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A Phase 1 Study Using Autologous Natural Killer Cells in Patients with HAIC-Hepatocellular Carcinoma
( Sung Bum Cho ),( Chung Hwan Jun ),( Sung Kyu Choi ),( Woo Kyun Bae ),( Je Jung Lee ),( Yang Jun Kang ),( Cheol Kyun Cho ),( Yang Seok Ko ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Aims: Natural killer (NK) cell-based immunotherapy has recently been tried with advances of understanding the role of immune defense against hepatocellular carcinoma (HCC). To improve NK cells therapy, we focused to increasing delivery of NK cells and synergic effect combined with hepatic arterial infusion chemotherapy (HAIC). Methods: We did a prospective, open label, phase 1 trial of the safety and efficacy of autologous NK cells through hepatic arterial infusion as sequential therapy after HAIC in advanced HCC patients. Between March 2016 and July 2017, 11 patients were included who showed favorable response more than stable disease (SD) after 2 sessions of HAIC in advanced HCC patients with child A. A total 4 sessions of HAIC were performed the protocols of infusion of cisplatin (25/m2) and 5-fluorouracil (750/m<sup>2</sup>) for 4 days every 3-4 weeks interval. The peripheral blood mononuclear cells of patients by leukapheresis were ob-tained after 3<sup>rd</sup> HAIC and NK cells were expanded for 2 weeks under Current Good Manufacturing Practices (cGMP). Patients received planned dosage of NK cells through chemoport into hepatic artery for 5 days after 4<sup>th</sup> HAIC (3 patients; 2.5x108, 3 patients; 5x10<sup>8</sup>, 5 patients; injection of 10x10<sup>8</sup> NK cells). The primary end point was safety of NK cell injection; secondary endpoint included objective response rate (modified Response Evaluation Criteria In Solid Tumors), time to progression, dura-tion of response and immunologic efficacy. Results: Any adverse events of NK cells injection were none according to dosage. An objective response was observed in 7 patients (63.6%) included three complete responses and four partial responses. Stable disease was observed in 2 patients and progressive disease was in 2 patients and thus disease control rate was 81.8%. The mean duration of time to progression was 9.7±5.3 month and duration of response without chemotherapy was 6.1±5.2 month. The newly metastatic lesion was occurred in 3 patents (27.2%; lymph node 1 patients, Lung 2 patients). Two patients were died by tumor progression and others were still alive. The increasing immunologic response was observed in 5 patients (55 %) to evaluate cytotoxicity and NK cell proportion of peripheral mononuclear cells after NK cell injection. Conclusions: The HAIC and NK cells immunotherapy is safe and effective treatment in the advance HCC patient with favorable liver function. The additional studies are urgently required to establish the new novel treatment.
( Sang Jun Song ),( Dae Kyung Bae ),( Se Hwan Park ),( Cheol Hee Park ) 대한슬관절학회 2023 대한슬관절학회지 Vol.35 No.-
Background Although intraoperative navigation can improve the surgeon’s proficiency, no studies have analyzed postoperative outcomes of high tibial osteotomy (HTO) after computer-assisted surgery (CAS) experience. The present study compared the clinical and radiographic results between conventional and CAS closed-wedge (CW) HTOs after CAS experience. Methods Each of the 50 conventional and CAS CW HTOs performed by single surgeon between 2015 and 2017 were included. The surgeon had experience of 140 cases of CAS CW HTOs before the study period. The groups were not different in terms of demographics. Clinically, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and range of motion (ROM) were investigated. Radiographically, the mechanical axis (MA), change in posterior tibial slope angle (PTS), and parallel angle were evaluated. The proportions of inlier groups for the postoperative MA (within valgus 2° ± 3°), change in the PTS (within ± 3°), and parallel angle (< 3°) were compared. Results There were no significant differences in postoperative clinical results between the conventional and CAS groups. The MA was appropriately corrected in both groups (2.4° versus 2.9°, p = 0.317). The amount of change in PTS was significantly greater in the conventional group (-2.2° versus -0.8°, p = 0.018). The parallel angle was 5.3° in the conventional groups and 3.1° in the CAS group (p = 0.003). The proportion of inlier group was not significantly different in the postoperative MA (72% versus 78%) and change in the PTS (52% versus 66%). The proportion of inlier for the parallel angle was significantly lower in the conventional group (36% versus 60%, p = 0.027). Conclusions The surgical proficiency after CAS experience could cover the advantages of an intraoperative navigation in coronal adjustment, not in the sagittal adjustments in CW HTOs. A larger cohort with multiple surgeons in multiple centers would be required to identify the general trend. Study design Level of evidence III.
SPA0355 attenuates ischemia/reperfusion-induced liver injury in mice
Bae, Ui-Jin,Yang, Jae Do,Ka, Sun-O,Koo, Jeung-Hyun,Woo, Seong Ji,Lee, Young-Rae,Yu, Hee Chul,Cho, Baik Hwan,Zhao, Hui-Yuan,Ryu, Jae-Ha,Lee, Sang-Myeong,Jeon, Raok,Park, Byung-Hyun Nature Publishing Group 2014 Experimental and molecular medicine Vol.46 No.8
<P>Hepatic ischemia/reperfusion (I/R) injury leads to oxidative stress and acute inflammatory responses that cause liver damage and have a considerable impact on the postoperative outcome. Much research has been performed to develop possible protective techniques. We aimed to investigate the efficacy of SPA0355, a synthetic thiourea analog, in an animal model of hepatic I/R injury. Male C57BL/6 mice underwent normothermic partial liver ischemia for 45 min followed by varying periods of reperfusion. The animals were divided into three groups: sham operated, I/R and SPA0355 pretreated. Pretreatment with SPA0355 protected against hepatic I/R injury, as indicated by the decreased levels of serum aminotransferase and reduced parenchymal necrosis and apoptosis. Liver synthetic function was also restored by SPA0355 as reflected by the prolonged prothrombin time. To gain insight into the mechanism involved in this protection, we measured the activity of nuclear factor-κB (NF-κB), which revealed that SPA0355 suppressed the nuclear translocation and DNA binding of NF-κB subunits. Concomitantly, the expression of NF-κB target genes such as <I>IL-1</I>β<I>, IL-6, TNF-</I>α and <I>iNOS</I> was significantly downregulated. Lastly, the liver antioxidant enzymes superoxide dismutase, catalase and glutathione were upregulated by SPA0355 treatment, which correlated with the reduction in serum malondialdehyde. Our results suggest that SPA0355 pretreatment prior to I/R injury could be an effective method to reduce liver damage.</P>
Bae, Sang-Eun,Oh, Mi-Kyung,Min, Nam-Ki,Paek, Se-Hwan,Hong, Suk-In,Lee, Chi-Woo J. Korean Chemical Society 2004 Bulletin of the Korean Chemical Society Vol.25 No.12
Electrochemical, in situ electrochemical scanning tunneling microscope (EC-STM), and attenuated total reflectance-FTIR (ATR-FTIR) spectroscopic methods were employed to investigate the preparation of atomically flat Si(111)-H surface in ammonium fluoride solutions. Electrochemical properties of atomically flat Si(111)-H surface were characterized by anodic oxidation and cathodic hydrogen evolution with the open circuit potential (OCP) of ca. -0.4 V in concentrated ammonium fluoride solutions. As soon as the natural oxide-covered Si(111) electrode was immersed in fluoride solutions, OCP quickly shifted to near -1 V, which was more negative than the flat band potential of silicon surface, indicating that the surface silicon oxide had to be dissolved into the solution. OCP changed to become less negative as the oxide layer was being removed from the silicon surface. In situ EC-STM data showed that the surface was changed from the initial oxidecovered silicon to atomically rough hydrogen-terminated surface and then to atomically flat hydrogenterminated surface as the OCP moved toward less negative potentials. The atomically flat Si(111)-H structure was confirmed by in situ EC-STM and ATR-FTIR data. The dependence of atomically flat Si(111)-H terrace on mis-cut angle was investigated by STM, and the results agreed with those anticipated by calculation. Further, the stability of Si(111)-H was checked by STM in ambient laboratory conditions.
Optimization of Isoflavone Extraction from Soy Germ
Sang-Moon Bae,Chan Ho Jang,Jang-Hoon Kim,Hyun Ae Lim,Joo-Ryong Kim,Jeong Hwan Kim,Jong-Sang Kim 한국식품영양과학회 2005 Preventive Nutrition and Food Science Vol.10 No.3
Soy isoflavones have drawn much attention due to their potential to prevent breast and prostate cancers, osteoporosis, heart disease, and other postmenopausal symptoms. Soy germ is one of the richest sources of isoflavones, and thus has good potential to be used as the ingredient of health foods. This study examined the extraction rate of isoflavones from soy germ at various conditions. After the effect of extraction temperature and duration on isoflavone extraction from soy germ was examined, the optimum concentration of ethanol as extraction solvent was determined. When ethanol concentration was fixed at 60% (v/v), the maximum isoflavone extraction was achieved at 2 hrs and 30℃. Among various concentrations of ethanol tested, 80% (v/v) ethanol showed the highest extraction efficiency. In conclusion, the maximum extraction of isoflavones was obtained using 80% (v/v) ethanol as a solvent, at 30℃ of temperature, and 2 hrs of extraction time.
A Gene-Networked Gel Matrix-Supported Lipid Bilayer as a Synthetic Nucleus System
Bae, Sun Ju,Song, Woo Chul,Jung, Sung Hwan,Cho, Seung-Woo,Kim, Dong-Ik,Um, Soong Ho American Chemical Society 2012 Langmuir Vol.28 No.49
<P>A spheroidal transgene-networked gel matrix was designed as a synthetic nucleus system. It was spheroidically manufactured using both advanced lithography and DNA nanotechnology. Stable Aqueorea coerulescens green fluorescent protein (AcGFP)-encoding gene cross-networks have been optimized in various parameters: the number of gene-networked gel (G-net-gel) spheroids, the concentration of a AcGFP plasmid in the scaffold, and the molar ratio between the X-DNA building blocks and the gene. It was then assessed that 800 units of the gene networked gel matrix at a 4000:1 molar ratio of X-DNA blocks and AcGFP gene components accomplished 20-fold enhanced in vitro protein expression efficiency for 36 h. Furthermore, once with lipid capping, it reproduced the natural nucleus system, demonstrating the 2-fold increased levels of messenger RNAs (mRNAs) relative to solution phase vectors.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/langd5/2012/langd5.2012.28.issue-49/la303498k/production/images/medium/la-2012-03498k_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/la303498k'>ACS Electronic Supporting Info</A></P>