Min A.,Seoul National University |
Im S.-A.,Seoul National University |
Kim D.K.,Seoul International School |
Song S.-H.,Seoul National University |
And 7 more authors.
Breast Cancer Research | Year: 2015
Introduction: Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, has been found to have therapeutic potential for treating cancers associated with impaired DNA repair capabilities, particularly those with deficiencies in the homologous recombination repair (HRR) pathway. Histone deacetylases (HDACs) are important for enabling functional HRR of DNA by regulating the expression of HRR-related genes and promoting the accurate assembly of HRR-directed sub-nuclear foci. Thus, HDAC inhibitors have recently emerged as a therapeutic agent for treating cancer by inhibiting DNA repair. Based on this, HDAC inhibition could be predicted to enhance the anti-tumor effect of PARP inhibitors in cancer cells by blocking the HRR pathway. Methods: We determined whether suberoylanilide hydroxamic acid (SAHA), a HDAC inhibitor, could enhance the anti-tumor effects of olaparib on breast cancer cell lines using a cytotoxic assay, cell cycle analysis, and Western blotting. We evaluated how exposure to SAHA affects the expression of HRR-associated genes. The accumulation of DNA double strand breaks (DSBs) induced by combination treatment was assessed. Induction of autophagy was monitored by imaging green fluorescent protein-tagged microtubule-associated protein 1A/1B-light chain 3 (LC3) expression following co-treatment with olaparib and SAHA. These in vitro data were validated in vivo using a human breast cancer xenograft model. Results: Triple-negative breast cancer cell (TNBC) lines showed heterogeneous responses to the PARP and HDAC inhibitors. Co-administration of olaparib and SAHA synergistically inhibited the growth of TNBC cells that expressed functional Phosphatase and tensin homolog (PTEN). This effect was associated with down-regulation of the proliferative signaling pathway, increased apoptotic and autophagic cell death, and accumulation of DNA damage. The combined anti-tumor effect of olaparib and SAHA was also observed in a xenograft model. These data suggest that PTEN expression in TNBC cells can sensitize the cell response to simultaneous inhibition of PARP and HDAC both in vitro and in vivo. Conclusion: Our findings suggest that expression of functional PTEN may serve as a biomarker for selecting TNBC patients that would favorably respond to a combination of olaparib with SAHA. This provides a strong rationale for treating TNBC patients with PTEN expression with a combination therapy consisting of olaparib and SAHA. © 2015 Min et al.; licensee BioMed Central.
Kim J.,Seoul National University |
Hong D.,Seoul International School |
Lee H.,Seoul National University |
Shin Y.,Samsung |
And 4 more authors.
Journal of Physical Chemistry C | Year: 2013
We report the large-scale fabrication of high-performance field effect transistors (FETs) based on pristine semiconducting single-walled carbon nanotube (s-SWCNT) networks without bundles or organic impurities, thus exhibiting its intrinsic characteristics. Here, the solution of pristine s-SWCNTs without bundles or organic impurities was prepared in nonpolar solvent via filtration and centrifugation processes, and the s-SWCNTs in the solution were selectively assembled onto specific regions on the solid substrates via a directed assembly strategy. The fabricated FET devices based on such pristine s-SWCNT networks could exhibit a rather large on-off ratio up to over ∼106 and a subthreshold swing as small as ∼490 mV/dec, which are comparable to those of a single s-SWCNT-based device with the same device structure. Importantly, the s-SWCNT devices exhibited anomalous gating behaviors such as an on-current saturation at a large gate bias and unconventional scaling behaviors, which are quite different from those of previous SWCNT network-based devices. Such anomalous behaviors can be explained by a simple model based on the networks of contact and CNT resistances, which implies that the anomalous behaviors are, in fact, the intrinsic characteristics of pristine s-SWCNT network-based devices. Our work provides a new insight about the intrinsic characteristics of pristine s-SWCNT network-based devices and, thus, should be an important guideline for the future research and applications of high-performance s-SWCNT network-based devices. © 2013 American Chemical Society.
Suh B.,Korea University |
Kim Y.,Korea University |
Kim T.,Seoul International School |
Jeon S.,Korea University
Journal of Electromagnetic Waves and Applications | Year: 2013
This paper presents a CMOS wideband miniature balun operating over the full K- and Ka-bands. The balun is based on a single spiral coupled structure where two symmetric spiral lines are stacked vertically (i.e. broadside-coupled) in an antipodal manner. The proposed structure provides ultra-wideband balun performance while occupying a minimal chip area compared with conventional spiral baluns. In order to offset residual inductance of the spirals, a compensation capacitor is shunted at the end of an unbalanced input line, which further improves the bandwidth. The proposed balun is implemented in a bulk 0.13-μm CMOS process. The measured insertion loss is less than 6.5 dB from 14 to 40 GHz. The amplitude and phase imbalances are less than 1 dB and 10°, respectively, over the entire bandwidth. The balun occupies an area of only 0.0095 mm2, which, to the authors knowledge, is significantly smaller than any previously reported CMOS baluns at similar frequency bands. © 2013 Copyright Taylor and Francis Group, LLC.
Kim J.H.,Korea University |
Choi H.,Korea University |
Suh M.J.,Seoul International School |
Shin J.H.,Korea University |
And 2 more authors.
Spine | Year: 2013
Study Design: Human annulus fibrosus (AF) cells were stimulated in vitro with interleukin (IL)-1β and exposed to biphasic electrical currents. Objective: To identify the effect of biphasic electrical currents on the production of the extracellular matrix-modifying enzymes and inflammatory mediators in IL-1β-stimulated AF cells. Summary of Background Data: Symptomatic disc degeneration is an important cause of chronic intractable lumbar pain and is associated with macrophage-mediated inflammation in the AF. The inflammatory reaction relationship has not been studied in the AF. Methods: Human AF cells were treated with 1 ng/mL IL-1β and cultured in a microcurrent generating chamber system. The levels of matrix metalloproteinase (MMP)-1, MMP-3, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, IL-6, IL-8, vascular endothelial growth factor (VEGF), insulin-like growth factor, and nitric oxide (NO) were measured. Expression of cyclooxygenase 2 and type I collagen mRNA was analyzed. Results: Compared with unstimulated cells, IL-1β-stimulated AF cells produced significantly higher levels of MMP-1, MMP-3, IL-6, IL-8, NO, and VEGF, and lower levels of TIMP-1 and TIMP-2. Exposure to a 250-mV/mm field induced time-dependent increases in IL-6, NO, MMP-1, TIMP-1, VEGF, and insulin-like growth factor-1 production. The cells exposed to 500-mV/mm field produced significantly less MMP-1, TIMP-1, IL-6, and VEGF than unexposed cells (MMP-1, 17.2 ± 4.7 ng/mL vs. 27.3 ± 3.9 ng/mL, P< 0.05; TIMP-1, 12.4 ± 3.3 ng/mL vs. 22.3 ± 2.1 ng/mL, P< 0.02; IL-6, 2.5 ± 0.9 ng/mL vs. 6.39 ± 1.90 ng/mL, P< 0.05; and VEGF, 0.1 ± 0.04 ng/mL vs. 0.44 ± 0.15 ng/mL, P< 0.03). NO production was markedly increased at 500 mV/mm (P< 0.0001). Conclusion: We showed that exposure of IL-1β-stimulated AF cells to a 500 mV/mm inhibited MMP-1, IL-6, VEGF, and TIMP-1 production. The results suggest that biphasic electrical current stimulation may have efficacy in diminishing symptomatic disc degeneration. © 2013 Lippincott Williams & Wilkins.
Kim J.,Gachon University |
Kim S.,Gachon University |
Nguyen T.T.,Gachon University |
Lee R.,Seoul International School |
And 6 more authors.
Journal of Electronic Materials | Year: 2016
We present a real-time quantitative immunoassay to detect fibrinogen in the blood plasma of Alzheimer’s disease patients using multimode fiber optical sensors in which surface plasmon resonance (SPR) was employed. Nanometer-thick bimetals including silver and aluminum were coated onto the core surface of the clad-free part (5 cm long) of the fiber for SPR excitation at the He-Ne laser wavelength of 632.8 nm. The histidine-tagged peptide was then coated on the metal surface to immobilize the fibrinogen antibody for the selective capture of fibrinogen among the proteins in the patient blood plasma. The SPR fiber optical sensor enabled quantitative detection of concentrations of fibrinogen from the different human patient blood at a detection limit of ∼20 ng/ml. We also observed a correlation in the fibrinogen concentration measurement between enzyme-linked immunosorbent assay and our SPR fiber-based sensors. This suggests that the presented SPR fiber-based sensors that do not rely on the use of labels such as fluorophores can be used for a real-time quantitative assay of a specific protein such as fibrinogen in a human blood that is known to contain many other kinds of proteins together. © 2016 The Minerals, Metals & Materials Society