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Kö,nig, Alexander,Yang, Jaewon,Jo, Eunji,Park, Kyu Ho Paul,Kim, Hyun,Than, Thoa Thi,Song, Xiyong,Qi, Xiaoxuan,Dai, Xinghong,Park, Soonju,Shum, David,Ryu, Wang-Shick,Kim, Jung-Hee,Yoon, Seung Kew,P Elsevier 2019 Journal of hepatology Vol.71 No.2
<P><B>Background & Aims</B></P> <P>As hepatitis B virus (HBV) spreads through the infected liver it is simultaneously secreted into the blood. HBV-susceptible <I>in vitro</I> infection models do not efficiently amplify viral progeny or support cell-to-cell spread. We sought to establish a cell culture system for the amplification of infectious HBV from clinical specimens.</P> <P><B>Methods</B></P> <P>An HBV-susceptible sodium-taurocholate cotransporting polypeptide-overexpressing HepG2 cell clone (HepG2-NTCPsec+) producing high titers of infectious progeny was selected. Secreted HBV progeny were characterized by native gel electrophoresis and electron microscopy. Comparative RNA-seq transcriptomics was performed to quantify the expression of host proviral and restriction factors. Viral spread routes were evaluated using HBV entry- or replication inhibitors, visualization of viral cell-to-cell spread in reporter cells, and nearest neighbor infection determination. Amplification kinetics of HBV genotypes B-D were analyzed.</P> <P><B>Results</B></P> <P>Infected HepG2-NTCPsec+ secreted high levels of large HBV surface protein-enveloped infectious HBV progeny with typical appearance under electron microscopy. RNA-seq transcriptomics revealed that HBV does not induce significant gene expression changes in HepG2-NTCPsec+, however, transcription factors favoring HBV amplification were more strongly expressed than in less permissive HepG2-NTCPsec−. Upon inoculation with HBV-containing patient sera, rates of infected cells increased from 10% initially to 70% by viral spread to adjacent cells, and viral progeny and antigens were efficiently secreted. HepG2-NTCPsec+ supported up to 1,300-fold net amplification of HBV genomes depending on the source of virus. Viral spread and amplification were abolished by entry and replication inhibitors; viral rebound was observed after inhibitor discontinuation.</P> <P><B>Conclusions</B></P> <P>The novel HepG2-NTCPsec+ cells efficiently support the complete HBV life cycle, long-term viral spread and amplification of HBV derived from patients or cell culture, resembling relevant features of HBV-infected patients.</P> <P><B>Lay summary</B></P> <P>Currently available laboratory systems are unable to reproduce the dynamics of hepatitis B virus (HBV) spread through the infected liver and release into the blood. We developed a slowly dividing liver-derived cell line which multiplies infectious viral particles upon inoculation with patient- or cell culture-derived HBV. This new infection model can improve therapy by measuring, in advance, the sensitivity of a patient’s HBV strain to specific antiviral drugs.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Cell culture system that mimicks complete HBV life cycle from entry to egress. </LI> <LI> Efficient <I>in vitro</I> infection with crude HBV patient sera. </LI> <LI> Up to 50- and 1,300-fold net amplification of patient- and cell culture-derived input HBV in the supernatant. </LI> <LI> Polyethylene glycol-independent HBV spread to adjacent cells, forming infected cell clusters. </LI> <LI> Evaluation of patient- and cell culture-derived HBV amplification w/wo antivirals over 8 weeks. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
김종화,박명균,양진승 명지대학교 산업기술연구소 2001 産業技術硏究所論文集 Vol.20 No.-
Usually the contact between fin collar and tube surface for fin-tube heat exchanger is secured by mechanical expansion of the tubes. The objective of the present study is to analyzed the stress distribution around the contact region between the tube and fin. Through this numerical analysis, the thermal contact resistance between them could be understood well so that the performance of heat exchanger could be improved.
Jin, Hua,Kim, Tae Hee,Hwang, Soon-Kyung,Chang, Seung-Hee,Kim, Hyun Woo,Anderson, Hanjo K,Lee, Han-Woong,Lee, Kee-Ho,Colburn, Nancy H,Yang, Hsin-Sheng,Cho, Myung-Haing,Cho, Chong Su American Association for Cancer Research, Inc 2006 Molecular cancer therapeutics Vol.5 No.4
<P>The low efficiency of conventional therapies in achieving long-term survival of patients with lung cancer calls for development of novel treatment options. Although several genes have been investigated for their antitumor activities through gene delivery, problems surrounding the methods used, such as efficiency, specificity, and toxicity, hinder application of such therapies in clinical settings. Aerosol gene delivery as nonviral and noninvasive method for gene therapy may provide an alternative for a safer and more effective treatment for lung cancer. In this study, imidazole ring-containing urocanic acid-modified chitosan (UAC) designed in previous study was used as a gene carrier. The efficiency of UAC carrier in lungs was confirmed, and the potential effects of the programmed cell death protein 4 (PDCD4) tumor suppressor gene on three major pathways (apoptosis, cell cycle, and angiogenesis) were evaluated. Aerosol containing UAC/PDCD4 complexes was delivered into K-ras null lung cancer model mice through the nose-only inhalation system developed by our group. Delivered UAC/PDCD4 complex facilitated apoptosis, inhibited pathways important for cell proliferation, and efficiently suppressed pathways important for tumor angiogenesis. In summary, results obtained by Western blot analysis, immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated nick end labeling assay suggest that our aerosol gene delivery technique is compatible with in vivo gene delivery and can be applied as a noninvasive gene therapy.</P>
Genomic Alterations in Biliary Tract Cancer Using Targeted Sequencing <sup>1</sup>
Yoo, Kwai Han,Kim, Nayoung K.D.,Kwon, Woo Il,Lee, Chung,Kim, Sun Young,Jang, Jiryeon,Ahn, Jungmi,Kang, Mihyun,Jang, Hyojin,Kim, Seung Tae,Ahn, Soomin,Jang, Kee-Taek,Park, Young Suk,Park, Woong-Yang,Le Neoplasia Press 2016 Translational oncology Vol.9 No.3
<P><I>Background:</I> Biliary tract cancers (BTCs) are rare and heterogeneous group of tumors classified anatomically into intrahepatic and extrahepatic bile ducts and gallbladder adenocarcinomas. Patient-derived tumor cell (PDC) models with genome analysis can be a valuable platform to develop a method to overcome the clinical barrier on BTCs. <I>Material and Methods:</I> Between January 2012 and June 2015, 40 BTC patients’ samples were collected. PDCs were isolated and cultured from surgical specimens, biopsy tissues, or malignant effusions including ascites and pleural fluid. Genome analysis using targeted panel sequencing as well as digital multiplexed gene analysis was applied to PDCs as well as primary tumors. <I>Results:</I> Extrahepatic cholangiocarcinoma (<I>N</I> = 15, 37.5%), intrahepatic cholangiocarcinoma (<I>N</I> = 10, 25.0%), gallbladder cancer (<I>N</I> = 14, 35.0%), and ampulla of Vater cancer (<I>N</I> = 1, 2.5%) were included. We identified 15 mutations with diverse genetic alterations in 19 cases of BTC from primary tumor specimens. The most common molecular alterations were in TP53 (8/19, 42.1%), including missense mutations such as C242Y, E285K, G112S, P19T, R148T, R248Q, and R273L. We also detected two NRAS mutations (G12C and Q61L), two KRAS mutations (G12A and G12S), two ERBB2 mutations (V777L and pM774delinsMA) and amplification, and three PIK3CA mutations (N345K, E545K, and E521K). PDC models were successfully established in 27 of 40 samples (67.5%), including 22/24 from body fluids (91.7%) and 5/16 from tissue specimens (31.3%). <I>Conclusions:</I> PDC models are promising tools for uncovering driver mutations and identifying rational therapeutic strategies in BTC. Application of this model is expected to inform clinical trials of drugs for molecular-based targeted therapy.</P>
Central Neurocytoma: A Review of Clinical Management and Histopathologic Features
Seung J. Lee,Timothy T. Bui,Cheng Hao Jacky Chen,Carlito Lagman,Lawrance K. Chung,Sabrin Sidhu,David J. Seo,William H. Yong,Todd L. Siegal,김민수,Isaac Yang 대한뇌종양학회 2016 Brain Tumor Research and Treatment Vol. No.
Central neurocytoma (CN) is a rare, benign brain tumor often located in the lateral ventricles. CN may cause obstructive hydrocephalus and manifest as signs of increased intracranial pressure. The goal of treatment for CN is a gross total resection (GTR), which often yields excellent prognosis with a very high rate of tumor control and survival. Adjuvant radiosurgery and radiotherapy may be considered to improve tumor control when GTR cannot be achieved. Chemotherapy is also not considered a primary treatment, but has been used as a salvage therapy. The radiological features of CN are indistinguishable from those of other brain tumors; therefore, many histological markers, such as synaptophysin, can be very useful for diagnosing CNs. Furthermore, the MIB-1 Labeling Index seems to be correlated with the prognosis of CN. We also discuss oncogenes associated with these elusive tumors. Further studies may improve our ability to accurately diagnose CNs and to design the optimal treatment regimens for patients with CNs.