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Ultrasound-Triggered Drug Release of Hydroxyapatite Coated Liposomes
조성근,위태인,하정,조선행,한건,한희동,신병철,Cho, Sung Keun,Wee, Tae In,Ha, Jeung,Cho, Sun Hang,Han, Kun,Han, Hee Dong,Shin, Byung Cheol Korean Chemical Society 2013 대한화학회지 Vol.57 No.4
리포솜은 표적 약물을 봉입하여 병소에 안전하게 전달할 수 있는 약물전달체로서 연구되고 있다. 그러나 일반적인 리포솜은 표적부위에서 약물방출이 제한적인 문제점이 있다. 따라서 본 연구에서는 리포솜의 안정성을 향상시키고 표적부위에서 외부 초음파로부터 약물의 방출을 극대화시키기 위하여 하이드록시아파타이트(hydroxyapatite, HA)가 코팅된 리포솜을 개발하였다. 대조군 리포솜은 인지질과 콜레스테롤을 이용하여 제조하였고, 대조군 리포솜의 표면에 칼슘 아세테이트, 포스포릭에시드, 그리고 25% 암모니아용액을 이용하여 HA를 코팅하였다. 모델 약물로는 독소루비신을 사용하였다. HA코팅 리포솜의 크기는 120 nm 이었고, 약물봉입효율은 95% 이상이었다. 30% 혈장용액 내에서 HA코팅 리포솜의 입자크기는 일정한 상태를 유지하였으며, 대조군 리포솜은 크기가 1.4배 증가하였다. 외부 초음파 자극에 의한 리포솜으로부터 약물 방출을 유도한 후, 방출된 약물의 세포 이입율은 HA 코팅된 리포솜이 3배 이상 대조군 리포솜에 비하여 증가하였다. 본 연구에서는 외부 초음파 자극에 의하여 리포솜으로부터 약물의 방출을 극대화시키기 위한 초음파 민감형 리포솜을 개발하였고, 본 제형은 표적부위에서 약물의 방출을 효과적으로 제어하기 위한 분야에 활용이 가능할 것이다. Liposomes, which can deliver payload at target site, have been studied as drug carrier. However, conventional liposomes have limitation for drug release at target site. Therefore, we developed hydroxyapatite (HA) coated ultrasound sensitive liposomes to increase drug release at target site and to enhance stability in blood stream. Control liposome was prepared using hydrogenated soy phosphatidylcholine (HSPC) and cholesterol, and then we assessed HA coating on the surface of control liposomes using calcium acetate, phosphoric acid, and 25% ammonium solution. Doxorubicin was used as a model drug. Size of HA coated liposomes was 120 nm and encapsulation efficiency of doxorubicin in liposomes was up to 95%. Size of HA coated liposomes are not changed in 30% serum solution, however, the control liposomes was 1.4 fold increased. After ultrasound triggered drug release from liposomes, intracellular efficiency of drug released from HA coated liposomes was 3 fold increased compared to control liposomes. In this study, we developed ultrasound sensitive liposomes to enhance drug release, which will be applied in controlled drug release at disease site.
( Hang Goo Yun ),( Jin Ha Kim ),( Tae Hwa Lee ) 대한산부인과학회 2012 Obstetrics & Gynecology Science Vol.55 No.8
We describe here the case of a 65-year-old women presenting with a hemorrhagic tumor around the anterior vaginal wall and vulva. She was diagnosed with malignant fibrous histiocytoma from the findings of cytological analysis of biopsied surface tissue, histopathologic analysis of biopsied, and immunohistochemical staining. In her past history, twenty years ago, she was diagnosed with cervical cancer, staging Ib and received surgical treatment and chemotherapy. Ten years ago, she received radiotherapy because of recurrence of cervical cancer in vaginal vault. After surgical excision for malignant fibrous histiocytoma, we recommended chemotherapy but she refused. After 24 months from initial diagnosis, she died.
<i>Anemone rivularis</i> inhibits pyruvate dehydrogenase kinase activity and tumor growth
Chung, Tae-Wook,Lee, Jung Hee,Choi, Hee-Jung,Park, Mi-Ju,Kim, Eun-Yeong,Han, Jung Ho,Jang, Se Bok,Lee, Syng-Ook,Lee, Sang Woo,Hang, Jin,Yi, Li Wan,Ha, Ki-Tae Elsevier 2017 Journal of Ethnopharmacology Vol.203 No.-
<P><B>Abstract</B></P> <P><B>Ethnopharmacological relevance</B></P> <P> <I>Anemone rivularis</I> Buch.-Ham. ex DC. (Ranunculaceae) have been used as a traditional remedy for treatment of inflammation and cancer. However, there is no report demonstrating experimental evidence on anti-tumor action of <I>A. rivularis</I>.</P> <P><B>Aim of study</B></P> <P>The Warburg's effect, preference of aerobic glycolysis rather than oxidative phosphorylation (OXPHOS) even in oxygen rich condition, is focused as one of major characteristics of malignant tumor. Thus, we investigated the effect of <I>A. rivularis</I> on the Pyruvate dehydrogenase (PDH) kinases (PDHKs), a major molecular targets for reducing aerobic glycolysis.</P> <P><B>Materials and methods</B></P> <P>The ethanol extract of whole plant of <I>A. rivularis</I> (ARE), fingerprinted by high performance liquid chromatography (HPLC), was applied to <I>in vitro</I> and cell-based PDHK activity assays. The effect of ARE on cell viabilities of several tumor cells was estimated by MTT assay. The expression of phosphor-PDH, PDH and PDHK1 were measured by Western blot analysis. The production of reactive oxygen species (ROS) and apoptosis was measured by fluorescence-activated cell sorting analysis, using 5-(and-6)-carboxy-2′,7′-dichlorodihydrofluorescein diacetate (carboxy-H2DCFDA) and Annexin V/propidium iodide (PI) staining, respectively. Mitochondrial membrane potential was examined by tetramethylrhodamine methyl ester (TMRM) staining. <I>In vivo</I> anti-tumor efficacy of ARE was estimated by means of tumor volume and weight using allograft injection of murine Lewis lung carcinoma (LLC) cells to dorsa of C57BL/6 mice.</P> <P><B>Results</B></P> <P>ARE inhibited the viabilities of several cancer cells, including MDA-MB321, K562, HT29, Hep3B, DLD-1, and LLC. ARE suppressed PDHK activity in <I>in vitro</I> kinase assay, and also inhibited aerobic glycolysis by reducing phosphorylation of PDHA in human DLD-1 colon cancer and murine LLC cells. The expression of PDHK1, a major isoform of PDHKs in cancer, was not affected by ARE treatment. Moreover, ARE increased the both ROS production and mitochondrial damage. In addition, ARE suppressed the <I>in vitro</I> tumor growth through mitochondria-mediated apoptosis. The growth rates of allograft LLC cells were also reduced by ARE treatment.</P> <P><B>Conclusions</B></P> <P>Here, we firstly report that ARE inhibits PDHK activity and growth of tumor in both <I>in vitro</I> and <I>in vivo</I> experiments. Therefore, we suggest ARE as a potential candidate for developing anti-cancer drugs.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Ryu, Ha-Jung,Jung, Ho-Youl,Park, Jung-Sun,Ryu, Gil-Mi,Heo, Jee Yeon,Kim, Jae-Jung,Moon, Song-Mean,Kim, Hung-Tae,Lee, Jong-Young,Koh, Insong,Kim, Jun-Woo,Rho, Jae Kyun,Han, Bok-Ghee,Kim, Hyungtae,Park, S.Karger 2006 International archives of allergy and immunology Vol.139 No.3
<P><I>Background and Methods:</I> Numerous genetic studies have mapped asthma susceptibility genes to a region on chromosome 5q31-33 in several populations. This region contains a cluster of cytokines and other immune-related genes important in immune response. In the present study, to determine the genetic variations and patterns of linkage disequilibrium (LD), we resequenced all the exons and promoter regions of the 29 asthma candidate genes in the chromosome 5q31-33 region. <I>Results:</I> We identified a total of 314 genetic variants, including 289 single nucleotide polymorphisms (SNPs), 22 insertion/deletion polymorphisms and 3 microsatellites. Standardized variance data for allele frequency revealed substantial differences in SNP allele frequencies among different ethnic groups. Interestingly, significant ethnic differences were observed mainly in intron SNPs. LD block analysis using 174 common SNPs with a frequency of >10% disclosed strong LD within most candidate genes. No significant LD was observed across genes, except for one LD block (CD14-IK block). Gene-based haplotype analyses showed that 1-5 haplotype-tagging SNPs may be used to define the six or fewer common haplotypes with a frequency of >5%, regardless of the number of SNPs. <I>Conclusion:</I> Overall, our results provide useful information for the identification of immune-mediated disease genes in the chromosome 5q31-33 region, as well as valuable evidence for gene-based haplotype analysis in disease association studies.</P><P>Copyright © 2006 S. Karger AG, Basel</P>
Trends in the prevalence of chronic liver disease in the Korean adult population, 1998–2017
Seung Ha Park,Lindsay D. Plank,석기태,Yong Eun Park,Jin Lee,Joon Hyuk Choi,Nae Yun Heo,Jongha Park,Tae Oh Kim,Young Soo Moon,Hyun Kuk Kim,Hang Jea Jang,Ha Young Park,김동준 대한간학회 2020 Clinical and Molecular Hepatology(대한간학회지) Vol.26 No.2
Background/Aims: Data on the trends in the prevalence of chronic liver disease (CLD) in Korea are scarce. This study aimed to evaluate whether the CLD prevalence changed between 1998–2001 and 2016–2017. Methods: Data were extracted from the Korea National Health and Nutrition Examination Survey (1998–2001 to 2016– 2017; n=25,893). Non-alcoholic fatty liver disease (NAFLD) was defined as a hepatic steatosis index >36 in the absence of any other evidence of CLD. The definition of alcohol-related liver disease (ALD) was excessive alcohol consumption (≥210 g/week for men and ≥140 g/week for women) and an ALD/NAFLD index >0. Results: The prevalence of NAFLD increased from 18.6% (95% confidence interval [CI], 17.8–19.5%) in 1998–2001 to 21.5% (95% CI, 20.6–22.6%) in 2016–2017. During the same time period, increases were observed in the prevalence of obesity (27.0 vs. 35.1%), central obesity (29.4 vs. 36.0%), diabetes (7.5 vs. 10.6%), and excessive drinking (7.3 vs. 10.5%). ALD prevalence also increased from 3.8% (95% CI, 3.4–4.2%) to 7.0% (95% CI, 6.4–7.6%). In contrast, chronic hepatitis B decreased from 5.1% (95% CI, 4.6–5.5%) to 3.4% (95% CI, 3.0–3.8%). The prevalence of chronic hepatitis C was approximately 0.3% in 2016–2017. Conclusions: The prevalence of NAFLD and ALD increase among Korean adults. Our results suggest potential targets for interventions to reduce the future burden of CLD.