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您的检索式：作者名="Hiroyuki SAKAUE"
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| 1 | Tumor-derived insulin-like growth factor-binding protein-1 contributes to resistance of hepatocellular carcinoma to tyrosine kinase inhibitors显示文摘Background:Antiangiogenic tyrosine kinase inhibitors(TKIs)provide one of the few therapeutic options for effective treatment of hepatocellular carcinoma(HCC).However,patients with HCC often develop resistance toward antiangiogenic TKIs,and the underlying mechanisms are not understood.The aim of this study was to determine the mechanisms underlying antiangiogenic TKI resistance in HCC.Methods:We used an unbiased proteomic approach to define proteins that were responsible for the resistance to antiangiogenic TKIs in HCC patients.We evaluated the prognosis,therapeutic response,and serum insulin-like growth factor-binding protein-1(IGFBP-1)levels of 31 lenvatinib-treated HCC patients.Based on the array of results,a retrospective clinical study and preclinical experiments using mouse and human hepatoma cells were conducted.Additionally,in vivo genetic and pharmacological gain-and loss-of-function experiments were performed.Results:In the patient cohort,IGFBP-1 was identified as the signaling molecule with the highest expression that was inversely associated with overall survival.Mechanistically,antiangiogenic TKI treatment markedly elevated tumor IGFBP-1 levels via the hypoxia-hypoxia inducible factor signaling.IGFBP-1 stimulated angiogenesis through activation of the integrinα5β1-focal adhesion kinase pathway.Consequently,loss of IGFBP-1 and integrinα5β1 by genetic and pharmacological approaches re-sensitized HCC to lenvatinib treatment.Conclusions:Together,our data shed light onmechanisms underlying acquired resistance of HCC to antiangiogenic TKIs.Antiangiogenic TKIs induced an increase of tumor IGFBP-1,which promoted angiogenesis through activating the IGFBP-1-integrinα5β1 pathway.These data bolster the application of a new therapeutic concept by combining antiangiogenic TKIs with IGFBP-1 inhibitors. | Hiroyuki Suzuki Hideki Iwamoto Takahiro Seki Toru Nakamura Atsutaka Masuda Takahiko Sakaue Toshimitsu Tanaka Yasuko Imamura Takashi Niizeki Masahito Nakano Shigeo Shimose Tomotake Shirono Yu Noda Naoki Kamachi Miwa Sakai Kazutoyo Morita Masamichi Nakayama Tomoharu Yoshizumi Ryoko Kuromatsu Hirohisa Yano Yihai Cao Hironori Koga Takuji Torimura | 2023 | Cancer Communications2023，43，4： | 0 |
| 2 | Observation of Magnetic Dipole Forbidden Transitions in LHD and Its Application to Burning Plasma Diagnostics显示文摘Magnetic dipole forbidden (M1) transition was studied in large helical device (LHD)and F-, Si- and Ti-like M1 transitions are successfully observed for highly ionized Ar, Kr, Mo andXe ions. The wavelengths measured in visible range for the heavy elements, which are carefullydetermined with extremely small uncertainties of 0.02~0.05 A as a standard wavelength of usualelectric dipole (E1) plasma emissions, are compared with theoretical predictions. The result showsa good agreement with recent Hatree-Fock calculation including semi-empirical adjustment. TheM1 intensity for the F-like ions is examined by analyzing the intensity ratio of M1 to E1. Densitydependence of the ratio is experimentally verified by comparing with collisional- radiative modelcalculation on level population. The M1/E1 line ratio for the F-like ions is applied to the(He^(2+)) particle diagnostics in ITER, in which a steady-state operation of burning plasmas basedon D-T fusion reaction is expected with α particle heating. Unfortunately, the present estimationsuggests a negative result for the α particle measurement because the ratio is largely enhanced bythe collisional excitation with bulk ions due to high ion temperature of ITER of 10 keV as assumedand the resultant effect of the collisional excitation with α particles becomes less. Meanwhile, theM1 transition, in particular, Ti-like WLⅢ (W^(52+)) transition (3627 A) emitted in visible range,is very useful for diagnostics of the impurity behavior and the core plasma parameters in ITER. | Shigeru MORITA Motoshi GOTO Ryuji KATAI Chunfeng DONG Hiroyuki SAKAUE Hangyu ZHOU | 2010 | Plasma Science and Technology2010，12，3： | 0 |
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