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      • Molecular mechanism of Jmjd3‐mediated interleukin‐6 gene regulation in endothelial cells underlying spinal cord injury

        Lee, Kwanghyun,Na, Wonho,Lee, Jee Youn,Na, Jungtae,Cho, Heejung,Wu, Hongjin,Yune, Tae Young,Kim, Won,Sun,Ju, Bong‐,Gun Blackwell Publishing Ltd 2012 Journal of Neurochemistry Vol.122 No.2

        <P><I>J. Neurochem.</I> (2012) <B>122</B>, 272–282.</P><P><B>Abstract</B></P><P>The inflammatory response contributes substantially to secondary injury cascades after spinal cord injury, with both neurotoxic and protective effects. However, epigenetic regulations of inflammatory genes following spinal cord injury have yet to be characterized thoroughly. In this study, we found that histone H3K27me3 demethylase Jmjd3 expression is acutely up‐regulated in blood vessels of the injured spinal cord. We also observed up‐regulation of <I>Jmjd3</I> gene expression in bEnd.3 endothelial cells that were subjected to oxygen‐glucose deprivation/reperfusion injury. When <I>Jmjd3</I> was depleted by siRNA, oxygen‐glucose deprivation/reperfusion injury‐induced up‐regulation of IL‐6 was significantly inhibited. In addition, Jmjd3 associated with NF‐κB (p65/p50) and CCAAT‐enhancer‐binding protein β at the <I>IL‐6</I> gene promoter. The recruitment of Jmjd3 coincided with decreased levels of tri‐methylated H3K27 as well as increased levels of mono‐methylated H3K27 at the <I>IL‐6</I> gene promoter. Furthermore, <I>Jmjd3</I> depletion did not result in significant changes of methylation level of H3K27 at the <I>IL‐6</I> gene promoter. Collectively, our findings imply that Jmjd3‐mediated H3K27me3 demethylation is crucial for <I>IL‐6</I> gene activation in endothelial cells, and this molecular event may regulate acute inflammatory response and integrity of the blood‐spinal cord barrier following spinal cord injury.</P>

      • KCI등재

        Management of Regional Lymph Nodes in Localized Vulvar Carcinoma

        Won Il Jang(장원일),Hong-Gyun Wu(우홍균),Charn Il Park(박찬일),Sung Whan Ha(하성환),Hyo Pyo Lee(이효표),Soon Beom Kang(강순범),Yong Sang Song(송용상) 대한방사선종양학회 2008 Radiation Oncology Journal Vol.26 No.1

        목 적: 외음부 암환자에서 국소영역 치료실패에 대한 수술 후 방사선치료의 영향을 평가하고 임상적으로 림프절이 전 이가 없는 환자들에서 서혜부 림프절에 대한 치료방침을 결정해 보고자 하였다. 대상 및 방법: 1979년 10월부터 2004년 6월까지 서울대학교병원에서 일차성 외음부 암으로 치료를 받은 환자 66명에 대해 후향적 분석을 시행하였다. 이들 중에서 원격전이가 있는 2명, 고식적 목적으로 치료를 받은 6명, 이전에 골반부위 방사선 치료의 병력이 있는 3명, 추적관찰이 탈락된 4명, 의무기록이 불충분한 1명을 포함하여 16명의 환자들은 이번 분석에서 제외되었다. 50 명 중에 수술만 받은 환자가 35명, 수술과 방사선 치료를 받은 환자가 10명, 방사선 치료만을 받은 환자가 5명이었다. 결 과: 5년 전체 생존율과 무병 생존율은 각각 91%, 78%였다. 12명(26%)에서 치료 실패를 보였으며, 국소 실패가 8명, 영역림프절 전이가 3명, 원격 전이가 1명이었다. 수술과 방사선치료를 같이 받은 환자들이 수술만을 받은 환자들보다 위험요인을 더 많이 가지고 있었지만, 무병 생존율은 두 집단에서 통계적으로 유의한 차이를 보이지 않았다(5년무병 생존율 78% vs. 83%, p=0.66). 잠재성 림프절 전이의 빈도는 10%였다. 임상적으로 림프절 전이가 없었던 31명의 환자들 중에서 10명은 서혜부 림프절 절제술을 받지 않았지만, 이들 중에서 영역림프절 전이를 경험한 사람은 아무도 없었다. 결 론: 치료실패의 위험요인을 가진 외음부 암자들에게 수술 후 방사선 치료는 잠재적인 이점을 가지고 있다. 임상적으로 림프절 전이가 없는 위험도가 낮은 환자들에게는 서혜부 림프절 절제술을 하지 않는 것이나 서혜부 림프절에 대해 예방적 방사선치료를 하는 것에 대해서 고려해 볼 수 있겠다. Purpose: To evaluate the impact of postoperative radiotherapy on loco-regional failure in patients with vulvar carcinoma and to determine the treatment strategy for inguinal lymph nodes. Materials and Methods: Sixty-six patients who received treatment for primary vulvar carcinoma at Seoul National University Hospital, from October 1979 through June 2004, were retrospectively analyzed. Sixteen patients were excluded from the analysis due to the following reasons: distant metastases in two patients; palliative intent for six patients; previous radiotherapy given to the pelvis in three patients; follow-up loss after surgery for four patient; insufficient medical records for one patient. Of 50 eligible patients, 35 were treated with surgery alone (S), ten were treated with surgery followed by radiotherapy (S+RT), and five were treated with radiotherapy alone. Results: The 5-year overall survival (OS) and disease-free survival (DFS) rates of all patients were 91% and 78%, respectively. Twelve patients (26%) experienced treatment failures and the sites of initial failure were as follows: a primary site in eight patients; regional lymph nodes in three patients; the lung in one patient. Although risk factors for failure were more common in the S+RT group than the S group of patients (p <0.05), the DFS rates were similar for the two groups (5-year DFS rates, 78% vs. 83%, p=0.66). The incidences of occult lymph node metastases was 10%. Ten of 31 patients with clinically negative lymph nodes did not received inguinal lymph node dissection, but no patient experienced regional failure. Conclusion: Postoperative radiotherapy may have a potential benefit for patients with risk factors for failure. The omission of inguinal dissection or elective radiotherapy to the inguinal lymph nodes may be considered in low-risk patients with clinically negative lymph nodes.

      • A Randomized, Multicenter, Phase II Study of Cetuximab With Docetaxel and Cisplatin as Induction Chemotherapy in Unresectable, Locally Advanced Head and Neck Cancer

        Lee, Keun-Wook,Koh, Youngil,Kim, Sung-Bae,Shin, Sang-Won,Kang, Jin-Hyoung,Wu, Hong-Gyun,Sung, Myung-Whun,Keam, Bhumsuk,Kim, Dong-Wan,Kim, Tae Min,Kim, Kwang Hyun,Kwon, Tack-Kyun,Hah, J. Hun,Kim, In-Ah AlphaMed Press 2015 The oncologist Vol.20 No.10

        <P><B>Lessons Learned</B></P><P><OL><LI>Addition of cetuximab may affect tolerability and, in turn, affect eventual outcomes.</LI><LI>The incidence of prior human papillomavirus infection has emerged as an important variable that can confound trials enrolling patients with oropharyngeal cancer.</LI></OL></P><P><B>Background.</B></P><P>We investigated the efficacy of cetuximab when added to induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) in patients with locally advanced head and neck squamous cell carcinoma.</P><P><B>Methods.</B></P><P>Patients were randomized to receive three cycles of docetaxel and cisplatin (TP regimen) with or without cetuximab (TP plus cetuximab [CTP] vs. TP) as induction chemotherapy. Patients in the CTP arm received CCRT with cetuximab and cisplatin, whereas patients in the TP arm received cisplatin alone. The primary endpoint was the objective response rate (ORR) after induction chemotherapy.</P><P><B>Results.</B></P><P>Overall, 92 patients were enrolled. The ORRs for induction chemotherapy in the CTP and TP arms were not different (81% vs. 82%). Adding cetuximab lowered the completion rate of induction chemotherapy and CCRT and resulted in more frequent dose reductions of the induction chemotherapy, although this did not reach statistical significance. In the CTP and TP arms, respectively, the 3-year progression-free survival (PFS) rates were 70% and 56% (<I>p</I> = .359), and the overall survival (OS) rates were 88% and 74% (<I>p</I> = .313). When limited to patients who completed induction chemotherapy, 3-year PFS rates of 78% and 59% (<I>p</I> = .085) and OS rates of 94% and 73% (<I>p</I> = .045) were observed in the CTP and TP arms, respectively.</P><P><B>Conclusion.</B></P><P>Adding cetuximab to sequential treatment did not increase the treatment efficacy and resulted in greater toxicity. In the intent-to-treat population, neither PFS nor OS was improved by the addition of cetuximab to sequential treatment; however, a suggestion of improved survival outcomes was observed in patients completing cetuximab-containing induction chemotherapy.</P><P><B></B></P><P>• , </P><P>• </P><P><B></B></P><P><B><I>.</I></B> (CCRT) </P><P><B><I>.</I></B> 3 (TP) [TP+ (CTP) vs. TP] CCRT CTP , TP (ORR)</P><P><B><I>.</I></B> 92 CTP TP ORR (81% vs. 82%) CCRT , , CTP TP 3 (PFS) 70% 56% (<I>P</I> = 0.359), (OS) 88% 74% (<I>P</I> = 0.313), CTP TP 3 PFS 78% 59% (<I>P</I> = 0.085), OS 94% 73% (<I>P</I> = 0.045)</P><P><B><I>.</I></B> , , PFS OS, <I><B>The Oncologist</B></I> 2015;20:1119–1120</P>

      • SCOPUSKCI등재

        An Environmentally Friendly Method for Controlling Biomass in Biotrickling Filters for Air Pollution Control

        Won, Yang-Soo,Lee, Tae-Jin,Wu, Yo-Ping G.,Deshusses, Marc A. 한국공업화학회 2004 Journal of Industrial and Engineering Chemistry Vol.10 No.1

        Biomass accumulation is a major obstacle for long-term, stable operation of biotrickling filters treating high loadings of volatile organic compounds (VOCs). Clogging reduces pollutant removal and increases the pressure drop in biotrickling filters. Several options exist to remove excess biomass or to slow down the accumulation rate, but so far none has succeeded in combining a high VOC removal rate with a low biomass net growth rate. Recently, we observed the invasion of some of our biotrickling filters by small flies. In the best cases, a rapid reduction of the biomass content was observed. The fly larvae rapidly spread throughout the reactor and biomass was rapidly removed from the packing, initially at a rate of 13.1 kg wet weight/m^(3).day and increasing up to 70-140 kg/m^(3) of reactor ' day. In that case, the wet biomass content in the reactor was reduced from 455 to 28 kg/m^(3) of reactor in 16 days with 80% of the biomass reduction occurring in 2-4 days. Analysis of the recycle liquid indicated that the major mechanism of biomass removal was detachment of biofilm, although experiments are underway to determine the exact proportion of biofilm detachment and consumption by larvae. We speculate that larval activity loosened the biofilm structure, thus enhancing biofilm detachment by shear-stress from the trickling liquid. Overall, the preliminary results presented herein highlight that the use of fly or other larvae presents a tremendous potential for controlling biomass in biotrickling filters.

      • SCOPUSSCIE

        Nanoscale Friction on Confined Water Layers Intercalated between MoS<sub>2</sub> Flakes and Silica

        Lee, Hyunsoo,Jeong, Hochan,Suh, Joonki,Doh, Won Hui,Baik, Jaeyoon,Shin, Hyun-Joon,Ko, Jae-Hyeon,Wu, Junqiao,Kim, Yong-Hyun,Park, Jeong Young American Chemical Society 2019 The Journal of Physical Chemistry Part C Vol. No.

        <P>Frictional energy dissipation at the interfaces of two-dimensional (2D) materials through the excitation and transfer processes of kinetic energy into the bulk can be easily influenced by an intercalated water film. An enhancement of friction on water-intercalated graphene has been observed. Is this frictional enhancement by confined water a general phenomenon? We address this issue by investigating the frictional behavior of confined water layers intercalated between single-layer molybdenum disulfide (MoS<SUB>2</SUB>), synthesized using chemical vapor deposition, and a silica substrate. The icelike water was intercalated by exposure to high-humidity air. We found that the intercalated water molecules morphologically deform the 2D MoS<SUB>2</SUB> sheet, forming distinct subdomains after the exposure to high humidity. We found that the adsorption of the icelike water layer between the MoS<SUB>2</SUB> and the silica leads to friction enhancement, compared with a pristine MoS<SUB>2</SUB>/silica sample, which is associated with additional phononic friction energy dissipation at the solid-liquid interface, as indicated by the phonon distribution analysis from the empirical force-field calculations. Moreover, the atomic stick-slip behavior shows that the lattice orientation of the hydrophilic MoS<SUB>2</SUB> affects water molecule diffusion at the interface of the MoS<SUB>2</SUB>/silica substrate. Chemical mapping of the water-intercalated MoS<SUB>2</SUB> on silica using scanning photoelectron microscopy and vacuum annealing processes shows water intercalation without changing the intrinsic composition of the MoS<SUB>2</SUB> on silica.</P> [FIG OMISSION]</BR>

      • <i>En bloc</i> and segmental deletions of human <i>XIST</i> reveal X chromosome inactivation-involving RNA elements

        Lee, Hyeon J,Gopalappa, Ramu,Sunwoo, Hongjae,Choi, Seo-Won,Ramakrishna, Suresh,Lee, Jeannie T,Kim, Hyongbum H,Nam, Jin-Wu Oxford University Press 2019 Nucleic acids research Vol.47 No.8

        <P><B>Abstract</B></P><P>The <I>XIST</I> RNA is a non-coding RNA that induces X chromosome inactivation (XCI). Unlike the mouse <I>Xist</I> RNA, how the human <I>XIST</I> RNA controls XCI in female cells is less well characterized, and its functional motifs remain unclear. To systematically decipher the XCI-involving elements of <I>XIST</I> RNA, 11 smaller <I>XIST</I> segments, including repeats A, D and E; human-specific repeat elements; the promoter; and non-repetitive exons, as well as the entire <I>XIST</I> gene, were homozygously deleted in K562 cells using the Cas9 nuclease and paired guide RNAs at high efficiencies, followed by high-throughput RNA sequencing and RNA fluorescence <I>in situ</I> hybridization experiments. Clones containing <I>en bloc</I> and promoter deletions that consistently displayed no <I>XIST</I> RNAs and a global up-regulation of X-linked genes confirmed that the deletion of <I>XIST</I> reactivates the inactive X chromosome. Systematic analyses of segmental deletions delineated that exon 5 harboring the non-repeat element is important for X-inactivation maintenance, whereas exons 2, 3 and 4 as well as the other repeats in exon 1 are less important, a different situation from that of mouse <I>Xist</I>. This Cas9-assisted dissection of <I>XIST</I> allowed us to understand the unique functional domains within the human <I>XIST</I> RNA.</P>

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