Trends in incidence and survival of esophageal cancer in Korea: Analysis of the Korea Central Cancer Registry Database

Shin, Aesun,Won, Young&#x2010,Joo,Jung, Hye&#x2010,Kyung,Kong, Hyun&#x2010,Joo,Jung, Kyu&#x2010,Won,Oh, Chang&#x2010,Mo,Choe, Sunho,Lee, Jihyun John Wiley and Sons Inc. 2018 Journal of gastroenterology and hepatology Vol.33 No.12

<P><B>Abstract</B></P><P><B>Background and Aim</B></P><P>The diagnostic and therapeutic modalities of esophageal cancer have recently improved in Asia, and its prognosis is expected to change. This study provides a population‐based report on the epidemiology of esophageal cancer in Korea.</P><P><B>Methods</B></P><P>Cancer incidence data from 1999 to 2013 were obtained from the Korea Central Cancer Registry, covering the entire population. Age‐standardized incidence rates and annual percent changes were calculated according to subsites and histological types. Five‐year relative survival rates were estimated for cases diagnosed between 1993 and 2013. Relative excess rates were compared between patients diagnosed from 2009 to 2013 and 2006 to 2008.</P><P><B>Results</B></P><P>The age‐standardized incidence rates decreased from 8.8 per 100 000 populations in 1999 to 5.9 in 2013 with an annual percent change of −2.6% in men and −2.2% in women. The most common histological type was squamous cell carcinoma, accounting for 90.2% of all esophageal cancers in 2013, followed by adenocarcinomas (3.1%), and their incidences decreased. The proportion of localized and regional cancer tended to increase compared with that of distant cancer. Five‐year relative survival of squamous cell carcinoma improved from 12.1% (1993–1995) to 34.6% (2009–2013). Relative excess rate was 0.72 (95% confidence interval 0.65–0.80) in localized stage and 0.88 (95% confidence interval, 0.82–0.95) in regional stage comparing patients diagnosed from 2009 to 2013 and 2006 to 2008.</P><P><B>Conclusions</B></P><P>The incidence of esophageal cancer has decreased in Korea for the past 15 years, and 5‐year survival rates have improved significantly. These increases may be attributable to more effective detection of early‐stage disease.</P>

Prognostic significance of c‐Met expression in glioblastomas

Kong, Doo&#x2010,Sik,Song, Sang&#x2010,Yong,Kim, Duk&#x2010,Hwan,Joo, Kyeung Min,Yoo, Jin&#x2010,San,Koh, Jong Sung,Dong, Seung Myung,Suh, Yeon&#x2010,Lim,Lee, Jung&#x2010,Il,Park, Kwan,Kim, Jong Hyun Wiley Subscription Services, Inc., A Wiley Company 2009 Cancer Vol.115 No.1

<P><B>Abstract</B></P><P><B>BACKGROUD:</B></P><P>The authors investigated whether expression of c‐Met protein in glioblastomas is associated with overall survival and biologic features representing tumor invasiveness in patients with glioblastomas.</P><P><B>METHODS:</B></P><P>Paraffin‐embedded specimens of glioblastomas from 62 patients treated in a single institution were assessed by immunohistochemical (IHC) analysis of c‐Met expression. On the basis of the clinical data for these patients, the association between c‐Met expression and clinicobiologic features representing tumor invasiveness was analyzed.</P><P><B>RESULTS:</B></P><P>c‐Met overexpression was detected in 29.0% (18 of 62) of glioblastomas. In patients with c‐Met overexpression, the median survival was 11.7 months (95% confidence interval [95% CI], 9.9 months‐13.5 months), compared with a median survival of 14.3 months (95% CI, 7.6 months‐21.0 months) for patients whose tumors had no or little expression of c‐Met (<I>P</I> = .031). On the radiographic analysis, 9 of 18 patients (50%) with tumors overexpressing c‐Met demonstrated invasive and multifocal lesions on the initial magnetic resonance images, whereas only 9 of 44 patients (20.5%) with tumors that expressed no or little c‐Met demonstrated these features (<I>P</I> = .030). Using immunohistochemistry, we also found a significant association between c‐Met expression and matrix metalloproteinase‐2,‐9 (<I>P</I> = .020 and <I>P</I> = .013). Furthermore, Myc overexpression was found to be closely correlated with c‐Met overexpression on IHC analysis (<I>P</I> = .004).</P><P><B>CONCLUSIONS:</B></P><P>The authors suggest that c‐Met overexpression is associated with shorter survival time and poor treatment response in glioblastomas, the mechanism for which is elevated tumor invasiveness on the molecular and clinical phenotypes. This implies that more effective therapeutic strategies targeting c‐Met receptors may have important clinical implication. Cancer 2009. © 2008 American Cancer Society.</P>

UTX inhibits EMT ‐induced breast CSC properties by epigenetic repression of EMT genes in cooperation with LSD 1 and HDAC 1

Choi, Hee&#x2010,Joo,Park, Ji&#x2010,Hye,Park, Mikyung,Won, Hee&#x2010,Young,Joo, Hyeong&#x2010,seok,Lee, Chang Hoon,Lee, Jeong&#x2010,Yeon,Kong, Gu EMBO 2015 EMBO reports Vol.16 No.10

<P>The histone H3K27 demethylase, UTX, is a known component of the H3K4 methyltransferase MLL complex, but its functional association with H3K4 methylation in human cancers remains largely unknown. Here we demonstrate that UTX loss induces epithelial-mesenchymal transition (EMT)-mediated breast cancer stem cell (CSC) properties by increasing the expression of the SNAIL, ZEB1 and ZEB2 EMT transcription factors (EMT-TFs) and of the transcriptional repressor CDH1. UTX facilitates the epigenetic silencing of EMT-TFs by inducing competition between MLL4 and the H3K4 demethylase LSD1. EMT-TF promoters are occupied by c-Myc and MLL4, and UTX recognizes these proteins, interrupting their transcriptional activation function. UTX decreases H3K4me2 and H3 acetylation at these promoters by forming a transcriptional repressive complex with LSD1, HDAC1 and DNMT1. Taken together, our findings indicate that UTX is a prominent tumour suppressor that functions as a negative regulator of EMT-induced CSC-like properties by epigenetically repressing EMT-TFs.</P>

Importance of Glu53 in the C‐terminal region of brazzein, a sweet‐tasting protein

Lim, Jin&#x2010,Kyung,Jang, Jin&#x2010,Chul,Kong, Ji&#x2010,Na,Kim, Myung&#x2010,Chul,Kong, Kwang&#x2010,Hoon John Wiley Sons, Ltd 2016 Journal of the Science of Food and Agriculture Vol.96 No.9

<P>BACKGROUND: The sweetness of brazzein, one of the known sweet proteins, is dependent on charges and/or structures of its specific amino acid side chains. As the residues in the C-terminus of brazzein are known to play a critical role in sweetness, the currently unknown function of Glu53 requires further study. RESULTS: To identify important residues responsible for the sweetness of the protein brazzein, four mutants of theGlu53 residue in the C-terminal region of des-pE1M-brazzein, which lacks the N-terminal pyroglutamate, were constructed using site-directed mutagenesis. Mutations of Glu53 substitution to Ala or Asp significantly decreased the sweetness. On the other hand, a Lys mutation resulted in a molecule with sweetness similar to that of des-pE1M-brazzein. Mutation of Glu53 to Arg resulted in a molecule significantly sweeter than des-pE1M-brazzein, which agrees with previous findings showing that mutation with positively charged residues results in a sweeter protein. CONCLUSION: Our results suggest that the residue at position 53 is crucial for the sweetness of brazzein, which may be interacting with the sweet-taste receptor. (C) 2015 Society of Chemical Industry</P>

Bioactive quinone derivatives from the marine brown alga <i>Sargassum thunbergii</i> induce anti‐adipogenic and pro‐osteoblastogenic activities

Kim, Jung&#x2010,Ae,Karadeniz, Fatih,Ahn, Byul&#x2010,Nim,Kwon, Myeong Sook,Mun, Ok&#x2010,Ju,Bae, Min Joo,Seo, Youngwan,Kim, Mihyang,Lee, Sang&#x2010,Hyeon,Kim, Yuck Yong,Mi&#x2010,Soon, Jang,Kong, C John Wiley Sons, Ltd 2016 Journal of the Science of Food and Agriculture Vol.96 No.3

<P>BACKGROUND: Health problems related to the lack of bone formation are a major problem for ageing populations in the modern world. As a part of the ongoing trend to develop natural substances that attenuate bone loss in osteoporosis, the effects of the edible brown alga Sargassum thunbergii and its active contents on adipogenic differentiation in 3T3-L1 fibroblasts and osteoblast differentiation inMC3T3-E1 pre-osteoblasts were evaluated. RESULTS: Treatment with S. thunbergii significantly reduced lipid accumulation and expression of adipogenic differentiation markers such as peroxisome proliferator-activated receptor gamma , CCAAT/enhancer- binding protein.. and sterol regulatory element binding protein 1c. In addition, S. thunbergii successfully enhanced osteoblast differentiation as indicated by increased alkaline phosphatase activity along raised levels of osteoblastogenesis indicators, namely bone morphogenetic protein-2, osteocalcin and collagen type I. Two compounds, sargaquinoic and sargahydroquinoic acid, were isolated fromactive extract and shown to be active by means of osteogenesis inducement. CONCLUSION: S. thunbergii could be a source for functional food ingredients for improved treatment of osteoporosis and obesity. (C) 2015 Society of Chemical Industry</P>

Loss of Mel‐18 enhances breast cancer stem cell activity and tumorigenicity through activating Notch signaling mediated by the Wnt/TCF pathway

Won, Hee&#x2010,Young,Lee, Jeong&#x2010,Yeon,Shin, Dong&#x2010,Hui,Park, Ji&#x2010,Hye,Nam, Jeong&#x2010,Seok,Kim, Hyoung&#x2010,Chin,Kong, Gu Federation of American Society for Experimental Bi 2012 The FASEB Journal Vol.26 No.12

<P>Mel-18 has been proposed as a negative regulator of Bmi-1, a cancer stem cell (CSC) marker, but it is still unclear whether Mel-18 is involved in CSC regulation. Here, we examined the effect of Mel-18 on the stemness of human breast CSCs. In Mel-18 small hairpin RNA (shRNA)-transduced MCF-7 cells, side population (SP) cells and breast CSC surface marker (CD44(+)/CD24(-)/ESA(+))-expressing cells, which imply a CSC population, were enriched. Moreover, the self-renewal of CSCs was enhanced by Mel-18 knockdown, as measured by the ability for tumorsphere formation in vitro and tumor-initiating capacity in vivo. Similarly, Mel-18 overexpression inhibited the number and self-renewal activity of breast CSCs in SK-BR-3 cells. Furthermore, our data showed that Mel-18 blockade up-regulated the expression of the Wnt/TCF target Jagged-1, a Notch ligand, and consequently activated the Notch pathway. Pharmacologic inhibition of the Notch and Wnt pathways abrogated Mel-18 knockdown-mediated tumorsphere formation ability. Taken together, our findings suggest that Mel-18 is a novel negative regulator of breast CSCs that inhibits the stem cell population and in vitro and in vivo self-renewal through the inactivation of Wnt-mediated Notch signaling.</P>

Effect of Ionizing Radiation on Rat Tissue: Proteomic and Biochemical Analysis

Park*, Eui&#x2010,Chul,Yoon, Jong&#x2010,Bok,Seong*, Jin&#x2010,Sil,Choi, Kyoung&#x2010,Soo,Kong, Eung&#x2010,Sik,Kim, Yun&#x2010,Jeong,Park, Young&#x2010,Mee,Park, Eun&#x2010,Mi Taylor Francis 2006 Preparative biochemistry & biotechnology Vol.36 No.1

<P>Reactive oxygen species (ROS), generated by ionizing radiation, has been implicated in its effect on living tissues. We confirmed the changes in the oxidative stress markers upon irradiation. We characterized the changes in the proteome profile in rat liver after administering irradiation, and the affected proteins were identified by MALDI-TOF-MS and ESI-MS/MS. The identified proteins represent diverse sets of proteins participating in the cellular metabolism. Our results demonstrated that proteomics analysis is a useful method for characterization of a global proteome change caused by ionizing radiation to unravel the molecular mechanisms involved in the cellular responses to ionizing radiation.</P>

Integrative molecular profiling identifies a novel cluster of estrogen receptor‐positive breast cancer in very young women

Park, Charny,Yoon, Kyong&#x2010,Ah,Kim, Jihyun,Park, In Hae,Park, Soo Jin,Kim, Min Kyeong,Jang, Wooyeong,Cho, Soo Young,Park, Boyoung,Kong, Sun&#x2010,Young,Lee, Eun Sook John Wiley and Sons Inc. 2019 Cancer Science Vol.110 No.5

<P>Very young breast cancer patients are more common in Asian countries than Western countries and are thought to have worse prognosis than older patients. The aim of the current study was to identify molecular characteristics of young patients with estrogen receptor (ER)‐positive breast cancer by analyzing mutations and copy number variants (CNV), and by applying expression profiling. The whole exome and transcriptome of 47 Korean young breast cancer (KYBR) patients (age <35) were analyzed. Genomic profiles were constructed using mutations, CNV and differential gene expression from sequencing data. Pathway analyses were also performed using gene sets to identify biological processes. Our data were compared with young ER+ breast cancer patients in The Cancer Genome Atlas (TCGA) dataset. <I>TP53</I>,<I>PIK3CA</I> and <I>GATA3</I> were highly recurrent somatic mutation genes. APOBEC‐associated mutation signature was more frequent in KYBR compared with young TCGA patients. Integrative profiling was used to classify our patients into 3 subgroups based on molecular characteristics. Group A showed luminal A‐like subtype and IGF1R signal dysregulation. Luminal B patients were classified into groups B and C, which showed chromosomal instability and enrichment for APOBEC3A/B deletions, respectively. Group B was characterized by 11q13 (CCND1) amplification and activation of the ubiquitin‐mediated proteolysis pathway. Group C showed 17q12 (ERBB2) amplification and lower ER and progesterone receptor expression. Group C was also distinguished by immune activation and lower epithelial‐mesenchyme transition (EMT) degree compared with group B. This study showed that integrative genomic profiling could classify very young patients with breast cancer into molecular subgroups that are potentially linked to different clinical characteristics.</P>

The histone demethylase KDM5A is required for the repression of astrocytogenesis and regulated by the translational machinery in neural progenitor cells

Kong, Sun&#x2010,Young,Kim, Woosuk,Lee, Ha&#x2010,Rim,Kim, Hyun&#x2010,Jung Federation of American Society for Experimental Bi 2018 The FASEB Journal Vol.32 No.2

<P>Histone demethylases are known to play important roles in the determination of the fate of stem cells and in cancer progression. In this study, we show that the lysine 4 of histone H3 (H3K4), lysine-specific demethylase 5A (KDM5A) is essential for the repression of astrocyte differentiation in neural progenitor cells (NPCs), and its expression is regulated by translational machinery. Knockdown of KDM5A in NPCs increased astrocytogenesis, and conversely, KDM5A overexpression reduced the transcriptional activity of the Gfap promoter. Induction of astrocytogenesis by ciliary neurotrophic factor (CNTF) or small interfering RNA-induced knockdown of KDM5A decreased KDM5A recruitment to the Gfap promoter and increased H3K4 methylation. The transcript level of Kdm5a was high, whereas KDM5A protein level was low in CNTF induced astrocytes. During astroglial differentiation, translational activity indicated by the phosphorylation of eukaryotic translation initiation factor (eIF)4E was decreased. Treatment of NPCs with the cercosporamide, a MAPK-interacting kinases inhibitor, reduced eIF4E phosphorylation and KDM5A protein expression, increased GFAP levels, and enhanced astrocytogenesis. These data suggest that KDM5A is a key regulator that maintains NPCs in an undifferentiated state by repressing astrocytogenesis and that its expression is translationally controlled during astrocyte differentiation. Thus, KDM5A is a promising target for the modulation of NPC fate.</P>

XRD studies on phase formation and the crystallite structure of BaTiO3 synthesized by HBM: the effect of calcination temperature

X.M. Chen,Y. Zhang,W.W. Kong,X.B. Bian,J.P. Zhou,P. Liu 한양대학교 세라믹연구소 2010 Journal of Ceramic Processing Research Vol.11 No.4

Barium titanate (BaTiO3, or BT) powders were synthesized via a solid state reaction of BaCO3-TiO2 by combining a highenergy ball milling (HBM) technique and a calcination method. Using X-ray diffraction (XRD) methods with a Rietveld refinement, the effects of calcination temperature on the phase formation and crystallite structure of BT powders were studied. It is found that by means of HBM the synthesis temperature for obtaining BT single phase is decreased to 960 oC, which is much lower than that required by the conventional solid-state reaction process, and the crystallite structure of BT is in the (pseudo)cubic form. As the calcination temperature is increased to 980 oC, the structure of BT crystallites transforms from the (pseudo)cubic to the tetragonal form. With an increase in the calcination temperature, both the tetragonality (c/a-1) and crystallite size are increased.