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F Doz

Publications and source records attributed to F Doz.

82 records · Page 5Linked to original sources
PubMed1992

Experimental basis for increasing the therapeutic index of cis-diamminedicarboxylatocyclobutaneplatinum(II) in brain tumor therapy by a high-zinc diet.

Metallothionein (MT), a ubiquitous intracellular protein, confers resistance to the toxic effects of platinum compounds. Since a high-zinc diet has been shown to induce MT synthesis in extracerebral tissues but not in brain, we investigated whether it could provide an experimental basis for decreasing the hematotoxicity of carboplatin without impairing its activity against brain tumors. After 2 weeks on either a high-zinc diet or a control diet (zinc content, 180 vs 10 ppm), mice and rats received various doses of carboplatin or Hanks' balanced salt solution by i.p. injection. The hematotoxicity of carboplatin was evaluated with an assay of colony-forming units of granulocytes and mononuclear cells in mice. The high-zinc diet enabled a 50% increase in the carboplatin dose without increasing hematotoxicity. The antitumor activity was evaluated with an assay of the colony-forming efficiency of gliosarcoma cells from 9L brain tumors in rats. The high-zinc diet did not alter the efficacy of carboplatin against this brain tumor. Northern blot analysis confirmed that the high-zinc diet induced MT mRNA in the kidney but not in the brain of mice and rats; it also showed MT mRNA induction in bone marrow cells of mice but not in rat 9L brain tumors. These results suggest that increasing the dietary intake of zinc might increase the therapeutic index of carboplatin in the treatment of brain tumors.

Animals↗
PubMed1991

Comparison of the cytotoxic activities of cisplatin and carboplatin against glioma cell lines at pharmacologically relevant drug exposures.

Carboplatin has lower nephro- and neurotoxicities and better penetration into brain tissue than cisplatin. If carboplatin has comparable cytotoxicity against glioma cells, it might have a therapeutic advantage in the treatment of malignant gliomas. Using an assay of colony-forming efficiency, we compared the cytotoxicity of these two drugs in human glioma cell lines SF-126, SF-188, U87-MG, and U251-MG. The experiments were designed so that the product of in vitro drug concentration (C) and time (T) would encompass the same range of values as the C x T of the ultrafilterable platinum plasma fraction as determined by pharmacokinetic studies in man. The in vitro stability of the drugs was evaluated by measuring the cytotoxicity of aged drugs with a microculture tetrazolium assay. Cisplatin and carboplatin were both stable during the 2-h treatment. The cytotoxic activities of these drugs at clinically achievable levels of drug exposure were of the same order of magnitude. These results, in conjunction with the lower nephro- and neurotoxicities of carboplatin, the higher platinum levels in brain tissue after treatment with carboplatin, and the encouraging results of carboplatin in the clinical treatment of brain tumors that have been demonstrated in other studies, suggest that carboplatin might be preferable to cisplatin in the treatment of patients with malignant glioma.

Carboplatin↗
PubMed1991

Experimental basis for increasing the therapeutic index of carboplatin in brain tumor therapy by pretreatment with WR compounds.

We tested an experimental strategy to decrease the dose-limiting hematotoxicity of carboplatin without compromising its activity against brain tumors. The effect of pretreatment with WR-1065, a chemomodifier that penetrates brain poorly, on carboplatin's cytotoxicity was evaluated in human hematopoietic granulocyte-monocyte progenitor cells and in three human glioblastoma cell lines. WR-1065 reduced bone marrow toxicity without decreasing carboplatin's activity against glioblastoma cells. These results suggest that the therapeutic index of carboplatin might be increased in the treatment of malignant brain tumors.

Bone Marrow↗
PubMed1990

Clinical trial and pharmacokinetics of carboplatin 560 mg/m2 in children.

We report a clinical trial with carboplatin (CBDCA) in 15 children with malignant solid tumors recurrent after or resistant to conventional treatment. Based on previous phase I clinical trials, these children were given a dose of CBDCA 560 mg/m2 by intravenous infusion every 4 weeks. The study includes a pharmacokinetic analysis of CBDCA in three patients. This clinical trial shows the feasibility of this CB-DCA schedule, even after high cumulative doses of previous chemotherapy. As expected the main toxicity was hematologic but the risk of renal and ototoxicity is not excluded and these functions have still to be monitored when this relatively high dose of CBDCA chemotherapy is used.

Adolescent↗
PubMed1987

[Transfontanelle echography: correlation with anatomopathological data. Apropos of 39 cases in newborn infants].

Thirty-nine neonates including 29 prematures had correlation studies of trans-fontanelle ultrasounds with post-mortem anatomic findings. Occipital hyper-echogenicity can be physiological when it is symmetric in the premature infant, and may indicate ischemia and/or anoxia when it is asymmetrical. No abnormal pathology went undetected by echo. Cortical gyri were never seen prior to 32 weeks gestational age.

Cerebral Hemorrhage↗