Paclitaxel (PTX) is one of the most effective anticancer agents. In clinical practice, however, high incidences of adverse reactions of the drug, for example, neurotoxicity, myelosuppression, and allergic reactions, have been reported. NK105, a micellar nanoparticle formulation, was developed to overcome these problems and to enhance the antitumour activity of PTX. Via the self-association process, PTX was incorporated into the inner core of the micelle system by physical entrapment through hydrophobic interactions between the drug and the well-designed block copolymers for PTX. NK105 was compared with free PTX with respect to their in vitro cytotoxicity, in vivo antitumour activity, pharmacokinetics, pharmacodynamics, and neurotoxicity. Consequently, the plasma area under the curve (AUC) values were approximately 90-fold higher for NK105 than for free PTX because the leakage of PTX from normal blood vessels was minimal and its capture by the reticuloendothelial system minimised. Thus, the tumour AUC value was 25-fold higher for NK105 than for free PTX. NK105 showed significantly potent antitumour activity on a human colorectal cancer cell line HT-29 xenograft as compared with PTX (Po0.001) because the enhanced accumulation of the drug in the tumour has occurred, probably followed by its effective and sustained release from micellar nanoparticles. Neurotoxicity was significantly weaker with NK105 than with free PTX. The neurotoxicity of PTX was attenuated by NK105, which was demonstrated by both histopathological (Po0.001) and physiological (Po0.05) methods for the first time. The present study suggests that NK105 warrants a clinical trial for patients with metastatic solid tumours.
International collaboration on development of a stellarator confinement database has progressed. More than 3000 data points from nine major stellarator experiments have been compiled. Robust dependences of the energy confinement time on the density and the heating power have been confirmed. Dependences on other operational parameters, i.e. the major and minor radii, magnetic field and the rotational transform
, have been evaluated using inter-machine analyses. In order to express the energy confinement in a unified scaling law, systematic differences in each subgroup are quantified. An a posteriori approach using a confinement enhancement factor on ISS95 as a renormalizing configuration-dependent parameter yields a new scaling expression ISS04;
. Gyro–Bohm characteristic similar to ISS95 has been confirmed for the extended database with a wider range of plasma parameters and magnetic configurations than in the study of ISS95. It has also been discovered that there is a systematic offset of energy confinement between magnetic configurations, and its measure correlates with the effective helical ripple of the external stellarator field. Full documentation of the International Stellarator Confinement Database is available at http://iscdb.nifs.ac.jp/ and http://www.ipp.mpg.de/ISS.
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