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Antineoplastic Effect of Several Herbal Medicine Mixtures on SNU-80 Anaplastic Thyroid Carcinoma Cell Line (수종 한약 복합물의 역형성갑상선암세포 SNU-80에 대한 항암효과)

  • Yeo, Hyun-Soo;Lee, Min-Hye;Choi, You-Kyung;Jun, Chan-Young;Park, Jong-Hyeong
    • The Journal of Internal Korean Medicine
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    • v.35 no.4
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    • pp.416-427
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    • 2014
  • Objectives: The purpose of this study was to investigate the antineoplastic effect of several herbal medicine mixtures (compositions of Astragalus membranaceu, Angelica gigas, Trichosanthes kirilowii, Panax ginseng, Rhus verniciflua Stokes) on the SNU-80 anaplastic thyroid carcinoma cell line. Methods: MTT assay was used to examine whether our herbal medicine mixtures decreased cell growth rate of SNU-80. Wound healing assay and Transwell invasion assay was performed to investigate whether our herbal medicine mixtures affect the migration and invasion of anaplastic cancer cells, SNU-80. ELISA assay was performed to know if our herbal medicine mixtures suppressed the expression of pro-invasive molecules, such as vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) secreted from SNU-80. Results: MTT assay demonstrated that A. membranaceus:A. gigas:T. kirilowii=1:1:1 or 3:1:1, A. membranaceus:A. gigas :T. kirilowii:P. ginseng=1:1:1:1 or 3:1:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng:R. verniciflua Stokes=1:1:1:1:1 or 3:1:1:1:1 strongly suppressed the growth of SNU-80. Wound healing assay demonstrated that A. membranaceus:A. gigas=3:1, A. membranaceus:A. gigas:T. kirilowii=1:1:1 or 3:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng=1:1:1:1 or 3:1:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng:R. verniciflua Stokes=1:1:1:1:1 or 3:1:1:1:1 inhibited the migration of SNU-80. Transwell invasion assay demonstrated that A. membranaceus:A. gigas=1:1, A. membranaceus:A. gigas:T. kirilowii =1:1:1 or 3:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng=1:1:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng :R. verniciflua Stokes=1:1:1:1:1 or 3:1:1:1:1 inhibited the invasion of SNU-80. ELISA assay demonstrated that A. membranaceus :A. gigas:T. kirilowii=1:1:1 or 3:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng:R. verniciflua Stokes=1:1:1:1:1 suppressed the expression of VEGF. Also, A. membranaceus:A. gigas=1:1, A. membranaceus:A. gigas:T. kirilowii=1:1:1 or 3:1:1, A. membranaceus :A. gigas:T. kirilowii:P. ginseng=1:1:1:1 or 3:1:1:1, A. membranaceus:A. gigas:T. kirilowii:P. ginseng:R. verniciflua Stokes =1:1:1:1:1 or 3:1:1:1:1 suppressed the expression of MMP-2. Conclusions: The results obtained in this study suggest that several herbal medicine mixtures suppresse the growth and inhibit the migration and invasion of SNU-80, which is anaplastic thyroid cancer cells. Especially, A. membranaceus:A. gigas: T. kirilowii=1:1:1 mixture had a stronger anti-cancer effect.

Long Noncoding RNA Expression Profiling Reveals Upregulation of Uroplakin 1A and Uroplakin 1A Antisense RNA 1 under Hypoxic Conditions in Lung Cancer Cells

  • Byun, Yuree;Choi, Young-Chul;Jeong, Yongsu;Yoon, Jaeseung;Baek, Kwanghee
    • Molecules and Cells
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    • v.43 no.12
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    • pp.975-988
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    • 2020
  • Hypoxia plays important roles in cancer progression by inducing angiogenesis, metastasis, and drug resistance. However, the effects of hypoxia on long noncoding RNA (lncRNA) expression have not been clarified. Herein, we evaluated alterations in lncRNA expression in lung cancer cells under hypoxic conditions using lncRNA microarray analyses. Among 40,173 lncRNAs, 211 and 113 lncRNAs were up- and downregulated, respectively, in both A549 and NCI-H460 cells. Uroplakin 1A (UPK1A) and UPK1A-antisense RNA 1 (AS1), which showed the highest upregulation under hypoxic conditions, were selected to investigate the effects of UPK1A-AS1 on the expression of UPK1A and the mechanisms of hypoxia-inducible expression. Following transfection of cells with small interfering RNA (siRNA) targeting hypoxia-inducible factor 1α (HIF-1α), the hypoxia-induced expression of UPK1A and UPK1A-AS1 was significantly reduced, indicating that HIF-1α played important roles in the hypoxia-induced expression of these targets. After transfection of cells with UPK1A siRNA, UPK1A and UPK1A-AS1 levels were reduced. Moreover, transfection of cells with UPK1A-AS1 siRNA downregulated both UPK1A-AS1 and UPK1A. RNase protection assays demonstrated that UPK1A and UPK1A-AS1 formed a duplex; thus, transfection with UPK1A-AS1 siRNA decreased the RNA stability of UPK1A. Overall, these results indicated that UPK1A and UPK1A-AS1 expression increased under hypoxic conditions in a HIF-1α-dependent manner and that formation of a UPK1A/UPK1A-AS1 duplex affected RNA stability, enabling each molecule to regulate the expression of the other.

2009 Pandemic Influenza A(H1N1) Infections in the Pediatric Cancer Patients and Comparative Analysis with Seasonal Influenza (소아암 환자에서 2009 대유행 인플루엔자 A(H1N1) 감염의 임상적 고찰 및 계절 인플루엔자와의 비교 분석)

  • Choi, Soo Han;Yoo, Keon Hee;Ahn, Kangmo;Sung, Ki Woong;Koo, Hong Hoe;Kim, Yae Jean
    • Pediatric Infection and Vaccine
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    • v.19 no.2
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    • pp.61-70
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    • 2012
  • Purpose: This study was performed to compare the clinical characteristics of 2009 pandemic influenza A(H1N1) [A(H1N1) pdm09] and seasonal influenza A infection in the pediatric cancer patients. Methods: A retrospective review was performed in the pediatric cancer patients who had confirmed A(H1N1)pdm09 infection at Samsung Medical Center from August 2009 to February 2010. For the comparison, the medical records of pediatric cancer patients with seasonal influenza A from January 2000 to May 2009 were reviewed retrospectively. Results: Eighty-two A(H1N1)pdm09 infections were confirmed in the pediatric cancer patients. Ten patients (12.2%) developed complicated clinical course by lower respiratory infections or extrapulmonary infections; 4 pneumonia, 1 bronchitis, 1 pericarditis with pneumonia, 1 encephalitis with pneumonia, 2 meningitis and 1 pericarditis. Three patients received mechanical ventilator and ICU care. Three pediatric cancer patients (3.7%) died. The risk factors related to complicated A(H1N1)pdm09 infections were date of infection (44-45th week 2009) and nosocomial infection. When comparing with previous seasonal influenza A infections, more prompt and aggressive antiviral therapy was given in A(H1N1)pdm09 infections. Conclusion: The A(H1N1)pdm09 infections caused a various clinical manifestations including fatal cases in pediatric cancer patient during pandemic season. There was no significant difference in clinical course between influenza A(H1N1)pdm09 and seasonal influenza A infections except the antiviral treatment strategy.

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Allele Distribution and Frequency of Human Surfactant Protein-A2 in Korean Neonates (한국 신생아의 폐 표면 활성제 단백-A2(Human Surfactant Protein-A2) 유전자 대립형질의 분포와 빈도)

  • Kim, Nyeon Cheon;Yoon, Hee Chul;Suk, Jung Su;Ko, Jung Ho;Yoo, Ook Joon;Lee, In Kyu;Oh, Myung Ho;Bae, Chong Woo
    • Clinical and Experimental Pediatrics
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    • v.46 no.4
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    • pp.340-344
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    • 2003
  • Purpose : We evaluated allele frequencies and distribution of surfactant protein A2(SP-A2) in Korean neonates in order to estimate the prevalence of RDS, to find out new SP-A alleles, and to establish new steroid therapy. Methods : Genomic DNA was extracted from 71 neonates and served as a template in PCR for genotype analysis. SP-A gene-specific amplications and gene-specific allele determinations were performed using PCR-cRFLP methods. Results : The distribution for the alleles of the SP-A2 gene in the study population was 1A, $1A^0$, $1A^1$, $1A^2$, $1A^3$, $1A^5$, $1A^6$, $1A^7$, $1A^8$, $1A^9$, $1A^{11}$, $1A^{12}$. The specific frequencies for the alleles of the SP-A2 gene in the study population were : 1A=11.3%, $1A^0=38%$, $1A^1=12.7%$, $1A^2=9.2%$, $1A^5=15.5%$, $1A^7=2.9%$, $1A^8=4.9%$, $1A^9=2.2%$, others=3.3%. Conclusion : The frequency of $1A^0$ was higher than the other SP-A2 alleles in Korean neonates. This finding suggests that the prevalence of RDS in Korea may be low compared with other countries. However, this finding also suggests that Korean neonates have a high risk of infection.

The Geometry of the Space of Symmetric Bilinear Forms on ℝ2 with Octagonal Norm

  • Kim, Sung Guen
    • Kyungpook Mathematical Journal
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    • v.56 no.3
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    • pp.781-791
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    • 2016
  • Let $d_*(1,w)^2 ={\mathbb{R}}^2$ with the octagonal norm of weight w. It is the two dimensional real predual of Lorentz sequence space. In this paper we classify the smooth points of the unit ball of the space of symmetric bilinear forms on $d_*(1,w)^2$. We also show that the unit sphere of the space of symmetric bilinear forms on $d_*(1,w)^2$ is the disjoint union of the sets of smooth points, extreme points and the set A as follows: $$S_{{\mathcal{L}}_s(^2d_*(1,w)^2)}=smB_{{\mathcal{L}}_s(^2d_*(1,w)^2)}{\bigcup}extB_{{\mathcal{L}}_s(^2d_*(1,w)^2)}{\bigcup}A$$, where the set A consists of $ax_1x_2+by_1y_2+c(x_1y_2+x_2y_1)$ with (a = b = 0, $c={\pm}{\frac{1}{1+w^2}}$), ($a{\neq}b$, $ab{\geq}0$, c = 0), (a = b, 0 < ac, 0 < ${\mid}c{\mid}$ < ${\mid}a{\mid}$), ($a{\neq}{\mid}c{\mid}$, a = -b, 0 < ac, 0 < ${\mid}c{\mid}$), ($a={\frac{1-w}{1+w}}$, b = 0, $c={\frac{1}{1+w}}$), ($a={\frac{1+w+w(w^2-3)c}{1+w^2}}$, $b={\frac{w-1+(1-3w^2)c}{w(1+w^2)}}$, ${\frac{1}{2+2w}}$ < c < ${\frac{1}{(1+w)^2(1-w)}}$, $c{\neq}{\frac{1}{1+2w-w^2}}$), ($a={\frac{1+w(1+w)c}{1+w}}$, $b={\frac{-1+(1+w)c}{w(1+w)}}$, 0 < c < $\frac{1}{2+2w}$) or ($a={\frac{1=w(1+w)c}{1+w}}$, $b={\frac{1-(1+w)c}{1+w}}$, $\frac{1}{1+w}$ < c < $\frac{1}{(1+w)^2(1-w)}$).

Molecular Cloning and Characterization of Bovine CYP26A1 Promoter (소 CYP26A1 유전자 프로모터의 molecular cloning 및 특성)

  • Kwak, Inseok
    • Journal of Life Science
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    • v.26 no.1
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    • pp.42-49
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    • 2016
  • The retinoic acid (RA) plays an important role in the growth and development of many cells, and bioactive RA concentration is regulated by several enzymes, including CYP26A1. The expression of the CYP26A1 gene is regulated by RA, and the CYP26A1 gene is one of the candidates for RA-responsive genes. Although CYP26A1 genes are cloned from several animals, cloning of the CYP26A1 gene from cows has not been reported yet. The promoter region of CYP26A1 from cows was cloned by PCR and analyzed by sequence alignment with human and mouse CYP26A1. The RA-responsive element (RARE), DR-5 (ttggg), was located in this region and was perfectly conserved. The promoter region of bovine CYP26A1, which contains DR-5, was ligated to the luciferase reporter gene on transient transfection assays. The expression of CYP26A1-Luc promoter was activated by ATRA treatment in lung-derived mtCC cells. Co-transfection with RAR-α or -β with ATRA significantly activates the expression of CYP26A1-Luc promoter; however, it was less effective with either RAR-γ or RXR-γ. In addition, the endogenous gene expressions measured by Q-RT-PCR in mtCC cells were not significantly affected by ATRA treatment for 2 days; however, the expression of the endogenous CYP26A1 gene was diminished sharply at day 3 with ATRA treatment. In conclusion, the promoter region of bovine CYP26A1 contains conserved DR-5 RARE, which functions as a binding site for RAR-α or -β, and it is involved in the regulation of CYP26A1 gene expression and the control of RA signaling in mtCC cells.

The UGT1A9*22 genotype identifies a high-risk group for irinotecan toxicity among gastric cancer patients

  • Lee, Choong-kun;Chon, Hong Jae;Kwon, Woo Sun;Ban, Hyo-Jeong;Kim, Sang Cheol;Kim, Hyunwook;Jeung, Hei-Cheul;Chung, Jimyung;Rha, Sun Young
    • Genomics & Informatics
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    • v.20 no.3
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    • pp.29.1-29.12
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    • 2022
  • Several studies have shown associations between irinotecan toxicity and UGT1A genetic variations in colorectal and lung cancer, but only limited data are available for gastric cancer patients. We evaluated the frequencies of UGT1A polymorphisms and their relationship with clinicopathologic parameters in 382 Korean gastric cancer patients. Polymorphisms of UGT1A1*6, UGT1A1*27, UGT1A1*28, UGT1A1*60, UGT1A7*2, UGT1A7*3, and UGT1A9*22 were genotyped by direct sequencing. In 98 patients treated with irinotecan-containing regimens, toxicity and response were compared according to the genotype. The UGT1A1*6 and UGT1A9*22 genotypes showed a higher prevalence in Korean gastric cancer patients, while the prevalence of the UG1A1*28 polymorphism was lower than in normal Koreans, as has been found in other studies of Asian populations. The incidence of severe diarrhea after irinotecan-containing treatment was more common in patients with the UGT1A1*6, UGT1A7*3 and UGT1A9*22 polymorphisms than in controls. The presence of the UGT1A1*6 allele also showed a significant association with grade III-IV neutropenia. Upon haplotype and diplotype analyses, almost every patient bearing the UGT1A1*6 or UGT1A7*3 variant also had the UGT1A9*22 polymorphism, and all severe manifestations of UGT1A polymorphism-associated toxicity were related to the UGT1A9*22 polymorphism. By genotyping UGT1A9*22 polymorphisms, we could identify high-risk gastric cancer patients receiving irinotecan-containing chemotherapy, who would experience severe toxicity. When treating high-risk patients with the UGT1A9*22 polymorphism, clinicians should closely monitor them for signs of toxicity such as severe diarrhea or neutropenia.

Effects of CYP1A2$^*$1C and CYP1A2$^*$1F Genotypes on the Activity and Inducibility of CYP1A2 Determined by Urinary Caffeine Metabolite Ratio in Koreans

  • Shin, Mi-Kyung;Yi, Hyeon-Gyu;Kwon, Yong-Hyun;Lee, Sung-Keun;Lim, Woo-Sung;Park, Chang-Shin;Kang, Ju-Hee
    • Molecular & Cellular Toxicology
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    • v.3 no.4
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    • pp.314-319
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    • 2007
  • The effects of common variants of CYP1A2 gene (CYP1A2$^*$1C and CYP1A2$^*$1F) on the CYP1A2 activity and inducibility were controversial. The aim of the present study is to investigate the effects of CYP1A2$^*$1C and CYP1A2$^*$1F on the activity of CYP1A2 determined by urinary caffeine metabolite ratio in Koreans. As might be expected, there was large inter-individual variation (16-folds) of CYP1A2 activity ranged from 2.41 to 39.58. The mean CYP1A2 activity of smokers was significantly higher than that of non-smokers. The frequencies of CYP1A2$^*$1C (-3858A) and $^*$1F (-164A) alleles were 0.219 and 0.646, respectively. The effect of CYP1A2$^*$1C on the CYP1A2 activity was not significant. However, the CYP1A2 activity of subjects with AA genotype for CYP1A2$^*$1F allele was significantly lower than that of non-AA genotypes (CC, or CA). Interestingly, the significant effect of CYP1A2$^*$1F allele on CYP1A2 activity was not observed in nonsmokers. Our results suggest that CYP1A2$^*$1F allele rather than CYP1A2$^*$1C allele significantly influences on the inducibility of CYP1A2 in Koreans. Owing to small sample size of our study, further studies should be conducted to reveal the inter-ethnic difference or the gene-environmental interaction.

Equol Modulates Induction of Hepatic CYP 1A1, 1B1, and AhR in Mice Treated with 7,12-Dimethylbenz(a)anthracene

  • Choi, Eun-Jeong;Kim, Gun-Hee
    • Food Science and Biotechnology
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    • v.18 no.1
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    • pp.245-248
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    • 2009
  • Present study was investigated the hepatic effects of equol on the 7,12-dimethylbenz(a)anthracene (DMBA)-induced enzymatic activity and expression of CYP1A1 and CYP1B1 in mice. Equol was administered orally at 5 and 25 mg/kg BW for 4 weeks. Subsequently, mice pretreated with equol received DMBA intragastrically twice a week for 2 weeks. DMBA induced CYP1 activity as well as the expression of CYP1A1 and CYP1B1. Each of these effects was significantly reduced by equol in dose-dependent manner (p<0.05). Equol also reduced the relative AhR mRNA expression, similar to its effect on CYP1A1. These results suggest that equol modulates the CYP1A1 through a reduction of AhR expression in mice treated with DMBA.

INVOLUTORY AND S+1-POTENCY OF LINEAR COMBINATIONS OF A TRIPOTENT MATRIX AND AN ARBITRARY MATRIX

  • Bu, Changjiang;Zhou, Yixin
    • Journal of applied mathematics & informatics
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    • v.29 no.1_2
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    • pp.485-495
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    • 2011
  • Let $A_1$ and $A_2$ be $n{\times}n$ nonzero complex matrices, denote a linear combination of the two matrices by $A=c_1A_1+c_2A_2$, where $c_1$, $c_2$ are nonzero complex numbers. In this paper, we research the problem of the linear combinations in the general case. We give a sufficient and necessary condition for A is an involutive matrix and s+1-potent matrix, respectively, where $A_1$ is a tripotent matrix, with $A_1A_2=A_2A_1$. Then, using the results, we also give the sufficient and necessary conditions for the involutory of the linear combination A, where $A_1$ is a tripotent matrix, anti-idempotent matrix, and involutive matrix, respectively, and $A_2$ is a tripotent matrix, idempotent matrix, and involutive matrix, respectively, with $A_1A_2=A_2A_1$.