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- 저자 : 조홍찬(Hongchan Cho) (검색결과 2 건)
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Naked DNA를 이용한 말초동맥폐색질환 치료용 VEGF 발현벡터의 안전성 실험
이영주(YoungJoo Lee),박은진(EunJin Park),조홍찬(HongChan Cho),서연림(Yeon-Lim Suh),김덕경(Duk-Kyung Kim),김선영(Sunyoung Kim) 한국독성학회 1999 Toxicological Research Vol.15 No.3
It has been demonstrated that injection of naked DNA expressing vascular endothelial growth factor (VEGF) to the affected area can provide significant therapeutic effects on peripheral artery occlusive disease. Success with this type of gene therapy highly depends on the quality of the vector delivering the therapeutic gene, especially in terms of the level and duration of gene expression in the localized area. We have recently developed an expression vector that can produce significantly higher levels of VEGF in the mouse model. This report is part of preclinical studies documenting the safety of this newly developed expression plasmids expressing VEGF165 (pCN-VEGF and pCK-VEGF) in the BALB/C mouse model. When these naked DNAs were introduced to the anterior tibialis muscle of the mouse, VEGF was transiently expressed at the site of injection. To test the possibility of movement of the injected plasmid to other tissues, which might potentially cause undesirable side effects, we have examined plasmid dissemination by polymerase chain reaction (PCR) of DNAs isolated from various tissues (heart, liver, lung, spleen, testis, muscle) at 2 days following the injection of naked DNA. Despite high level expression of the VEGF protein in anterior tibialis muscle treated with naked DNA, the exogenously added gene was not detectable in tissues other than the injected area. This is probably due to the instability of naked DNA in the blood stream as well as the extreme inefficiency of naked DNA in reaching the nucleus and driving gene expression in cell types other than muscle. We have systematically retrieved various tissue sections (liver, heart, testis, lung, spleen, muscle) and examined for pathological features that could be caused by the presence of naked DNA and expression of VEGF. No pathological features were found in all tissues and organs tested. Specifically, no evidence of neoangiogenisis was identified in any tissue specimens. Similarly, no histological evidence of a pathologic immune response was observed.
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마우스에서 VEGF 발현 Naked DNA 벡터인 pCK-VEGF의 약동력학 및 조직내 분포
도현미(Hyounmie Doh),고준일(Jun-IL Ko),이종진(Jong-Jin Lee),손미원(Miwon Son),조홍찬(Hongchan Cho),김종묵(Jong-Mook Kim ),김병문(Byong-Moon Kim),김선영(Sunyoung Kim) 大韓藥學會 2001 약학회지 Vol.45 No.1
We recently developed a high dfficiency expression vector, pCK, which drives a high level of gane expresion in the skeletal muscles of mice. In this study, we investigated the pharmacokinetics and biodistribution of pCK-VEGF expressing human VEGF165 after intravenous or intramuscular administration. The quantity of pCK-VEGF in the tissues of mice was measured by the PCR method which has a detection limit of approxinately 1 pg of the exogenously added plasmid In the case of intravenous administration, the half life of the pCK-VEGF plasmid in the bloodstream was 1.68 min. After inter-muscular adminstration, the half life of pCK-VEGF plasmid in the bloodstrean was 6.78 min. At 90 min post-administration, 30% of the injected pCK-VEGF was found at the site of injection, where it persisted for up to 8 hours. Less than 1.6% of the injected pCK-VEGF plasmid DNA was detected in highly vascularized tissues such as the lung, kidney, and liver at 90 min post-administration administrated pCK- VEGF presisted for longer periods of time in muscls than in other tissues and that direct intra-muscular injection of pCK-VEGF might be useful for local therapeutic angiogensis.
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