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J Riondel

Publications and source records attributed to J Riondel.

At least 19 recordsLinked to original sources

2'-deoxyguanosine oxidation is associated with decrease in the DNA-binding activity of the transcription factor Sp1 in liver and kidney from diabetic and insulin-resistant rats.

Over the years, several lines of evidence have emerged supporting the role of oxidative stress in the development of diabetic complications. This could involve the increase in the production of reactive oxygen species and the decrease in antioxidative defense systems. Modulation of the level of intracellular reactive oxygen species is likely to affect the intracellular redox homeostasis, which is crucial for numerous biological events such as the transcriptional activation of genes. In this work we studied the binding of the redox transcription factors Sp1 and NF-kappaB extracted from kidney and liver of streptozotocin diabetic (STZ) and fructose-fed rats using electrophoretic mobility shift (EMSA) assay. In addition, the level in 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) was assessed within DNA by high performance liquid chromatography with electrochemical detection (HPLC-EC). A decrease in the affinity of Sp1 to DNA was observed in the kidney of STZ rats and fructose-fed rats (15% +/- 8.3 and 54% +/- 6.9, respectively, versus control group set to 100%). This was also found to occur to a lower extent, in the liver. Interestingly, higher levels of 8-oxodGuo, a biomarker of DNA oxidation, were measured in the kidney of diabetic rats. Therefore, the modification in the binding efficiency of Sp1 or NF-kappaB could be related to reactive oxygen species-mediated DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗

Prion infection impairs the cellular response to oxidative stress.

The molecular mechanism of neurodegeneration in transmissible spongiform encephalopathies remains uncertain. In this study, it was demonstrated that prion-infected hypothalamic neuronal GT1 cells displayed a higher sensitivity to induced oxidative stress over noninfected cells. In addition, the infected cells presented an increased lipid peroxidation and signs of apoptosis associated with a dramatic reduction in the activities of the glutathione-dependent and superoxide dismutase antioxidant systems. This study indicates for the first time that prion infection results in an alteration of the molecular mechanisms promoting cellular resistance to reactive oxygen species. This finding is vital for future therapeutic approaches in transmissible spongiform encephalopathies and the understanding of the function of the prion protein.

Blotting, Western↗

Diels-Alder reactions between dienamides and quinones: stereochemistry of the cycloadditions and cytotoxic activity of the adducts.

Tetrahydronaphthoquinones and tetrahydroanthraquinones bearing an amido group have been prepared by Diels-Alder reactions between (E)-1-(N-carbobenzyloxyamino)-1,3-butadiene (2) or (E)-1-(N-benzoyl-N-benzylamino)-1,3-butadiene (5) and benzoquinone or 5-substituted naphthoquinones. The stereochemistry of the cycloadditions was investigated. A high regioselectivity was observed in the reaction of the diene carbamate 2 with 5-methoxy and 5-acetoxy naphthoquinones. This latter gave the unexpected 1,8-regioisomer 3d. The cycloadditions of the dienamide 5 with naphthoquinones 1 (R = OH, OMe, OAc) are regiospecific. Assignment of the structure of the tetrahydroanthraquinone 6b is in good agreement with the known directing effect of the 5-hydroxy group of juglone 1b in analogous Diels-Alder reactions. With 5-methoxy and 5-acetoxy naphthoquinones, the opposite regiochemistry observed is consistent with the electron-donating influence of the methoxy or acetoxy group, making the C-3 carbon atom more electron deficient. Aromatization of the adducts 6b and 7c was accompanied by an unusual elimination of the amido moiety. Thus, 1-hydroxy and 1-methoxy anthraquinones were obtained. Reactions of the dienes 2 and 5 with benzoquinone gave the tetrahydronaphthoquinones 9 and 10 with an endo stereospecificity. Oxidation of 9 by activated manganese dioxide gave the naphthoquinone 11. These compounds were submitted to in vitro cytotoxic assays towards murine L 1210 leukemia cells and clonogenic human tumor cell line MDA-MB 231. The naphthoquinone derivatives 9, 10 and 11 had significant activities with IC50 less than or equal to 0.4 microgram/ml towards these two tumor cell systems.

Amides↗

[3 experimental models applied to the study of urothelial tumors of the bladder].

Three important models can be used in experimental carcinogenesis: Clonogenic assays which can be used to study tumor cells in vitro. This method is particularly useful in order to investigate biochemical markers and chromosomal spreads. Chemically-induced bladder tumors in various animals are used to analyse the mechanisms of induction and development of these cancers. The athymic mice have provided, over the last twenty years, an immunological system suitable for the heterotransplantation of human tumor tissues. These three experimental models, which are complementary, are reviewed and discussed.

Animals↗

In vivo 31P nuclear magnetic resonance studies of T1 and T2 relaxation times in rat brain and in rat brain tumors implanted to nude mice.

31P NMR spin-lattice (T1) and spin-spin (T2) relaxation times of phosphocreatine, ATP, inorganic phosphate, and phosphomonoesters have been measured in vivo at 4.7 T in rat brain and rat brain tumors implanted on nude mice. The relaxation data were acquired using a phase-cycled saturation-recovery spin-echo sequence. The problems associated with the phase modulation of the ATP lines by the homonuclear coupling constants were overcome by using selective refocusing pulses for the T2 measurements. In all the metabolites, large differences (1 to 2 orders of magnitude) are observed between the two relaxation times. T1 values in rat brain tumors are 30 to 90% longer than their counterparts in normal rat brain. T2 values follow the same trend with smaller variations except for phosphocreatine values which seem much less sensitive to the metabolic state of the tissues.

Animals↗

Therapeutic response to taxol of six human tumors xenografted into nude mice.

To test the antineoplastic activity of taxol, a natural product isolated from yew (Taxus baccata L.), six human tumors transplanted into athymic mice were used (primary tumors of breast, endometrium, ovary, brain, lung and a recurrence of tongue tumor). While the growth rates varied with the histopathological characteristics of different tumor types, all mice were treated at a mean tumor volume of 200 +/- 8 mm3. Taxol was given SC at a dose level of 12.5 mg/kg per injection per day for 5 consecutive days out of 7 over a period of 3 weeks. With this schedule antitumor responses were obtained in all of the six neoplasms xenografted into nude mice. In the case of the ductal carcinoma of the breast total tumor regressions were observed in four of the five treated animals. In the five other experimental models taxol produced significant growth delays. We believe that the results of these initial tests on the nude mouse--human tumor xenograft system are convincing and justify clinical assessment of this drug.

Adult↗

[Action of taxol on human tumors transplanted in athymic mice].

In order to study the antitumour activity of taxol (a diterpene of the taxane type) isolated from Yew: Taxus baccata L. (Taxacae), human tumours implanted as xenografts in athymic Mice were used. Swiss nude mice were treated subcutaneously (12.5 mg/kg/injection/day for 5 consecutive days out of 7, over a period of 3 weeks). Treatment by taxol of a liver metastasis of a breast tumour, a tongue primary tumour and a skin metastasis of bronchial carcinoma gave statistically significant results (0,01 greater than P greater than 0,001 and P less than 0,001). However, taxol showed a very moderate antitumour activity against a transplanted primary tumour of the colon.

Adult↗

Studies of antitumor activity of the culture filtrate of Hohenbuehelia geogenius (D.C. ex Fr.) Sing (basidiomycete).

The antitumor activity of the culture filtrate of the fungus Hohenbuehelia geogenius (basidiomycete) was investigated on two rapidly growing grafted tumors: Ehrlich's ascites carcinoma and L1210 lymphoid leukemia and also on a slow growing spontaneous mammary tumor in PS strain mice. The mycelial culture filtrate inhibited the growth of these three tumors. An active substance was isolated from the mycelial culture filtrate by solid-liquid extraction and column chromatography. Its chemical structure was elucidated with ultraviolet and infrared spectra, mass spectrum, nuclear magnetic resonance, and X-ray diffraction.

Agaricales↗

[Myocardial metabolism after one hour of anoxia and deep generalised hypothermia. Experimental study in the dog (author's transl)].

Fifteen young dogs weighing less than six kilograms underwent circulatory arrest for one hour and profound hypothermia with extra-corporeal circulation. During reperfusion, myocardial metabolism was studied by comparing the oxygen arterio-venus (02 A-V) difference and lactate consumption at different temperatures. As the myocardial temperature rose, 02 A-V difference increased from 4 vl/100 cc at 25 degrees C to 10 vol/100 cc and K1 lactate balance rose from -19,3% to + 8% which indicates a large increase in lactate consumption. This study shows that profound and generalized hypothermia ensures good myocardial protection during at least one hour of ischemia. This experimental study confirms results obtained with other forms of cardiac hypothermia.

Animals↗

Antioxidant status and lipid peroxidation in athymic mice xenografted with two types of human tumors.

Antioxidants and reactive oxygen species are considered to play an important role in experimental in vivo carcinogenesis studies. We attempted in this study to evaluate the repercussions on the antioxidant and lipid peroxide status of the growth of human malignant tumors xenografted into athymic mice. We selected three tumor models: two urothelial carcinomas (bladder tumors stage 3) and one brain tumor (glioblastoma stage 4). All these tumors exhibited a fast growth pattern when xenografted into athymic mice. Tumoral tissue was implanted subcutaneously. After growth establishment each tumor size was measured at regular intervals: every 2 d for bladder tumor and twice a week for glioblastoma. The period of observation was 3 wk for bladder tumors and 5 wk for glioblastoma. At the end of the observation period, all mice were sacrificed; tumoral tissue was taken and blood collected. Superoxide dismutase activity (SOD), glutathione peroxidase activity (GSH-Px), zinc (Zn), selenium (Se), and thiobarbituric acid reactive substances (TBARS) were measured in blood. TBARS alone were measured into tumoral tissue. A modification of the antioxidant blood status was observed in mice xenografted with bladder tumors with decrease in Se status and GSH-Px activities, and increase in TBARS. Such an effect was absent in mice xenografted with glioblastoma. It would appear that an oxygen-mediated stress exists in the animal bearing an implanted tumor compared with the control group, and that tumoral tissue itself is able to induce an oxidative stress into its host. All this leads to a disturbance of the antioxidant defense system.

Animals↗

Effects of selenium supplementation on malignant lymphoproliferative pathologies associated with OF1 mouse ageing.

Low plasma selenium (Se) levels have been shown to correlate with increased cancer incidence in humans and in mice. This study was undertaken to investigate the ability of Se to decrease mortality rate and tumor production in ageing mice. Se (2.5 ppm) given as sodium selenite in drinking water to 8 months old OF1 mice, for 4 consecutive months, reduced significantly the mortality of mice with 6% and 50% mortality rate for Se and control groups, respectively. In addition 80% of control deaths resulted from a lymphoid cell neoplasma, while no one of Se supplemented mice produced tumor. Evaluation of parameters of free radical metabolism showed highly significant reduction of the antioxidant defence system in the liver of cancer mice, with a 78% decrease in GSH-Px activity, a 65% decrease in superoxide dismutase (SOD) activity, a 75% decrease in the GSH/GSSG ratio and a 62% decrease of plasma Se level, as compared to healthy old mice. Nevertheless in the conditions of our experiment, Se didn't really improve the endogenous antioxidant status of ageing mice.

Aging↗

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↗