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- 저자 : Toshikazu Kimura (검색결과 2 건)
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Yoshihiko Fujita,Masahiko Kimura,Hiroki Sato,Toshikazu Takata,Nobufumi Ono,Kazuto Nishio 대한약학회 2016 Archives of Pharmacal Research Vol.39 No.6
Rotaxanes comprise a class of interlocked moleculescontaining a wheel threaded onto an axle with blockinggroups on the ends to keep thewheel fromsliding off.Here,weshow that [2][bis(2-(3,5-dimethylphenylcarbonyloxy)ethyl)ammoniumtrifluoromethanesulfonate]-[dibenzo-24-crown-8]rotaxane (TRO-A0001), a rotaxane compound, exerted agrowth inhibitory effect on several human cancer cell lines.AnMTT assay revealed an IC50 of 14-830 nMfor TRO-A0001 inthese cells. Neither the wheel nor the axle part alone inhibitedtumor cell growth, suggesting that the complete rotaxanemolecule with its unique ‘‘intramolecular mobility’’ is requiredto inhibit cell growth. Annexin-V/PI staining provided evidenceof the induction of apoptosis, which was further confirmedby the observation of poly (ADP-ribose) polymerasecleavage. Furthermore, a cell cycle analysis using flowcytometry showed that TRO-A0001 treatment resulted in G1arrest in glioblastoma T98G and melanoma G361 cells. Animmunoblot analysis revealed that in both cell lines, TROA0001treatment caused the induction of p21/Cip1, therebydown-regulating Cdks 2, 4 and 6 and reducing Cyclins D1 andE. The results presented in this study demonstrate cytotoxicityof the rotaxane compound and its potential as a lead compoundfor the development of a chemotherapeutic agent againstcancer.
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Mayte Sánchez van Kammen,Jacoba P. Greving,Satoshi Kuroda,Daina Kashiwazaki,Akio Morita,Yoshiaki Shiokawa,Toshikazu Kimura,Christophe Cognard,Anne C. Januel,Antti Lindgren,Timo Koivisto,Juha E. Jääske 대한뇌졸중학회 2019 Journal of stroke Vol.21 No.3
Background and purpose Prediction of intracranial aneurysm growth risk can assist physicians in planning of follow-up imaging of conservatively managed unruptured intracranial aneurysms. We therefore aimed to externally validate the ELAPSS (Earlier subarachnoid hemorrhage, aneurysm Location, Age, Population, aneurysm Size and Shape) score for prediction of the risk of unruptured intracranial aneurysm growth. Methods From 11 international cohorts of patients ≥18 years with ≥1 unruptured intracranial aneurysm and ≥6 months of radiological follow-up, we collected data on the predictors of the ELAPSS score, and calculated 3- and 5-year absolute growth risks according to the score. Model performance was assessed in terms of calibration (predicted versus observed risk) and discrimination (c-statistic). Results We included 1,072 patients with a total of 1,452 aneurysms. During 4,268 aneurysm-years of follow-up, 199 (14%) aneurysms enlarged. Calibration was comparable to that of the followdevelopment cohort with the overall observed risks within the range of the expected risks. The c-statistic was 0.69 (95% confidence interval [CI], 0.64 to 0.73) at 3 years, compared to 0.72 (95% CI, 0.68 to 0.76) in the development cohort. At 5 years, the c-statistic was 0.68 (95% CI, 0.64 to 0.72), compared to 0.72 (95% CI, 0.68 to 0.75) in the development cohort. Conclusions The ELAPSS score showed accurate calibration for 3- and 5-year risks of aneurysm growth and modest discrimination in our external validation cohort. This indicates that the score is externally valid and could assist patients and physicians in predicting growth of unruptured intracranial aneurysms and plan follow-up imaging accordingly.
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