• Title/Summary/Keyword: UI-152

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Autophagy-Dependent Survival of Mutant B-Raf Melanoma Cells Selected for Resistance to Apoptosis Induced by Inhibitors against Oncogenic B-Raf

  • Ahn, Jun-Ho;Lee, Michael
    • Biomolecules & Therapeutics
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    • v.21 no.2
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    • pp.114-120
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    • 2013

  • Most patients with mutant B-Raf melanomas respond to inhibitors of oncogenic B-Raf but resistance eventually emerges. To better understand the mechanisms that determine the long-term responses of mutant B-Raf melanoma cells to B-Raf inhibitor, we used chronic selection to establish B-Raf (V600E) melanoma clones with acquired resistance to the new oncogenic B-Raf inhibitor UI-152. Whereas the parental A375P cells were highly sensitive to UI-152 ($IC_{50}$ < $0.5{\mu}M$), the resistant sub-line (A375P/Mdr) displayed strong resistance to UI-152 ($IC_{50}$ < $20{\mu}M$). Immunofluorescence analysis indicated the absence of an increase in the levels of P-glycoprotein multidrug resistance (MDR) transporter in A375P/Mdr cells, suggesting that resistance was not attributable to P-glycoprotein overexpression. In UI-152-sensitive A375P cells, the anti-proliferative activity of UI-152 appeared to be due to cell-cycle arrest at $G_0/G_1$ with the induction of apoptosis. However, we found that A375P/Mdr cells were resistant to the apoptosis induced by UI-152. Interestingly, UI-152 preferentially induced autophagy in A375P/Mdr cells but not in A375P cells, as determined by GFP-LC3 puncta/cell counts. Further, autophagy inhibition with 3-methyladenine (3-MA) partially augmented growth inhibition of A375P/Mdr cells by UI-152, which implies that a high level of autophagy may protect UI-152-treated cells from undergoing growth inhibition. Together, our data implicate high rates of autophagy as a key mechanism of acquired resistance to the oncogenic B-Raf inhibitor, in support of clinical studies in which combination therapy with autophagy targeted drugs is being designed to overcome resistance.

  • https://doi.org/10.4062/biomolther.2013.012 인용 PDF KSCI

Implement of The Authoring Tool for WIPI Business Program using UIDL(User Interface Description Language) (사용자 인터페이스 명세 언어를 이용한 위피 비즈니스 프로그램 저작도구 구현)

  • Lee, Dong-Su;Park, Ki-Chang;Kim, Byung-Ki
    • The Journal of the Korea Contents Association
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    • v.9 no.2
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    • pp.152-162
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    • 2009

  • At present, Authoring tools, which are used to develop the WIPI applications are less convenient to be coded. Usually, the programming tools only focus on the grammar while scarcity of visualization. Developer forced directly codes all times during the development by this cause. As a procedure for rapid WIPI Application Development, in this paper, WIPI API High Level Component is first visualized, in order words, graphic control is developed. Second this control is used in designing the mobile layout. Then UI Markup Language and source code can be generated automatically. With this view, we propose the JIML(Jlet Interface Markup Language) with UI Markup Language based XML of WIPI Jlet Platform and also present the transformable rule for generation to the WIPI code about WIPI Jlet UI from offered JIML. Also we implement the WIPI Jlet Generation System to make the generation to JIML, WIPI code. The Implemented System provides efficiency when developing WIPI Business Application, and helps to enable rapid development.

  • https://doi.org/10.5392/JKCA.2009.9.2.152 인용 PDF