Biomedical subjects

J Riondel

Publications and source records attributed to J Riondel.

26 records · Page 2Linked to original sources

PubMedDate not supplied

Effects of free and liposome-encapsulated taxol on two brain tumors xenografted into nude mice.

Free taxol and liposome-encapsulated taxol were compared for their antitumoral activities on two human brain tumors serially grafted into female athymic mice in the scapular region. In the first experiment, a human glioblastoma (15th and 16th passages) was studied. In the second experiment, a fast growing human gliosarcoma (19th passage) was used. Free taxol and liposomal taxol were administered intraperitoneally, at the same dose; 12.5 mg/kg (i.e. 1/15 of the evaluated LD 50 value). In the first experiment, the treatment was performed for four consecutive days, with four courses separated by three rest periods of three days in between. Both free taxol and encapsulated taxol produced a statistically significant delay in tumor growth, and at the end of the experiment some total tumor regressions were obtained. However, liposomes were observed to be more effective in their action on the two consecutive passages of the glioblastoma, giving a marked increase of the number of total tumor regressions. In the second experiment another schedule of treatment was chosen because of the fast growth pattern of the xenografted human gliosarcoma: free taxol and liposome-encapsulated taxol were administered for five consecutive days and three courses of treatment were performed with two rest periods of two days. The two forms of taxol had a significant inhibitory effect on gliosarcoma tumor growth; as before encapsulation in liposomes was found to increase the anti-tumoral activity of taxol, although, in this case no tumor regression was observed.

Alkaloids↗

PubMedDate not supplied

Amplification of oncogenes in lung carcinoma grafted in nude mice.

Seven lung carcinomas were grafted on nude mice and continuously propagated as in vivo models on which the amplification of 9 oncogenes (N-myc, v-erb A, v-abl, v-sis, c-myc, c-myb, v-Ha-ras, c-Kiras, and v-scr) was studied by Southern blot hybridization. Only c-myc was amplified (20 copies) in an adenocarcinoma. The presence of 2 bands at 9 kb and 6.6 kb in addition to the normal 12.7 kb in EcoR1 digested DNAs suggested a polymorphism of the c-myc gene in this tumor. The other 8 oncogenes were not amplified in this tumor. The 5 small cell lung carcinomas of this study did not show any amplification of any of the 9 oncogenes tested.

Adenocarcinoma↗

PubMedDate not supplied

Antineoplastic activity of two taxol derivatives on an ovarian tumor xenografted into nude mice.

In order to compare the antineoplastic activities of taxol A, taxol B, a mixture of the two (taxol A 72%) and vinblastine, a human ovarian tumor serially transplanted into 104 female athymic mice was used. In the first experiment (11th passage), the antineoplastic activities of taxol A, taxol B and the mixture taxol AB were tested. The same dose was used in each case (12.5 mg/kg i.e. 1/20 of the evaluated LD50 value). It was administered subcutaneously for 5 consecutive days. Three courses of treatment were performed, with 2 rest periods of 1 week in between. All the taxol derivatives produced a statistically significant delay in the tumor growth. However, taxol B had the lowest chemotherapeutic response. In the second experiment (18th passage), different dose levels were administered (mixture 12.5 mg/kg/day x 4 - taxol A 8.8. mg/kg/day x 4 - taxol B 3.5 mg/kg/day x 4 - vinblastine 0.5 mg/kg/day x 2). For all the taxol derivatives 4 treatment courses with 3 rest periods of 4 days were used, and for vinblastine 4 treatment courses with 3 rest periods of 1 week. At the end of the second experiment, vinblastine, taxol A and a mixture of the two showed similar significant activity, whereas no objective antitumor response was observed following the taxol B treatment at the dose level chosen. The experimental results obtained clearly demonstrate that, in the taxane system, the greatest degree of antineoplastic activity can be attributed to taxol A.

Alkaloids↗

PubMedDate not supplied

Effect of oestrone on the natural killer (NK) cell activity, antioxidant status and tumour growth in athymic mice xenografted with human tumours.

Natural killer (NK) cells have been described as being very sensitive to oxidative stress. Thus it has been previously shown that chronic administration of oestrone in drinking water of athymic mice xenografted with a wide variety of human tumours, increases their growth and development. In this study an investigation was made to see whether oestrone supplementation could influence the NK cell activity by changes in the antioxidant defences which result in an oxidative stress and influence the proliferation of tumours. Supplementary oestrone was administered in drinking water of athymic mice xenografted with two different human tumours which lack oestrogen receptors: a bladder carcinoma and a small-cell lung carcinoma. The growth of the urothelial carcinoma was poorly affected by oestrone, but oestrone significantly (p<0.01) increased the proliferation of the small-cell lung carcinoma. The average uterus weight was increased by 62% in oestrone treated mice with no modifications in plasma zinc and selenium status, nor in erythrocyte copper zinc superoxide dismutase level. Nevertheless a slight decrease in erythrocyte glutathione peroxidase activity was noted. Trace elements and antioxidant enzymes in liver homogenates remained unchanged. Oestrone treatment also had no effect on plasma and liver lipid peroxides. The immune response was evaluated by measuring NK activity of splenocytes against 51Cr labelled YAC-I target cells. A 35.5% decrease in the NK activity (p<0.001) was observed after oestrone treatment and may be responsible for graft tolerance. However, the results of these experiments seem to exclude the role of oxidative stress in the modulation of NK activity.

Animals↗

PubMedDate not supplied

Beta-carotene enhances natural killer cell activity in athymic mice.

To study the effects of beta-carotene on Natural Killer (NK) cells, we chose athymic mice whose spleens have a higher percentage of NK cells than conventional mice. Preliminary studies conducted with beta-carotene given intraperitoneally to athymic mice xenografted with a small-cell lung carcinoma resulted in a slight but significant antiproliferative effect (unpublished observations). We speculated that such an activity of beta-carotene was related to its immunostimulating properties. NK cell activity in ungrafted athymic mice as influenced by beta-carotene was studied. Mice received beta-carotene intraperitoneally. Splenic NK cells were labelled with monoclonal antibody and numeration was completed by measurement of their functional activity against YAC-1 malignant cells with a 51Cr release assay. In addition, splenic lymphocytes were evaluated for their reduced glutathione (GSH) content. There was a non-significant increase in the number of NK cells in the spleen, however their killing capacity was significantly (p < 0.01) enhanced after beta-carotene treatment. Also the GSH content of splenic lymphocytes was significantly higher in beta-carotene treated mice. Comparison of the average body weights of treated animals and of their respective controls showed that treatment had no adverse effects.

Animals↗

PubMedDate not supplied

Modulation of natural killer cell functional activity in athymic mice by beta-carotene, oestrone and their association.

In athymic mice, Natural Killer (NK) cells influence the take rate and growth of human malignant tissue xenografts. To confirm preliminary results, comparative experiments were conducted to study the effects of beta-carotene, oestrone and their association on the cytolysis mediated by spleen NK cells from athymic mice receiving these different treatments. Target cells consisted of YAC-1 malignant cells. With a 65% increase of cytolysis (ratio effector/target 50:1), beta-carotene induced a significant activation of NK cells (p < 0.002). This effect could be attributed to its antioxidant properties and confirmed by a moderate increase in erythrocyte glutathione peroxidase activity. On the contrary, oestrone resulted in a significant decrease of cytolysis (p < 0.001). In this case, the prooxidant properties of oestrone could explain its effect on NK cells and agree with the increase of intracellular reduced glutathione level observed. When mice received the combination beta-carotene-oestrone, their opposite effects on NK cell activity were counterbalanced, leading to a moderate change of cytolysis.

Animals↗

PubMedDate not supplied

In vitro comparative study of cytolysis mediated by natural killer cells towards malignant cells preincubated with antioxidants.

We have previously reported that antioxidants such as beta-carotene, were able to enhance cytolytic activity of NK cells. The aim of the present study was to investigate whether preincubating YAC-1 tumor cells in culture with different antioxidants, affected their NK cell-mediated cytolysis. The antioxidants studied were enzymes (superoxide dismutase and catalase), hydroxyl radical scavengers (thiourea, mannitol, dimethyl sulfoxide) and a singlet oxygen quencher: beta-carotene. After 24 hours coincubation with the antioxidants, radiolabeled YAC-1 cells were submitted to the cytotoxic activity of NK cells for a 4 hour period. For some antioxidants, a moderate increase of cytotoxic potential occurred for weak NK cell number. By contrast, a clear decrease of cytotoxic potential was induced with high NK cell number. An antioxidant, with a protective effect which appeared stronger was thiourea, which induced 20, 58 and 36% decrease of cytolysis in the effector-target ratios 50:1, 100:1 and 200:1 respectively. These studies suggest that the malignant YAC-1 cells are vulnerable to treatment by different antioxidants.

Animals↗

PubMedDate not supplied

Comparative distribution of beta-carotene and lycopene after intraperitoneal administration in mice.

To determine the kinetics of accumulation of beta-carotene and lycopene, and their main storage sites, they were separately administered in OFI mice at a single dose of 10 mg/kg body weight or in combination. Animals were sacrificed at given time intervals after intraperitoneal administration and carotenoids were dosed in serum, liver, spleen, kidneys and lungs. A single injection of beta-carotene led to a serum peak at t = 2 h and high levels were detected in the liver after 0.75 hours and in the spleen after 5 hours, with peak values of 10.46 +/- 0.62 and 134 +/- 6 micrograms/g tissue respectively. In contrast, lungs and kidneys did not appear as main accumulation sites. After administration of the carotenoid association, beta-carotene distribution in the four organs was strongly inhibited by lycopene. Concerning lycopene distribution, the concentration values were lower than beta-carotene, the spleen and liver remaining the main storage sites. After administration of a combined dose carotene/lycopene, the percentage of lycopene distribution inhibition was lower compared to the beta-carotene distribution inhibition induced by lycopene. This unusual and non-physiological way of administration for micronutrients leads to high levels of beta-carotene and lycopene in the liver and spleen, and seems of interest in the experimental study and understanding of the biomolecular mechanisms of their activities when administered alone or together.

Animals↗