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Homocamptothecin (hCPT), a camptothecin (CPT) analogue with a seven membered β-hydroxylactone which combines enhanced plasma stability and potent topoisomerase I (Topo I)-mediated activity, is an attractive template for the elaboration of new anticancer agents. Like CPT, hCPT carries an asymmetric tertiary alcohol and displays stereoselective inhibition of Topo I. The preparation and biological screening of racemic hCPT analogues are described. The 10 hCPTs tested were better Topo I inhibitors than CPT. Fluorinated hCPTs 23c,d,f,g were found to have potent cytotoxic activity on A427 and PC-3 tumor cell lines. Their cytotoxicity remained high on the K562adr and MCF7mdr cell lines, which overexpress a functionally active P-glycoprotein. Fluorinated hCPTs were more efficacious in vivo than CPT on HT-29 xenografts. In this model, a tumor growth delay of 25 days was reached with hCPT 23g at a daily dose of 0.32 mg/kg, compared to 4 days with CPT at 0.625 mg/kg. Thus difluorinated hCPT 23g warrants further investigation as a novel Topo I inhibitor with high cytotoxicity toward tumor cells and promising in vivo efficacy.

A simple dynamic model accounting for atomic interactions between nearest neighbors is presented and demonstrated to predict correctly the anisotropy for production of defects in n-GaAs by electron irradiation. A hard core potential is used to describe the atomic interactions. A reasonable agreement between the model and the experimental results is obtained if As displacements are assumed to be responsible for the observed defects, with a hard core radius equal to about 1 Å and an isotropic threshold energy for displacement equal to 9 eV. The anisotropy for production of hole traps in p-GaAs has been experimentally studied. The main hole traps are shown to exhibit exactly the same anisotropy as the electron traps in n-GaAs, and are concluded to originate also in As displacements.

Bulk Czochralski and VPE layers of n-GaAs have been irradiated with 1 MeV electrons at about 300°C, temperature at which primary defects are not stable. Up to seven electron traps are thus observed to be introduced. The dominant trap (I1) has an activation energy and a capture cross section very close to the so-called EL2 center, which suggests that EL2 could be introduced by a high temperature electron irradiation. The introduction rate of I1 is about 1cm-1, that is the same order of magnitude as those of the traps (E-traps) introduced by a room temperature irradiation, and two orders of magnitude larger than those of the traps observed after the annealing (200–300°C) of the E-traps. With a starting dopant concentration of 2×1016cm-3, we have obtained a quite complete compensation of free carriers after a total fluence of 1017e/cm2.

Ruthenium complexes catalyze the oxidation of alcohols to the corresponding ketones or aldehydes when Ca(OCl)2 or NaIO4 are used as oxygen donors in the presence of water (5-10 equiv.). The reactions take place at room temperature affording products in yields of 45-80%.

Abstract: Percutaneous coronary intervention (PCI) has become an effective therapy to treat coronary artery diseases. However, one of the major drawbacks of PCI is the occurrence of restenosis in 8 to 40% of all treated patients. The GENetic Determinants of Restenosis (GENDER) project was designed to study the association between genetic polymorphisims and clinical restenosis. The discovery of genetic variants associated to the occurrence of restenosis after PCI may provide a more tailored therapy and may serve as rationale for new antirestenotic therapies. So far, several candidate gene approaches had already been performed in the GENDER samples but a Genome Wide Association Scan (GWAS) was still lacking. Here, we present preliminary results from the GWAS we are currently carrying out in the GENDER population. (Neth Heart J 2009;17:262–4.)

Abstract: In the past decade, research into cardiovascular diseases, such as atherosclerosis and restenosis, has been focused on the identification of genetic factors that determine disease risk besides clinical risk factors. Many genes in lipid metabolism, vascular homeostasis, haemostasis and inflammation have been found to be related to coronary artery disease1 and the multifactorial nature of the disease suggests a role for many other, yet uninvestigated genes. Previous research from our department has demonstrated the importance of genetics in restenosis after a percutaneous coronary intervention (PCI). Polymorphisms in several inflammatory genes, such as TNFα, eotaxin, CD14, GM-CSF, IL-10, caspase-1, but also noninflammatory genes, such as LPL, stromelysin-1 and the β adrenergic receptor have been found to be associated with the risk of restenosis.2-5 It has become clear, however, that part of the gene-environmental interactions relevant for complex diseases is regulated by epigenetic mechanisms such as histone acetylation and DNA methylation.