Radotinib induces high cytotoxicity in c-KIT positive acute myeloid leukemia cells

Heo, S.K.,Noh, E.K.,Kim, J.Y.,Jo, J.C.,Choi, Y.,Koh, S.,Baek, J.H.,Min, Y.J.,Kim, H. North-Holland 2017 European journal of pharmacology Vol.804 No.-

<P>Previously, we reported that radotinib, a BCR-ABL1 tyrosine kinase inhibitor, induced cytotoxicity in acute myeloid leukemia (AML) cells. However, the effects of radotinib in the subpopulation of c-KIT-positive AML cells were unclear. We observed that low-concentration radotinib had more potent cytotoxicity in c-KIT-positive cells than c-KIT-negative cells from AML patients. To address this issue, cell lines with high c-KIT expression, HEL92.1.7, and moderate c-KIT expression, H209, were selected. HEL92.1.7 cells were grouped into intermediate and high c-HIT expression populations. The cytotoxicity of radotinib against the HEL92.1.7 cell population with intermediate c-HIT expression was not different from that of the population with high c-KIT expression. When H209 cells were grouped into c-KIT expression-negative and c-HIT expression-positive populations, radotinib induced cytotoxicity in the c-KIT-positive population, but not the c-KIT-negative population. Thus, radotinib induces cytotoxicity in c-KIT-positive cells, regardless of the c-KIT expression intensity. Therefore, radotinib induces significant cytotoxicity in c-KIT-positive AML cells, suggesting that radotinib is a potential target agent for the treatment of c-KIT-positive malignancies including AML.</P>

Korean Byungkyul - Citrus platymamma Hort.et Tanaka flavonoids induces cell cycle arrest and apoptosis, regulating MMP protein expression in Hep3B hepatocellular carcinoma cells

Hong, G. E.,Lee, H. J.,Kim, J. A.,Yumnam, S.,Raha, S.,Saralamma, V. Venkatarame Gowda,Heo, J. D.,Lee, S. J.,Kim, E. H.,Won, C. K. Lychnia 2017 International journal of oncology Vol.50 No.2

<P>Citrus platymamma Hort.et Tanaka is an indigenous fruit of Jeju island in Korea. In this study the bioactivity of C. platymamma flavonoids were evaluated on human hepatoma Hep3B cell lines. Eleven flavonoids were identified from the peels of C. platymamma Hort.et Tanaka through high-performance liquid chromatography-Tandem mass spectrometry and the anticancer effect of these C. platymamma flavonoids on human hepatoma Hep3B were studied. Chromatin condensation was observed in Hep3B cells treated with C. platymamma flavonoids. DNA fragmentation was confirmed through agarose gel electrophoresis and TUNEL assay. An increase in the total apoptotic cells and G2/M cell cycle arrest with decreased protein expression of CDC25C, CDK1, cycl in B1 and p21 were observed in Hep3B cells treated with flavonoids of C. platymamma. Further, protein expression of Bcl-XL, Bax, caspase-3 and -9 were also modulated by C. platymamma flavonoids treatment indicating that cell death is through intrinsic apoptotic pathway. Moreover, C. platymamma flavonoids also regulated the phosphorylation of MAPKs, PI3K, and Akt in Hep3B cells. Relevant to inhibiting metastasis, C. platymamma treatment reduced wound closure of Hep3B cells and the protein expression of matrix metalloproteinase-2 and -9 were reduced in C. platymamma treated cells. The results show that C. platymamma flavonoids induce cell cycle arrest and apoptosis following activation of MAPKs and suppression of PI3K/Akt pathway which eventually inhibits cell migration in Hep3B cells. The finding provides evidence on biochemical activities of C. platymamma Hort.et Tanaka, which would be an essential agent for hepatocellular carcinoma (HCC) treatment.</P>

Covariant representations on Krein C^*-modules associated to pairs of two maps

Heo, J.,Ji, U.C.,Kim, Y.Y. Academic Press 2013 Journal of mathematical analysis and applications Vol.398 No.1

In this paper we construct a KSGNS type covariant representation on a Krein C<SUP>*</SUP>-module for a covariant α-completely positive map, and the result is applied to construct a KSGNS type covariant representation associated with a pair of two maps (ρ,Φ) where ρ is a covariant α-completely positive map on a C<SUP>*</SUP>-algebra and Φ is a covariant ρ-map on a Krein C<SUP>*</SUP>-module. The KSGNS type covariant representation for a pair (ρ,Φ) is applied to give a new covariant J-representation of a crossed product of a C<SUP>*</SUP>-algebra and a new covariant map of a crossed product of a Hilbert C<SUP>*</SUP>-module by a discrete group.

Quantum stochastic processes for maps on Hilbert C^*-modules (16 pages)

Heo, J.,Ji, U.C. AMERICAN INSTITUTE OF PHYSICS 2011 Journal of mathematical physics Vol.52 No.5

C++ 프로그램을 위한 복잡도 척도

유철중,오재철,허영남 순천대학교 기초과학연구소 1990 基礎科學硏究誌 Vol.1 No.-

객체중심언어에 있어서 자료추상화(data abstraction)에 의한 켑슐화(encapsulation)와 상속성(inheritance)이 가장 중요한 개념으로 인식되고 있다. 특히, 프로그램이 객체(object)간의 메시지 전달(message passing)에 의해서 수행되고 상속에 의해 재사용되는 특성이 있으므로, 이러한 객체중심프로그램의 복잡도(complexity)를 보다 잘 나타내기 위해서는 클래스(class)에 기반을 둔 척도가 요구된다. 따라서 본 논문에서는 객체중심 언어인 C++에 적합한 척도를 얻기 위해 고려하여야 할 특성들을 제시하였으며 이를 바탕으로 클래스에 기반을 둔 새로운 복잡도 척도를 제안하고 그 타당성을 보였다. Object oriented languages have major properties of encapsulation and inheritance by data abstraction. In this paper, we discuss major properties of several complexity metrics, and also object oriented programs. We propose metrics complexity measurement of object oriented programs (especially, C++), and evaluate the validity of the proposed measures. The metric is a class-based measures.

On KSGNS representations on Krein C^*-modules (13 pages)

Heo, J.,Hong, J.P.,Ji, U.C. AMERICAN INSTITUTE OF PHYSICS 2010 Journal of mathematical physics Vol.51 No.5

Comparison of inflammatory markers between diabetic and nondiabetic ST segment elevation myocardial infarction

Heo, J.M.,Park, J.H.,Kim, J.H.,You, S.H.,Kim, J.S.,Ahn, C.M.,Hong, S.J.,Shin, K.H.,Lim, D.S. Japanese College of Cardiology 2012 Journal of cardiology Vol.60 No.3

Background: Inflammation plays a significant role in acute coronary syndrome (ACS) and type 2 diabetes mellitus (DM). There may be similar inflammatory changes in non-DM patients with ST elevation myocardial infarction (STEMI) and DM patients with stable angina (SA), and DM patients with STEMI may have more severe changes than the former two groups. The objectives of this study were to investigate whether the level of inflammation was similar in patients with non-DM STEMI and DM SA, and to evaluate whether the changes in the level of inflammation were more severe in patients with DM STEMI compared to the other two groups. Methods and results: A variety of inflammatory markers including: highly sensitive C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), IL-18, vascular cell adhesion molecule-1 (VCAM-1), and matrix metallopeptidase-9 (MMP-9) as well as insulin resistance were compared among the three groups: DM STEMI (90 patients), DM SA (91 patients), and non-DM STEMI (76 patients). Inflammatory marker levels were not significantly different between the DM SA and non-DM STEMI groups. However, hsCRP and IL-6 were increased in the DM STEMI compared to the DM SA patients (p=0.005 and p=0.004, respectively). In addition, hsCRP, ESR, and IL-18 were increased in the DM STEMI compared to the non-DM STEMI patients (p=0.017, p=0.020, and p=0.033, respectively). Furthermore, the fasting insulin and the homeostasis model assessment were significantly increased in the DM STEMI compared to the DM SA patients (p=0.04 and p=0.004, respectively). Conclusions: DM SA and non-DM STEMI may have similar inflammatory changes. DM STEMI may be a more severe inflammatory condition compared to patients with DM SA or non-DM STEMI.

Rosmarinic acid potentiates ATRA-induced macrophage differentiation in acute promyelocytic leukemia NB4 cells

Heo, S.K.,Noh, E.K.,Yoon, D.J.,Jo, J.C.,Koh, S.,Baek, J.H.,Park, J.H.,Min, Y.J.,Kim, H. North-Holland ; Elsevier Science Ltd 2015 european journal of pharmacology Vol.747 No.-

Rosmarinic acid (RA, an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid) has a number of biological activities, but little is known about anti-leukemic activities of RA combined with all-trans retinoic acid (ATRA) against acute promyelocytic leukemia (APL) cells. We examined the differentiation marker, CD11b, in bone marrow cells (BMC) of an APL patient, in NB4 cells (APL cell line), and in normal BMC and peripheral blood mononuclear cells (PBMC) of healthy subjects by flow cytometric analysis. ATRA/RA induced expression of CD11b in the BMC of the APL patient and in NB4 cells, but not in normal BMC or PBMC. Therefore, we realized that RA potentiated ATRA-induced macrophage differentiation in APL cells. Further characterization of the induced macrophages showed that they exhibited morphological changes and were able to phagocytose and generate reactive oxygen species. Th also had typical expression of C-C chemokine receptor type 1 (CCR1), CCR2, and intercellular adhesion molecule-1 (ICAM-1). Moreover, the expression of CD11b<SUP>+</SUP> and CD14<SUP>+</SUP> cells depended on ERK-NF-κB axis activation. Together, these results indicate that RA potentiates ATRA-induced macrophage differentiation in APL cells. Thus, RA may play an important role as an appurtenant differentiation agent for functional macrophage differentiation in APL. Additionally, the differentiated macrophages might have a normal life span and, they could die. These data indicate that co-treatment with RA and ATRA has potential as an anti-leukemic therapy in APL.

Crystal structure of Streptomyces coelicolor RraAS2, an unusual member of the RNase E inhibitor RraA protein family

Park, N.,Heo, J.,Song, S.,Jo, I.,Lee, K.,Ha, N. C. MICROBIOLOGICAL SOCIETY OF KOREA 2017 JOURNAL OF MICROBIOLOGY -SEOUL- Vol. No.

<P>Bacterial ribonuclease E (RNase E) plays a crucial role in the processing and decay of RNAs. A small protein named RraA negatively regulates the activity of RNase E via protein-protein interaction in various bacteria. Recently, RraAS1 and RraAS2, which are functional homologs of RraA from Escherichia coli, were identified in the Gram-positive species Streptomyces coelicolor. RraAS1 and RraAS2 inhibit RNase ES ribonuclease activity in S. coelicolor. RraAS1 and RraAS2 have a C-terminal extension region unlike typical bacterial RraA proteins. In this study, we present the crystal structure of RraAS2, exhibiting a hexamer arranged in a dimer of trimers, consistent with size exclusion chromatographic results. Importantly, the C-terminal extension region formed a long alpha-helix at the junction of the neighboring subunit, which is similar to the trimeric RraA orthologs from Saccharomyces cerevisiae. Truncation of the C-terminal extension region resulted in loss of RNase ES inhibition, demonstrating its crucial role. Our findings present the first bacterial RraA that has a hexameric assembly with a C-terminal extension alpha-helical region, which plays an essential role in the regulation of RNase ES activity in S. coelicolor.</P>

Influence of growth temperature and post-annealing on an n-ZnO/p-GaN heterojunction diode

Sharma, S.K.,Heo, S.,Lee, B.,Lee, H.,Kim, C.,Kim, D.Y. Elsevier 2014 CURRENT APPLIED PHYSICS Vol.14 No.12

We report on an n-ZnO/p-GaN heterojunction diode fabricated from zinc oxide (ZnO) films at various growth temperatures (450, 500, 550, and 600 <SUP>o</SUP>C) by RF sputtering. The films were subsequently annealed at 700 <SUP>o</SUP>C in N<SUB>2</SUB> ambient. To investigate the influence of the growth temperature of n-ZnO films, the microstructural, optical, and electrical properties were measured using scanning electron microscopy (SEM), X-ray diffraction (XRD), photoluminescence (PL), and Hall measurements. The XRD pattern showed the preferred orientation along the c-axis (002) regardless of growth temperature. The PL spectra showed a dominant sharp near-band-edge (NBE) emission. Current-voltage (I-V) curves showed excellent rectification behavior. The turn-on voltage of the diode was observed to be 3.2 V for the films produced at 500 <SUP>o</SUP>C. The ideality factor of ZnO film was observed to be 1.37, which showed the best performance of the diode.