Hepatic differentiation of the human hepatic progenitor cells (HPCs) by sodium butyrate (초)

( Pei Pei Hao ),( Xiang Dan Cui ),( Mi Jin Lee ),( Gyung Ran Yu ),( Dae Ghon Kim ) 대한간학회 2010 Clinical and Molecular Hepatology(대한간학회지) Vol.16 No.3(S)

HCV : PE-108 ; Progenitor cell-derived hepatocytes and their characteristics in human

( Pei Pei Hao ),( Mi Jin Lee ),( Goung Ran Yu ),( N Hee Kim ),( Dae Ghon Kim ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1

Background: Hepatic progenitor cells (HPCs) are capable of differentiating along the hepatic lineage into hepatocytes or cholangiocytes (bile duct cells), hence play a critical role in the process of liver regeneration. Their biological discrimination and characterization are critical for therapeutic potential. Aims of this study is to establish progenitor cell-derived hepatocytes and to characterize their specific markers. Methods: Potential liver progenitor cells (HNK-1) were established and their various HPC protein expressions were investigated by immunoblotting, immunofluorescence and fluorescence-activated cell sorting (FACS) analyses, compared with those of other HCC cells. Immunohistochemistry was performed to detect these HPC antigen expression in the tissues of hepatic cirrhosis. Anchorage-independent growth and tumorigenicity were determined using soft agar and xenograft assay. Results: The HNK-1 cells highly expressed HPC markers such as EpCAM, CK7, CK19, AFP, CK8, CK18, EFNA1, and Thy1. Whereas, CD133 was barely expressed. In contrast, malignant Hep3B cells were positive in both EpCAM and CD133. Ductular reactions at the periphery of the cirrhotic nodules were immunohistochemically positive for these HPC markers. Sodium butyrate could induce hepatocyte-like morphological changes in HNK-1 cells, accompanying down-regulation of the hepatic progenitor cell markers (EpCAM, CK7, CK19, and EFNA1) and up-regulation of mature hepatocyte markers (albumin, CK8, and CK18) in both dose-dependent and timedependent manners. Colony formation in vitro and tumorigenesis in vivo showed that there were no tumorigenesis capacity in EpCAM (+)/CD133(-) HNK1cells at the 0-2nd, 10th, 25th, and 50th passages, while the positive control EpCAM (+)/CD133(+) Hep3B cells could induce tumor in the mice model. Conclusions: Taken together, our results suggest that HNK1 cells are progenitor cell-derived hepatocytes and their stemmnessrelated markers EpCAM (+)/CD133(-) may be a distinguished marker for nonmalignant, progenitor cell-derived hepatocytes.

Basic, Research : Isolation of EpCAM+/CD133? Hepatic Progenitor Cells

( Pei Pei Hao ),( Mi Jin Lee ),( Goung Ran Yu ),( In Hee Kim ),( Dae Ghon Kim ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

Background/Aim: Hepatic progenitor cells (HPCs) are capable of differentiating along the hepatic lineage into hepatocytes or cholangiocytes. Progenitor cell-derived hepatocytes are critical for hepatocyte replenishment. Therefore, we have established human hepatic progenitor cells (HNK1) and determined their biological characteristics for experimental and therapeutic applications. Methods: Potential liver progenitor cells (HNK1) were established and their various HPC protein expressions were investigated by immunoblotting, immunofluorescence and fluorescence- activated cell sorting (FACS) analyses, compared with those of other HCC cells. Immunohistochemistry was performed to detect these HPC antigen expression in the tissues of hepatic cirrhosis. Albumin, ureagenesis and CYP450 activity were measured. Anchorage-independent growth and tumorigenicity were determined using soft agar and xenograft assay. Genetic constitution of the HNK1 was examined by karyotyping. Chromaosomal rearrangements at metaphase were detedted by Giemsa banding. Results: The HNK1 cells highly expressed HPC markers such as EpCAM, CK7, CK19, AFP, CK8, CK18, EFNA1, and Thy1. Whereas, CD133 was barely expressed. In contrast, malignant Hep3B cells were positive in both EpCAM and CD133. Ductular reactions at the periphery of the cirrhotic nodules were immunohistochemically positive for these HPC markers. Sodium butyrate could induce hepatocyte-like morphological changes in HNK1 cells, accompanying down-regulation of the hepatic progenitor cell markers (EpCAM, CK7, CK19, and EFNA1) and up-regulation of mature hepatocyte markers (albumin, CK8, and CK18). Albumin, ureagenesis, and CYP450 activity were also significantly increased by serial passages after treatment with sodium butyrate. Colony formation in vitro and tumorigenesis in vivo showed that there were no tumorigenesis capacity in EpCAM (+)/CD133(-) HNK1 cells at the 0-2nd,10th,25th,and 50th passages, while the positive co ntrol EpCAM (+)/CD133(+) Hep3B cells could induce tumor in the mice model. Conclusions: HNK1 cells were found to be EpCAM+/CD133? hepatic progenitor cells without spontaneous malignant transformation ability that could be useful for experimental and therapeutic applications. Moreover, EFNA1 should be recognized as an HPC marker.

Basic, HCC basic : PE-108 ; Progenitor cell-derived hepatocytes and their characteristics in human

( Pei Pei Hao ),( Mi Jin Lee ),( Goung Ran Yu ),( In Hee Kim ),( Dae Ghon Kim ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.-

Background: Hepatic progenitor cells (HPCs) are capable of differentiating along the hepatic lineage into hepatocytes or cholangiocytes (bile duct cells), hence play a critical role in the process of liver regeneration. Their biological discrimination and characterization are critical for therapeutic potential. Aims of this study is to establish progenitor cell-derived hepatocytes and to characterize their specific markers. Methods: Potential liver progenitor cells (HNK-1) were established and their various HPC protein expressions were investigated by immunoblotting, immunofluorescence and fluorescence-activated cell sorting (FACS) analyses, compared with those of other HCC cells. Immunohistochemistry was performed to detect these HPC antigen expression in the tissues of hepatic cirrhosis. Anchorage-independent growth and tumorigenicity were determined using soft agar and xenograft assay. Results: The HNK-1 cells highly expressed HPC markers such as EpCAM, CK7, CK19, AFP, CK8, CK18, EFNA1, and Thy1. Whereas, CD133 was barely expressed. In contrast, malignant Hep3B cells were positive in both EpCAM and CD133. Ductular reactions at the periphery of the cirrhotic nodules were immunohistochemically positive for these HPC markers. Sodium butyrate could induce hepatocyte-like morphological changes in HNK-1 cells, accompanying down-regulation of the hepatic progenitor cell markers (EpCAM, CK7, CK19, and EFNA1) and up-regulation of mature hepatocyte markers (albumin, CK8, and CK18) in both dose-dependent and time- dependent manners. Colony formation in vitro and tumorigenesis in vivo showed that there were no tumorigenesis capacity in EpCAM (+)/CD133(-) HNK1cells at the 0-2nd, 10th, 25th, and 50th passages, while the positive control EpCAM (+)/CD133(+) Hep3B cells could induce tumor in the mice model. Conclusions: Taken together, our results suggest that HNK1 cells are progenitor cell-derived hepatocytes and their stemmness- related markers EpCAM (+)/CD133(-) may be a distinguished marker for nonmalignant, progenitor cell-derived hepatocytes.

Fatty Acid Synthesis Pathway Genetic Variants and Clinical Outcome of Non-Small Cell Lung Cancer Patients after Surgery

Jin, Xin,Zhang, Ke-Jin,Guo, Xu,Myers, Ronald,Ye, Zhong,Zhang, Zhi-Pei,Li, Xiao-Fei,Yang, Hu-Shan,Xing, Jin-Liang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.17

Over-expression of de novo lipogenesis (DNL) genes is associated with the prognosis of various types of cancers. However, the effects of single nucleotide polymorphisms (SNPs) in these genes on recurrence and survival of non-small cell lung cancer (NSCLC) patients after surgery are still unknown. In this study, a total of 500 NSCLC patients who underwent surgery treatment were included. Eight SNPs in 3 genes (ACACA, FASN and ACLY) of the DNL pathway were examined using the Sequenom iPLEX genotyping system. Multivariate Cox proportional hazards regression and Kaplan-Meier curves were used to analyze the association of SNPs with patient survival and tumour recurrence. We found that two SNPs in the FASN gene were significantly associated with the recurrence of NSCLC. SNP rs4246444 had a significant association with lung cancer recurrence under additive model (hazard ratio [HR], 0.82; 95% confidence interval [95%CI], 0.67-1.00; p=0.05). Under the dominant model, rs4485435 exhibited a significant association with recurrence (HR, 0.75; 95%CI, 0.56-1.01; p=0.05). Additionally, SNP rs9912300 in ACLY gene was significantly associated with overall survival in lung cancer patients (HR, 1.41; 95%CI, 1.02-1.94, p=0.04) under the dominant model. Further cumulative effect analysis showed moderate dose-dependent effects of unfavorable SNPs on both survival and recurrence. Our data suggest that the SNPs in DNL genes may serve as independent prognostic markers for NSCLC patients after surgery.

Basic, HCCbasic : PO-20 ; DUSP1 induces p53 target gene expression through p38MAPK/HSP27 pathway and tumor suppression in hepatocellular carcinoma

( Pei Pei Hao ),( Mi Jin Lee ),( Yun Peng Wang ),( Goung Ran Yu ),( In Hee Kim ),( Dae Ghon Kim ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1

Background: Constitutive DUSP1 expression has been shown to be involved in cell cycle inhibition, apoptosis, and senescence. This study was aimed to examine whether DUSP1 functions as tumor suppressor in hepatocarcinogenesis and to explore underlying mechanism whereby DUSP1 suppresses hepatocarcinogenesis. Methods: Immunohistochemistry and real-time PCR analysis were performed in HCC tissues. Cellular localization of DUSP1 was detected by immunofluorescence. Cell proliferation was tested by MTT assay. Cell death and cell cycle were measured by FACS analysis. Apoptotic and kinase signaling were explored by western blot analysis. Tumorigenicity and survival analysis were tested by xenotransplant of SH-J1 cells stably expressing DUSP1 or infected with Ad-DUSP1 in mouse model. Phospho-related factors expression profile in DUSP1 stable cell lines as determined by phospho-kinase array. Results: The mRNA and protein expression level of DUSP1 was down-regulated in tumor than that of the corresponding non-tumor in HCC tissues. Cellular localization of DUSP1 showed that the endogenous DUSP1 and ectopic expression of GFP-tagged DUSP1 was mainly located in the nucleus. DUSP1 down-regulation was associated with reciprocal activation of ERK1/2 in HCC cell lines. DUSP1 was up-regulated in a dose dependent manner after parthenolide or doxorubicin treatment. DUSP1 over-expression was correlated with the increased susceptibility to apoptotic cell death through caspase activation. Ectopic DUSP1 over-expression resulted in the inhibitions of cell cycle progression, colony generation, and tumor growth in vitro and in vivo system. Furthermore, survival rate of mice xenoplanted with DUSP1 overexpressed HCC cells is significantly higher than control group. Inhibition of tumorigenic potential by DUSP1 may involve in p38MAPK- HSP27-P53 pathway. Conclusions: DUSP1 functions as a tumor suppressor during hepatocarcinogenesis, which seemed to be mainly associated with the activation of p53 target genes through p38MAPK/ HSP27 pathway.

‘Queer’ that Matters in Taiwan

Pei jin Chen 이화여자대학교 아시아여성학센터 2005 이화여자대학교 아시아여성학센터 학술대회자료집 Vol.2005 No.6

中國學界의 高句麗와 慕容鮮卑 관계 연구

金洪培(JIN, Hong-pei) 고구려발해학회 2016 고구려발해연구 Vol.55 No.-

중국 학계의 慕容鮮卑 연구는 주로 起源, 漢化, 문화 등 측면에 치중되어 있다. 대외관계 측면에서는 모용선비와 晉, 後趙, 前秦, 北魏 등 중원 정권과의 관계에 주목하였을 뿐, 중국 동북변강지역의 여러 민족들과의 관계, 특히나 고구려와의 관계에 대한 언급은 많지 않다. 또한 고구려의 대외관계연구에도 고구려가 취한 ‘西進戰略’의 가장 큰 걸림돌이었던 모용선비에 관한 논의가 많지 않다. 양자의 관계는 당시 중국 동북지역 내지는 朝鮮半島와 동북아지역의 세력 균형과 정치적 판도의 변화에 큰 영향을 미쳤다. 고구려와 모용선비 관계사에 관한 중국학계의 연구는 주로 고구려와 모용선비의 정치적 관계, 人的왕래, 三燕文化의 전파 및 영향 등에 초점이 맞춰져 있다. 전문 연구논저가 있기는 하나, 내용이 중복되는 경우가 많으며, 체계적으로 깊이 있게 다룬 연구는 아직 미흡한편이다. 기존연구에는 다음과 같은 문제점들이 나타나고 있다. 우선, 양자의 관계를 다룬 전문저서가 아직 발표되지 못하고 있으며, 다음으로, 아직 연구 시야가 제한적이며, 또 연구 성과가 비교적 적으며, 중복되는 현상이 나타나고 있다. 그리고 지명 고증 문제에 있어서, 진일보한 연구가 필요하며, 문화교류에 충분히 주목하지 못했다. 중국학계의 고구려와 모용선비 관계 연구는 아직 보완되어야 할 부분이 많이 남아 있다. 예를 들어, 고구려 대외관계사에서 모용선비는 어떤 위치에 있었는지, 고구려의 대외 전략 중심은 어디에 있었는지, ‘南進’과 ‘西進’은 어떠한 내재적 연관성을 가지고 있는지, 고구려의 요동지역 경영과 개발 문제, 고구려와 모용선비의 문화적 연관성 등은 향후 중국 학계에서 깊이 있게 연구 및 논의해야할 과제라 하겠다.

A Sphingosine Kinase-1 Inhibitor, SKI-II, Induces Growth Inhibition and Apoptosis in Human Gastric Cancer Cells

Li, Pei-Hua,Wu, Jin-Xia,Zheng, Jun-Nian,Pei, Dong-Sheng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.23

SKI-II has been reported as an inhibitor of sphingosine kinase 1 and has been extensively used to prove the involvement of sphingosine kinase and sphingosine-1-phosphate (Sphk1) in cellular processes. In the current study, we investigated the effects of SKI-II and its potential mechanisms in human gastric cancer SGC7901 cells. After treatment with SKI-II, cell growth, cell cycle distribution, apoptosis, expression of Sphk1, NF-${\kappa}B$, Bcl-2, Bax and p27 were assessed by MTT assay, flow cytometry, electron microscopy, immunocytochemistry and Western-blot assay, respectively. Our results showed that SKI-II markedly inhibited SGC7901 cell survival in a dose-dependent manner, reduced cell proliferation with accumulation of cells in the G0/G1 phase and induced apoptosis in the tumor cells. Furthermore, Western blotting and immunocytochemistry showed that the expression of p27 and Bax was increased significantly, but the expression of NF-${\kappa}B$, Bcl-2 and Sphk1 decreased by different degrees. These results indicate that SKI-II induced cell growth arrest and apoptosis. The increased apoptotic sensitivity of SGC7901 was correlated with NF-${\kappa}B$ or Bcl-2/Bax activation.

Microwave dielectric properties of BaV2O6 ceramics with ultra-low sintering temperature

Cui Jin Pei,Guog Guang Yao,Zhao Yu Ren 한양대학교 세라믹연구소 2016 Journal of Ceramic Processing Research Vol.17 No.7

Microwave dielectric properties of BaV2O6 ceramics were investigated for the first time. The BaV2O6 ceramic was preparedby the solid-state ceramic route. The phase constitution, microstructure, and compatibility with aluminum electrode wereinvestigated using XRD, Raman spectra and SEM. The results confirmed that that pure phase BaV2O6 could be obtained inthe sintering temperature range of 525 oC-600 oC. With an increase in the sintering temperature, the dielectric constant (εr)and quality factor (Qxf) first increase and decrease thereafter, the temperature coefficient of resonant frequency (τf) changesslightly. The BaV2O6 ceramic sintered at 575 oC/4 hr exhibited good microwave dielectric properties of εr = 11.5, τf = 38 ppm/ oC and Qxf = 21 800 GHz (at 10.1 GHz). Moreover, the material had a chemical compatibility with aluminum powders, whichrepresented a promising candidate material for ULTCC applications.