• Bulletin of the Korean Chemical Society
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• 제32권7호
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• pp.2325-2331
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• 2011

Human CDX1 and CDX2 genes play important roles in the regulation of cell proliferation and differentiation in the intestine. Hox genes clustered on four chromosomal regions (A-D) specify positional signaling along the anterior-posterior body axis, including intestinal development. Using glutathione S-transferase (GST) pulldown assays, molecular interaction measurements, and fluorescence measurements, we found that the homeodomains (HDs) of CDX1 and CDX2 directly interact with that of HOXD8 in vitro. CDX1 showed significant affinity for HOXD8, but CDX2 showed weak affinity for HOXD8. Thus far, three-dimensional structures of CDX1/2 and HOXD8 have not been determined. In this study, we developed a molecular docking model by homology modeling based on the structures of other HD members. Proteins with mutations in the HD of CDX1 (S185A, N190A, T194A, and V212A) also bound to the HD of HOXD8. Our study suggests that the HDs of CDX1/2 resemble those of HOXD8, and we provide the first insight into the interaction between the HDs of CDX1/2 proteins and those of HOXD8.

• 생명과학회지
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• 제21권2호
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• pp.194-201
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• 2011

Caudal homeodomain 단백질은 초파리에서 사람에 이르기까지 보존되어 있으며, 장조직의 발생과 유지에 필수적인 역할을 한다. CDX1과 CDX2의 발현 감소 혹은 소실이 대장암과 연관되어 있음이 잘 알려져 있다. 대장암 발생은 산화성 스트레스와 밀접한 관련이 있으며, 대장암 조직에서 항산화효소인 catalase의 발현이 감소되어 있다. 하지만 그 분자적 기전은 잘 밝혀져 있지 않다. 본 연구에서는 초파리와 사람의 caudal homeodomain 단백질들이 catalase의 발현을 조절하는 것을 보여준다. 초파리 caudal heterozygous 돌연변이체의 대장조직에서 catalase의 발현이 감소되어 있고 ROS 생성이 증가되어 있음을 관찰하였다. 그리고 caudal 유전자의 과발현에 의해 catalase promoter의 활성과 mRNA 수준이 각각 증가함을 확인하였다. 또한 사람의 대장암 세포주인 HCT116 세포에서 CDX1과 CDX2가 catalase promoter의 활성과 단백질 수준에서 catalase를 상향 조절함을 관찰하였다. 이러한 결과들은 CDX1과 CDX2가 catalase 발현 조절을 통하여 장의 항상성 유지와 암발생 과정에 관여함을 시사한다.

• Journal of Microbiology and Biotechnology
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• 제19권12호
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• pp.1557-1564
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• 2009

Human CDX2 is known as a caudal-related homeodomain transcription factor that is expressed in the intestinal epithelium and is important in differentiation and maintenance of the intestinal epithelial cells. The caudal-related homeobox proteins bind DNA according to a helix-turn-helix structure, thereby increasing the structural stability of DNA. A cancer-tumor suppressor role for Cdx2 has been shown by a decrease in the level of the expression of Cdx2 in colorectal cancer, but the mechanism of transcriptional regulation has not been examined at the molecular level. We developed a large-scale system for expression of the recombinant, novel CDX2, in Escherichia coli. A highly purified and soluble CDX2 protein was obtained in E. coli strain BL21(DE3)RIL and a hexahistidine fusion system using Ni-NTA affinity column, anion exchange, and gel filtration chromatographies. The identity and secondary structure of the purified CDX2 protein were confirmed by MALDI-TOF MS, Western blot, and a circular dichroism analyses. In addition, we studied the DNA-binding activity of recombinant CDX2 by ELISA experiment and isolated human CDX2-binding proteins derived from rat cells by an immobilized GST-fusion method. Three CDX2-binding proteins were found in the gastric tissue, and those proteins were identified to the homeobox protein Hox-D8, LIM homeobox protein 6, and SMC1L1 protein.

• Asian Pacific Journal of Cancer Prevention
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• 제13권1호
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• pp.247-250
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• 2012

Objective: To determine whether CDX2 and villin protein expression are associated with intestinal metaplasia (IM) in gastric cardiac mucosa and to explore the relationship with evolution of gastric cardiac adenocarcinoma (GCA). Methods: We studied 143 gastric cardiac biopsy or resection specimens from Henan province China, including 25 cardiac gastritis specimens with IM, 65 dysplasia specimens with IM and 35 gastric cardiac adenocarcinoma specimens and stained them for CDX2 and villin by the immunohistochemical SP method. 15 normal gastric cardiac biopsy specimens were also collected as control. Results: (1) Normal gastric mucosa presented no CDX2 and villin expression. The positive rates of CDX2 protein in cardiac gastritis with IM, dysplasia with IM, and carcinoma tissues were 84.0% (21/25), 66.7% (32/48) and 36.4% (20/55), respectively. While the positive rates of villin protein in cardiac gastritis with IM, dysplasia with IM, and carcinoma tissues were 76.0% (19/25), 70.8% (34/48) and 45.5% (25/55), respectively. There were significant differences among the three groups for both CDX2 and villin (P<0.01). Spearman's rank correlation coefficient(rho) showed a close correlation between the two proteins (r=0.843, P<0.01) and both were positively related with tumor differentiation (both P<0.05), but not associated with age, sex, invasion and metastasis of lymph node (P>0.05). Conclusion: Our results suggest that ectopic expression of CDX2 and villin may be involved in early-stage IM and tumorigenesis in gastric cardia and the expression of villin may be regulated by CDX2.

• 한국동물생명공학회지
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• 제34권4호
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• pp.292-299
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• 2019

Interferon tau (IFNT) regulation, an anti-luteolytic factor produced by conceptuses of the ruminant ungulates, is essential for the maintenance of early pregnancy, but a definitive mechanism for its temporal transcription has not been elucidated. We and others have observed the T-box protein eomesodermin (EOMES) exhibited high mRNA expression in the ovine embryonic trophectoderm; thus, both caudal-relatedhomeobox-2 (CDX2) and EOMES coexist during the early stages of conceptus development. Objective of this study was to examine the effect of EOMES on ovine IFNT gene transcription when evaluated with CDX2, ETS2 and AP1 transcription factors implicated in the control of cell differentiation in the trophectoderm. In this study, quantitatively via reverse transcription-polymerase chain reaction (RT-PCR) analysis between ovine trophoblast cells was initially performed, finding that transcription factors CDX2 and 'EOMES transcription factor mRNAs' were specific to trophectoderm cells. These mRNAs were also found in days 15, 17, and 21 ovine conceptuses. Furthermore, human choriocarcinoma JEG3 cells (trophoblast cell line) were cotransfected with an ovine IFNT (-654bp)-luciferase reporter (-654-oIFNT-Luc) construct and several transcription factor expression plasmids. Cotransfection of the reporter construct with CDX2, ETS2 and AP1 increased transcription of -654-oIFNT-Luc by about 11-fold compared with transfection of the construct alone. When cells were initially transfected with EOMES followed by transfection with CDX2, ETS2 and/or AP1, the expression of -654-oIFNT-Luc was decreased. Also, EOMES factor inhibited the stimulatory activity of CDX2 alone. These results suggest that when conceptuses attach to the uterine epithelium, ovine IFNT gene transcription is down-regulated by an increase of EOMES factor expression in the attached ovine trophoblast cells.

• Asian-Australasian Journal of Animal Sciences
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• 제26권5호
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• pp.638-645
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• 2013

Interferon-tau (IFNT) is thought to be the conceptus protein that signals maternal recognition of pregnancy in ruminants. We and others have observed that OCT4 expression persists in the trophectoderm of ruminants; thus, both CDX2 and OCT4 coexist during the early stages of conceptus development. The aim of this study was to examine the effect of CDX2 and OCT4 on IFNT gene transcription when evaluated with other transcription factors. Human choriocarcinoma JEG-3 cells were cotransfected with an ovine IFNT (-654-bp)-luciferase reporter (-654-IFNT-Luc) construct and several transcription factor expression plasmids. Cotransfection of the reporter construct with Cdx2, Ets2 and Jun increased transcription of -654-IFNT-Luc by about 12-fold compared with transfection of the construct alone. When cells were initially transfected with Oct4 (0 h) followed by transfection with Cdx2, Ets2 and/or Jun 24 h later, the expression of -654-IFNT-Luc was reduced to control levels. OCT4 also inhibited the stimulatory activity of CDX2 alone, but not when CDX2 was combined with JUN and/or ETS2. Thus, when combined with the other transcription factors, OCT4 exhibited little inhibitory activity towards CDX2. An inhibitor of the transcriptional coactivator CREB binding protein (CREBBP), 12S E1A, reduced CDX2/ETS2/JUN stimulated -654-IFNT-Luc expression by about 40%, indicating that the formation of an appropriate transcription factor complex is required for maximum expression. In conclusion, the presence of OCT4 may initially minimize IFNT expression; however, as elongation proceeds, the increasing expression of CDX2 and formation of the transcription complex leads to greatly increased IFNT expression, resulting in pregnancy establishment in ruminants.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5199-5205
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• 2013

Background/Aim: The Hippo signaling pathway is a newly discovered and conserved signaling cascade, which regulates organ size control by governing cell proliferation and apoptosis. This study aimed to investigate its effects in human gastric cancer. Methods: Tumor tissues (n=60), adjacent non-tumor tissues (n=60) and normal tissues (n=60) were obtained from the same patients with primary gastric cancer (GC). In addition, 70 samples of chronic atrophic gastritis (CAG) tissues were obtained from patients with intestinal metaplasia (IM) by endoscopic biopsy. Hippo signaling molecules, including Mst1, Lats1, YAP1, TAZ, TEAD1, Oct4 and CDX2, were determined by quantitative polymerase chain reaction (qPCR). Protein expression of Mst1, Lats1, YAP1, TEAD1 and CDX2 was assessed by immunohistochemistry and Western blotting. Results: Mst1, Lats1 and Oct4 mRNA expression showed an increasing tendency from GC tissues to normal gastric tissues, while the mRNA expression of YAP1, TAZ and TEAD1 was up-regulated (all P<0.01). Mst1 and Lats1 protein expression presented a similar trend with their mRNA expression. In addition, YAP1 and TEAD1 protein expression in GC was significantly higher than in the other groups (all P<0.01). CDX2 mRNA and protein expression in the CAG group were higher than in the other groups (all P<0.01). In GC, mRNA expression of Mst1, Lats1, Oct4, YAP1, TAZ, TEAD1 and CDX2 had a close correlation with lymphatic metastasis and tumor TNM stage (all P<0.01). Furthermore, protein expression of Mst1, Lats1, YAP1, TAZ, TEAD1 and CDX2 had a close correlation between each other (P<0.05). Conclusion: The Hippo signaling pathway is involved in the development, progression and metastasis of human gastric cancer. Therefore, manipulation of Hippo signaling molecules may be a potential therapeutic strategy for gastric cancer.

• 한국임상약학회지
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• 제5권2호
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• pp.13-16
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• 1995

The Minimum Inhibitory Concentration (MIC) of a first-generation cephalosporin derivative, Cefazedone (CZD; $PAZERON^R$ inj.) was determined by the two-fold serial agar dilution method. The in-vitro antibacterial activity of CZD against a wide variety of clinical isolates was compared with those of other first generation cephalosporins such as Methylol Cephalexin (CEX), Cefazolin (CEZ), Cefadroxil (CDX), Cephradine (CED), Ceftezol (CTZ) and one of second generation cephalsporin antibiotics, Cefotaxime (CTX). CZD had the most potent inhibitory effect against Gram-positive strains, when compared to the first-generation cephalosporin antibiotics tested in this study and CTX. The geometric MIC mean of CZD for Gram-positive strains was calculated as 0.386 kg/m{\ell}$, and those of CEX, CEZ, CDX, CTZ, CED, and CTX were 6.073, 0.894, 3.399, 0.748, 7.884 and 1.502 $kg/m{\ell}$, respectively. In addition, the geometric mean of CZD for staphylococclJs aureus strains was obtained as 0.340 $kg/m{\ell}$ and those of CEX, CEZ, CDX, CTZ, CED, and CTX 6.145, 0.534, 4.126, 0.442, 10.51, and 2.500 $kg/m{\ell}$, respectively. Against Gram-negative strains, CZD showed better antibacterial activity than CEZ, CDX, CTZ, and CED.

• 한국재료학회:학술대회논문집
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• 한국재료학회 1992년도 춘계학술발표회
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• pp.121-122
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• 1992

• Imaging Science in Dentistry
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• 제33권1호
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• pp.27-33
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• 2003

Purpose : The purpose of this experiment was to evaluate the diagnostic ability of a CCD-based digital system (CDX-2000HQ) in the detection of incipient dental caries. Materials and Methods : 93 extracted human teeth with sound proximal surfaces and interproximal artificial cavities were radiographed using 4 imaging methods. Automatically processed No.2 Insight film (Eastman Kodak Co., U.S.A.) was used for conventional radiography, scanned images of conventional radiograms for indirect digital radiography were used. For the direct digital radiography, the CDX-2000HQ CCD system (Biomedisys Co. Korea) was used. The subtraction images were made from two direct digital images by Sunny program in the CDX-2000HQ system. Two radiologists and three endodontists examined the presence of lesions using a five-point confidence scale and compared the diagnostic ability by ROC (Receiver Operating Characteristic) analysis and one way ANOV A test. Results: The mean ROC areas of conventional radiography, indirect digital radiography, direct digital radiography, and digital subtraction radiography were 0.9093, 0.9102, 0.9184, and 0.9056, respectively. The diagnostic ability of direct digital radiography was better than the other imaging modalities, but there were no statistical differences among these imaging modalities (p > 0.05). Coclusion : These results indicate that new CCD-based digital systems (CDX-2000HQ) have the potential to serve as an alternative to conventional radiography in the detection of incipient dental caries.