[Use of biodegradable microspheres in experimental anticancer therapy. Chronopharmacological application]. / Utilisation des microsphères biodégradables en thérapie anti-cancéreuse expérimentale. Application chronopharmacologique.

We describe the initial experimentations which show that is possible to chronomodulate the cisplatin liberation out of some microspheres. The goal is to generate, inside one tumeur embolished by those cisplatin loaded microspheres, some concentration peaks at the best tolerance time. The cancer is than more hit, by the high local anticancer drug concentration, and doses chronomodulations preserve the patient by following his tolerance. The experimentation on cancerous mice show that this technique could lead to great survival increases. Such a protocol might usefuly improve the anticancer therapy.

[Chronotolerance of corticosterone on DNA synthesis in young growing rats]. / Chronotolérance de la corticostérone sur la synthèse du DNA chez le jeune rat en croissance.

Plasma corticosterone and DNA synthesis were measured during 2 circadian periodes following the 25th day of rats. Corticosterone (5 mg/kg) injected at 05 h (1 h before the normal corticosterone bathyphase) inhibits and dissynchronizes the nycthemeral evolution of the two parameters during the two subsequent periods. The same corticosterone administration injected at 17 h (1 h before the normal corticosterone acrophase) inhibits the first DNA synthesis wave but both parameters are nycthemerally restored from the second period. In this last case, the area under the second DNA curve compensates the inhibition of the first wave. The results are discussed in the view of chronocorticotherapy recommended in patients.

Importance of cell kinetics rhythmicity for the control of cell proliferation and carcinogenesis in rat liver (review).

The circadian control of cell Proliferation and Differentiation has been studied principally in rat liver. The comparison between the differentiation by hepatic enzymes and the division by the cell cycle under various experimental conditions (postnatal maturation, regeneration after partial hepatectomy, adrenalectomy, corticosterone treatments etc.) leads to the following conclusions: Under physiological conditions, proliferation and differentiation activities present a mutually exclusive relationship with a specific circadian rhythm. For both functions, the circadian variation of corticosterone plays the role of synchronizer, each evening (peak) it induces the synthesis of tissue specific enzymes in G0 cells and simultaneously inhibits the DNA synthesis in cycling cells. The same parameters have been studied during the different stages of hepatocarcinogenesis induced by Diethylnitrosamine (DEN). After initiation alone, (DEN for 2 weeks) circadian control is unchanged and precancerous cells are not able to reach malignancy. Promotion (DEN for 6 weeks) consists of disturbing the circadian synchronization to liberate the selective growth of initiated precancerous cells. This proliferation advantage favours the accumulation of chromosomal aberrations including those implicated in malignant transformation: i.e. activation of oncogenes or inhibition of antioncogenes.