CCNU (10 mg/kg), as compared to animals receiving CCNU alone. The inhibition, which reached a maximum of about 35% 24 hr after the administration of CCNU, was not observed when AMB was given after CCNU. The inhibition of RNA synthesis was also observed in mice treated with AMB and cyclohexyl isocyanate (5.4 mg/kg), a degradation product of CCNU. Measurements of [14C]leucine incorporation showed that AMB did not increase the inhibition of protein synthesis produced by CCNU. These observations suggest that AMB increases the uptake of a cyclohexyl derivative arising from the degradation of CCNU. The increased uptake of this compound results in inhibition of RNA synthesis. This mechanism could account for the potentiation of the CCNU therapeutic effect produced by AMB, at least in murine ependymoblastoma.

Amphotericin B↗
PubMed1977

Isolation of plasma membranes from murine ependymoblastoma and subcellular distribution of amphotericin B in this tumor.

A method for the isolation of plasma membranes from an experimental murine ependymoblastoma is described. In this procedure, 5'-nucleotidase was used as the plasma membrane marker, since cytochemical methods demonstrated that the enzyme was present on this subcellular structure only. The final plasma membrane preparation showed a 15-fold enrichment in 5'-nucleotidase activity and a 17-fold enrichment in the activity of phosphodiesterase I, another plasma membrane marker. The specific activity of beta-glucuronidase (lysosomal enzyme) was twice that of the whole homogenate, the specific activity of arylesterase (microsomal enzyme) was similar to that of the whole homogenate and succinate dehydrogenase (mitochondrial marker) was not detected. Electron microscopy of this fraction showed vesicles on which 5'-nucleotidase activity could be demonstrated. The subcellular distribution of [3H]amphotericin B per mg of protein was similar in the plasma membrane preparation and in the whole homogenate. It is concluded that, in ependymoblastoma, amphotericin B shows no selective affinity for the plasma membrane.

Amphotericin B↗