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        Improved antitumor activity and tumor targeting of NH(2)-terminal-specific PEGylated tumor necrosis factor-related apoptosis-inducing ligand.

        Chae, Su Young,Kim, Tae Hyung,Park, Kyeongsoon,Jin, Cheng-Hao,Son, Sohee,Lee, Seulki,Youn, Yu Seok,Kim, Kwangmeyung,Jo, Dong-Gyu,Kwon, Ick Chan,Chen, Xiaoyuan,Lee, Kang Choon American Association for Cancer Research, Inc 2010 Molecular Cancer Therapeutics Vol.9 No.6

        <P>Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered an attractive anticancer agent due to its tumor cell-specific cytotoxicity. However, its low stability, solubility, unexpected side effects, and weak pharmacokinetic profiles restrict its successful clinical application. To develop efficient TRAIL-based anticancer biotherapeutics, a new version of trimeric TRAIL was constructed by incorporating trimer-forming zipper sequences (HZ-TRAIL), and then NH(2)-terminal-specific PEGylation was done to produce PEGylated TRAIL (PEG-HZ-TRAIL). The biological, physicochemical, and pharmaceutical characteristics of PEG-HZ-TRAIL were then investigated using various in vitro and in vivo experiments, including a cell-based cytotoxicity test, a solubility test, pharmacokinetic analysis, and antitumor efficacy evaluations. Although slight activity loss occurred after PEGylation, PEG-HZ-TRAIL showed excellent tumor cell-specific cytotoxic effects via apoptotic pathways with negligible normal cell toxicity. The stability and pharmacokinetic problems of HZ-TRAIL were successfully overcome by PEGylation. Furthermore, in vivo antitumor tests revealed that PEG-HZ-TRAIL treatment enhanced therapeutic potentials compared with HZ-TRAIL in tumor xenograft animal models, and these enhancements were attributed to its better pharmacokinetic properties and tumor-targeting performance. These findings show that PEG-HZ-TRAIL administration provides an effective antitumor treatment, which exhibits superior tumor targeting and better inhibits tumor growth, and suggest that PEG-HZ-TRAIL should be considered a potential candidate for antitumor biotherapy.</P>

      • KCI등재

        우울증 환자에서 Cortisol 일일변화 검사의 의의

        채영래,한상익,백인호 大韓神經精神醫學會 1988 신경정신의학 Vol.27 No.4

        This study was designed to investigate whether depressed patient showed increased plasma contisol level compared with nondepressed patients and to examine whether diurnal variation is preserved or flattened in depressed patients and whether diurnal variation itself could be a useful diagnostic procedure in depression. We studied also the possible relationship between the diurnal variation of cortisol secretion and the degree of symptomatic improvement with antidepressant administration in major depression patients. The results were as follows : 1) The value of serum cortisol levels checked before antidepressant administration were 8.44±4.89㎍/dl, 5.74±3.19㎍/dl, 3.18±3.54㎍/dl, 10.75±5.23㎍/dl at 12AM, 4PM, 11PM and 8AM respectively in endogenous depression group, and 6.39±3.29㎍/dl, 6.25±3.75㎍/dl, 2.74±1.85㎍/dl, 10.79±4.77㎍/dl respectively in control group. There were no significant differences in serum cortisol levels between both groups(Table 2). 2) In 31 endogenous depressives, 18(58.1%) maintained diurnal variation of cortisol level and 13(41.9%) showed flattened variation. However, of 16 control group(schizophrenics and dysthymic disorder patients), 11(68.8%) maintained diurnal variation of cortisol secretion and5(31.2%) showed flattened variation. As a result, the sensitivity, specificity and predictive value of diurnal cortisol test for endogenous depression were 42%, 67%, and 72% respectively 3) In 26 major depression patients, 11 patients who showed flattened diurnal variation of cortisol secretion had significantly high "agitative depression" factors of Hamiltion Rating Scale for Depression compared with 15 patients who maintained diurnal variation. 4) Among 15 major depression patients whose diurnal variation was preserved, 12(80.0%) showed marked improvement of depressive symptoms with antidepressant administration and 3(20.0%) did not. Among 11 major depression patients whose diurnal variation was disturbed, 6(54.5%) improved and 5(45.5%) did not. There were no significant differences in symptomatic improvement between two groups.

      • KCI등재후보

        Changes of depression and job stress in workers after merger without downsizing

        Jun Ick Jung,Jun Seok Son,Young Ouk Kim,Chang Ho Chae,Chan Woo Kim,Hyoung Ouk Park,Jun Ho Lee,Young Hoo Shin,Jea Chul Ha 대한직업환경의학회 2018 대한직업환경의학회지 Vol.30 No.-

        Background: Since the 1980s, restructuring, which includes downsizing, closures, mergers, and privatization, has expanded worldwide, and various studies have investigated its effect on health. However, previous studies have mainly focused on restructuring accompanied by massive lay-offs, and the effect of a merger on workers’ health is still controversial. This study aims to investigate changes in worker depression and job stress after a merger without downsizing, which is unusual in Korea. Methods: Repeated surveys were done in April 2014, April 2015, and April 2016 involving the participation of 209 subjects. Participants were divided into two groups, which were comprised of blue-collar workers (104) and whitecollar workers (105). Sociodemographic characteristics, including age, education level, job tenure, gender, marital status, smoking status, and alcohol consumption, were measured via a survey. To determine the level of depression, the Korean version of the Center for Epidemiologic Studies Depression Scale (CES-D) was employed, and to investigate job stress, the Korean Occupational Stress Scale-Short Form (KOSS-SF) was used. For statistical analyses, Pearson’s chi-square test, the Student’s t-test, and repeated measure analysis of variance (ANOVA) were performed. Results: The results showed that depression (CES-D, F[2, 400] = 0.466, p = 0.628) was changed but without significance and job stress (KOSS-SF, F[1.899, 379.831] = 3.192, p = 0.045) were significantly different. The betweengroup difference in the CES-D score between the blue- and white-collar workers by survey administration time was not statistically significant (F = 0.316, p = 0.574). The interaction between the survey time and occupational group was also not statistically significant (F = 0.967, p = 0.381). The between-group difference in the KOSS-SF total score was not statistically significant (F = 1.132, p = 0.289), and the interaction between the survey administration time and occupational group was also not significant (F = 0.817, p = 0.437). In the job stress subgroup analyses Job insecurity and Lack of reward showed a significant difference by survey administration time. Conclusion: This study showed that a merger without massive downsizing can cause negative health effects such as an changes in depression and increase in job stress. To improve the health of workers, both the immediate negative effects on health, and the long-term effects or their resolution over time should be considered prior to the merger.

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      • KCI등재

        '1998 한국인 우울증 선별의 날' 참가자들의 사회인구통계학적 특성과 우울증 선별검사 결과

        한상익,이성필,고효진,박원명,장계호,유태열,전태연,채정호,방승규,김광수,최보문,이정태,백인호 大韓神經精神醫學會 1999 신경정신의학 Vol.38 No.5

        연구목적 : 1998년 정신건강의 날 기념 한국인 우울증 선별의 날 행사에 자발적으로 참여한 참가자들의 사회인구 통계학적 특성을 분석하고 우울증 선별검사 결과를 평가하기 위하여 본 연구를 시행하였다. 방 법 : 8개 병원에서 얻어진 619명의 자료를 사용하여 선별검사로 밝혀진 우울증의 유병율과 사회인구통계학적 특성 및 응답자의 정신과적 치료를 포함한 과거력 등을 조사하였다. 결 과 : 우울증 척도 점수는 응답자 전체 평균 57.5±13.8로 경도의 우울 증상이 있는 것에 해당되었다. 전체 응답자의 69.5%(430명)가 최소한 경도 이상의 우울 증상을, 43.1%(267명)가 중등도 이상의 우울 증상을, 18.4%(114명)가 고도의 우울 증상을 보였다. 고도의 우울 증상이 있는 응답자의 56.8%와 중등도의 우울 증상이 있는 응답자의 63.9%가 정신과 치료를 받은 적이 전혀 없었다. 나이가 29세 이하인 것과 전임근무 중인 직업상태는 각각 나이가 60세 이상인 것과 직업이 없는 것에 비교하여 우울증으로부터 보호하는 인자임을 시사하였다. 결 론 : '1998 한국인 우울증 선별의 날' 행사를 통하여 많은 우울증 환자들을 선별해낼 수 있었고, 이들의 우울 증상은 몇몇 사회인구통계학적 특성과 유의한 관계가 있음을 확인하였다. 우울증 선별의 날 행사를 통한 우울증에 대한 교육과 우울증 선별검사는 치료받지 못하고 있는 우울증 환자 및 기존의 치료 중인 환자 모두에게 유용한 프로그램임을 알 수 있었다. Objectives : This study was performed to analyze the sociodemographic characteristics of participants in '1998 Korean Depression Screening Day' and to evaluate the results of the screening test. Methods : By using the survey results of 619 volunteers from 8 hospitals, the authors examined the prevalence of depression detected at the screening test and sociodemographic characteristics and the psychiatric treatment history of respondents. The assessment measure was the Zung Self-Rating Depression Scale. Results : The mean depression score of all participants was 57.5±13.8 and it came under mild depression. Of all participants, 69.5%(N=430) had at least mild depressive symptoms, 43.1%(N=267) had at least moderate symptoms, and 18.4%(N=114) had severe symptoms. Never have 56.8% of respondents in the severely depressed range and 63.9% of those in the moderately depressed range had psychiatric treatment. The results suggest that the age group of 29-year-old or younger(relative to 60-year-old or older group) and full-time employment status(relative to unemployment) are protective factors of depression. Conclusions : By '1998 Korean Depression Screening Day', many depressed patients were detected and their depressive symptoms had statistically significant relationships with some sociodemographic characteristics. The results suggest that the education and screening test programs for depressive illness facilitated by Depression Screening Day are useful to the patients regardless of being under current treatment or not.

      • β-Adrenergic signaling is required for the induction of a labile state during memory reconsolidation

        Lim, Chae-Seok,Kim, Jae-Ick,Kwak, Chuljung,Lee, Jaehyun,Jang, Eun Hae,Oh, Jihae,Kaang, Bong-Kiun Elsevier 2018 Brain research bulletin Vol.141 No.-

        <P><B>Abstract</B></P> <P>Memory reconsolidation is the process by which previously consolidated memories reenter a labile state through reactivation of the memory trace and are actively consolidated through <I>de novo</I> protein synthesis. Although extensive studies have shown that β-adrenergic signaling plays a critical role in the restabilization of reactivated memory, its role in the destabilization of long-term memory is not well-studied. In this study, we found that membrane excitability increased in hippocampal CA1 neurons immediately after the retrieval of contextual fear memory. Interestingly, this increase in membrane excitability diminished after treatment with propranolol (a β-adrenergic receptor antagonist), an NMDA receptor antagonist, and a PKA inhibitor. In addition, we found that administration of propranolol prior to, but not after, the retrieval of fear memory ameliorated the memory impairment caused by anisomycin, indicating that inhibition of β-adrenergic signaling blocks the destabilization of contextual fear memory. Taken together, these results indicate that β-adrenergic signaling via NMDA receptors and PKA signaling pathway induces a labile state of long-term memory through increased neuronal membrane excitability.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Retrieval of contextual fear memory increases the membrane excitability. </LI> <LI> Propranolol or NMDAR and PKA inhibition diminishes membrane hyperexcitability. </LI> <LI> β-adrenergic signaling is required for the destabilization of contextual fear memory. </LI> </UL> </P>

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