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- 저자 : Chaoyang Ju (검색결과 4 건)
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Sun, Chaoyang,Yin, Jun,Fang, Yong,Chen, Jian,Jeong, Kang Jin,Chen, Xiaohua,Vellano, Christopher P.,Ju, Zhenlin,Zhao, Wei,Zhang, Dong,Lu, Yiling,Meric-Bernstam, Funda,Yap, Timothy A.,Hattersley, Mauree Cell Press 2018 CANCER CELL Vol. No.
<P><B>Summary</B></P> <P>Poly(ADP-ribose) polymerase inhibitors (PARPi) are selectively active in cells with homologous recombination (HR) deficiency (HRD) caused by mutations in <I>BRCA1</I>, <I>BRCA2</I>, and other pathway members. We sought small molecules that induce HRD in HR-competent cells to induce synthetic lethality with PARPi and extend the utility of PARPi. We demonstrated that inhibition of bromodomain containing 4 (BRD4) induced HRD and sensitized cells across multiple tumor lineages to PARPi regardless of <I>BRCA1/2</I>, <I>TP53</I>, <I>RAS</I>, or <I>BRAF</I> mutation status through depletion of the DNA double-stand break resection protein CtIP (C-terminal binding protein interacting protein). Importantly, BRD4 inhibitor (BRD4i) treatment reversed multiple mechanisms of resistance to PARPi. Furthermore, PARPi and BRD4i are synergistic in multiple <I>in vivo</I> models.</P> <P><B>Highlights</B></P> <P> <UL> <LI> BRD4 inhibition decreases homologous recombination competency by decreasing CtIP </LI> <LI> PARP and BRD4 inhibitors demonstrate synergy in multiple cancer lineages </LI> <LI> CtIP rescues DNA end resection and HR defect caused by BRD4 inhibition </LI> <LI> BRD4 inhibition resensitizes cells with acquired PARPi resistance to PARPi </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>
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Sun, Chaoyang,Fang, Yong,Yin, Jun,Chen, Jian,Ju, Zhenlin,Zhang, Dong,Chen, Xiaohua,Vellano, Christopher P.,Jeong, Kang Jin,Ng, Patrick Kwok-Shing,Eterovic, Agda Karina B.,Bhola, Neil H.,Lu, Yiling,Wes American Association for the Advancement of Scienc 2017 Science translational medicine Vol.9 No.392
<P>Mutant <I>RAS</I> has remained recalcitrant to targeted therapy efforts. We demonstrate that combined treatment with poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors and mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitors evokes unanticipated, synergistic cytotoxic effects in vitro and in vivo in multiple <I>RAS</I> mutant tumor models across tumor lineages where <I>RAS</I> mutations are prevalent. The effects of PARP and MEK inhibitor combinations are independent of <I>BRCA1/2</I> and <I>p53</I> mutation status, suggesting that the synergistic activity is likely to be generalizable. Synergistic activity of PARP and MEK inhibitor combinations in <I>RAS</I> mutant tumors is associated with (i) induction of BIM-mediated apoptosis, (ii) decrease in expression of components of the homologous recombination DNA repair pathway, (iii) decrease in homologous recombination DNA damage repair capacity, (iv) decrease in DNA damage checkpoint activity, (v) increase in PARP inhibitor–induced DNA damage, (vi) decrease in vascularity that could increase PARP inhibitor efficacy by inducing hypoxia, and (vii) elevated PARP1 protein, which increases trapping activity of PARP inhibitors. Mechanistically, enforced expression of FOXO3a, which is a target of the RAS/MAPK pathway, was sufficient to recapitulate the functional consequences of MEK inhibitors including synergy with PARP inhibitors. Thus, the ability of mutant <I>RAS</I> to suppress FOXO3a and its reversal by MEK inhibitors accounts, at least in part, for the synergy of PARP and MEK inhibitors in <I>RAS</I> mutant tumors. The rational combination of PARP and MEK inhibitors warrants clinical investigation in patients with <I>RAS</I> mutant tumors where there are few effective therapeutic options.</P>
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Adaptive Extraction Method for Phase Foreground Region in Laser Interferometry of Gear
Xian Wang,Yichao Zhao,Chaoyang Ju,Chaoyong Zhang 한국광학회 2023 Current Optics and Photonics Vol.7 No.4
Tooth surface shape error is an important parameter in gear accuracy evaluation. When tooth surface shape error is measured by laser interferometry, the gear interferogram is highly distorted and the gray level distribution is not uniform. Therefore, it is important for gear interferometry to extract the foreground region from the gear interference fringe image directly and accurately. This paper presents an approach for foreground extraction in gear interference images by leveraging the sinusoidal variation characteristics shown by the interference fringes. A gray level mask with an adaptive threshold is established to capture the relevant features, while a local variance evaluation function is employed to analyze the fluctuation state of the interference image and derive a repair mask. By combining these masks, the foreground region is directly extracted. Comparative evaluations using qualitative and quantitative assessment methods are performed to compare the proposed algorithm with both reference results and traditional approaches. The experimental findings reveal a remarkable degree of matching between the algorithm and the reference results. As a result, this method shows great potential for widespread application in the foreground extraction of gear interference images.
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Qingxiao Zhou,Yongliang Yong,Weiwei Ju,Xiangying Su,Xiaohong Li,Chaoyang Wang,Zhibing Fu 한국물리학회 2018 Current Applied Physics Vol.18 No.1
Dioxins are highly toxic to humans and environment, and developing the effective methods to control and detect the organic pollutant is particular important. Here we performed a density functional theory (DFT) study on the adsorption of 2, 3, 7, 8-tetrachlorodibenzofuran (TCDF) molecules on the modified graphene substrates. The results indicated that the introducing of vacancy-defect and dopants (Mn and Fe) significantly improves the sensitivity toward TCDF molecules. The impurity played a crucial role for interacting with TCDF molecules. Furthermore, the adsorption of TCDF induced band-gap open in defected graphene substrates, which could be seen as electric signal to detect TCDF pollutant. The present study is expected to be useful to explore effective materials to detect and remove dioxin pollutants based on graphene.
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