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Comparison of Efficacy of Tenofovir and Entecavir in Chronic Hepatitis B Patients with High HBV DNA
( Hongkeun Ahn ),( Yoon Jun Kim ),( Hyeki Cho ),( Young Youn Cho ),( Minjong Lee ),( Jeong-ju Yoo ),( Yuri Cho ),( Dong Hyeon Lee ),( Eun Ju Cho ),( Jeong-hoon Lee ),( Su Jong Yu ),( Jung-hwan Yoon ) 대한내과학회 2015 대한내과학회 추계학술대회 Vol.2015 No.1
Background and Aim: High Hepatitis B Virus (HBV) DNA is associated with increased risk of cirrhosis and hepatocellular carcinoma in chronic hepatitis B patients. There are few studies comparing the efficacy of tenofovir disoproxil fumarate (TDF) and entecavir (ETV) in patients with high HBV DNA. This study aimed to evaluate the efficacy of TDF and ETV in chronic hepatitis B patients with high HBV DNA. Methods: We conducted a retrospective analysis of data from 135 consecutive chronic hepatitis B patients with high HBV DNA titers (≥108 IU/mL). We included nucleos(t)ide analogue (NA) treatment-naive patients or NA-experienced patients without detectable genotypic resistance. 54 patients were treated with TDF and 81 were treated with ETV. Complete virologic response (CVR) rate in two groups was analyzed by Kaplan-Meier curve analysis and Cox proportional hazards model. Results: The median duration of follow-up was 16.6 months. The median time to CVR was 12.8 and 18.8 months in TDF group and ETV group, respectively (p=0.025 by log-rank test). In multivariate analysis, TDF group had significantly higher probability of CVR (hazard ratio [HR]= 1.64, 95% confidence interval [CI]=1.04-2.62; p=0.033) after adjustment for age, HBeAg status, and previous NA experience. The cumulative probability of HBeAg loss was not significantly different between two groups (p=0.163 by log-rank test). None of the patients had discontinued medication due to adverse reactions and GFR at each time point was not significantly different in two groups (p=0.106 by linear mixed model). Conclusions: Tenofovir disoproxil fumarate is superior to entecavir in achieving complete virologic response in chronic hepatitis B patients with HBV DNA greater than 108 IU/mL.
김도연,Park Suhyun,Yoo Hongkeun,Park Suhyeon,Kim Jeewon,Yum Kyuhee,김광명,Kim Hyuncheol 나노기술연구협의회 2020 Nano Convergence Vol.7 No.30
One of the major obstacles to successful chemotherapy is multi-drug resistance (MDR). A multi-drug resistant cancerous cell abnormally overexpresses membrane transporters that pump anticancer drugs out of the cell, resulting in low anticancer drug delivery efficiency. To overcome the limitation, many attempts have been performed to inhibit the abilities of efflux receptors chemically or genetically or to increase the delivery efficiency of anticancer drugs. However, the results have not yet been satisfactory. In this study, we developed nanoparticle-microbubble complexes (DOX-NPs/Ce6-MBs) by conjugating doxorubicin loaded human serum albumin nanoparticles (DOX-NPs) onto the surface of Chlorin e6 encapsulated microbubbles (Ce6-MBs) in order to maximize anticancer efficiency by overcoming MDR. Under the ultrasound irradiation, DOX-NPs and Ce6 encapsulating self-assembled liposomes or micelles were effectively delivered into the cells due to the sonoporation effect caused by the microbubble cavitation. At the same time, reactive oxygen (ROS) generated from intracellularly delivered Ce6 by laser irradiation arrested the activity of ABCG2 efflux receptor overexpressed in doxorubicin-resistant breast cancer cells (MCF-7/ADR), resulting in increased the chemotherapy efficacy. In addition, the total number of side population cells that exhibit the properties of cancer stem-like cells were also reduced by the combination of photodynamic therapy and chemotherapy. In conclusion, DOX-NPs/Ce6-MBs will provide a platform for simultaneously overcoming MDR and increasing drug delivery and therefore, treatment efficiency, under ultrasound irradiation.
External Stimuli-Responsive Melanin-Like Nanoparticles for Photoacoustic Imaging-Guided Therapy
Lee, Sunho,Lee, Hohyeon,Han, Hyounkoo,Yoo, Hongkeun,Kim, Haemin,Chang, Jin Ho,Kim, Hyuncheol American Scientific Publishers 2018 Science Of Advanced Materials Vol.10 No.5
<P>Photoacoustic (PA) imaging potential for biomedical applications, such as image-guide therapy, has been accelerated by exogenous contrast agent development, because of its real-time functional imaging and non-ionizing. The goal of this study was to develop melanin-like nanoparticles (MeINPs) for amplified PA imaging and pH stimuli-responsive local drug delivery. MeINPs were produced with dopamine hydrochloride and included catechol and quinone functional groups on the surface. pH sensitive MeINPs (pH-MeINPs) were synthesized by reversibly blocking free primary amines. pH-MeINPs are stable in pH > 7; however, in slightly acidic conditions (pH 5.6), pH-MeINPs are aggregated, resulting in the amplification of PA signals. Additionally, the chemotherapeutic agent, doxorubicin (DOX), was bound onto the surface of pH-MeINPs by pi-pi and hydrogen bonding. Finally, pH-MeINPs conjugated onto the surface of a 1-2-mu m sized microbubble (MB) for an externally ultrasound-controlled release of pH-MeINPs around a local tumor site. In addition, the efficient delivery and penetration of released pH-MeINPs into tumor cells can be expected because of the sonoporation of microbubbles. Results showed that under the exposure of ultrasound, DOX-pH-MeINPs were released from the microbubbles and delivered into cells more efficiently, compared to the ultrasound non-exposed control group, because of the sonoporation. The pH-MeINPs released the loaded DOX more effectively in acidic than neutral conditions. Therefore, MB-DOX-pH-MeINPs could be applied to tumor-specific PA amplification strategies; DOX-pH-MeINPs nanoparticles could be released around a tumor site with focused ultrasound, and then control DOX release locally in tumors in response to stimuli such as low pH and reactive oxygen species.</P>