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        Paraquat 중독 환자에서 전폐 방사선치료의 효과

        이창걸(Chang Geol Lee),김귀언(Gwi Eon Kim),서창옥(Chang Ok Suh) 대한방사선종양학회 1995 Radiation Oncology Journal Vol.13 No.4

        목적 : 제초제로 사용되는 Paraquat(Gramoxone??)는 10cc미만의 소량복용으로 사망이 가능하여 자살목적 혹은 사고로 복용한 후 응급실로 내원하게 되는데 적극적인 치료방법으로 신장 및 간장에 대한 독성은 가역적으로 회복이 가능하나 폐에 대한 독성은 가장 치명적으로 초기에 폐부종, 폐출혈등의 성인형호흡곤란증후군의 양상을 보이며 더욱 진행하면 폐섬유화를 초래하여 궁극적으로 사망하게 된다. 1984년 Webb등이 폐부종이 진행되는 paraquat중독환자에서 전폐방사선치료를 시행, 폐섬유화로의 진행을 억제하여 생존시킨 예를 보고한 이래 전폐 방사선치료가 paraquat에 의한 폐독성을 방지할 수 있는 가에 대한 연구가 시도되었다. 저자들은 연세의대 치료방사선과에서 paraquat중독으로 전폐방사선치료를 시행받은 환자들을 후향적으로 분석하여 폐섬유화 예방에 대한 효과 및 궁극적으로 생존율 향상에 기여하였는지 보고자 하였다. 방법 : 1987년 6월부터 1993년 8월까지 paraquat중독으로 연세의료원에 내원하여 치료하였던 30명의 환자들을 대상으로 분석하였다. 이 중 14예에서 전폐방사선치료를 시행받았다. 환자들의 특성을 보면 남녀비가 12:18 이었고 3-76세의 연령에서 20-30세사이가 가장 많았고, 자살목적이 22예, 우발적인 사고로 복용한 예가 8예였다. 환자 및 보호자의 진술에 따라, 복용한 양을 소량(<5cc), 한모금(5-50cc) 그리고 과량(>50cc)군으로 세 군으로 나누어 분석하였다. 방사선치료는 응급실에 도착하여 적극적인 치료와 함께 24시간 이 내 시작하였고 방사선량은 10Gy/5ft/1주으로, 전폐를 범위로 폐밀도 보상 없이 전후 2문 대향조사하였다. 3예에서 방사선치료도중 중단하였는데 치료거절(2Gy) 및 사망(2Gy, 6Gy)이 원인이었다. 결과 : 소량복용군에서는 방사선치료와 상관없이 7예 전원이 생존하였고 대조군에서 2예의 경미한 폐부종이 나타났으나 방사선치료군에서는 나타나지 않았다. 한모금 복용군의 경우 15예 전예에서 폐독성이 나타났는데, 대조군에서는 7예중 1예(14%0에서만 회복된 반면 방사선치료군에서는 8예중 4예(50%)에서 폐독성에서 회복되었다. 한모금 복용군에서 음독후 4일이내에 방사선치료를 받은 경우 5예중 4예(80%)에서 폐독성이 회복된 반면 5일 이후에 치료한 3예에서는 전원(100%)이 호흡부전으로 사명하여 차이를 보였다. 4일이내 방사선치료군에서 2Gy 조사 후 치료를 거절한 1예를 제외하면 4예 전원(100%)에서 폐섬유화를 예방할 수 있었다. 과량복용군에서는 방사선치료와 상관없이 8예 전원이 다기관 손상과 함께 호흡부전으로 사명하였는데 방사선치료는 3예 모두 음독2일 이내에 시행되었지만 모두 폐섬유화로 진행되어 사망하였다. 결과 : Paraquat중독으로 궁극적인 사망의 원인이되는 폐섬유화를 방지하기 위한 방법으로 전폐방사선치료는 비록 복용량이 정확하지는 않으나 약 한모금(5-50cc)정도 복용한 경우 paraquat배설을 위한 적극적인 치료와 함께 조기에(적어도 4일 이내에) 시행될 경우 폐섬유화로의 이행을 방지하여 궁극적으로 생존이 가능함을 알 수 있었고, 소량복용의 경우와 과량을 복용한 경우 전폐방사선치료는 필요가 없을 것으로 생각되었다. 향후 음독후 정확한 혈중 paraquat농도를 측정하여 대조군과 비교하여 전폐방사선효과를 규명하는 임상실험이 필요하리라 사료된다. Purpose : To evaluate whether the early pulmonary irradiation can prevent or decrease the pulmonary damage and contribute to improve ultimate survival in paraquat lung. Materials and Methods : From Jun. 1987 to Aug. 1993. thirty patients with paraquat poisoning were evaluated. Fourteen of these patients were received pulmonary irradiation(RT). All of the patients were managed with aggressive supportive treatment such as gastric lavage, forced diuresis, antioxidant agents and antifibrosis agents. Ingested amounts of paraquat were estimated into three groups(A: minimal <about 5cc. B: mouthful 5-50cc. c: large>50cc). Pulmonary irradiation was strated within 24 hours after admission(from day 1 to day 11 after ingestion of paraquat). Both whole lungs were irradiated with AP/PA parallel opposing fields using Co-60 teletherapy machine. A total of 10Gy(2Gy/fr. x 5days) was delivered without correction of lung density. Results : In group A, all patients were alive regardless of pulmonary irradiation and in group C, all of the patients were died due to multi-organ failure, especially pulmonary fibrosis regardless of pulmonary irradiation. However, in group, six of 7 patients(86%) with no RT were died due to respiratory failure, but 4 fo 8 patients with RT were alive and 4 of 5 patients who were received pulmonary irradiation within 4 days after ingestion of paraquat were all alive though radiological pulmonary change. One patient who refused RT after 2Gy died due to pulmonary fibrosis. All 3 patients who were received pulmonary irradiation after 4 days after ingestion were died due to pulmonary fibrosis in spite of recovery from renal and hepatic toxicity Conclusion : It is difficult to find out the effect of pulmonary irradiation on the course of the paraquat lung because the precise plasma and urine paraquat concentration were not available between control and irradiation groups. But early pulmonary irradiation within 4 days after paraquat poisoning with aggresive supportive treatment appears to decrease pulmonary toxicity and contribute survival in patients with mouthful ingestion of paraquat who are destined to have reversible renal and hepatic damage but irreversible pulmonary toxicity.

      • Electro-hyperthermia up-regulates tumour suppressor Septin 4 to induce apoptotic cell death in hepatocellular carcinoma

        Jeon, Tae-Won,Yang, Heebum,Lee, Chang Geol,Oh, Sang Taek,Seo, Daekwan,Baik, In Hye,Lee, Eun Hye,Yun, Ina,Park, Kyung Ran,Lee, Yun-Han Informa UK (TaylorFrancis) 2016 International journal of hyperthermia Vol.32 No.6

        <P>Purpose: Modulated electro-hyperthermia (mEHT) has been shown to be effective against various types of human tumours, including hepatocellular carcinoma (HCC). Here we aimed to investigate the molecular mechanism underlying the cytotoxic effects of mEHT to HCC cells. Materials and methods: Human liver cancer cell lines, Huh7 and HepG2, were treated with mEHT (42 degrees C/60 min) three times at 2-day intervals. Growth inhibition and apoptotic induction were evaluated using MTS, microscopic analysis, a clonogenic assay, annexin V/PI staining and a ccK18 ELISA. Global changes in gene expression were examined using RNA sequencing to obtain insights into molecular changes in response to mEHT. For in vivo evaluation of mEHT we used HepG2 HCC xenografts grown in nude mice. Results: mEHT suppressed HCC cell proliferation and long-term colony formation through induction of apoptosis. The growth inhibitory effects are induced through a subset of molecular changes. Notably the expression level of septin 4 (SEPT4) (involved in pro-apoptotic activity and growth suppression) was up-regulated, whereas a key regulator of invasiveness G-Protein coupled receptor 64 (GPR64) was repressed. Subsequent Western blotting confirmed that the common increase in tumour suppressor SEPT4 in both Huh7 and HepG2 cells is accompanied by the restoration of cyclin-dependent kinase (CDK) inhibitor p21 and decrease in pro-caspase 7 and pro-caspase 3, thereby accelerating apoptotic signalling in HCC cells. Additionally, mEHT significantly inhibited the growth of human HCC xenografts in nude mice. Conclusions: These findings suggest that apoptotic cell death induced by mEHT is mediated by the up-regulation of tumour suppressor SEPT4 in human HCC cells.</P>

      • SCISCIESCOPUS

        Development of a minipig model for lung injury induced by a single high-dose radiation exposure and evaluation with thoracic computed tomography

        Lee, Jong-Geol,Park, Sunhoo,Bae, Chang-Hwan,Jang, Won-Suk,Lee, Sun-Joo,Lee, Dal Nim,Myung, Jae Kyung,Kim, Cheol Hyeon,Jin, Young-Woo,Lee, Seung-Sook,Shim, Sehwan Oxford University Press 2016 JOURNAL OF RADIATION RESEARCH Vol.57 No.3

        <P>Radiation-induced lung injury (RILI) due to nuclear or radiological exposure remains difficult to treat because of insufficient clinical data. The goal of this study was to establish an appropriate and efficient minipig model and introduce a thoracic computed tomography (CT)-based method to measure the progression of RILI. Göttingen minipigs were allocated to control and irradiation groups. The most obvious changes in the CT images after irradiation were peribronchial opacification, interlobular septal thickening, and lung volume loss. Hounsfield units (HU) in the irradiation group reached a maximum level at 6 weeks and decreased thereafter, but remained higher than those of the control group. Both lung area and cardiac right lateral shift showed significant changes at 22 weeks post irradiation. The white blood cell (WBC) count, a marker of pneumonitis, increased and reached a maximum at 6 weeks in both peripheral blood and bronchial alveolar lavage fluid. Microscopic findings at 22 weeks post irradiation were characterized by widening of the interlobular septum, with dense fibrosis and an increase in the radiation dose–dependent fibrotic score. Our results also showed that WBC counts and microscopic findings were positively correlated with the three CT parameters. In conclusion, the minipig model can provide useful clinical data regarding RILI caused by the adverse effects of high-dose radiotherapy. Peribronchial opacification, interlobular septal thickening, and lung volume loss are three quantifiable CT parameters that can be used as a simple method for monitoring the progression of RILI.</P>

      • KCI등재

        Structural insights into the psychrophilic germinal protease PaGPR and its autoinhibitory loop

        Chang Woo Lee,Saeyoung Lee,Chang-Sook Jeong,Jisub Hwang,Jeong Ho Chang,In-Geol Choi,T. Doohun Kim,HaJeung Park,Hye-Yeon Kim,Jun Hyuck Lee 한국미생물학회 2020 The journal of microbiology Vol.58 No.9

        In spore forming microbes, germination protease (GPR) plays a key role in the initiation of the germination process. A critical step during germination is the degradation of small acidsoluble proteins (SASPs), which protect spore DNA from external stresses (UV, heat, low temperature, etc.). Inactive zymogen GPR can be activated by autoprocessing of the N-terminal pro-sequence domain. Activated GPR initiates the degradation of SASPs; however, the detailed mechanisms underlying the activation, catalysis, regulation, and substrate recognition of GPR remain elusive. In this study, we determined the crystal structure of GPR from Paenisporosarcina sp. TG-20 (PaGPR) in its inactive form at a resolution of 2.5 Å. Structural analysis showed that the active site of PaGPR is sterically occluded by an inhibitory loop region (residues 202–216). The N-terminal region interacts directly with the self-inhibitory loop region, suggesting that the removal of the N-terminal pro-sequence induces conformational changes, which lead to the release of the self-inhibitory loop region from the active site. In addition, comparative sequence and structural analyses revealed that PaGPR contains two highly conserved Asp residues (D123 and D182) in the active site, similar to the putative aspartic acid protease GPR from Bacillus megaterium. The catalytic domain structure of PaGPR also shares similarities with the sequentially non-homologous proteins HycI and HybD. HycI and HybD are metalloproteases that also contain two Asp (or Glu) residues in their active site, playing a role in metal binding. In summary, our results provide useful insights into the activation process of PaGPR and its active conformation.

      • SCISCIESCOPUS
      • KCI등재

        직렬 배열된 두 기포의 bursting jet에 대한 수치적 연구

        이창걸(Chang Geol Lee),이선엽(Sun Youb Lee),Cong-Tu Ha,이재화(Jae Hwa Lee) 한국가시화정보학회 2020 한국가시화정보학회지 Vol.18 No.3

        When a bubble reaches a free surface, a bursting of the bubble produces a high speed jet. Despite its practical importance, significant effort has been devoted to investigate a bursting jet by a single bubble near a free surface. In the present study, we perform numerical simulations of bubbles in a tandem arrangement at Bo=0.05. The configuration of the tandem bubbles is systematically varied by changing a radius of a following bubble (RF) and the gap distance between two bubbles (L). Compared to a single bubble case, we show that the bursting bubble in the tandem arrangement accelerates, and the jet velocity increases. Moreover, we find that a critical gap distance at which the jet velocity unexpectedly changes exists in the tandem case.

      • SCOPUSKCI등재

        Multi-institutional analysis of T3 subtypes and adjuvant radiotherapy effects in resected T3N0 non-small cell lung cancer patients

        Choi, Yunseon,Lee, Ik Jae,Lee, Chang Young,Cho, Jae Ho,Choi, Won Hoon,Yoon, Hong In,Lee, Yun-Han,Lee, Chang Geol,Keum, Ki Chang,Chung, Kyung Young,Haam, Seok Jin,Paik, Hyo Chae,Lee, Kang Kyoo,Moon, Su The Korean Society for Radiation Oncology 2015 Radiation Oncology Journal Vol.33 No.2

        Purpose: We evaluated the prognostic significance of T3 subtypes and the role of adjuvant radiotherapy in patients with resected the American Joint Committee on Cancer stage IIB T3N0M0 non-small cell lung cancer (NSCLC). Materials and Methods: T3N0 NSCLC patients who underwent resection from January 1990 to October 2009 (n = 102) were enrolled and categorized into 6 subgroups according to the extent of invasion: parietal pleura chest wall invasion, mediastinal pleural invasion, diaphragm invasion, separated tumor nodules in the same lobe, endobronchial tumor <2 cm distal to the carina, and tumor-associated collapse. Results: The median overall survival (OS) and disease-free survival (DFS) were 55.3 months and 51.2 months, respectively. In postoperative T3N0M0 patients, the tumor size was a significant prognostic factor for survival (OS, p = 0.035 and DFS, p = 0.035, respectively). Patients with endobronchial tumors within 2 cm of the carina also showed better OS and DFS than those in the other T3 subtypes (p = 0.018 and p = 0.016, respectively). However, adjuvant radiotherapy did not cause any improvement in survival (OS, p = 0.518 and DFS, p = 0.463, respectively). Only patients with mediastinal pleural invasion (n = 25) demonstrated improved OS and DFS after adjuvant radiotherapy (n = 18) (p = 0.012 and p = 0.040, respectively). Conclusion: The T3N0 NSCLC subtype that showed the most favorable prognosis is the one with endobronchial tumors within 2 cm of the carina. Adjuvant radiotherapy is not effective in improving survival outcome in resected T3N0 NSCLC.

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