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진보환(Bohwan Jin),성제경(Je Kyung Seong),류덕영(Doug-Young Ryu) 한국환경성돌연변이발암원학회 2006 한국환경성돌연변이·발암원학회지 Vol.26 No.2
Background: Inorganic arsenic is a human carcinogen that can target the liver, but its carcinogenic mechanisms are still unknown. Inorganic arsenic induces a spectrum of tumors including hepatocellular carcinoma in mice. Methods: Pregnant C3H mice were supplied with drinking water containing 50 ppm sodium arsenite during their pregnancy. The protein expression profile in the liver of 0.5-day-old male offsprings exposed transplacentally to sodium arsenite was analyzed using protein 2D gel electrophoresis followed by mass spectrometry (MALDI-TOF). Results: Expression of proteins such as hydroxymethylglutaryl-CoA synthase mitochondrial precursor (HMG-CoA synthase), β-actin (cytoplasmic 1) and apolipoprotein A-IV precursor (Apo-AIV) were induced in mouse liver by sodium arsenite, while uricase (urate oxidase), guanine nucleotidebinding protein beta subunit 2-like 1 (RACK1) and fructose-bisphosphate aldolase B (Aldolase 2) were downregulated. Summary: Expression of proteins that have been implicated in carcinogenesis, such as HMG-CoA, β-actin, and RACK1, was regulated in the liver of mice transplacentally exposed to inorganic arsenic.
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Diethylnitrosamine에 의하여 유발된 마우스 간 종양의 CYP1A2 메틸화와 발현
진보환(Bohwan Jin),오새진(Saejin Oh),류덕영(Doug-Young Ryu) 한국환경성돌연변이발암원학회 2006 한국환경성돌연변이·발암원학회지 Vol.26 No.3
Cytochrome P450 1A2 (CYP1A2) is a xenobiotic metabolizing enzyme that is tissue-specifically expressed in the mammalian liver. In this study, the extent of CYP1A2 promoter methylation was analyzed to determine its potential role in the regulation of CYP1A2 in diethylnitrosamine (DEN)-induced mouse liver tumors. CYP1A2 mRNA was under-expressed about three fold in DEN-induced liver tumors compared to agematched control livers. The CYP1A2 promoter was hypermethylated in DEN-induced liver tumors compared to controls, especially in a promoter domain close to the coding region. These results suggest that promoter methylation is involved in the regulation of CYP1A2 in mouse liver tumors.
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세 겹 구조 자가팽창형 스텐트그라프트의 혈관생체적합성: 개 모델 연구
배재익,원제환,장은호,이성영,고광태,진보환,이준우,김지대 대한영상의학회 2012 대한영상의학회지 Vol.66 No.2
Purpose: To evaluate performance and biocompatibility of a newly designed self-expanding stent graft, which consisted of two nitinol stents and an intervening expanded polytetrafluoroethylene membrane in a dog artery model. Materials and Methods: Twelve stent grafts were placed in the aorta of 6 dogs (beagle, mean body weight 11 kg) for 4 weeks (n = 4) and 12 weeks (n = 8). Luminal diameters were measured for each segment (the proximal bare, the middle graft, the distal bare) by angiographies after implantation and follow up periods. Percent luminal stenosis based on angiographies, histomorphometric, histologic, and scanning electron microscopic analyses of each segments were performed. Results: Blood flow through the stent grafts was good after implantation and during the follow up period, without thrombotic occlusion or stent graft migration. The mean percent luminal stenosis of the proximal bare, the middle grafted and the distal bare segments after 12 weeks were 13.5%, 3.9%, 9.6% retrospectively. The mean neointimal areas of the middle grafted segment were 4.39 mm2 (4 week) and 4.92 mm2 (12 week). Mature endothelialization was evident in over 70% of the area of the stented artery after 4 weeks and in over 90% after 12 weeks. Conclusion: The stent graft was well placed in the attempted area without migration. During the 12-week-follow up period, it showed a good patency without thrombotic occlusion or significant in-stent luminal stenosis. Endothelialization was rapid and nearly complete. Neointima was thin and smooth on the middle graft segment and thicker and irregular on the bare segments. 목적: 새로 디자인된 형태로써 두 겹의 니티놀 스텐트 사이에 폴리테트로플루오르에틸렌막을 끼워서 고정한 세 겹 구조의 자가팽창형 스텐트그라프트의 혈관생체적합성을 개 모델에서 알아보고자 하였다. 대상과 방법: 여섯 마리의 개(평균체중 11 kg)에 각각 두 개의 스텐트그라프트(총 12개)를 대동맥 설치하고 2마리는 4주간 나머지 4마리는 12주간 추적관찰하였다. 스텐트그라프트 설치부의 내강의 변화를 보기 위하여 설치 전후 및 추적기간 후 혈관조영을 시행하였다. 신생내막의 증식정도와 염증정도는 광학현미경으로 관찰하고 측정하였다. 내막세포화의 정도와 성숙도는 전자현미경 검사를 시행하여 관찰하였다. 결과: 설치 후 혈류는 전 기간 동안 잘 유지되었고 혈전발생이나 스텐트그라프트 이동은 없었다. 12주 후 근위 비막(proximal bare)부분, 중간 막(middle graft)부분, 원위 비막(distal bare)부분 내강의 평균 퍼센트협착은 각각 13.5%, 3.9%, 9.6%였다. 4주군과 12주군의 중간 막부분의 평균 신생내막면적은 각각 평균 4.39 mm2와 4.92 mm2였다. 성숙된 혈관내피화는 4주군에서 70% 이상, 12주군에서 90% 이상의 범위에서 관찰되었다. 결론: 스텐트그라프트는 성공적으로 혈관 내 의도부위로 진입하여 잘 설치되었으며 위치의 이동은 발생하지 않았다. 또한 추적기간 동안 혈전 발생에 의한 내강협착이나 폐쇄는 없었다. 12주의 추적기간 이후에도 의미 있는 내강협착 없이 혈류가 잘 유지되었고, 내피세포화는 매우 빠르게 진행되었다. 신생내막은 그라프트막 부위에서는 얇고 균질하였으나 양끝의 비막부위에서는 불규칙하고 다소 두꺼웠다.
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Antitumor effect of TW-37, a BH3 mimetic in human oral cancer
안치현,이원우,정윤찬,신지애,홍경옥,최수정,Neeti Swarup,김지훈,안민혜,정민정,진보환,조성대 한국실험동물학회 2019 Laboratory Animal Research Vol.35 No.4
TW-37 is a small molecule B cell lymphoma-2 (Bcl-2) homology 3 mimetic with potential anticancer activities. However, the in vivo anti-cancer effect of TW-37 in human oral cancer has not been properly studied yet. Here, we attempted to confirm antitumor activity of TW37 in human oral cancer. TW-37 significantly inhibited cell proliferation and increased the number of dead cells in MC-3 and HSC-3 human oral cancer cell lines. TW-37 enhanced apoptosis of both cell lines evidenced by annexin V/propidium iodide double staining, sub-G1 population analysis and the detection of cleaved poly (ADP-ribose) polymerase and caspase-3. In addition, TW-37 markedly downregulated the expression of Bcl-2 protein, while not affecting Bcl-xL or myeloid cell leukemia-1. In vivo, TW-37 inhibited tumor growth in a nude mice xenograft model without any significant liver and kidney toxicities. Collectively, these data reveal that TW-37 may be a promising small molecule to inhibit human oral cancer.
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