• Title/Summary/Keyword: Gli

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Expression of Smoothened Protein in Colon Cancer and its Prognostic Value for Postoperative Liver Metastasis

  • Ding, Yin-Lu;Wang, Qi-San;Zhao, Wei-Min;Xiang, Lei
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.4001-4005
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    • 2012
  • Backgrouds: The hedgehog (Hh) signaling pathway is composed of patched (PTCH) and smoothened (SMO), two transmembrane proteins, and downstream glioma-associated oncogene homolog (Gli) transcription factors. Hh signaling plays a pathological role in the occurrence and development of various cancers. Methods: To investigate the expression of SMO protein in colon cancer and its association with clinicopathological parameters and postoperative liver metastasis, immunohistochemistry was performed with paraffin-embedded specimens of 96 cases. Relationships between SMO protein expression and clinicopathological parameters, postoperative liver metastasis were analyzed. Results: IHC examination showed that SMO protein expression was significantly increased in colon cancer tissues compared to normal colon tissues (P = 0.042), positively related to lymph node metastases (P = 0.018) and higher T stages (P = 0.026). Postoperative live metastasis-free survival was significantly longer in the low SMO expression group than in those with high SMO expression ($48.7{\pm}8.02$ months vs $28.0{\pm}6.86$ months, P=0.036). Multivariate analysis showed SMO expression level to be an independent prognostic factor for postoperative live metastasis-free survival (95% confidence interval [CI] =1.46-2.82, P = 0.008). Conclusions: Our results suggest that in patients with colon cancer, the SMO expression level is an independent biomarker for postoperative liver metastasis, and SMO might play an important role in colon cancer progression.

Vasodilation of Ethanol Extract of Cinnamomi Ramulus via Voltage Dependent $Ca^{2+}$ Channel Blockage (전압의존성 $Ca^{2+}$ 통로 억제를 통한 계지(桂枝) 에탄올 추출물의 혈관이완 효능)

  • Kim, Jong-Bong;Shin, Heung-Mook
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.24 no.4
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    • pp.592-597
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    • 2010
  • Cinnamomi Ramulus is one of the medicinal plants that have been used to improve various diseases caused by insufficient blood circulation. This study was performed for the investigation of vasodilation efficacy ethanol extract of Cinnamomi Ramulus (CR). CR exhibited vascular relaxation against phenylephrine (PE, $10^{-6}M$)-, KCl- and NaF-induced contraction in rat thoracic aorta. In addition, its relaxation was endothelium-independent. Treatment of potassium channel blockers such as gilbenclamide (Gli, $10^{-5}M$), tetraethylammonium (TEA, 1 mM) and 4-aminopyridine (4-AP, 0.2 mM) did not effect on the relaxation of CR. The relaxant effects were also not inhibited by pre-treatment of rat aorta with L-NAME ($10^{-4}M$), methylene blue ($10^{-5}M$), indomethacin ($10^{-5}M$), and atropine ($10^{-6}M$). However, nifedipine ($10^{-5}M$), L-type $Ca^{2+}$ channel blocker, in part attenuated the relaxation of CR ($0.2\;mg/m{\ell}$), but SK&F96365 ($3{\times}10^{-5}M$), receptor activated $Ca^{2+}$ channel blocker and 2-APB ($10^{-4}M$), store operated $Ca^{2+}$ channel blocker did not affact dilation of CR. These findings suggest that the endothelium-independent relaxation effect of CR is partly related with inhibition of $Ca^{2+}$ influx via voltage dependent $Ca^{2+}$ channel.

A Study on The Improvement of Profile Tilting or Bottom Distortion in HARC (높은 A/R의 콘택 산화막 에칭에서 바닥모양 변형 개선에 관한 연구)

  • Hwang, Won-Tae;Kim, Gli-Ho
    • Journal of the Korean Institute of Electrical and Electronic Material Engineers
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    • v.18 no.5
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    • pp.389-395
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    • 2005
  • The etching technology of the high aspect ratio contact(HARC) is necessary at the critical contact processes of semiconductor devices. Etching the $SiO_{2}$ contact hole with the sub-micron design rule in manufacturing VLSI devices, the unexpected phenomenon of 'profile tilting' or 'bottom distortion' is often observed. This makes a short circuit between neighboring contact holes, which causes to drop seriously the device yield. As the aspect ratio of contact holes increases, the high C/F ratio gases, $C_{4}F_{6}$, $C_{4}F_{8}$ and $C_{5}F_{8}$, become widely used in order to minimize the mask layer loss during the etching process. These gases provide abundant fluorocarbon polymer as well as high selectivity to the mask layer, and the polymer with high sticking yield accumulates at the top-wall of the contact hole. During the etch process, many electrons are accumulated around the asymmetric hole mouth to distort the electric field, and this distorts the ion trajectory arriving at the hole bottom. These ions with the distorted trajectory induce the deformation of the hole bottom, which is called 'profile tilting' or 'bottom distortion'. To prevent this phenomenon, three methods are suggested here. 1) Using lower C/F ratio gases, $CF_{4}$ or $C_{3}F_{8}$, the amount of the Polymer at the hole mouth is reduced to minimize the asymmetry of the hole top. 2) The number of the neighboring holes with equal distance is maximized to get the more symmetry of the oxygen distribution around the hole. 3) The dual frequency plasma source is used to release the excessive charge build-up at the hole mouth. From the suggested methods, we have obtained the nearly circular hole bottom, which Implies that the ion trajectory Incident on the hole bottom is symmetry.

A whole genomic scan to detect selection signatures between Berkshire and Korean native pig breeds

  • Edea, Zewdu;Kim, Kwan-Suk
    • Journal of Animal Science and Technology
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    • v.56 no.7
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    • pp.23.1-23.7
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    • 2014
  • Background: Scanning of the genome for selection signatures between breeds may play important role in understanding the underlie causes for observable phenotypic variations. The discovery of high density single nucleotide polymorphisms (SNPs) provide a useful starting point to perform genome-wide scan in pig populations in order to identify loci/candidate genes underlie phenotypic variation in pig breeds and facilitate genetic improvement programs. However, prior to this study genomic region under selection in commercially selected Berkshire and Korean native pig breeds has never been detected using high density SNP markers. To this end, we have genotyped 45 animals using Porcine SNP60 chip to detect selection signatures in the genome of the two breeds by using the $F_{ST}$ approach. Results: In the comparison of Berkshire and KNP breeds using the FDIST approach, a total of 1108 outlier loci (3.48%) were significantly different from zero at 99% confidence level with 870 of the outlier SNPs displaying high level of genetic differentiation ($F_{ST}{\geq}0.490$). The identified candidate genes were involved in a wide array of biological processes and molecular functions. Results revealed that 19 candidate genes were enriched in phosphate metabolism (GO: 0006796; ADCK1, ACYP1, CAMK2D, CDK13, CDK13, ERN1, GALK2, INPP1; MAK, MAP2K5, MAP3K1, MAPK14, P14KB, PIK3C3, PRKC1, PTPRK, RNASEL, THBS1, BRAF, VRK1). We have identified a set of candidate genes under selection and have known to be involved in growth, size and pork quality (CART, AGL, CF7L2, MAP2K5, DLK1, GLI3, CA3 and MC3R), ear morphology and size (HMGA2 and SOX5) stress response (ATF2, MSRB3, TMTC3 and SCAF8) and immune response (HCST and RYR1). Conclusions: Some of the genes may be used to facilitate genetic improvement programs. Our results also provide insights for better understanding of the process and influence of breed development on the pattern of genetic variations.

Molecular Mechanism of Runx2-Dependent Bone Development

  • Komori, Toshihisa
    • Molecules and Cells
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    • v.43 no.2
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    • pp.168-175
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    • 2020
  • Runx2 is an essential transcription factor for skeletal development. It is expressed in multipotent mesenchymal cells, osteoblast-lineage cells, and chondrocytes. Runx2 plays a major role in chondrocyte maturation, and Runx3 is partly involved. Runx2 regulates chondrocyte proliferation by directly regulating Ihh expression. It also determines whether chondrocytes become those that form transient cartilage or permanent cartilage, and functions in the pathogenesis of osteoarthritis. Runx2 is essential for osteoblast differentiation and is required for the proliferation of osteoprogenitors. Ihh is required for Runx2 expression in osteoprogenitors, and hedgehog signaling and Runx2 induce the differentiation of osteoprogenitors to preosteoblasts in endochondral bone. Runx2 induces Sp7 expression, and Runx2, Sp7, and canonical Wnt signaling are required for the differentiation of preosteoblasts to immature osteoblasts. It also induces the proliferation of osteoprogenitors by directly regulating the expression of Fgfr2 and Fgfr3. Furthermore, Runx2 induces the proliferation of mesenchymal cells and their commitment into osteoblast-lineage cells through the induction of hedgehog (Gli1, Ptch1, Ihh), Fgf (Fgfr2, Fgfr3), Wnt (Tcf7, Wnt10b), and Pthlh (Pth1r) signaling pathway gene expression in calvaria, and more than a half-dosage of Runx2 is required for their expression. This is a major cause of cleidocranial dysplasia, which is caused by heterozygous mutation of RUNX2. Cbfb, which is a co-transcription factor that forms a heterodimer with Runx2, enhances DNA binding of Runx2 and stabilizes Runx2 protein by inhibiting its ubiquitination. Thus, Runx2/Cbfb regulates the proliferation and differentiation of chondrocytes and osteoblast-lineage cells by activating multiple signaling pathways and via their reciprocal regulation.

L'idea dell'umanità nuova nelle tragedie Saul e Mirra di Alfieri (알피에리의 비극 『사울Saul』과 『미라Mirra』에 나타난 새로운 인간의 이상)

  • Jang, Ji Yeon
    • Lettere Italiane
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    • no.36
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    • pp.125-150
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    • 2012
  • Vittorio Alfieri fu celebrato dagli uomini del Risorgimento come "l'iniziatore ed il padre della rinascita" e il creatore della coscienza nazionale. Per questo è lodato da Foscolo, Manzoni, Leopardi, Mazzini, Gioberti, Oriani, Carducci. Ma insieme con i suoi meriti politici, anche i valori artistici delle sue opere non debbono essere dimenticati. Anche sul pensiero e sull'opera dell'Alfieri influirono le ideologie tipiche del secondo Settecento, l'Illuminismo e il nascente Romanticismo, in lui intrecciandosi e scontrandosi ad un tempo. Il suo interesse per lo studio dell'uomo, per la concezione meccanicistica del mondo, la lontananza dalla religione per l'assoluta libertà e l'avversione verso il dispotismo, collegano Alfieri alla dottrina illuminista. I temi letterari illuministici, volti a chiarificare le coscienze e ad apportare il progresso sociale e civile, sono affrontati dal poeta non in modo distaccato, ma con l'emotività e le inquietudini del pensiero romantico. Ma i letterati romantici dell'Ottocento furono piuttosto ostili all'opera dell'Alfieri, accusandola di astratezza, di lontananza dagli interessi e dalla realtà della vita moderna e di assenza di senso storico. Invece nei primi anni del Novecento, Croce lo presenta come iniziatore della nuova letteratura italiana, con la quale egli avrebbe in comune l'individualismo, la passionalità, l'amore per la solitudine, la malinconia. Anche se gli manca l'ansia religiosa sul fine e il valore della vita e l'interessamento per la storia, ecc., secondo il Croce si può definire un protoromantico. Nelle sue opere ci sono, sotto l'aspetto dell'Illuminismo l'odio istintivo contro la tirannide e l'amore per la libertà, e sotto quello protoromantico esplode l'urto violento di sentimenti e passioni e l'esaltazione della morte eroica dei protagonisti. E anche Saul e Mirra descrivono l'idea dell'umanità eroica che muore dopo una lunga vicenda di miseria e di abbiezione. L'idea dell'umanità nuova in Saul e Mirra è l'idea degli uomini nuovi che egli desiderava.

Submentovertex cephalometrics in korean adults (한국 성인에서 이하 두정 방사선 계측사진 분석)

  • Nahm, Dong-Seok;Suhr, Chung-Hoon;Yang, Won-Sik;Chang, Young-Il
    • The korean journal of orthodontics
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    • v.30 no.1 s.78
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    • pp.1-7
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    • 2000
  • It is important that the orthodontist accurately assess the degree to which facial asymmetry contributes to a given malocclusion before treatment planning. P-A, submentovertex and verticosubmental view have been used in the assessment of facial asymmetry. Among them, submentovertex view is rarely used because it has low reproducibility and is short of normal data and proper analysis method. The purpose of this study was to develop a submentovertex cephalomentrics and obtain normal data in Korean adults. The subjects consisted of 40 normal adults (male : 22, female 18) without the experience of orthodontic treatment. We find the 2 angular and 9 linear measurements. Though submentovertex cephalomentrics has the limitation in comparing the absolute length between right and left, it is useful to examine the relationship of skeletal and dental midline, the shape and location of condyle head and the shape of mandibular body in submentovertex view Therefore, if we understand the limitation of submentovertex cephalomentrics and use lateral , P-A and submentovertex cephalomentrics together, we will measure the location and amount of skeletal disharmony more exactly.

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Differential Mechanisms of Vascular Relaxation between Alcohol Steamed Rhei Tangutici Radix et Rhizoma and Rhei Tangutici Radix et Rhizoma (당고특대황(唐古特大黃)의 주증(酒蒸) 여부가 혈관이완 기전에 미치는 영향)

  • Yang, Jae-Kyung;Shin, Heung-Mook
    • The Korea Journal of Herbology
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    • v.25 no.4
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    • pp.17-21
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    • 2010
  • Objectives : The aim of this study was to evaluate the differential mechnism of vasodilation of alcohol steamed Rhei Tangutici Radix et Rhizoma. (ART) and Rhei Tangutici Radix et Rhizoma. (RT) in rat thoracic aorta. Methods : Rat aortic ring preparations were mounted in organ baths with oxygenated (95% $O_2$-5% $CO_2$) Krebs-Ringer bicarbonate solutions at $37{\pm}0.5^{\circ}C$ and subjected to contractions or relaxations. Results : ART exerted vasorelaxation on phenylephrine(PE)-induced contraction in a dose dependent manner. Vasorelaxation effects of ART and RT were endothelium-independent. In the $Ca^{2+}$-free high KCl (60 mM) baths, the contraction of aortic rings induced by accumulative addition of $Ca^{2+}$ (0.3-10.0 mM) was significantly reduced by pre-treatment with both ART and RT for 10 min. The magnitude of vasodilatation was biggerin ART. Moreover, verapamil ($0.001{\mu}M$) and diltiazem ($10{\mu}M$), voltage operative $Ca^{2+}$channel blockers, attenuated the relaxation effect of ART but not that of RT. In the absence of extracellular $Ca^{2+}$, pre-incubation of the aortic rings with RT ($1.0mg/m{\ell}$) significantly reduced the contraction caused by PE but not that of ART. $K^+$ channel inhibitors such as glibenclamide (Gli, $10^{-5}M$), tetraethylammonium (TEA, 1 mM) and 4-aminopyridine (4-AP, 0.2 mM) significantly reduced the ART's vasorelaxation efficacy, but not that of RT. However, the relaxation effects of ART and RT were not inhibited by pre-treatment with indomethacin ($10^{-5}M$), and atropine ($10^{-6}M$). Conclusions : These results suggest that the endothelium-independent relaxation is due to inhibition of $Ca^{2+}$ influx via the suppression of $Ca^{2+}$ release from intracelluar store in RT but via both voltage operative $Ca^{2+}$channel blockage and $K^+$ channel activation in ART.

Transcriptional Properties of the BMP, $TGF-\beta$, RTK, Wnt, Hh, Notch, and JAK/STAT Signaling Molecules in Mouse Embryonic Stem Cells

  • Rho Jeung-Yon;Bae Gab-Yong;Chae Jung-Il;Yu Kweon;Koo Deog-Bon;Lee Kyung-Kwang;Han Yong-Mahn
    • Reproductive and Developmental Biology
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    • v.30 no.2
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    • pp.143-156
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    • 2006
  • Major characteristics of embryonic stem cells (ESCs) are sustaining of sternness and pluripotency by self-renewal. In this report, transcriptional profiles of the molecules in the developmentally important signaling pathways including Wnt, BMP4, $TGF-\beta$, RTK, Hh, Notch, and JAK/STAT signaling pathways were investigated to understand the self-renewal of mouse ESCs (mESCs), J1 line, and compared with the NIH3T3 cell line and mouse embryonic fibroblast (MEF) cells as controls. In the Wnt signaling pathway, the expression of Wnt3 was seen widely in mESCs, suggesting that the ligand may be an important regulator for self-renewal in mESCs. In the Hh signaling pathway, the expression of Gli and N-myc were observed extensively in mESCs, whereas the expression levels of in a Shh was low, suggesting that intracellular molecules may be essential for the self-renewal of mESCs. IGF-I, IGF-II, IGF-IR and IGF-IIR of RTK signaling showed a lower expression in mESCs, these molecules related to embryo development may be restrained in mESCs. The expression levels of the Delta and HESS in Notch signaling were enriched in mESCs. The expression of the molecules related to BMP and JAK-STAT signaling pathways were similar or at a slightly lower level in mESCs compared to those in MEF and NIH3T3 cells. It is suggested that the observed differences in gene expression profiles among the signaling pathways may contribute to the self-renewal and differentiation of mESCs in a signaling-specific manner.