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Cell cycle progression corresponds to a series of events, which succeed one another to end in the division of a mother cell to give two daughter cells. The processes that allow the cell to divide are very precisely controlled by a multitude of enzymatic reactions among which protein phosphorylation, carried out by protein kinases, plays a key role. Serine/threonine kinases are enzymes that catalyse the transfer of a phosphate from ATP to a protein substrate, more precisely on a serine or threonine amino acid residue. Three important families of serine/threonine kinases are involved in the regulation of cell cycle progression, the cyclin dependent kinase (CDK) the polo-like kinase (PLK) and those of the Aurora family. The cancer is described as an uncontrolled cell division process. Cancer cells proliferate indeed in an anarchic way, and carry out cycles of cellular division by being unaware of the signals of alarm. A simple idea thus appeared soon: to stop or to slow down cell cycle progression would result in inhibiting cell proliferation and thus fighting against cancer. Cell cycle progression being controlled in particular by protein kinases of the CDK, PLK and Aurora families, it was rapidly decided to look for inhibitors of those protein kinases. We will first make a general recall on cell cycle progression and the mechanisms that control it. The functions of protein kinases of the CDK, PLK and Aurora families will then be described by concentrating on the sensitive phase of the cell cycle progression, i.e. mitosis. Finally, we will approach the consequences of the inhibition of these protein kinases within the framework of the fight against cancer.

Centrosomes are essential protagonists during cell division through microtubule nucleation and spindle formation which are key to the harmonious distribution of sister chromatids in the two daughter cells. However, during the past decade, a wealth of new observations has extended their role beyond mitosis, particularly in the asymmetrical partition of cell fate determinants. Remarkably, asymmetric centrosome inheritance per se, through the segregation of differently aged mother -centrioles, seems to regulate the differential behaviour of daughter cells, in part through asynchronous expression of primary cilia, governing the response to environmental signals. It is thus understandable why any quantitative or qualitative dysfunction of centrioles contributes to genomic -instability and thus -tumorigenesis.

The effects of prostacycline (PGI2), the most powerful known platelet antiaggregant on platelet count and function during cardiopulmonary bypass, were assessed in a double blind study. One group of 13 patients received 2,5 mg/Kg of Heparin with an infusion of 25 ng/Kg/min of prostacycline instituted 15 minutes before the Heparin, continued at the beginning of cardiopulmonary bypass at a dose of 50 ng/Kg/min and terminated at the end of bypass. A second group of 15 patients were studied by the same protocol with a placebo infusion. The platelet count was significantly higher at the end of cardiopulmonary bypass in the Prostacycline group. Platelet aggregation was reduced by comparison with the control group from the beginning of Prostacycline infusion. The active thrombin time was significantly longer in the Prostacycline group. However, blood loss did not differ significantly between the two groups although it was less in the study group. The platelet count and function during cardiopulmonary bypass with Prostacycline was therefore increased and resulted in a reduction in Heparin consumption.

An anatomo-clinical entity, fibrous constrictive endocarditis can betreated srugically, and we carried out this procedure for the first time in 1971, since when we have used it seven times; it consists of an internal stripping of one or both centricles, with removal of one or both the mitral and tricuspid valves. The results were encouraging in the first two cases, and so good in the succeeding ones that this endocardial resection could be put forward as the treatment of choice for a condition whose aetiology is still unclear.