Glucocorticoid-induced tumor necrosis factor receptor–related protein co-stimulation facilitates tumor regression by inducing IL-9–producing helper T cells

Kim, Il-Kyu,Kim, Byung-Seok,Koh, Choong-Hyun,Seok, Jae-Won,Park, Jun-Seok,Shin, Kwang-Soo,Bae, Eun-Ah,Lee, Ga-Eun,Jeon, Hyewon,Cho, Jaebeom,Jung, Yujin,Han, Daehee,Kwon, Byoung S,Lee, Ho-Young,Chung, Nature Publishing Group, a division of Macmillan P 2015 Nature medicine Vol.21 No.9

<P>T cell stimulation via glucocorticoid-induced tumor necrosis factor receptor (TNFR)-related protein (GITR) elicits antitumor activity in various tumor models; however, the underlying mechanism of action remains unclear. Here we demonstrate a crucial role for interleukin (IL)-9 in antitumor immunity generated by the GITR agonistic antibody DTA-1. IL-4 receptor knockout (Il4ra(-/-)) mice, which have reduced expression of IL-9, were resistant to tumor growth inhibition by DTA-1. Notably, neutralization of IL-9 considerably impaired tumor rejection induced by DTA-1. In particular, DTA-1-induced IL-9 promoted tumor-specific cytotoxic T lymphocyte (CTL) responses by enhancing the function of dendritic cells in vivo. Furthermore, GITR signaling enhanced the differentiation of IL-9-producing CD4(+) T-helper (T(H)9) cells in a TNFR-associated factor 6 (TRAF6)- and NF-kappa B-dependent manner and inhibited the generation of induced regulatory T cells in vitro. Our findings demonstrate that GITR co-stimulation mediates antitumor immunity by promoting T(H)9 cell differentiation and enhancing CTL responses and thus provide a mechanism of action for GITR agonist-mediated cancer immunotherapies.</P>

세신약침(細辛藥鍼)의 천식억제 및 면역조절효과에 대한 실험적 연구

김일구 ( Il Gu Kim ),김영일 ( Young Il Kim ),홍권의 ( Kwon Eui Hong ),임윤경 ( Yun Kyoung Yim ),이현,이병렬 ( Byung Ryul Lee ) 대한경락경혈학회 2004 Korean Journal of Acupuncture Vol.21 No.1

Objectives and methods: The aim of this study was to investigate the effect of AHCR(ASARI HERBA CUM RADICE) herbal acupuncture at St36 on ovalbumin-induced asthma in mice. C57BL/6 mice were sensitized and challenged with OVA(ovalbumin) for 12 weeks(once a week). Two experimental groups were treated with different concentrations(1%, 0.1%) of AHCR-HAS at Chok-samni (St36) for the later 8 weeks (3times/week). Results: 1. Lung weight of the mice group treated with AHCR-HA decreased significantly compared with that of control group. 2. Total Leukocytes in BALF of the mice group treated wtih AHCR-HA decreased significantly compared with those of control group. 3. The number of Eosinophils in BALF of the mice group treated wtih AHCR-HA decreased significantly compared with that of control group. 4. The number of Gr-1+ /CD11b+, CCR3+, CD4+, CD3e+/CD69+, IgE+/B220+ cells in the lungs of the mice group treated with AHCR-HA decreased significantly compared with that of control group. 5. The number of CD8+ cells in the lungs of the mice group treated with AHCR-HA didn`t show significant difference compared with that of control group. 6. The concentration of IgE, IL-13, IL-4 in serum of the mice group treated with AHCR-HA decreased significantly compared with that of control group. Conclusion: We conclude that AHCR-HA is effective on OVA-induced asthma in C57BL/6 mouse.

방풍의 항염 효과 기전

노성일 ( Sung Il Noh ),김상돈 ( Sang Don Kim ),박성철 ( Sung Cheul Park ),서병윤 ( Byung Yun Seo ),염승룡 ( Seung Ryong Yeom ),권영달 ( Young Dal Kwon ),신병철 ( Byung Cheul Shin ),송용선 ( Yung Sun Song ) 한방재활의학과학회 2005 한방재활의학과학회지 Vol.15 No.2

목적 : 방풍은 임상적으로 관절염을 포함한 다양한 염증성 질환 치료제로 사용되어 왔다. 본 연구에서는 인간 비만세포를 이용하여 세포 독성에 영향을 주지 않는 농도에서 방풍의 항염 효과 및 그 기전을 검토했다. 방법 : 인간의 HMC-1세포를 IMDM에서 페니실린, 스트렙토마이신, 모노티오글리세린를 첨가하여 배양하고 방풍추출액을 투여하였다. 그 다음 MTT, ELISA, RT-PCR, 세포내 칼슘측정, 핵단백분석을 이용하여 TNF-α, IL-6, IL-8 각각의 형성과 mRNA발현, 세포내 칼슘 수준, NF-κB 발현에 대한 방풍추출액의 반응을 측정하고 통계처리 하였다. 결과 : 방풍은 PMA와 calcium ionophore A23187로 활성화된 비만세포에서 세포내 칼슘 수준과 NF-κB, TNF-α와 IL-6의 발현을 억제 시켰고 RT-PCR을 이용한 mRNA 발현에서 TNF-α와 IL-6의 발현을 억제하였다. 결론 : 방풍은 비만세포내 칼슘 수준 및 NF-κB의 활성을 억제하고 염증성 세포 활성 물질인 TNF-α와 IL-6의 분비도 억제하여 항염 효과를 나타냄을 암시하고 있다.

세신약침(細辛藥鍼)의 천식억제 및 면역조절효과에 대한 실험적 연구

김일구,김영일,홍권의,이현,이병렬,임윤경,Kim, Il-Gu,Kim, Young-Il,Hong, Kwon-Eui,Lee, Hyeon,Lee, Byung-Ryul,Yim, Yun-Kyoung 경락경혈학회 2004 대한침구의학회지 Vol.21 No.1

Objectives and methods : The aim of this study was to investigate the effect of AHCR(ASARI HERBA CUM RADICE) herbal acupuncture at St36 on ovalbumin-induced asthma in mice. C57BL/6 mice were sensitized and challenged with OVA(ovalbumin) for 12 weeks(once a week). Two experimental groups were treated with different concentrations(1%, 0.1%) of AHCR-HAS at Chok-samni (St36) for the later 8 weeks (3times/week). Results 1. Lung weight of the mice group treated with AHCR-HA decreased significantly compared with that of control group. 2. Total Leukocytes in BALF of the mice group treated wtih AHCR-HA decreased significantly compared with those of control group. 3. The number of Eosinophils in BALF of the mice group treated wtih AHCR-HA decreased significantly compared with that of control group. 4. The number of $Gr-1^+/CD11b^+,\;CCR3^+,\;CD4^+,\;CD3e^+/CD69^+,\;IgE^+/B220^+$ cells in the lungs of the mice group treated with AHCR-HA decreased significantly compared with that of control group. 5. The number of $CD8^+$ cells in the lungs of the mice group treated with AHCR-HA didn't show significant difference compared with that of control group. 6. The concentration of IgE, IL-13, IL-4 in serum of the mice group treated with AHCR-HA decreased significantly compared with that of control group. Conclusion We conclude that AHCR-HA is effective on OVA-induced asthma in C57BL/6 mouse.

상엽약침(桑葉藥鍼)의 천식억제효과(喘息抑制效果)에 대한 실험적 연구

신성찬 ( Sung Chan Shin ),김영일 ( Young Il Kim ),홍권의 ( Kwon Eui Hong ),임윤경 ( Yun Kyoung Yim ),이현 ( Hyun Lee ),이병렬 ( Byung Ryul Lee ) 대한경락경혈학회 2004 Korean Journal of Acupuncture Vol.21 No.3

Objective: The aim of this study was to investigate the effect of Mori Folium herbal acupuncture at St36 on ovalbumin-induced asthma hi mice. Methods: C57BL/6 mice were sensitized and challenged with OVA (ovalbumin) for 12 weeks (once a week) Two experimental groups were treated with different concentrations (1%, 0.1%) of Mori Folium herbal acupuncture at Chok-samni (St36) for the later 8 weeks (3times/week). Result: 1. Lung weight of the mice group treated with Mori Folium herbal acupuncture decreased significantly compared with that of control group. 2. Total Leukocytes in BALE of the mice soup treated with Mori Folium herbal acupuncture decreased significantly compared with those of control group. 3. The number of Eosinophils in BALF of the mice group treated with Mori Folium herbal acupuncture decreased significant1y compared with that of control group. 4. The number of Gr-1+/CD11b, CCR3+, CD4+, CD8+, CD3e+/CD69+, IgE+/B220+ cells in the lung of the mice group treated with Mon Folium herbal acupuncture deceased significantly compared with that of group. 5. The concentration of IgE, IL-13, IL-4 in serum of the mice group treated with Mori Folium herbal acupuncture deceased significantly compared with that of control group. 6. The concentration of IL-4 in BALF of the mice group treated with Mori Folium herbal acupuncture decreased signifint1y compared with that of control group. Conclusion: We conclude that Mori Folium herbal acupuncture is effective on OVA-induced asthma of C57BL/6 mouse.

혈소판 응집 억제제의 효과 측정법에 대한 고찰과 지원자에서 Triflusal의 혈소판 응집 억제능 평가

이병요,장힘찬,백인환,윤휘열,권광일 충남대학교 약학대학 의약품개발연구소 2010 藥學論文集 Vol.25 No.-

The anti-platelet agent is a member of a class of pharmaceuticals that decreases platelet aggregation and inhibits thrombus formation. They are effective in the arterial circulation and widely used in primary and secondary prevention of thrombotic cerebrovascular or cardiovascular disease. As a method for estimating the effects of anti-platelet agent, platelet aggregation was conventionally measured using the optical method or the impedance method. Several alternate methods currently in development or recently developed were considered, including luminescence method, flow cytometry, laser-light scattering method, and Verify Now-P2Y12 assay. Principles, advantages, and disadvantages of the optical method, impedance method, and the other alternate platelet aggregation methods were discussed in this report. 15 human volunteers were recruited for the evaluation of the efficacy of triflusal using the optical method. After the oral administration of a single dose of 900mg, 15 subjects received eight doses administered at 24-hour intervals of 600mg triflusal. Using platelet rich-plasma from above subjects, we performed baseline platelet aggregation test induced by adenosine diphosphate(ADP), collagen, and arachidonic acid. The results of platelet aggregation test after triflusal administration were compared with the baseline study. Triflusal significantly inhibited platelet aggregation induced by ADP (33.0±21.3%) and arachidonic acid (99.1±1.2%), respectively. Therefore, we concluded that anti-platelet aggregation effect of triflusal can be studied successfully with the optical method. Each of the platelet aggregation methods has value for evaluating the effects by various mechanisms of the anti-platelet agents. The ideal method for estimating the platelet aggregation as it relates to safety and efficacy in patients treated with anti-platelet agents will need to be determined in clinical trials.

후직장의 위장관 간질 종양 1예

최영일,이승현,안병권,백승언 고신대학교의과대학 2008 고신대학교 의과대학 학술지 Vol.23 No.2

The retrorectal gastrointestinal stromal tumor is very rare. An 24-year-old woman patient was admitted for huge pelvic mass with constipation, lower abdominal discomfort. The pelvic mass was palpable on posterior rectal wall on digital rectal examination. On exploration, tumor excision was performed. Gross finding shows 14x11x10.5 cm sized grayish tan and irregular mass. The cut surface is solid, bright yellow to grayish yellow with foci of hemorrhage and calcification. The tumor show spindle shaped cells and mitosis. It showed positive staining for c-kit. The tumor was diagnosed as gastrointestinal stromal tumor in rectrorectal space.

황련해독탕 및 귀비탕의 발효 전후 혈소판 응집 억제 효과에 대한 비교 연구

송병정,이수진,권광일 충남대학교 약학대학 의약품개발연구소 2012 藥學論文集 Vol.27 No.-

Recently interest of fermented oriental medicines is increasing for the purpose of disease prevention. Hwangryunghaedok-tang (HR) and Guibi-tang (GB) are widely used oriental medicines in Korea. HR and GB are well known for anti-inflammatory and anti-stress effect. Glycosides in herbal medicines are transformed to aglycone via fermentation. The fermented medicines are absorbed more and have less individual variation. In this study, HR and GB were compared before and after fermentation by anti-platelet aggregation effect. HR and GB were fermented by various lactobacillus species. The anti-platelet aggregation effect of HR and GB were measured using aggregometer by optical method. Collagen (4 μg/mL) was used as a inducer of platelet aggregation. After measuring anti-platelet aggregation effect, we analysed the data using WinnonlinⓇ program to fit simple Emax model. Then Emax and EC50 values were estimated. In results, GB had little antiplatelet effects. Emax of 5 GB samples (127, 164, 402, 442, 3163) were estimated near zero and others (129, 144, 166, 693, 744) had high EC50 values (> 1500 μg/mL). In contrast with GB, HR had antiplatelet effects. HR which was fermented by Lactobacillus casei and Lactobacillus plantarum (HR-127,HR-144) were most effective sample. Emax and EC50 of HR-127 and HR-144 was 99.99%, 174.73 μg/mL and 100.00% 160.48 μg/mL, respectively. These results indicated that Guibi-tang was inappropriate as anti-platelet aggregation agent and Hwangryunhaedok-tang would be more effective after fermentation as anti-platelet aggregation agent, warranting further study.

내측회장동맥에 의해 형성된 척수경막동정맥루로 인한 척수병증 1예

이일형,배재천,이상무,김진혁,권기한,이병철 대한신경과학회 1999 대한신경과학회지 Vol.17 No.3

초·중·고 학생들의 과학 지식 성취 수준 추이 분석을 위한 종단적 연구

권재술,최병순,권치순,양일호,이경호,김지나 한국교원대학교 과학교육연구소 1999 청람과학교육연구논총 Vol.9 No.1

학생의 과학 지식 성취도에 대한 장기간의 경향성은 과학 교육 정책의 효율성을 점검하는데 매우 중요한 요인이다. 그러나 지금까지 우리 나라 학생들의 학업 성취도의 경향성을 이해해보려는 진지한 노력이 현실적으로 거의 없었다. 최근까지 한국교원대학교 과학교육연구소에서는 전국에 있는 초·중·고 학생들을 대상으로 학생들의 과학 지식 성취도를 알아보기 위한 연구를 진행시켜왔다. 연구의 첫 단계에서는 평가 문항을 개발하였다. 두 번째 단계에서는 개발된 문항을 전국적으로 투입하고 그 결과를 수집하여 2년간의 변화를 분석하는 것으로써, 이 논문은 두 번째 단계에 관한 내용을 담고있다. 이 연구에서는 권재술 등(1998)이 개발한 국가 수준의 과학 지식 평가 도구를 일부 수정하여 사용하였다. 1997년에는 전국적으로 8,766명의 학생을, 1999년에는 4,398명의 학생을 조사 대상으로 하였다. 조사 대상은 지역별, 성별 등을 고려하여 우리 나라 전체 학생의 모집단을 대표할 수 있는 표본으로 선정되었다. 연구 결과, 2년 동안 초·중·고 학생들의 과학 지식 성취 수준의 서로 다른 변화를 확인할 수 있었다. 초등학생의 경우는 성취도가 감소하였으나, 고등학생의 경우는 증가하였고 중학생의 경우는 두 시기에 의미 있는 차이가 없었다. 과학 지식 영역의 하위 영역별 분석 결과를 보면, 초등학생의 경우 개념 체계에 대한 지식 수준을 유의미하게 향상되었으나, 사실과 원리에 관한 지식 수준은 낮아졌다. 반면 고등학생의 경우는 지식 수준이 향상되었으며 특히, 사실 영역에서 크게 향상 되었다. 연구에서는 이 자료를 성별, 지역별, 행동 목표 수준 그리고 검사 문항의 상황 등으로도 나누어서 분석하였다. 한국교원대학교 과학교육연구소에서 개발한 과학 성취 수준 점검 시스템은 국가 수준에서 학생들의 과학성취도를 점검하는데 효과적인 도구가 될 것이다. The long term trend of studensts' science achievement is a very important factor to check the effectiveness of science educational policy. However, up to date no such effort to understand the trend of Korean students' science achievement has been put into action. Recently, the Science Education Center in Korea National University of Education has been attempted to collect nation wide data for students' science achievement. The first part of the effort was to develop item pools. This study was the second part to collect nation wide data and to check any change during the two year time interval. In this study, the item pools developed by Kwon et. al.(1998) were used with some modification. The data were collected two times; February 1997 and March 1999. The subjects collected nationally were 8,766 students in 1997 and were 4,398 in 1999. The subjects were collected randomly but stratified by region and sex. As the results, the trends of achievement change during the two years were different from elementary to high school. The achievement scores were decreased in elementary schools and increased in high school. In case of middle schools, the change was not significant. However, even in elementary schools the knowledge on theory was increased significantly while knowledge on facts and principles were decreased. In contrast, the knowledge on fact showed the most increase in high schools. In this study, the data were analysed in light of region, sex, behavioral objective levels(ability) and context of test items. The science achievement monitoring system developed by the Science Education Center in Korea National University of Education can be an effective tool for monitoring students' achievement on the national level.