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Choi H.,Chonnam National University | Cha K.,Daegu Gyeongbuk Medical Innovation Foundation | Jeong S.,Chonnam National University | Park J.-O.,Chonnam National University | Park S.,Chonnam National University
IEEE/ASME Transactions on Mechatronics | Year: 2013

For 3-D locomotion and drilling of a microrobot, we proposed an electromagnetic actuation (EMA) system consisting of three pairs of stationary Helmholtz coils, a pair of stationary Maxwell coils, and a pair of rotating Maxwell coils in the previous research. However, this system could have limited medical applications because of the pair of rotational Maxwell coils. In this paper, we propose a new EMA system with three pairs of stationary Helmholtz coils, a pair of stationary Maxwell coils, and a new locomotive mechanism for the same 3-D locomotion and drilling of the microrobot as achieved by the previously proposed EMA system. For the performance evaluation of the proposed EMA system, we perform a 3-D locomotion and drilling test in a blood vessel phantom. In addition, the two EMA systems are compared to show that the newly proposed EMA system has 440% wider working space and 49% less power consumption than the previous EMA system. © 2012 IEEE.

Kim C.Y.,Daegu Gyeongbuk Medical Innovation Foundation | Sung J.H.,Korea Conformity Laboratories | Chung Y.H.,Korea Institute of Toxicology | Park J.D.,Chung - Ang University | And 4 more authors.
Inhalation Toxicology | Year: 2013

To define the relationship between the brain concentration of manganese and neurological signs, such as locomotion, after prolonged welding-fume exposure, cynomolgus monkeys were acclimated for 1 month and then divided into three concentration groups: unexposed, low concentration (31-mg/m total suspended particulate (TSP), 0.9-mg/m of Mn), and high concentration (62-mg/m TSP, 1.95-mg/m of Mn) of TSP. The monkeys were exposed to manual metal-arc stainless steel (MMA-SS) welding fumes for 2-h per day over 8 months in an inhalation chamber system equipped with an automatic fume generator. The home cage locomotor activity and patterns were determined using a camera system over 2-4 consecutive days. After 25 and 32 weeks of exposure, the home cage locomotor activity of the high-concentration primates was found to be 5-6 times higher than that of the unexposed primates, and this increased locomotor activity was maintained for 7 weeks after ceasing the welding-fume exposure, eventually subsiding to three times higher after 13 weeks of recovery. Therefore, the present results, along with our previous observations of a high magnetic resonance imaging (MRI) T1 signal in the globus pallidus and increased blood Mn concentration, indicate that prolonged welding-fume exposure can cause neurobehavioral changes in cynomolgus monkeys. © 2013 Informa Healthcare USA, Inc. All rights reserved.

Kim H.,Korea Institute of Science and Technology | Kim H.,Yonsei University | Kim N.D.,Daegu Gyeongbuk Medical Innovation Foundation | Lee J.,Korea Institute of Science and Technology | And 3 more authors.
Biochemical and Biophysical Research Communications | Year: 2013

The focal adhesion kinase (FAK) signaling cascade in cancer cells was profoundly inhibited by methyl violet 2B identified with the structure-based virtual screening. Methyl violet 2B was shown to be a non-competitive inhibitor of full-length FAK enzyme vs. ATP. It turned out that methyl violet 2B possesses extremely high kinase selectivity in biochemical kinase profiling using a large panel of kinases. Anti-proliferative activity measurement against several different cancer cells and Western blot analysis showed that this substance is capable of suppressing significantly the proliferation of cancer cells and is able to strongly block FAK/AKT/MAPK signaling pathways in a dose dependent manner at low nanomolar concentration. Especially, phosphorylation of Tyr925-FAK that is required for full activation of FAK was nearly completely suppressed even with 1. nM of methyl violet 2B in A375P cancer cells. To the best of our knowledge, it has never been reported that methyl violet possesses anti-cancer effects. Moreover, methyl violet 2B significantly inhibited FER kinase phosphorylation that activates FAK in cell. In addition, methyl violet 2B was found to induce cell apoptosis and to exhibit strong inhibitory effects on the focal adhesion, invasion, and migration of A375P cancer cells at low nanomolar concentrations. Taken together, these results show that methyl violet 2B is a novel, potent and selective blocker of FAK signaling cascade, which displays strong anti-proliferative activities against a variety of human cancer cells and suppresses adhesion/migration/invasion of tumor cells. © 2013 Elsevier Inc.

Yoon H.,Korea Institute of Science and Technology | Kwak Y.,Korea University | Choi S.,Korea University | Cho H.,Korea University | And 3 more authors.
Journal of Medicinal Chemistry | Year: 2016

Aberrant RET kinase signaling plays critical roles in several human cancers such as thyroid carcinoma. The gatekeeper mutants (V804L or V804M) of RET are resistant to currently approved RET inhibitors such as cabozantinib and vandetanib. We, for the first time, report a highly selective and extremely potent RET inhibitor, 6i rationally designed. Compound 6i inhibits strongly RET gatekeeper mutants and other clinically relevant RET mutants as well as wt-RET. This substance also significantly suppresses growth of thyroid cancer-derived TT cell lines and Ba/F3 cells transformed with various RET mutants. Docking studies reveal that the isoxazole moiety in 6i is responsible for binding affinity improvement by providing additional site for H-bonding with Lys758. Also, 6i not only substantially blocks cellular RET autophosphorylation and its downstream pathway, it markedly induces apoptosis and anchorage-independent growth inhibition in TT cell lines while having no effect on normal thyroid Nthy ori-3-1 cells. © 2015 American Chemical Society.

Kim D.-H.,Korea Institute of Science and Technology | Kwak Y.,Korea University | Kim N.D.,Daegu Gyeongbuk Medical Innovation Foundation | Sim T.,Korea Institute of Science and Technology | Sim T.,Korea University
Cancer Biology and Therapy | Year: 2016

Aberrant mutational activation of FGFR2 is associated with endometrial cancers (ECs). AP24534 (ponatinib) currently undergoing clinical trials has been known to be an orally available multi-targeted tyrosine kinase inhibitor. Our biochemical kinase assay showed that AP24534 is potent against wild-type FGFR1-4 and 5 mutant FGFRs (V561M-FGFR1, N549H-FGFR2, K650E-FGFR3, G697C-FGFR3, N535K-FGFR4) and possesses the strongest kinase-inhibitory activity on N549H-FGFR2 (IC50 of 0.5 nM) among all FGFRs tested. We therefore investigated the effects of AP24534 on endometrial cancer cells harboring activating FGFR2 mutations and explored the underlying molecular mechanisms. AP24534 significantly inhibited the proliferation of endometrial cancer cells bearing activating FGFR2 mutations (N549K, K310R/N549K, S252W) and mainly induced G1/S cell cycle arrest leading to apoptosis. AP24534 also diminished the kinase activity of immunoprecipitated FGFR2 derived from MFE-296 and MFE-280 cells and reduced the phosphorylation of FGFR2 and FRS2 on MFE-296 and AN3CA cells. AP24534 caused substantial reductions in ERK phosphorylation, PLCγ signaling and STAT5 signal transduction on ECs bearing FGFR2 activating mutations. Akt signaling pathway was also deactivated by AP24534. AP24534 causes the chemotherapeutic effect through mainly the blockade of ERK, PLCγ and STAT5 signal transduction on ECs. Moreover, AP24534 inhibited migration and invasion of endometrial cancer cells with FGFR2 mutations. In addition, AP24534 significantly blocked anchorage-independent growth of endometrial cancer cells. We, for the first time, report the molecular mechanisms by which AP24534 exerts antitumor effects on ECs with FGFR2 activating mutations, which would provide mechanistic insight into ongoing clinical investigations of AP24534 for ECs. © 2016, 2016 © Taylor & Francis Group, LLC.

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