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

  • 여현수;이민혜;최유경;전찬용;박종형
    • 대한한방내과학회지
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    • 제35권4호
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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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    • 제43권12호
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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.

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

  • 최수한;유건희;안강모;성기웅;구홍회;김예진
    • Pediatric Infection and Vaccine
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    • 제19권2호
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    • pp.61-70
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    • 2012
  • 목적: 본 연구는 단일 기관에서 소아암 환자의 2009 인플루엔자 A(H1N1) [A(H1N1)pdm09] 감염 양상을 조사하고 이전의 계절 인플루엔자 감염과 비교 분석하고자 하였다. 방법: 삼성서울병원에서 2009년 8월부터 2010년 2월까지 A(H1N1)pdm09 감염, 2000년 1월부터 2009년 5월까지 계절 인플루엔자 A 감염이 확진된 소아암 환자의 의무기록을 후향적으로 분석하였다. 결과: 82명의 소아암 환자에서 A(H1N1)pdm09 감염이 확진되었다. 10명(12.2%)의 환자에서 하기도 감염증 또는 호흡기 외 감염이 발생하였다. 3명(3.7%)의 환자가 사망하였고 그 중 2명은 A(H1N1)pdm09 기여 사망이었다. 합병된 감염증과 관련하여 유의성을 가지는 위험인자는 감염의 시점(2009년 44-45주)과 병원 내 감염이었다. 이전의 계절 인플루엔자 A 감염과 비교하였을 때 임상적 특성에는 유의한 차이가 없었으나 A(H1N1) pdm09 감염에서 적극적인 항바이러스제 치료가 시행되었다. 결론: 소아암 환자에서 A(H1N1)pdm 감염은 경증부터 중증까지 다양한 임상 경과를 보였으며 이전의 계절 인플루엔자와 비교했을 때 임상 양상의 유의한 차이는 없었다.

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

  • 김년천;윤희철;석정수;고정호;유욱준;이인규;오명호;배종우
    • Clinical and Experimental Pediatrics
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    • 제46권4호
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    • pp.340-344
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    • 2003
  • 목 적 : RDS 발생과 BPD로의 이행을 예측 할 수 있고, 스테로이드 치료에 새로운 지표로서 사용 될 수 있는 SP-A2의 유전자 대립형질의 한국분포 및 빈도를 밝히고 새로운 종류의 유전자 대립형질을 발견하기 위하여 본 연구를 하였다. 방 법 : 2002년 4월부터 2002년 6월까지 순천향대학교 천안병원과 경희대학교병원 신생아실에 입원한 정상 신생아 71명을 대상으로 하였다. SP-A2 유전자의 대립 형질을 위하여 시발체(primer) 726/96, 727/21, 799/28A, 805/494를 이용하여 증폭시킨 후 9, 91, 140, 223위치의 뉴클레오티드(nucleotide)를 알아 보기 위하여 각 위치에 맞는 제한 효소(restriction enzyme)를 이용하여(PCR-cRFLP-based methodology) 자른 후 전기 영동하여 염기서열의 차이를 알아냈다. 결 과 : 아미노산 염기서열의 차이에 의하여, 1A, $1A^0$, $1A^1$, $1A^2$, $1A^3$, $1A^5$, $1A^6$, $1A^7$, $1A^8$, $1A^9$, $1A^{11}$, $1A^{12}$ 등의 12개의 대립형질이 발견되었으며, SP-A2 중 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%의 분포를 보였다. 결 론 : RDS에 대해 보호체(protector)로 작용하는 $1A^5$의 빈도가 많은 것으로 보아 실질적으로도 우리나라에서 RDS의 발생률이 적을 것으로 생각된다. 스테로이드를 사용 할 때 유전자 발현에 많은 억제를 보이는 1A도 우리나라에서 많은 빈도를 보이므로 스테로이드 치료에 있어서 치료에 신중을 기해야겠다.

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

  • Kim, Sung Guen
    • Kyungpook Mathematical Journal
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    • 제56권3호
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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 < $\frac{1}{(1+w)^2(1-w)}$).

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

  • 곽인석
    • 생명과학회지
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    • 제26권1호
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    • pp.42-49
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    • 2016
  • 레티노산(RA)는 많은 유형의 세포에서 성장 및 발달에 중요한 역할을 수행하며 생체 활성화에 적합한 RA의 농도는 CYP26A1 등 여러 가지 효소에 의해 조절된다. CYP26A1의 발현은 RA에 의해서 조절되며 CYP26A1는 RA에 반응하는 유전자 중 하나이다. CYP26A1 유전자 클로닝은 여러 동물에서 보고되어 있지만, 소에서 CYP26A1 유전자의 클로닝은 아직 보고되지 않았다. 소로부터 CYP26A1의 프로모터 부위를 중합효소 연쇄반응을 이용하여 클로닝 한 후 다른 동물과 염기 서열 비교분석 결과 RARE DR-5 (ttggg)의 존재를 확인하였고, DR-5의 염기서열은 분석한 종 에서 완전히 일치하였다. DR-5 motif를 함유한 소의 CYP26A1 프로모터 부위를luciferase리포터 유전자에 결합한 후 transient transfection에 의해 promoter 발현을 분석하였다. 폐 유래 세포주인 MTCC 세포에서 CYP26A1 promoter의 발현은 ATRA의 처리에 의하여 촉진되었다. CYP26A1 유전자의 발현은 ATRA 의존적으로 RAR-α 및 RAR-β에 의하여 현저하게 촉진되었다. 그러나 RAR-γ나 RXR-γ는 CYP26A1 발현에 별다른 영향을 미치지는 않았다. 또한 MTCC 세포주가 생산하는 내인성 CYP26A1 유전자 발현을 Q-RT-PCR로 분석한 결과 1-2일간의 ATRA 처리에 의해서는 현저한 영향을 받지 않으나, 3일 동안 ATRA를 처리한 샘플에서는 CYP26A1의 발현이 현저하게 감소하였다. 결론적으로, 소의 CYP26A1유전자의 프로모터 부위에 존재하는 DR-5 RARE는 RAR-α 및 RAR-β의 결합부위로 작용하여 MTCC 세포에서 CYP26A1 유전자 발현 조절과 RA signal의 조절에 관여하는 것을 확인하였다.

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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    • 제20권3호
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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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    • 제3권4호
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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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    • 제18권1호
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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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    • 제29권1_2호
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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 $A_1A_2=A_2A_1$.