• Radiation Oncology Journal
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• 제24권4호
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• pp.230-236
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• 2006

목 적: 국소진행성 비소세포폐암 환자에 대한 매주 paclitaxel 항암화학요법과 방사선치료 동시 요법의 안정성과 효과를 알아보고 재발 양상 및 생존율을 분석하고자 하였다. 대상 및 방법: 1999년 10월부터 2004년 9월까지 국소진행성 비소세포폐암으로 진단받고 근치적 목적으로 항암화학방사선 동시요법을 시행 받은 환자 23명을 대상으로 후향적 분석을 시행하였다. 방사선치료는 일일 1회 1.8 Gy씩 주5회 분할 조사하여 $7{\sim}8$주에 걸쳐 총 선량 $55.8{\sim}64.8$ (median 64.8) Gy를 조사하였다. 항암화학요법은 매주 paclitaxel 50 또는 $60\;mg/m^2$ 용량으로 방사선치료 1일, 8일, 15일, 22일, 29일 36일째에 투여하였다. 항암화학방사선 동시요법을 마친 4주 후부터 paclitaxel $135\;mg/m^2$와 cisplatin $75\;mg/m^2$ 용량으로 3주 간격으로 3주기의 공고 항암화학요법을 추가 시행하였다. 결 과: 동시 항암화학방사선요법을 시행받은 23명의 환자 중 3명이 도중에 환자 임의로 치료를 중단하였고 1명이 5,580 cGy까지 방사선치료를 시행 받고 세균성 폐렴으로 사망하였다. 주된 급성 부작용은 방사선 식도염으로 4명(17%)의 환자에서 2도의 식도염이 관찰되었으며 3도 이상의 부작용은 관찰되지 않았다. 16명의 환자가 추가 공고 항암화학요법을 시행 받았으며 공고 항암화학요법 중의 급성 부작용으로 3도 이상의 호중구 감소증이 8명(50%)의 환자에서 관찰되었으며 그중 한 명은 패혈증으로 사망하였다. 동시 항암화학방사선요법을 끝까지 시행 받은 20명의 환자에서 치료에 대한 반응을 조사할 수 있었으며 완전 관해 4명(20%), 부분 관해 14명(70%)으로 전체 관해율은 90%이었다. 관해를 보인 환자들 중 추적 관찰이 가능했던 16명 중 14명에서 재발이 확인되었고 국소 재발이 9명(56%), 국소 재발과 원격 전이가 3명(19%), 원격 전이가 2명(13%)이었다. 동시 항암화학방사선요법을 끝까지 시행받은 환자들에서의 무진행 생존 기간의 중앙값은 9.5개월이었으며, 2년 무진행 생존율은 18%이었다. 재발된 환자 중 11명에서 2차(second-line) 또는 3차(third-line) 항암화학요법이 시행되었다. 전체 환자 23명의 중앙 생존 기간은 21개월, 2년 및 5년 생존율은 각각 43%, 33%였다. 다변량 분석을 시행했을 때 환자의 나이, 수행 능력, 종양의 크기는 무진행 생존율에 영향을 주는 유의한 예후 인자로 나타났다. 결 론: 국소진행성 비소세포폐암 환자에서 paclitaxel 매주 투여 항암화학요법과 방사선치료 동시요법은 안전하고 종양의 관해율도 높았다. 그러나 국소 재발률이 높고 특히 종양의 크기가 큰 환자에서 예후가 나쁜 것을 알 수 있었다. 따라서 향후 부작용은 증가시키지 않으면서 국소제어율을 향상시키기 위한 노력이 필요하다.

• 농약과학회지
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• 제6권2호
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• pp.96-104
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• 2002

Paraquat의 세포독성을 알아보기 위하여 NIH 3T3 섬유모세포에 적용한 후 MTT와 NR 분석법을 이용하여 세포독성을 측정하고, paraquat의 세포독성에 대한 3-MC의 독성경감효과를 알아보기 위하여 Spraque Dawley계 수컷 랫드에 paraquat 단독 및 paraquat와 3-MC 병용투여 후 랫드의 폐를 경시적으로 채취하여 관찰하였다. Paraquat의 NIH 3T3 섬유모세포에 대한 $MTT_{50}$은 $1668.97{\mu}M$, $NR_{50}$은 $1030.25{\mu}M$로 산출되어 Borefreund와 Puemer(1984)의 독성판정기준에 의하면 저독성 물질이었다. Paraquat 단독 투여 군은 H&E 염색에서 3시간째부터 폐 모세혈관 내에 적혈구 수가 증가하기 시작하여 24시간째에는 충혈상태에 이르렀으며, 폐포사이 중격에서는 큰폐포상피수가 증가하였다. 또한 폐 조직을 둘러싸고 있는 결합조직 내에는 임파구, 대식세포 및 다형핵 백혈구 등이 다수 관찰되었고, 48시간째부터 폐포사이 중격과 폐포내에 폐포큰포식세포가 증가하기 시작하여 96시간째에는 다수의 폐포큰포식세포가 관찰되었다. Verhoeff의 iron hematoxylin 염색에서도 paraquat 단독 투여 후 24시간째에 조직변화가 가장 심하였고, 교원섬유량의 급격한 증가, 폐포의 넓이와 폐포 구멍(alveolar pore) 간격의 확장 등이 관찰되었다. 한편, paraquat와 3-MC 병용투여군은 paraquat 단독 투여 군에 비하여 조직변화가 약하게 관찰되었는데, 병용투여 후 3시간째에는 단독투여 3시간째의 소견과 유사하였으나 점차 회복되어 폐 모세혈관 내에 적혈구 수가 증가하여 24시간째에는 대조군의 구조와 거의 유사하였다. 또한 폐 조직을 둘러싸고 있는 결합조직과 임파소절에서도 paraquat 단독 투여 군에서 보였던 변화가 거의 관찰되지 않았다. Verhoeff의 iron hematoxylin 염색에서도 병용투여 후 24시간째에는 교원섬유량이 단독 투여 군에 비하여 크게 감소하였고 폐포와 폐포 구멍의 넓이도 대조군과 유사하였다.

• Tuberculosis and Respiratory Diseases
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• 제58권4호
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• pp.344-351
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• 2005

배 경 : Gemcitabine, paclitaxel, docetaxel, vinorelbine, irrinotecan 새로운 항종양제의 출현으로 일차 치료의 효과가 증대 되고 있고 재발시에도 좋은 신체 활동도를 보이고 있어서 이차 치료의 대상군도 늘어나는 효과를 보이고 있다. 치료의 필요성은 증대 되고 있지만 현재까지 표준 치료가 확립되지 않은 상황에서 Gemcitabine과 Vinorelbine 모두 독성이 강하지 않아서 혼합 요법이 가능한 장점이 있고 비소세포폐암에 대한 효과도 입증이 되어있어서 본 연구는 반응이 없거나 반응을 보인후에 재발된 진행된 비소세포 폐암에 gemcitabine과 vinorelbine 혼합 요법을 시행하여서 치료 반응률과 생존율 그리고 부작용을 평가하였다. 대상 및 방법 : 2000년 6월부터 2004년 3월까지 충남대학교병원에 내원하여 진행성 비소세포 폐암 IIIA/IIIB, IV로 진단을 받고 일차 항암화학요법치료를 받은 환자중에 초기 치료에 반응이 없거나, 치료에 반응이 있었으나 병이 진행된 환자로 추적 관찰 기간이 6개월 이상인 환자를 대상으로 생존율과 반응률 그리고 독성을 분석하였다. 결 과 : 총 치료 반응률은 17%, 반응 유지기간의 중앙값은 3.1개월(1-10개월)이었고 생존기간의 중앙값은 8.2개월(1-23개월) 그리고 1년 생존율은 35%였다. 항암화학요법에 의한 독성은 3도 이상의 중성구 감소가 12%, 오심과 구토가 12.5% 였다. 결 론 : 일차 치료에 반응이 없거나 재발한 비소세포 폐암환자의 이차 치료로 gemcitabine과 vinorelbine 혼합요법은 효과적이라고 생각되며 향후 3상 연구를 통한 다른 약제와의 비교 연구가 필요하다고 생각된다.

• Toxicological Research
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• 제21권2호
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• pp.151-160
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• 2005

In order to monitor the histological and general profiles of lung after direct expose of p,p-DDE, 1, 5 and 10 mg/ml of p,p-DDE were sprayed to male ICR mouse, and seven days after exposure, changes of body weight, lung weight, clinical signs, histological profiles of lung and total WBC in blood were investigated with changes of total cell number and their differential count in bronchoalveolar lavage fluid (BALF). In the present study, a significant and dosage-dependent decrease of body weight was detected in p,p-DDE exposed groups and body weight gains during observational periods (7 days) were also significantly and dosage-dependently decreased in p,p-DDE exposed groups compared to that of vehicle control group. In addition general depression signs were detected in all p,p-DDE exposed groups with dosage-dependent manners, and lung weights were also increased in p,p-DDE exposed groups. Congestion, hemorrhage and severe exudate were observed in the lung of p,p-DDE exposed groups with sarcomatous changes and these signs were also showed by dosage-dependent manners. In addition, foreign body pneumonia signs were observed in the lung of p,p-DDE exposed groups in histological levels. The percentage of ALSA (Area of luminal surface of alveoli) was also significantly and dosage-dependently decreased in p,p-DDE exposed groups and total blood WBC and BALF cell numbers were significantly and dosage-dependently increased in p,p­DDE exposed groups compared to that of vehicle control group and increase percentage of neutrophil, eosinophil, and lymphocyte in BALF were monitored in p,p-DDE exposed groups compared to that of vehicle control group. In conclusion, severe allergic response and/or foreign body pneumonitic changes were induced by direct exposure of p,p-DDE containing beverage. So it is considered that strong and powerful regulation was need to control production of residence of environmental pollutant especially to p,p-DDE.

• 한국환경보건학회지
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• 제48권6호
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• pp.324-330
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• 2022

Background: Lung injuries due to exposure to humidifier disinfectants (HDs) were reported in 2011 in South Korea. As a result of the government's epidemiological investigation and toxicity test study, it was found that HDs caused health damage such as lung disease. Objectives: The purpose of this study was to classify HD exposure ratings and analyze the affecting factors that could identify the relationship with lung disease. Methods: Exposure assessment for HDs was conducted using a questionnaire during face-to-face interviews with the applicants. Ratings of high exposure (Class 1) and low exposure (Class 2) were cross-tabulated with clinical ratings (acceptable and unacceptable). Logistic regression analysis was carried out by setting the clinical rating of lung disease as a dependent variable and the socio-demographic and exposure characteristics obtained through the questionnaire as independent variables. Results: The concentration in air of polyhexamethylene guanidine (PHMG) was 71.96±107.47 ㎍/m³, and the exposure concentration was 15.21±23.28 ㎍/m³ . The exposure rating was overestimated with 97.1% of affected subjects having high exposure using margin of exposure (MOE), but only 9.9% matching the clinical class. In the overestimated group, it could be explained by the fact that the exposure time was long and the subjects had already recovered from damage symptoms. As a result of logistic regression analysis, ten variables were found to be significant influencing factors. Conclusions: A new exposure rating could be calculated based on the MOE, and factors affecting lung disease could be estimated through comparative evaluation with the clinical rating.

• 한국환경성돌연변이발암원학회지
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• 제18권2호
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• pp.93-97
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• 1998

The results of chromosome aberration test in mammalian cells in culture (Chinese hamster lung fibroblast cells) showed no induction of structural and numerical aberrations by antifungal agents of YH1715 series regardless of metabolic activation. While positive control group (mitomycin C and benzo(a)pyrene) showed structural chromosome aberrations of 37% and 23%, respectively. The in vivo induction of micronuclei was measured in polychromatic erythrocytes in bone marrow of male ddY mouse given YH1715R and YH1729R at 1, 0.5, 0.25 g/kg by p.o. once. After 24 hours, animals were sacrificed and evaluated 40 the incidence of micronucleated polychromatic erythrocytes in whole erythrocytes. Although a positive response for induction of micronuclei in animals treated with mitomycin C demonstrated the sensitivity of the test system for detection of a chemical clastogen, YH1715R did not induce micronuclei in bone marrow of ddY male mice but induced cytotoxicity to bone marrow cells at the highest concentration (1 g/kg, p〈0.05), and YH1729R induced micronuclei in bone marrow of ddY male mice dose dependently (p<0.05) but did not induce cytotoxicity to bone marrow cells.

• 대한한의학방제학회지
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• 제19권2호
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• pp.151-160
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• 2011

Objectives : The purpose of this study was to investigate Armeniacae Amarum Semen of poison and the Pragmatic significance of the processing method. Methods : We researched several books dealing with Armeniacae Amarum Semen of poison and the Pragmatic significance of the processing method. Results & Conclusions : Armeniacae Amarum Semen is sweet, bitter, warm and harmful in nature. It is known as moistening the lung to arrest cough, moistening the colon, to move the bowels and promoting digestion and curing dog bites. Armeniacae Amarum Semen has toxicity, decreasing toxicity of Armeniacae Amarum Semen is boiling, peeling or roasting. If Armeniacae Amarum Semen has two seeds in one apricot or has six-floral leaf, do not used for medicinal purposes.

• Journal of Preventive Medicine and Public Health
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• 제47권5호
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• pp.245-252
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• 2014

Arsenic is a unique element with distinct physical characteristics and toxicity whose importance in public health is well recognized. The toxicity of arsenic varies across its different forms. While the carcinogenicity of arsenic has been confirmed, the mechanisms behind the diseases occurring after acute or chronic exposure to arsenic are not well understood. Inorganic arsenic has been confirmed as a human carcinogen that can induce skin, lung, and bladder cancer. There are also reports of its significant association to liver, prostate, and bladder cancer. Recent studies have also suggested a relationship with diabetes, neurological effects, cardiac disorders, and reproductive organs, but further studies are required to confirm these associations. The majority of research to date has examined cancer incidence after a high exposure to high concentrations of arsenic. However, numerous studies have reported various health effects caused by chronic exposure to low concentrations of arsenic. An assessment of the health effects to arsenic exposure has never been performed in the South Korean population; thus, objective estimates of exposure levels are needed. Data should be collected on the biological exposure level for the total arsenic concentration, and individual arsenic concentration by species. In South Korea, we believe that biological exposure assessment should be the first step, followed by regular health effect assessments.

• Toxicological Research
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• 제32권1호
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• pp.21-33
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• 2016

Dichlorodiphenyltrichloroethane (DDT) is still used in certain areas of tropics and subtropics to control malaria and other insect-transmitted diseases. DDT and its metabolites have been extensively studied for their toxicity and carcinogenicity in animals and humans and shown to have an endocrine disrupting potential affecting reproductive system although the effects may vary among animal species in correlation with exposure levels. Epidemiologic studies revealed either positive or negative associations between exposure to DDT and tumor development, but there has been no clear evidence that DDT causes cancer in humans. In experimental animals, tumor induction by DDT has been shown in the liver, lung, and adrenals. The mechanisms of hepatic tumor development by DDT have been studied in rats and mice. DDT is known as a non-genotoxic hepatocarcinogen and has been shown to induce microsomal enzymes through activation of constitutive androstane receptor (CAR) and to inhibit gap junctional intercellular communication (GJIC) in the rodent liver. The results from our previously conducted 4-week and 2-year feeding studies of p,p'-DDT in F344 rats indicate that DDT may induce hepatocellular eosinophilic foci as a result of oxidative DNA damage and leads them to hepatic neoplasia in combination with its mitogenic activity and inhibitory effect on GJIC. Oxidative stress could be a key factor in hepatocarcinogenesis by DDT.

• Molecular & Cellular Toxicology
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• 제4권4호
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• pp.267-277
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• 2008

Benzene and ethylbenzene (BE), the volatile organic compounds (VOCs) are common constituents of cleaning and degreasing agents, paints, pesticides, personal care products, gasoline and solvents. VOCs are evaporated at room temperature and most of them exhibit acute and chronic toxicity to human. Chronic exposure of benzene is responsible for myeloid leukemia and also ethylbenzene is also recognized as a possible carcinogen. To evaluate the BE effect on human, whole human genome 35 K oligonucleotide microarray were screened for the identification of the differential expression profiling. We identified 280 up-regulated and 201 down-regulated genes changed by more than 1.5 fold by BE exposure. Functional analysis was carried out by using DAVID bioinformatics software. Clustering of these differentially expressed genes were associated with immune response, cytokine-cytokine receptor interaction, toll-like signaling pathway, small cell lung cancer, immune response, apoptosis, p53 signaling pathway and MAPKKK cascade possibly constituting alternative or subordinate pathways of hematotoxicity and immune toxicity. Gene ontology analysis methods including biological process, cellular components, molecular function and KEGG pathway thus provide a fundamental basis of the molecular pathways through BEs exposure in human lymphoma cells. This may provides a valuable information to do further analysis to explore the mechanism of BE induced hematotoxicity.