The aim of this study was to investigate the mechanism of inhibition of Eg5 (kinesin spindle protein), a mitotic kinesin that plays an essential role in establishing mitotic spindle bipolarity, by the novel small molecule inhibitor K858. K858 was selected in a phenotype-based forward chemical genetics screen as an antimitotic agent, and subsequently characterized as an inhibitor of Eg5. K858 blocked centrosome separation, activated the spindle checkpoint, and induced mitotic arrest in cells accompanied by the formation of monopolar spindles. Long-term continuous treatment of cancer cells with K858 resulted in antiproliferative effects through the induction of mitotic cell death, and polyploidization followed by senescence. In contrast, treatment of nontransformed cells with K858 resulted in mitotic slippage without cell death, and cell cycle arrest in G 1 phase in a tetraploid state. In contrast to paclitaxel, K858 did not induce the formation of micronuclei in either cancer or nontransformed cells, suggesting that K858 has minimal effects on abnormalities in the number and structure of chromosomes. K858 exhibited potent antitumor activity in xenograft models of cancer, and induced the accumulation of mitotic cells with monopolar spindles in tumor tissues. Importantly, K858, unlike antimicrotubule agents, had no effect on microtubule polymerization in cell-free and cellbased assays, and was not neurotoxic in a motor coordination test in mice. Taken together, the Eg5 inhibitor K858 represents an important compound for further investigation as a novel anticancer therapeutic. [Cancer Res 2009;69(9):3901-9]

These results indicate that olopatadine is an antihistamine agent having inhibitory activities against chronic inflammatory dermatitis, possibly resulting from its diminishing effect on elevated cytokines.

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Whole-body counter measurements of residents of Fukushima Prefecture have been extensively performed after the Fukushima Dai-ichi Nuclear Power Plant accident in March 2011. These measurements have demonstrated that the levels of internal contamination with radioactive cesium (Cs and Cs) in the residents are very low. This article provides an overview of and lessons learned from these whole-body counter measurements with emphasis on the technical problems encountered, and it discusses the effective use of whole-body counters for assessing the internal thyroid doses of individuals when direct measurements of I in the thyroid are difficult or impossible to implement for the total affected population in a short time after a nuclear reactor accident. The application of this dose reconstruction method requires determining the intake ratio of I to cesium isotopes at appropriate times and considers the short biological half-lives of cesium isotopes, in particular for children.

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