Identification of Biomarkers for Breast Cancer Using Databases

Eunhye Lee,,Aree Moon 대한암예방학회 2016 Journal of cancer prevention Vol.21 No.4

Breast cancer is one of the major causes of cancer death in women. Many studies have sought to identify specific molecules involved in breast cancer and understand their characteristics. Many biomarkers which are easily measurable, dependable, and inexpensive, with a high sensitivity and specificity have been identified. The rapidly increasing technology development and availability of epigenetic informations play critical roles in cancer. The accumulated data have been collected, stored, and analyzed in various types of databases. It is important to acknowledge useful and available data and retrieve them from databases. Nowadays, many researches utilize the databases, including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Surveillance, Epidemiology and End Results (SEER), and Embase, to find useful informations on biomarkers for breast cancer. This review summarizes the current databases which have been utilized for identification of biomarkers for breast cancer. The information provided by this review would be beneficial to seeking appropriate strategies for diagnosis and treatment of breast cancer.

Tumor-associated macrophages secrete CCL2 and induce the invasive phenotype of human breast epithelial cells through upregulation of ERO1-α and MMP-9

Lee, Seungeun,Lee, Eunhye,Ko, EunYi,Ham, Mina,Lee, Hye Min,Kim, Eun-Sook,Koh, Minsoo,Lim, Hyun Kyung,Jung, Joohee,Park, So Yeon,Moon, Aree Elsevier 2018 Cancer letters Vol.437 No.-

<P><B>Abstract</B></P> <P>Tumor-associated macrophages (TAMs) are major components of tumor microenvironment that promote invasion and metastasis of cancer cells. In this study, we investigated the effect of TAMs on phenotypic conversion of non-neoplastic MCF10A human breast epithelial cells using an indirect co-culture system. Co-culture with TAMs induced epithelial-to-mesenchymal transition, invasive phenotype, and MMP-9 upregulation in MCF10A cells. Comparative proteomic analysis revealed that endoplasmic reticulum oxidoreductase (ERO)1-α was increased in MCF10A cells co-cultured with TAMs compared to that in mono-cultured cells. ERO1-α was crucial for TAMs-induced invasive phenotype and MMP-9 upregulation involving transcription factors c-fos and c-Jun. Cytokine array analysis showed that levels of interleukin (IL)-6, C-X-C motif ligand (CXCL)1, C-C motif ligand (CCL)2, growth-regulated protein (GRO), IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were increased in conditioned media of co-cultured cells. Among these cytokines increased in conditioned media of co-cultured cells, CCL2 was secreted from TAMs, leading to induction of ERO1-α, MMP-9 upregulation, and invasiveness in MCF10A cells. Our findings elucidated a molecular mechanism underlying the aggressive phenotypic change of non-neoplastic breast cells by co-culture with TAMs, providing useful information for prevention or treatment of recurrent breast cancer.</P> <P><B>Highlights</B></P> <P> <UL> <LI> TAMs induced invasion in MCF10A cells non-neoplastic human breast epithelial cells. </LI> <LI> ERO1-α was increased in MCF10A cells co-cultured with TAM. </LI> <LI> ERO1-α was crucial for the TAMs-induced invasive phenotype and MMP-9 upregulation. </LI> <LI> CCL2 was secreted from TAMs co-cultured with MCF10A cells. </LI> <LI> CCL2 induced ERO1-α, resulting MMP-9 upregulation and invasiveness in MCF10A cells. </LI> </UL> </P>

IL-32-induced Inflammatory Cytokines Are Selectively Suppressed by α1-antitrypsin in Mouse Bone Marrow Cells

Lee, Siyoung,Choi, Dong-Ki,Kwak, Areum,Kim, Sinae,Nguyen, Tam Thanh,Gil, Gaae,Kim, Eunhye,Yoo, Kwang Ha,Kim, In Ae,Lee, Youngmin,Jhun, Hyunjhung,Chan, Edward D.,Bai, Xiyuan,Kim, Hyunwoo,Kim, Yong-Sung 한국조명·전기설비학회 2017 한국조명·전기설비학회 학술대회논문집 Vol. No.

<P>The induction of interleukin (IL)-32 in bone marrow (BM) inflammation is crucial in graft versus host disease (GvHD) that is a common side effect of allogeneic BM transplantation. Clinical trials on α-1 antitrypsin (AAT) in patients with GvHD are based on the preliminary human and mouse studies on AAT reducing the severity of GvHD. Proteinase 3 (PR3) is an IL-32-binding protein that was isolated from human urine. IL-32 primarily induces inflammatory cytokines in myeloid cells, probably due to PR3 expression on the membrane of the myeloid lineage cells. The inhibitory activity of AAT on serine proteinases may explain the anti-inflammatory effect of AAT on GvHD. However, the anti-inflammatory activity of AAT on BM cells remains unclear. Mouse BM cells were treated with IL-32γ and different inflammatory stimuli to investigate the anti-inflammatory activity of AAT. Recombinant AAT-Fc fusion protein inhibited IL-32γ-induced IL-6 expression in BM cells, but failed to suppress that induced by other stimuli. In addition, the binding of IL-32γ to PR3 was abrogated by AAT-Fc. The data suggest that the specific anti-inflammatory effect of AAT in mouse BM cells is due to the blocking of IL-32 binding to membrane PR3.</P>

Simultaneously enhanced device efficiency, stabilized chromaticity of organic light emitting diodes with lambertian emission characteristic by random convex lenses

Lee, Keunsoo,Lee, Jonghee,Kim, Eunhye,Lee, Jeong-Ik,Cho, Doo-Hee,Lim, Jong Tae,Joo, Chul Woong,Kim, Joo Yeon,Yoo, Seunghyup,Ju, Byeong-Kwon,Moon, Jaehyun IOP 2016 Nanotechnology Vol.27 No.7

<P>An optical functional film applicable to various lighting devices is demonstrated in this study. The phase separation of two immiscible polymers in a common solvent was used to fabricate the film. In this paper, a self-organized lens-like structure is realized in this manner with optical OLED functional film. For an OLED, there are a few optical drawbacks, including light confinement or viewing angle distortion. By applying the optical film to an OLED, the angular spectra distortion resulting from the designed organic stack which produced the highest efficiency was successfully stabilized, simultaneously enhancing the efficiency of the OLED. We prove the effect of the film on the efficiency of OLEDs through an optical simulation. With the capability to overcome the main drawbacks of OLEDs, we contend that the proposed film can be applied to various lighting devices.</P>

Pyrazole C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists

Lee, Sunho,Kim, Changhoon,Ann, Jihyae,Thorat, Shivaji A.,Kim, Eunhye,Park, Jongmi,Choi, Sun,Blumberg, Peter M.,Frank-Foltyn, Robert,Bahrenberg, Gregor,Stockhausen, Hannelore,Christoph, Thomas,Lee, Jee Pergamon Press 2017 Bioorganic & medicinal chemistry letters Vol.27 No.18

<P><B>Abstract</B></P> <P>A series of 1-substituted 3-(<I>t</I>-butyl/trifluoromethyl)pyrazole C-region analogues of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides were investigated for <I>h</I>TRPV1 antagonism. The structure activity relationship indicated that the 3-chlorophenyl group at the 1-position of pyrazole was the optimized hydrophobic group for antagonistic potency and the activity was stereospecific to the <I>S</I>-configuration, providing exceptionally potent antagonists <B>13<I>S</I> </B> and <B>16<I>S</I> </B> with <I>K<SUB>i(CAP)</SUB> </I> =0.1nM. Particularly significant, <B>13<I>S</I> </B> exhibited antagonism selective for capsaicin and NADA and not for low pH or elevated temperature. Both compounds also proved to be very potent antagonists for <I>r</I>TRPV1, blocking <I>in vivo</I> the hypothermic action of capsaicin, consistent with their <I>in vitro</I> mechanism. The docking study of compounds <B>13<I>S</I> </B> and <B>16<I>S</I> </B> in our <I>h</I>TRPV1 homology model indicated that the binding modes differed somewhat, with that of <B>13<I>S</I> </B> more closely resembling that of <B>GRT12360</B>.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Rapid and Simultaneous Analysis of 360 Pesticides in Brown Rice, Spinach, Orange, and Potato Using Microbore GC-MS/MS

Lee, Jonghwa,Kim, Leesun,Shin, Yongho,Lee, Junghak,Lee, Jiho,Kim, Eunhye,Moon, Joon-Kwan,Kim, Jeong-Han American Chemical Society 2017 Journal of agricultural and food chemistry Vol.65 No.16

<P>A multiresidue method for the simultaneous and rapid analysis of 360 pesticides in representative agricultural produce (brown rice, orange, spinach, and potato) was developed using a modified QuEChERS procedure combined with gas chromatography tandem mass spectrometry (GC-MS/MS). Selected reaction monitoring transition parameters (e.g., collision energy, precursor and product ions) in MS/MS were optimized to achieve the best selectivity and sensitivity for a wide range of GC-amenable pesticides. A short (20 m) microbore (0.18 mm i.d.) column resulted in better signal-to-noise ratio with reduced analysis time than a conventional narrowbore column (30 m X 0.25 mm i.d.). The priming injection dramatically increased peak areas by masking effect on a new GC liner. The limit of quantitation was <0.01 mg/kg, and the correlation coefficients (r(2)) of matrix-matched standards were >0.99 within the range of 0.0025-0.1 mg/kg. Acetonitrile with 0.1% formic acid without additional buffer salts was used for pesticide extraction, whereas only primary secondary amine (PSA) was used for dispersive solid phase extraction (dSPE) cleanup, to achieve good recoveries for most of the target analytes. The recoveries ranged from 70 to 120% with relative standard deviations of <= 20% at 0.01 and 0.05 mg/kg spiking levels (n = 6) in all samples, indicating acceptable accuracy and precision of the method. Seventeen real samples from local markets were analyzed by using the optimized method, and 14 pesticides in 11 incurred samples were found at below the maximum residue limits.</P>

High Performance Liquid Chromatographic Method for Determination of Metazosulfuron Residue in Representative Crops

Lee, Hyeri,Kim, Eunhye,Lee, Young Deuk,Kim, Jeong-Han The Korean Society of Environmental Agriculture 2013 한국환경농학회지 Vol.32 No.2

BACKGROUND: This study was performed to develop a single residue analytical method for new herbicide metazosulfuron in crops. METHODS AND RESULTS: Brown rice, apple, mandarin, Kimchi cabbage and soybean were selected as representative crops, and clean-up system, partition solvent and extraction solvent were optimized. Instrumental limit of quantitation (ILOQ), linearity of calibration curve and method limit of quantitation (MLOQ) were determined based on the chromatography and whole procedures. For recovery tests, brown rice, apple, mandarin, Kimchi cabbage and soybean samples were macerated and fortified with metazosulfuron standard solution at three levels (MLOQ, 10 MLOQ and 100 MLOQ). And then those were extracted with acetonitrile, concentrated, and partitioned with ethyl acetate. Then the extracts were concentrated again and cleaned-up through $NH_2$ (aminopropyl) SPE cartridge with acetone : dichloromethane (1% acetic acid) (20 : 80, v/v) before concentration and analysis with HPLC. CONCLUSION(S): ILOQ of metazosulfuron was 2 ng (S/N${\geq}$10) and good linearity was achieved between 0.05 and 12.5 mg/Kg of metazosulfuron standard solutions, with coefficients of determination of 0.9999. MLOQ was 0.02 mg/Kg. Good recoveries from 74.1 to 116.9% with coefficients of variation (C.V.) of less than 10% were obtained, regardless of sample type, which satisfies the criteria of Korea Food and Drug Administration (KFDA). Those results were reconfirmed with LC-MS (SIM). The method established in this study is simple, economic and efficient to be applied to most of crops as an official and general method for residue analysis of metazosulfuron.

Identification of the Antidepressant Vilazodone as an Inhibitor of Inositol Polyphosphate Multikinase by Structure-Based Drug Repositioning

Lee, Boah,Park, Seung Ju,Lee, Seulgi,Park, Seung Eun,Lee, Eunhye,Song, Ji-Joon,Byun, Youngjoo,Kim, Seyun Korean Society for Molecular and Cellular Biology 2020 Molecules and cells Vol.43 No.3

Inositol polyphosphate multikinase (IPMK) is required for the biosynthesis of inositol phosphates (IPs) through the phosphorylation of multiple IP metabolites such as IP3 and IP4. The biological significance of IPMK's catalytic actions to regulate cellular signaling events such as growth and metabolism has been studied extensively. However, pharmacological reagents that inhibit IPMK have not yet been identified. We employed a structure-based virtual screening of publicly available U.S. Food and Drug Administration-approved drugs and chemicals that identified the antidepressant, vilazodone, as an IPMK inhibitor. Docking simulations and pharmacophore analyses showed that vilazodone has a higher affinity for the ATP-binding catalytic region of IPMK than ATP and we validated that vilazodone inhibits IPMK's IP kinase activities in vitro. The incubation of vilazodone with NIH3T3-L1 fibroblasts reduced cellular levels of IP5 and other highly phosphorylated IPs without influencing IP4 levels. We further found decreased Akt phosphorylation in vilazodone-treated HCT116 cancer cells. These data clearly indicate selective cellular actions of vilazodone against IPMK-dependent catalytic steps in IP metabolism and Akt activation. Collectively, our data demonstrate vilazodone as a method to inhibit cellular IPMK, providing a valuable pharmacological agent to study and target the biological and pathological processes governed by IPMK.

CNBP acts as a key transcriptional regulator of sustained expression of interleukin-6

Lee, Eunhye,Lee, Taeyun A.,Kim, Ji Hyun,Park, Areum,Ra, Eun A.,Kang, Sujin,Choi, Hyun jin,Choi, Junhee L.,Huh, Hyunbin D.,Lee, Ji Eun,Lee, Sungwook,Park, Boyoun Oxford University Press 2017 Nucleic acids research Vol.45 No.6

<P><B>Abstract</B></P><P>The transcription of inflammatory genes is an essential step in host defense activation. Here, we show that cellular nucleic acid-binding protein (CNBP) acts as a transcription regulator that is required for activating the innate immune response. We identified specific CNBP-binding motifs present in the promoter region of sustained inflammatory cytokines, thus, directly inducing the expression of target genes. In particular, lipopolysaccharide (LPS) induced <I>cnbp</I> expression through an NF-κB-dependent manner and a positive autoregulatory mechanism, which enables prolonged <I>il-6</I> gene expression. This event depends strictly on LPS-induced CNBP nuclear translocation through phosphorylation-mediated dimerization. Consequently, <I>cnbp</I>-depleted zebrafish are highly susceptible to <I>Shigella flexneri</I> infection <I>in vivo</I>. Collectively, these observations identify CNBP as a key transcriptional regulator required for activating and maintaining the immune response.</P>

Antitumor Effect of Low Molecular Weight Chitosan (LMWC) - Paclitaxel

Eunhye Lee,Jinju Lee,Sangyong Jon 한국고분자학회 2006 한국고분자학회 학술대회 연구논문 초록집 Vol.2006 No.10