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Articles by Y Kondo
Total Records ( 6 ) for Y Kondo
  K Kawaguchi , H Murakami , T Taniguchi , M Fujii , S Kawata , T Fukui , Y Kondo , H Osada , N Usami , K Yokoi , Y Ueda , Y Yatabe , M Ito , Y Horio , T Hida and Y. Sekido

Malignant pleural mesothelioma (MPM) is an aggressive neoplasm associated with asbestos exposure. Although expression and activation of receptor tyrosine kinases (RTKs), including MET, have been reported in most MPM, specific RTK inhibitors showed less than the expected response in MPM cells. To determine whether the lack of response of MET inhibitors was due to cooperation with other RTKs, we determined activation status of MET and other RTKs, including epidermal growth factor receptor (EGFR) family of 20 MPM cell lines, and tested whether dual RTK inhibition is an effective therapeutic strategy. We detected MET upregulation and phosphorylation (thus indicating activation) in 14 (70%) and 13 (65%) cell lines, but treatment with MET-specific inhibitors showed weak or modest effect of suppression in most of the cell lines. Phospho-RTK array analysis revealed that MET was simultaneously activated with other RTKs, including EGFR, ErbB2, ErbB3 and platelet-derived growth factor receptor-β. Combination of MET and EGFR inhibitors triggered stronger inhibition on cell proliferation and invasion of MPM cells than that of each in vitro. These results indicated that coactivation of RTKs was essential in mesothelioma cell proliferation and/or survival, thus suggesting that simultaneous inhibition of RTKs may be a more effective strategy for the development of molecular target therapy for MPM.

  M. R. H Estecio , J Gallegos , C Vallot , R. J Castoro , W Chung , S Maegawa , Y Oki , Y Kondo , J Jelinek , L Shen , H Hartung , P. D Aplan , B. A Czerniak , S Liang and J. P. J. Issa

Epigenetic silencing plays an important role in cancer development. An attractive hypothesis is that local DNA features may participate in differential predisposition to gene hypermethylation. We found that, compared with methylation-resistant genes, methylation-prone genes have a lower frequency of SINE and LINE retrotransposons near their transcription start site. In several large testing sets, this distribution was highly predictive of promoter methylation. Genome-wide analysis showed that 22% of human genes were predicted to be methylation-prone in cancer; these tended to be genes that are down-regulated in cancer and that function in developmental processes. Moreover, retrotransposon distribution marks a larger fraction of methylation-prone genes compared to Polycomb group protein (PcG) marking in embryonic stem cells; indeed, PcG marking and our predictive model based on retrotransposon frequency appear to be correlated but also complementary. In summary, our data indicate that retrotransposon elements, which are widespread in our genome, are strongly associated with gene promoter DNA methylation in cancer and may in fact play a role in influencing epigenetic regulation in normal and abnormal physiological states.

  H Sawada , T Sasaki , F Hosokawa , S Yuasa , M Terao , M Kawazoe , T Nakamichi , T Kaneyama , Y Kondo , K Kimoto and K. Suenaga

A new concept of a spherical aberration correction system using three dodecapoles is proposed. The system compensates for higher order aberration of 6-fold astigmatism, which generally limits a uniform phase area for image forming and probe forming in an electron microscope with a conventional two-hexapole corrector. Triple 3-fold astigmatism field is used to correct the spherical aberration of the objective lens, and the total 3-fold astigmatism is eliminated by their combination. The optimum azimuth relationship among three dodecapoles is calculated to eliminate the 6-fold astigmatism. The principle of the method was verified using a mathematically complex representation. This new concept was experimentally tested with a scanning transmission electron microscope at 60 kV acceleration. The 6-fold astigmatism was certainly compensated and the coherent convergent angle became almost twice compared to a conventional double hexapole system.

  H Sawada , Y Tanishiro , N Ohashi , T Tomita , F Hosokawa , T Kaneyama , Y Kondo and K. Takayanagi

A spherical aberration-corrected electron microscope has been developed recently, which is equipped with a 300-kV cold field emission gun and an objective lens of a small chromatic aberration coefficient. A dumbbell image of 47 pm spacing, corresponding to a pair of atomic columns of germanium aligned along the [114] direction, is resolved in high-angle annular dark field (HAADF) scanning transmission electron microscopy (STEM) with a 0.4-eV energy spread of the electron beam. The observed image was compared with a simulated image obtained by dynamical calculation.

  Y Oshima , H Sawada , F Hosokawa , E Okunishi , T Kaneyama , Y Kondo , S Niitaka , H Takagi , Y Tanishiro and K. Takayanagi

We visualized lithium atom columns in LiV2O4 crystals by combining scanning transmission electron microscopy with annular bright field (ABF) imaging using a spherical aberration-corrected electron microscope (R005) viewed from the [110] direction. The incident electron beam was coherent with a convergent angle of 30 mrad (semi-angle), and the detector collected scattered electrons over 20–30 mrad (semi-angle). The ABF image showed dark dots corresponding to lithium, vanadium and oxygen columns.

  N Shibata , Y Kohno , S. D Findlay , H Sawada , Y Kondo and Y. Ikuhara

A new area detector for atomic-resolution scanning transmission electron microscopy (STEM) is developed and tested. The circular detector is divided into 16 segments which are individually optically coupled with photomultiplier tubes. Thus, 16 atomic-resolution STEM images which are sensitive to the spatial distribution of scattered electrons on the detector plane can be simultaneously obtained. This new detector can be potentially used not only for the simultaneous formation of common bright-field, low-angle annular dark-field and high-angle annular dark-field images, but also for the quantification of images by detecting the full range of scattered electrons and even for exploring novel atomic-resolution imaging modes by post-processing combination of the individual images.

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