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데페록사민 전처치가 토끼 심근경색 크기의 감소에 미치는 효과
양관모,오동렬,박승현,박규남,이원재,김형국,황두영,최승필,채장성 대한응급의학회 1998 대한응급의학회지 Vol.9 No.4
Background: Reperfusion of ischemic myocardium has been postulated to result in a specific oxygen radical mediated tissue injury. Iron may liberate during ischemia and we hypothesized that administration of the iron chelator, deferoxamine during ischemia would result in improved recovery after postischemic reperfusion. Purpose: To test whether iron-catalyzed processes contribute to myocardial necrosis during ischemia and reperfusion, deferoxamine was administered to block iron catalyzed hydroxyl radical formation in rabbits. Methods: Eleven rabbits were divided into two groups : control group (n=5) and deferoxamine pretreatment group (n=6). The left circumflex coronay artery was ligated for 30 minutes and reperfused for 180 minutes. Area at risk (AR) was measured by non-stained area with methylene blue injection into left atrium after left circumflex coronary artery ligation. Infarct size was measured by weighing after triphenyltetrazolium chloride staining. Heart rate was measured using electrocardiographic recording and systemic blood pressure was monitored by pressure transducer connected to the catheter in the left ventricle. Results: 1. There was no significant difference of heart rate and blood pressure in deferoxamine pretreatment group compared with control group. 2. There was significant decrease of serum iron concentration after continuous infusion of deferoxamine compared with serum iron concentration before ligation of coronary artery(P<0.05). 3. There was no significant difference of area at risk between control and deferoxamine pretreatment group. 4. Area at necrosis to area at risk was significantly reduced in deferoxamine pretreatment group compared with control group(P<0.05). The results suggest that deferoxamine infusion prior to coronary artery occlusion has a significant benefit in reducing infarct size in this model.
House Dust Mite Increases pro-Th2 Cytokines IL-25 and IL-33 via the Activation of TLR1/6 Signaling
Jang, Yong Hyun,Choi, Jin Kyeong,Jin, Meiling,Choi, Young-Ae,Ryoo, Zae Young,Lee, Hyun-Shik,Park, Pil-Hoon,Kim, Sun-Uk,Kwon, Taeg Kyu,Jang, Myoung Ho,Im, Sin-Hyeog,Moon, Sun Young,Lee, Weon Ju,Lee, Se Williams & Wilkins 2017 The Journal of investigative dermatology Vol.137 No.11
( Pil Soo Sung ),( Jeong Won Jang ),( Jaejun Lee ),( Soon Kyu Lee ),( Hae Lim Lee ),( Hyun Yang ),( Hee Chul Nam ),( Sung Won Lee ),( Si Hyun Bae ),( Jong Young Choi ),( Nam Ik Han ),( Seung Kew Yoon 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1
Aims: Real-world results of nivolumab monotherapy against HCC are lacking in the hepatitis B virus (HBV)-endemic, Asia-Pacific regions. Moreover, heterogeneous responses to immune checkpoint inhibitors have rarely been described in advanced HCC. The aim of this study is to evaluate the efficacy and safety of nivolumab monotherapy in a real-world setting in 33 Korean patients with unresectable HCC. Methods: Data was collected between October 2016 and November 2019 from 33 consecutive patients treated at three university- affiliated hospitals in Korea. Among the enrolled patients, 31 patients were enrolled between February 2018 and November 2019. Clinical parameters and outcome were assessed. Results: In our cohort, twenty-nine patients (88%) showed HBsAg positivity. At the time of nivolumab initiation, 4 among 33 patients (12%) were classified as Barcelona Clinic Liver Cancer (BCLC)-B stage and 29 (88%) as BCLC-C stage, respectively. Prior sorafenib treatment was given to 31 (94%) patients, and 13 (39%) received prior regorafenib treatment. For the liver reserve, patients were classified as Child-Pugh class A (79%) and B (21%), respectively. Grade 3 toxicities occurred in one patient, who developed pneumonitis after 5 cycles of nivolumab treatment. Best overall responses were complete response in 2 patients out of the 33 enrolled patients (6%), partial response in 4 patients (12%) and stable disease in 4 patients (12%). With 29 patients having images for the response evaluation, the objective response rate was 21.4%. The median overall survival (OS) of the cohort was 26.4 weeks (range 2.3-175.1). Achieving objective responses, pre-treatment small tumours (maximal diameter less than 5 cm) and favourable liver function as assessed by Albumin-Bilirubin grade were significant factors for the favourable OS. Interestingly, differential responses to nivolumab among multiple tumours in a single patient were noted in 6 patients (18%). In these patients, small metastatic tumours were regressed, although their larger tumours did not respond to nivolumab monotherapy. Conclusions: In summary, nivolumab treatment seems clinically efficacious in treating unresectable HCC in an endemic area of HBV infection. Further prospective evaluation is required to overcome the heterogeneous efficacy of nivolumab monotherapy according to the baseline tumour burden.
( Pil Soo Sung ),( Dong Jun Park ),( Gil Won Lee ),( Sung Woo Cho ),( Jaejun Lee ),( Hyun Yang ),( Soon Kyu Lee ),( Hee Chul Nam ),( Jeong Won Jang ),( Si Hyun Bae ),( Jong Young Choi ),( Seung Kew Yo 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1
Aims: Recently, lenvatinib was demonstrated to be non-inferior to sorafenib in a phase 3 randomized controlled trial in unresectable hepatocellular carcinoma (HCC). In this study, we investigated whether the response to lenvatinib is affected by the immunogenicity of the tumor. Methods: Between April 2019 and March 2020, 10 patients with intermediate-to-advanced HCC who were administered lenvatinib treatment after liver biopsy were enrolled. Immunohistochemical staining and multi-color flow cytometry were performed with the liver biopsy specimen. Results: Among 10 patients enrolled, 4 patients showed objective responses (complete response + partial response). Immunohistochemical staining of CD3, CD68, and PD-L1 demonstrated that patients with objective responses showed marked infiltration of T cells and PD-L1-expressing tumor-associated macrophages in intratumoral and peritumoral tissues than those without objective responses. There was a significant difference in the number of infiltrated T cells in responders than in non-responders (P<0.01). For the number of tumor-associated macrophages, there was no significant difference between the responders and the non-responders, although the number of PD-L1-expressing tumor-associated macrophages was significantly higher in responders than in non-responders (P<0.05). Flow cytometry analyses demonstrated the positive correlation of PD-L1 and HLA-DR (P<0.01), suggesting that PD-L1 expression in tumor-associated macrophages in HCC is associated with the capability of antigen presentation of these cells. Conclusions: Tumor immunogenicity reflected by T cell and PD-L1-positive macrophage infiltration affects the responses to lenvatinib in unresectable HCC. This work was supported by the Scientific Research Fund of the Korean Liver Cancer Study Group. This research was also supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) and funded by the Ministry of Education (NRF-2019R1I1A1A01059642) (P.S.S.). This study was partly supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2020R1A2C3011569).
( Pil Soo Sung ),( Moon Hyung Choi ),( Hyun Yang ),( Ho Jong Chun ),( Soon Kyu Lee ),( Jeong Won Jang ),( Jong Young Choi ),( Seung Kew Yoon ),( Joon-il Choi ),( Young Joon Lee ),( Si Hyun Bae ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1
Aims: This study aimed to identify the utility of diffusion- weighted magnetic resonance (MR) imaging with an apparent diffusion coefficient (ADC) map as a predictor of the intrahepatic response of hepatocellular carcinoma (HCC) to cisplatin- based hepatic arterial infusion chemotherapy (HAIC). Methods: We evaluated 113 consecutive patients with HCC who underwent after gadoxetic acid-enhanced and diffusion- weighted MR imaging were retrospectively evaluated. Significant findings for differentiating the two groups were identified at univariate and multivariate analyses. By using receiver operating characteristic analysis, the optimal cut-off values for quantitative variables were determined. The treatment response was evaluated using modified Response Evaluation Criteria in Solid Tumors. Overall survival times after HAIC were also compared between groups by log-rank tests. Results: The appropriate cut-off for the tumor-to-liver ADC ratio was determined as 0.741. Of the 113 patients, 51 (45%) presented with a tumor-to-liver ADC ratio < 0.741. Evaluation of the intrahepatic treatment response after 2-3 cycles of HAIC in these 51 patients revealed that 20 patients (39%) experienced an objective response to HAIC. On the other hand, 10 of the 62 patients with a tumor-to-liver ADC ratio ≥ 0.741 (16%) experienced an objective response. Thus, the objective response rate was significantly higher in patients with a tumor-to-liver ADC ratio < 0.741 than in those with a tumor-to-liver ADC ratio ≥ 0.741 (P=0.006). Multivariate logistic regression analysis using parameters including perfusion alteration, percentage of a non-enhancing portion, and tumor-to-liver ADC ratio revealed that a tumor-to-liver ADC ratio < 0.741 (odds ratio 3.03; P=0.015) is a sole predictor of an objective response to HAIC. Overall survival rates were significantly higher in patients with objective responses to HAIC compared with those without ob jective responses (P=0.001 by log-rank test). Conclusions: Patients with unresectable HCC with tumor-to-liver ADC ratio < 0.741 showed a favorable intrahepatic response to HAIC. Therefore, diffusion-weighted MR imaging can take a critical role as a predictor of a response to cisplatin-based HAIC in unresectable HCC.