Publications by authors named "Jiyeon Ryu"

12 Publications

  • Page 1 of 1

An Immune-Magnetophoretic Device for the Selective and Precise Enrichment of Circulating Tumor Cells from Whole Blood.

Micromachines (Basel) 2020 May 30;11(6). Epub 2020 May 30.

Laboratory of Molecular Pathology and Cancer Genomics, College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul 08826, Korea.

Here, we validated the clinical utility of our previously developed microfluidic device, GenoCTC, which is based on bottom magnetophoresis, for the isolation of circulating tumor cells (CTCs) from patient whole blood. GenoCTC allowed 90% purity, 77% separation rate, and 80% recovery of circulating tumor cells at a 90 μL/min flow rate when tested on blood spiked with epithelial cell adhesion molecule (EpCAM)-positive Michigan Cancer Foundation-7 (MCF7) cells. Clinical studies were performed using blood samples from non-small cell lung cancer (NSCLC) patients. Varying numbers (2 to 114) of CTCs were found in each NSCLC patient, and serial assessment of CTCs showed that the CTC count correlated with the clinical progression of the disease. The applicability of GenoCTC to different cell surface biomarkers was also validated in a cholangiocarcinoma patient using anti-EPCAM, anti-vimentin, or anti-tyrosine protein kinase MET (c-MET) antibodies. After EPCAM-, vimentin-, or c-MET-positive cells were isolated, CTCs were identified and enumerated by immunocytochemistry using anti-cytokeratin 18 (CK18) and anti-CD45 antibodies. Furthermore, we checked the protein expression of PDL1 and c-MET in CTCs. A study in a cholangiocarcinoma patient showed that the number of CTCs varied depending on the biomarker used, indicating the importance of using multiple biomarkers for CTC isolation and enumeration.
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http://dx.doi.org/10.3390/mi11060560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345362PMC
May 2020

Spirobifluorene-Based o-Carboranyl Compounds: Insights into the Rotational Effect of Carborane Cages on Photoluminescence.

Chemistry 2020 Jan 10;26(2):548-557. Epub 2019 Dec 10.

Department of Chemistry, Institute for Molecular Science and Fusion Technology, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of Korea.

9,9'-Spirobifluorene-based closo-o-carboranyl (SFC1 and SFC2) compounds and their nido-derivatives (nido-SFC1 and nido-SFC2) were prepared and characterized. The two closo-compounds displayed major absorption bands assignable to π-π* transitions involving the spirobifluorene group, as well as weak intramolecular charge-transfer (ICT) transitions between the o-carboranes and their spirobifluorene moieties. The nido-compounds exhibited slightly blueshifted absorption bands resulting from the absence of the ICT transitions corresponding to the o-carborane moieties due to the anionic character of the nido-o-carboranes. While SFC1 exhibited only high-energy emissions in THF at 298 K (only from locally excited (LE) states assignable to π-π* transitions on the spirobifluorene group), remarkable emissions in the low-energy region were observed in the rigid state such as in THF at 77 K and in the film state. SFC2 displayed intense emissions in the low-energy region in all states. The fact that neither of the nido-derivatives of SFC1 and SFC2 exhibited low-energy emissions and the TD-DFT calculation results of each closo-compound clearly verified that the low-energy emission was based on ICT-based radiative decay. The conformational barriers from each relative energy calculation upon changing the dihedral angles around the o-carborane cages for both compounds confirmed that the rotation of the o-carborane cages and terminal phenyl rings for SFC1 is freer than that for SFC2.
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http://dx.doi.org/10.1002/chem.201904491DOI Listing
January 2020

Highly Expressed Integrin-α8 Induces Epithelial to Mesenchymal Transition-Like Features in Multiple Myeloma with Early Relapse.

Mol Cells 2016 Dec 21;39(12):898-908. Epub 2016 Dec 21.

Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.

Despite recent groundbreaking advances in multiple myeloma (MM) treatment, most MM patients ultimately experience relapse, and the relapse biology is not entirely understood. To define altered gene expression in MM relapse, gene expression profiles were examined and compared among 16 MM patients grouped by 12 months progression-free survival (PFS) after autologous stem cell transplantation. To maximize the difference between prognostic groups, patients at each end of the PFS spectrum (the four with the shortest PFS and four with the longest PFS) were chosen for additional analyses. We discovered that integrin-α8 () is highly expressed in MM patients with early relapse. The integrin family is well known to be involved in MM progression; however, the role of integrin-α8 is largely unknown. We functionally overexpressed integrin-α8 in MM cell lines, and surprisingly, stemness features including HIF1α, VEGF, OCT4, and Nanog, as well as epithelial mesenchymal transition (EMT)-related phenotypes, including N-cadherin, Slug, Snail and CXCR4, were induced. These, consequently, enhanced migration and invasion abilities, which are crucial to MM pathogenesis. Moreover, the gain of integrin-α8 expression mediated drug resistance against melphalan and bortezomib, which are the main therapeutic agents in MM. The cBioPortal genomic database revealed that have significant tendency to co-occur with and and their mRNA expression were up-regulated in overexpressed MM cells. In summary, integrin-α8, which was up-regulated in MM of early relapse, mediates EMT-like phenotype, enhancing migration and invasion; therefore, it could serve as a potential marker of MM relapse and be a new therapeutic target.
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http://dx.doi.org/10.14348/molcells.2016.0210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5223107PMC
December 2016

Cross-regulation between protein L-isoaspartyl O-methyltransferase and ERK in epithelial mesenchymal transition of MDA-MB-231 cells.

Acta Pharmacol Sin 2011 Sep 15;32(9):1165-72. Epub 2011 Aug 15.

Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Korea.

Aim: Protein L-isoaspartyl O-methyltransferase (PIMT) regulates cell adhesion in various cancer cell lines through activation of integrin αv and the PI3K pathway. The epithelial mesenchymal transition (EMT) enables epithelial cells to acquire the characteristics of mesenchymal cells, and to allow them to migrate for metastasis. Here, we examined the relationship between PIMT and EMT with attached or detached MDA-MB 231 cells.

Methods: Human breast cancer cell line MDA-MB-231 cells were maintained in a suspension on poly-HEMA in the presence or absence of PIMT siRNA or ERK inhibitor PD98059. The mRNAs and proteins were analyzed using RT-PCR and immunoblotting, respectively.

Results: During cellular incubation under detached conditions, PIMT, integrin αv and EMT proteins, such as Snail, Slug and matrix metalloproteinase 2 (MMP-2), were significantly increased in correlation with the phosphorylation of ERK1/2. The ERK inhibitor PD98059 (25 μmol/L) strongly suppressed the expression of the proteins and PIMT. Interestingly, PIMT siRNA blocked the phosphorylation of ERK and the expression of the EMT proteins. Additionally, PIMT and ERK phosphorylation were both co-activated by treatment with TGF-β (10 ng/mL) and TNF-α (10 ng/mL).

Conclusion: A tight cross-regulation exists between ERK and PIMT in regards to their activation and expression during the EMT.
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http://dx.doi.org/10.1038/aps.2011.94DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4003306PMC
September 2011

Protein L-isoaspartyl O-methyltransferase inhibits amyloid beta fibrillogenesis in vitro.

Pharmazie 2011 Jul;66(7):529-34

Department of Genetic Engineering, Sungkyunkwan University, Suwon, Korea.

Fibrillar aggregates of beta-amyloid peptide (Abeta) are major constituents of the senile plaques found in the brains of patients suffering from Alzheimer's disease (AD). Previous studies have shown that spontaneous isomerization or racemization of aspartyl residues in Abeta peptides leads to conformational changes in the secondary structure and increased aggregative ability of the peptides. Protein L-isoaspartyl O-methyltransferase (PIMT, EC 2.1.1.77) is a repairing enzyme converting L-isoaspartyl/D-aspartyl residues in damaged proteins to normal L-aspartyl residues. In this study it was investigated, whether PIMT is able to modulate Abeta fibrillogenesis in vitro by methylation of isoaspartyl residue using purified 5Abeta and PIMT. A Thioflavin-T (Th-T) binding assay conducted after aging Abeta in vitro (37 degrees C, pH 7.4 in PBS) revealed that PIMT inhibited the increase of fluorescence caused by amyloid fibrillogenesis. Western blot analysis revealed that high molecular Abeta aggregates (> 200 kDa) only occurred during Abeta incubation, while they were reduced in response to incubation with PIMT and AdoMet. Additionally, circular dichroism (CD) showed that the beta-sheet structure was increased in Abeta peptides in a time-dependent fashion, while PIMT suppressed the beta-sheet transition after 24 h. Finally, transmission electron microscopy (TEM) revealed that PIMT reduced the size of the Abeta aggregates and induced a different pathway, leading to the formation of amorphous structures. Taken together, these findings indicate that isoaspartyl methylation leads to partial blockade of fibrillogenesis of Abeta by inhibiting the beta transition in the Abeta peptide.
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July 2011

Unsuccessful attempts to add alcohols to transient 2-amino-2-siloxy-silenes - leading to a new benign route for base-free alcohol protection.

Dalton Trans 2010 Oct 24;39(39):9379-85. Epub 2010 Aug 24.

Department of Biochemistry and Organic Chemistry, Uppsala University, Box 576, 751 23, Uppsala, Sweden.

Thermolytic formation of transient 1,1-bis(trimethylsilyl)-2-dimethylamino-2-trimethylsiloxysilene (2) from N,N-dimethyl(tris(trimethylsilyl)silyl)methaneamide (1) in presence of a series of alcohols was investigated. The products are, however, not the expected alcohol-silene addition adducts but silylethers formed in nearly quantitative yields. Thermolysis of 1 in the presence of both alcohols (MeOH or iPrOH) and 1,3-dienes (1,3-butadiene or 2,3-dimethyl-1,3-butadiene) gives alkyl-tris(trimethylsilyl)silylethers and the [4+2] cycloadducts between the silene and diene, which confirms the presence of 2 and that it is unreactive towards alcohols. The observed silylethers are substitution adducts where the amide group of the silylamide is replaced by an alkoxy group, and the reaction time is reflected in the steric bulk of the alcohol. Indeed, the formation of silylethers from the reaction of alcohols with silylamide represents a new base-free method for protection of alcohols. The protection reactions using 1 progresses at elevated temperatures, or alternatively, under acid catalysis at ambient temperature, and similar protections can be carried out with N-cyclohexyl(triphenylsilyl)methaneamide and N,N-dimethyl(trimethylsilyl)methaneamide. The latter silylamide can be used under neutral conditions at room temperature. The only by-products are formamides (N,N-dimethylformamide (DMF) or N-cyclohexylformamide), and the reactions can be performed without solvent. In addition to alcohols we also examined the method for protection of diols, thiols and carboxylic acids, and also these reactions proceeded in high yields and with good selectivities.
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http://dx.doi.org/10.1039/c0dt00323aDOI Listing
October 2010

Chemical speciation of individual airborne particles by the combined use of quantitative energy-dispersive electron probe X-ray microanalysis and attenuated total reflection Fourier transform-infrared imaging techniques.

Anal Chem 2010 Oct;82(19):7987-98

Department of Chemistry, Inha University, 253, Yonghyun-dong, Nam-gu, Incheon 402-751, Korea.

In our previous work, it was demonstrated that the combined use of attenuated total reflectance (ATR) FT-IR imaging and quantitative energy-dispersive electron probe X-ray microanalysis (ED-EPMA), named low-Z particle EPMA, had the potential for characterization of individual aerosol particles. Additionally, the speciation of individual mineral particles was performed on a single particle level by the combined use of the two techniques, demonstrating that simultaneous use of the two single particle analytical techniques is powerful for the detailed characterization of externally heterogeneous mineral particle samples and has great potential for characterization of atmospheric mineral dust aerosols. These single particle analytical techniques provide complementary information on the physicochemical characteristics of the same individual particles, such as low-Z particle EPMA on morphology and elemental concentrations and the ATR-FT-IR imaging on molecular species, crystal structures, functional groups, and physical states. In this work, this analytical methodology was applied to characterize an atmospheric aerosol sample collected in Incheon, Korea. Overall, 118 individual particles were observed to be primarily NaNO(3)-containing, Ca- and/or Mg-containing, silicate, and carbonaceous particles, although internal mixing states of the individual particles proved complicated. This work demonstrates that more detailed physiochemical properties of individual airborne particles can be obtained using this approach than when either the low-Z particle EPMA or ATR-FT-IR imaging technique is used alone.
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http://dx.doi.org/10.1021/ac1014113DOI Listing
October 2010

Speciation of individual mineral particles of micrometer size by the combined use of attenuated total reflectance-Fourier transform-infrared imaging and quantitative energy-dispersive electron probe X-ray microanalysis techniques.

Anal Chem 2010 Jul;82(14):6193-202

Department of Chemistry, Inha University, 253, Yonghyun-dong, Nam-gu, Incheon 402-751, Korea.

Our previous work demonstrated for the first time the potential of the combined use of two techniques, attenuated total reflectance FT-IR (ATR-FT-IR) imaging and a quantitative energy-dispersive electron probe X-ray microanalysis, low-Z particle EPMA, for the characterization of individual aerosol particles. In this work, the speciation of mineral particles was performed on a single particle level for 24 mineral samples, including kaolinite, montmorillonite, vermiculite, talc, quartz, feldspar, calcite, gypsum, and apatite, by the combined use of ATR-FT-IR imaging and low-Z particle EPMA techniques. These two single particle analytical techniques provide complementary information, the ATR-FT-IR imaging on mineral types and low-Z particle EPMA on the morphology and elemental concentrations, on the same individual particles. This work demonstrates that the combined use of the two single particle analytical techniques can powerfully characterize externally heterogeneous mineral particle samples in detail and has great potential for the characterization of airborne mineral dust particles.
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http://dx.doi.org/10.1021/ac101006hDOI Listing
July 2010

Single-particle characterization of summertime arctic aerosols collected at Ny-Alesund, Svalbard.

Environ Sci Technol 2010 Apr;44(7):2348-53

Department of Chemistry, Inha University, Incheon, Korea.

Single-particle characterization of summertime Arctic aerosols is useful to understand the impact of air pollutants on the polar atmosphere. In the present study, a quantitative single particle analytical technique, low-Z particle electron probe X-ray microanalysis, was used to characterize 8100 individual particles overall in 16 sets of aerosol samples collected at Ny-Alesund, Svalbard, Norway on 25-31 July, 2007. Based on their X-ray spectral and secondary electron image data of individual particles, 13 particle types were identified, in which particles of marine origin were the most abundant, followed by carbonaceous and mineral dust particles. A number of aged (reacted) sea salt (and mixture) particles produced by the atmospheric reaction of genuine sea-salts, especially with NO(x) or HNO(3), were significantly encountered in almost all the aerosol samples. They greatly outnumbered genuine sea salt particles, implying that the summertime Arctic atmosphere, generally regarded as a clean background environment, is disturbed by anthropogenic air pollutants. The main sources of airborne NO(x) (or HNO(3)) are probably ship emissions around the Arctic Ocean, industry emission from northern Europe and northwestern Siberia, and renoxification of NO(3)(-) within or on the melting snow/ice surface.
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http://dx.doi.org/10.1021/es903268jDOI Listing
April 2010

Attenuated total reflectance FT-IR imaging and quantitative energy dispersive-electron probe X-ray microanalysis techniques for single particle analysis of atmospheric aerosol particles.

Anal Chem 2009 Aug;81(16):6695-707

Department of Chemistry, Inha University, 253, Yonghyun-dong, Nam-gu, Incheon 402-751, Korea.

This work demonstrates the practical applicability of the combined use of attenuated total reflectance (ATR) FT-IR imaging and low-Z particle electron probe X-ray microanalysis (EPMA) techniques for the characterization of individual aerosol particles. These two single particle analytical techniques provide complementary information on the physicochemical characteristics of the same individual particles, that is, the low-Z particle EPMA for the information on the morphology and elemental concentration and the ATR-FT-IR imaging on the functional group, molecular species, and crystal structure. It was confirmed that the ATR-FT-IR imaging technique can provide sufficient FT-IR absorption signals to perform molecular speciation of individual particles of micrometer size when applied to artificially generated aerosol particles such as ascorbic acid and NaNO(3) aerosols. An exemplar indoor atmospheric aerosol sample was investigated to demonstrate the practical feasibility of the combined application of ATR-FT-IR imaging and low-Z particle EPMA techniques for the characterization of individual airborne particles.
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http://dx.doi.org/10.1021/ac9007545DOI Listing
August 2009

Multivalent & multifunctional ligands to beta-amyloid.

Curr Pharm Des 2009 ;15(6):637-58

Center for Chemoinformatics Research, Life Sciences Research Division, Korea Institute of Science and Technology, Seoul, South Korea.

Ligands selectively targeting beta-amyloid in the living brain are promising candidates of therapeutics and early diagnosis tools for Alzheimer's disease. Among the major stages of beta-amyloid aggregation, monomers and oligomers are excellent targets to reduce neurotoxic brain damages for prevention of the disease progression, while oligomers and fibrils, abundant in the late stage of the disease, are pathological objectives to develop reliable imaging probes. So far, there have been many efforts to develop a wide variety of monovalent beta-amyloid ligands such as thioflavin T, PIB, FDDNP, curcumin, and tramiprosate. However, pathology of Alzheimer's disease is not fully understood yet so that there is currently no cure and further investigations on Alzheimer's disease are needed. For past several years, multivalent beta-amyloid ligands have offered an alternative route by enhancing binding affinity of drug candidates. In addition, it has been revealed that not only neurotoxicity due to the protein misfolding but also other factors are involved in the beta-amyloid cascade such as oxidative stress, inflammation, metal chelation, and several types of neurotransmitters. Thus, there have been numerous studies to improve binding affinities of single beta-amyloid ligands via adopting multivalent effects or to develop drug candidates targeting multiple stages of the pathological cascade. In this review, multivalent and multifunctional beta-amyloid ligands and their promising aspects as an alternative approach to Alzheimer's disease are discussed.
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http://dx.doi.org/10.2174/138161209787315648DOI Listing
May 2009

Simplified LCA and matrix methods in identifying the environmental aspects of a product system.

J Environ Manage 2005 May;75(3):229-37

Department of Materials Chemistry and Engineering, Innovative Environmental Technology center, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, South Korea.

In order to effectively integrate environmental attributes into the product design and development processes, it is crucial to identify the significant environmental aspects related to a product system within a relatively short period of time. In this study, the usefulness of life cycle assessment (LCA) and a matrix method as tools for identifying the key environmental issues of a product system were examined. For this, a simplified LCA (SLCA) method that can be applied to Electrical and Electronic Equipment (EEE) was developed to efficiently identify their significant environmental aspects for eco-design, since a full scale LCA study is usually very detailed, expensive and time-consuming. The environmentally responsible product assessment (ERPA) method, which is one of the matrix methods, was also analyzed. Then, the usefulness of each method in eco-design processes was evaluated and compared using the case studies of the cellular phone and vacuum cleaner systems. It was found that the SLCA and the ERPA methods provided different information but they complemented each other to some extent. The SLCA method generated more information on the inherent environmental characteristics of a product system so that it might be useful for new design/eco-innovation when developing a completely new product or method where environmental considerations play a major role from the beginning. On the other hand, the ERPA method gave more information on the potential for improving a product so that it could be effectively used in eco-redesign which intends to alleviate environmental impacts of an existing product or process.
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http://dx.doi.org/10.1016/j.jenvman.2004.11.014DOI Listing
May 2005
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