• Asian Pacific Journal of Cancer Prevention
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• 제13권10호
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• pp.5177-5182
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• 2012

Purpose: To compare the efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitormonotherapy (EFGR-TKIs: gefitinib or erlotinib) with standard second-line chemotherapy (single agent docetaxel or pemetrexed) in previously treated advanced non-small-cell lung cancer (NSCLC). Methods: We systematically searched for randomized clinical trials that compared EGFR-TKI monotherapy with standard second-line chemotherapy in previously treated advanced NSCLC. The end points were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), 1-year survival rate (1-year SR) and grade 3 or 4 toxicities. The pooled hazard ratio (HR) or risk ratio (RR), with their corresponding 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. Results: Eight randomized controlled trials (totally 3218 patients) were eligible. Our meta-analysis results showed that EGFR-TKIs were comparable to standard second-line chemotherapy for advanced NSCLC in terms of overall survival (HR 1.00, 95%CI 0.92-1.10; p=0.943), progression-free survival (HR 0.90, 95%CI 0.75-1.08, P=0.258) and 1-year-survival rate (RR 0.97, 95%CI 0.87-1.08, P=0.619), and the overall response rate was higher in patients who receiving EGFR-TKIs(RR 1.50, 95%CI 1.22-1.83, P=0.000). Sub-group analysis demonstrated that EGFR-TKI monotherapy significantly improved PFS (HR 0.73, 95%CI: 0.55-0.97, p=0.03) and ORR (RR 1.96, 95%CI: 1.46-2.63, p=0.000) in East Asian patients, but it did not translate into increase in OS and 1-year SR. Furthermore, there were fewer incidences of grade 3 or 4 neutropenia, febrile neutropenia and neutrotoxicity in EGFR-TKI monotherapy group, excluding grade 3 or 4 rash. Conclusion: Both interventions had comparable efficacy as second-line treatments for patients with advanced NSCLC, and EGFR-TKI monotherapy was associated with less toxicity and better tolerability. Moreover, our data also demonstrated that EGFR-TKImonotherapy tended to be more effective in East Asian patients in terms of PFS and ORR compared with standard second-line chemotherapy. These results should help inform decisions about patient management and design of future trials.

• 농약과학회지
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• 제7권3호
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• pp.198-206
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• 2003

Benzimidazole계 살균제의 세포독성을 평가하기 위하여 CHL(chinese hamster lung) 세포를 이용한 Giemsa stain assay, Lactic dehydrogenase(LDH) activity, MTT assay, DNA synthesis inhibition test 및 Sulforhodamin B(SRB) assay를 수행하여 benzimidazole 계 살균제에 대한 약제별 세포독성을 평가하고 위해도 평가를 위한 자료로 사용하고자 하였다. 시험결과 LDH 활성은 carbendazim 4.0, 16.0 및 $32.0{\mu}g/mL$을 24 시간 처리하였을 때 음성대조군에 비해 농도별로 세포독성이 각각 2.16, 2.94 및 2.64배 강하게 나타났다. DNA 합성시험에서는 carbendazim $2.0{\mu}g/mL$ 농도에서 약 45% DNA 합성을 저해하였으며, Giemsa assay와 MTT assay에서도 세포와 mitochondria에 독성을 일으키는 것으로 나타났다. Giemsa assay의 $IC_{50}$은 thiophanate-methyl, benomyl, carbendazim 및 양성대조 약제인 captafol에서 각각 >125, 1.2, 30.0 및 $0.3{\mu}g/mL$ 이었고, MTT assay의 $IC_{50}$은 thiophanate-methyl, benomyl, carbendazim 및 captafol에서 각각 >125, 18.7, 20.4 및 $2.6{\mu}g/mL$이었다. 그리고 세포 증식에 대한 영향을 조사하기 위하여 수행된 SRB assay 의 $IP_{50}$(반수세포증 식억제농도)에서도 thiophanate-methyl, carbendazim, benomyl 및 captafol이 각각 17.4, 5.3, 1.5, 및 $0.5{\mu}g/mL$으로 관찰되었다. 이상의 결과는 급성독성이 낮은 benzimidazole계 살균제가 유전독성 등 특수독성이 강하게 나타나는 원인일 것으로 판단되었다.

• Toxicological Research
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• 제35권1호
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• pp.45-63
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• 2019

In view of the growing industrial use of Bacterial cellulose (BC), and taking into account that it might become airborne and be inhaled after industrial processing, assessing its potential pulmonary toxic effects assumes high relevance. In this work, the murine model was used to assess the effects of exposure to respirable BC nanofibrils (nBC), obtained by disintegration of BC produced by Komagataeibacter hansenii. Murine bone marrow-derived macrophages ($BMM{\Phi}$) were treated with different doses of nBC (0.02 and 0.2 mg/mL, respectively 1 and $10{\mu}g$ of fibrils) in absence or presence of 0.2% Carboxymethyl Cellulose (nBCMC). Furthermore, mice were instilled intratracheally with nBC or nBCMC at different concentrations and at different time-points and analyzed up to 6 months after treatments. Microcrystaline $Avicel-plus^{(R)}$ CM 2159, a plant-derived cellulose, was used for comparison. Markers of cellular damage (lactate dehydrogenase release and total protein) and oxidative stress (hydrogen peroxidase, reduced glutathione, lipid peroxidation and glutathione peroxidase activity) as well presence of inflammatory cells were evaluated in brochoalveolar lavage (BAL) fluids. Histological analysis of lungs, heart and liver tissues was also performed. BAL analysis showed that exposure to nBCMC or CMC did not induce major alterations in the assessed markers of cell damage, oxidative stress or inflammatory cell numbers in BAL fluid over time, even following cumulative treatments. $Avicel-plus^{(R)}$ CM 2159 significantly increased LDH release, detected 3 months after 4 weekly administrations. However, histological results revealed a chronic inflammatory response and tissue alterations, being hypertrophy of pulmonary arteries (observed 3 months after nBCMC treatment) of particular concern. These histological alterations remained after 6 months in animals treated with nBC, possibly due to foreign body reaction and the organism's inability to remove the fibers. Overall, despite being a safe and biocompatible biomaterial, BC-derived nanofibrils inhalation may lead to lung pathology and pose significant health risks.

• Molecular & Cellular Toxicology
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• 제3권4호
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• pp.299-305
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• 2007

The endocrine disrupting chemical, di (2-ethylhexyl) phthalate (DEHP) is a plasticizer used in polyvinyl chloride products ubiquitous in our daily lives. DEHP has potentially adverse effects on the liver, kidney, lung, heart, reproductive organs and endocrine systems. Many toxicological data on the DEHP toxicity have been stated, but complete protein profiles have not yet been reported. In this study, DEHP-induced oxidative DNA damage in rat lymphocyte was evaluated by Comet assay (single-cell gel electrophoresis) for the first time. Moreover, DEHP-induced protein profile alterations were examined in rat liver by using toxicoproteomic tools. 34 protein spots in the liver were identified to be significantly deregulated by DEHP on the 2-dimensional gel. Among them, 20 spots were up-regulated and 14 spots down-regulated by DEHP.

• Tuberculosis and Respiratory Diseases
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• 제77권6호
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• pp.262-265
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• 2014

The combination chemotherapy of irinotecan with 5-fluorouracil and leucovorin (FOLFIRI regimen) was recently proven to be beneficial in patients with advanced colorectal cancer. Pulmonary toxicity is very rare in adverse effects of irinotecan. No case of organizing pneumonia (also known as bronchiolitis obliterans organizing pneumonia) associated with FOLFIRI chemotherapy has been reported. We experienced a case of a 62-year-old man who presented persistent dry cough and progressive dyspnea after receiving chemotherapy with FOLFIRI regimen. After surgical lung biopsy, the patient was diagnosed with FOLFIRI chemotherapy-induced organizing pneumonia which was successfully treated with steroid therapy.

• 생약학회지
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• 제31권1호
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• pp.45-50
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• 2000

The root of Pseudostellaria heterophylla Pax et Hoffm. (Caryophyllaceae) is a herbal medicine called Taejasam(太子蔘) and used as a good tonic in China that strengthens the functions of the lung and the stomach like Ginseng in Korea. It has been known to have the antitussive activity for tuberculosis, appetizing effect and antifatigue activity, and so on. Especially it has been known to generate body fluids for the severe thirst and the shortage of water in body after a febrile disease for a long time. Recently some components of cyclic peptides, pseudostellarins A,B,C,D,E,F,G, that inhibit the activity of tyrosinase, were separated from this root. In this report several biological activities including acute toxicity, analgesic activity, antifatigue activity, bile juice increasing activity, hepatoprotective activity and antiinflammatory activity were investigated. These results showed as such; $LD_{50}$ of methanol extracts was above 10,000 mg/kg. The analgesic effect was revealed in the writhing test using rats. The BuOH fractions showed a prominent antifatigue effect against immobilized stress, significant hepatoprotective activities against $CCl_4$ intoxication and inhibitory effect on carrageenin-induced edema in rat's paw.

• Journal of Pharmaceutical Investigation
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• 제9권3호
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• pp.9-21
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• 1979

This study was undertaken to establish the different pharmaceutical properties between promethazine HCl and promethazine pamoate. First, promethazine pamoate was prepared by using the modified method of Saias. Second, in order to study the different pharmacokinetics between promethazine pamoate and promethazine HCl, absorption rate, plasma concentration, and distribution, as well as urinary excretion of the both compounds were examined in rabbits as an experimental animal: The results were as follows. 1. In the in vitro isolated intestine of rabbit, the rate constant for absorption of promethazine pamoate was $0.347hr^{-1}$ and that of promethazine HCl was $0.532hr^{-1}$. 2. After oral administration of promethazine pamoate, the increase of plasma concentration of promethazine was much slower than that of promethazine HCl. 3. The urinary excretion rate of promethazine pamoate was significantly low in comparison to that of promethazine-HCl; i. e. about 50% of promethazine HCl was excreted within 3 hours, and 5 to 15 hours for that of promethazine pamoate. 4. The tissue concentration of promethazine after oral administration of promethazine pamoate in rabbit was steadily increased for 5 hours. However, promethazine HCl concentration reached to maximum 1 hour after administration, then decreased slowly. 5. A significant amount of promethazine was mainly distributed in spleen, kidney, lung, liver and heart in this order, rather than other organs, such as brain, and muscle. 6. In the toxicity test by using mouse, $LD_{50}$ for promethazine pamoate was 3,250 mg/kg, while $LD_{50}$ for promethazien HCl was 298mg/kg.

• Tuberculosis and Respiratory Diseases
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• 제74권3호
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• pp.120-123
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• 2013

Inhalation of toxic gases can lead to pneumonitis. It has been known that methane gas intoxication causes loss of consciousness or asphyxia. There is, however, a paucity of information about acute pulmonary toxicity from methane gas inhalation. A 21-year-old man was presented with respiratory distress after an accidental exposure to methane gas for one minute. He came in with a drowsy mentality and hypoxemia. Mechanical ventilation was applied immediately. The patient's symptoms and chest radiographic findings were consistent with acute pneumonitis. He recovered spontaneously and was discharged after 5 days without other specific treatment. His pulmonary function test, 4 days after methane gas exposure, revealed a restrictive ventilatory defect. In conclusion, acute pulmonary injury can occur with a restrictive ventilator defect after a short exposure to methane gas. The lung injury was spontaneously resolved without any significant sequela.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2002년도 추계국제학술대회
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• pp.155-155
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• 2002

Ambient urban particulate matters contain various transition metals. When the particulate matters are inhaled into the lung, not all but some part of metals from the particles might be mobilized to participate in a reaction that can damage various biomolecules, such as DNA and proteins. The dust particle size as well as organic acids may influence the metal mobilization. Thus, the mobilization of the metal from SRM1648 (NIST, USA) and urban particulate matters (PM2.5 and PM10) was measured in the presence of artificial or biological chelator with or without reductant. The degree of the mobilization was higher with the artificial or biological chelator than the control with saline. In some cases, a reductant increased the mobilization as much as about 5 times the control without the reductant. Especially, the mobilization of Fe was greatly influenced by the presence of reductants. In general, the degree of the mobilization of the transition metal was higher with PM2.5 than with PM10. Therefore, it is expected that, considering the previously known toxicities of the transition metals, the PM2.5 is more damaging to various biomolecules than PM10. The results also suggest that not the total amount but the mobilizable fraction of the metal in the dust particles should be considered with regard to the toxicity of the urban particulate matters.

• 한국식품위생안전성학회지
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• 제13권2호
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• pp.135-142
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• 1998

국내 화장품 업계에서 실제 사용되고 있는 합성타르색소인 적색 204호 , 적색215호, 등색 203호의 3가지 색소에 대하여 유전독성시험을 행하였다.Chinese hamster lung(CHL) 세포에서의 염색체이상시험과 ddY 마우스를 이용한 소핵시험 및 초파리 날개를 이용한 체세포돌연변이 재조합 시험을 실시하였다. 그 결과 염색체이상시험과 소핵시험에서는 적색 204, 적색 215, 등색 203호 에서는 유전독성을 나타내는 변이원인으로는 작용하지 않는 것으로 나타났고 초파리 날개를 이용한 체세포돌연변이 시험에서는 각각 100mg/ml에서 single small spot의 출현빈도가 p<0.05의 유의수준에서 대조군에 비해 증가양상을 보였고, twin spot의 빈도 수는 적색 204호의 경우는 50mg/ml 농도에서, 적색 215호의 경우는 100mg/ml 농도에서 p<0.05의 유의수준에서 증가양상을 보여 약한 돌연 변이 원성을 나타내었다.