[Inhibitors of aurora kinases]. / Les inhibiteurs des kinases Aurora.

Aurora kinases (A, B and C) are proteins expressed only in cells which divide actively and their increase is a factor of bad prognosis in cancer. They regulate the maturation of centrosomes, the separation and the condensation of chromosomes, mitotic checkpoint and cytokinesis. The inhibition of aurora kinases, by powerful and selective inhibitors, is due to the formation of abnormal cells which are eliminated by apoptosis. The purpose of this article is to present the role, the antitumor activity and the tolerability of these inhibitors. They can be administered orally or intravenously, on weekly or monthly schedules. In our knowledge, twelve molecules are evaluated at the present time and will be discussed only the most advanced namely: VX-680, ZM 447439, MLN 8054, AZD 1152, PHA 739358, SU 6668 and AT 9283. The main indications are breast, colon, lung, pancreas and bladder cancers as well as hematologic tumors such as leukemia (ALL, AML, CML) and lymphoma. These inhibitors can be associated with other chemotherapies. They seem well tolerated; the reported side effects are digestive disorders (diarrhea), fever, asthenia, alopecia, slumber, neutropenia, myelosuppression and disturbance of the biological markers.

Chromate reduction at low sulphate concentration in hydrogen-fed bioreactors.

Aimed at developing a bioremediation process to treat Cr(VI)-bearing water at low sulphate concentration in order to reduce excess sulphide production, the highly toxic, mutagenic, and soluble Cr(VI) was reduced to the less toxic and insoluble Cr(III) in 2-litre fixed-bed reactors inoculated with the sulphate-reducing bacterium (SRB) Desulfomicrobium norvegicum, capable of performing direct enzymatic Cr(VI) reduction. H2 was used as the electron source. The fixed-films were developed on three different supports: a PVC cross-flow material, a pozzolana, and a ceramic granulate. The phased experiments began with a progressive increase of the Cr(VI) concentration in the feed to the column reactors, followed by a progressive decrease of the sulphate concentration. Inhibition by Cr(VI) was less pronounced with pozzolana than with the other supports; when the pozzolana column was fed with a medium containing 100 mg l(-1) Cr(VI) and only 250 mg l(-1) sulphate, the lowest residence time that could be applied for complete Cr(VI) reduction was 16 h. The molar ratio between the sulphate and Cr(VI) reduction rates was decreased down to 1.5, suggesting that indirect reaction with HS was not the sole mechanism of Cr(VI) reduction.

Monitoring of a pyrite-oxidising bacterial population using DNA single-strand conformation polymorphism and microscopic techniques.

The single-strand conformation polymorphism (SSCP) technique was used to study the evolution of a bacterial consortium during the batch oxidation of a cobaltiferous pyrite in two types of bio-reactor: a bubble column and a classical stirred tank. Sequencing 16S rDNA revealed the presence of three organisms affiliated to Leptospirillum ferrooxidans, Acidithiobacillus thiooxidans and Sulfobacillus thermosulfidooxidans, respectively. Attempts were made to determine the proportions of bacteria attached to solid particles or freely suspended in the medium using a combination of PCR-SSCP and a microscopic technique. Ac. thiooxidans-related bacteria were dominant in the liquid during the early phase of the batch, but were later supplanted by L. ferrooxidans-related bacteria. L. ferrooxidans-related organisms were always in the majority on the solids. The growth of S. thermosulfidooxidans-related bacteria seemed to be favoured by the bubble-column reactor.

Design of poly-epsilon-caprolactone nanospheres coated with bioadhesive hyaluronic acid for ocular delivery.

This study was performed to design a new ocular drug delivery system based on poly-epsilon-caprolactone (PCL) biodegradable nanospheres (NS) coated with a bioadhesive polymer, hyaluronic acid (HA), in order to combine ophthalmic prolonged action with the ease of application. The aim of this work was to investigate three strategies to attach HA on NS surface: (1) coating the core by chain entanglement with HA; (2) coating NS by HA adsorption; (3) coating NS by electrostatic interactions between negatively charged HA and a cationic surfactant (stearylamine, SA, or benzalkonium chloride, BKC). A radioimmunoassay technique, usually used for HA quantification in serum, was transposed to determine the amount of HA on the NS. The results show that HA is strongly attached on NS positively charged by cationic surfactant. This system is stable and not influenced by dilution. These results show the possibility of using cationic surfactants to obtain a HA coating by electrostatic interactions. BKC, approved for ophthalmic administration, was retained because it was more firmly anchored within the PCL matrix and the amount of HA attached was high (41.6 microg HA/mg PCL). Moreover, the yield of fixation reached 50%. Therefore, by using a simple preparation method, it was possible to obtain stable HA and intact HA-coated NS.

Reduction of chromate by fixed films of sulfate-reducing bacteria using hydrogen as an electron source.

The ability of sulfate-reducing bacteria (SRB) to reduce chromate, Cr(VI), was evaluated using fixed-film growth systems and H2 as the electron source. A main objective of the experiment was to distinguish between direct enzymatic reduction and indirect reduction by hydrogen sulfide, in order to subsequently verify and control the synergy of these two mechanisms. In batch experiments with the sulfate-reducing consortium CH10 selected from a mining site, 50 mg l(-1) Cr(VI) was reduced in 15 min in the presence of 500 mg l(-1) hydrogen sulfide compared to 16 mg l(-1) reduced in 1 h without hydrogen sulfide. Fixed films of a CH10 population and Desulfomicrobium norvegicum were fed-batch grown in a column bioreactor. After development of the biofilm, hydrogen sulfide was removed and the column was fed continuously with a 13-mg l(-1) Cr(VI) solution. Specific Cr(VI) reduction rates on pozzolana were close to 90 mg Cr(VI) h(-1) per gram of protein. Exposure to Cr(VI) had a negative effect on the subsequent ability of CH10 to reduce sulfate, but the inhibited bacteria remained viable.

Multiscale MAP filtering of SAR images.

Synthetic aperture radar (SAR) images are disturbed by a multiplicative noise depending on the signal (the ground reflectivity) due to the radar wave coherence. Images have a strong variability from one pixel to another reducing essentially the efficiency of the algorithms of detection and classification. We propose to filter this noise with a multiresolution analysis of the image. The wavelet coefficient of the reflectivity is estimated with a Bayesian model, maximizing the a posteriori probability density function. The different probability density function are modeled with the Pearson system of distributions. The resulting filter combines the classical adaptive approach with wavelet decomposition where the local variance of high-frequency images is used in order to segment and filter wavelet coefficients.