• Radiation Oncology Journal
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• v.13 no.4
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• pp.321-330
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• 1995

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 50cc). Pulmonary irradiation was started 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 B, six of 7 patients($86{\%}$) with no RT were died due to respiratory failure, but 4 of 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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.1
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• pp.78-88
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• 2002

Experimental animals were divided into 5 groups; normal, cadmium control, and 3 experimental groups. Cadmium control and experimental groups were exposed to 1 mg/㎥ of cadmium aerosol in air by inhalation exposure for 6 hours/day, 5 days/week during 4 weeks. Dosages of 20, 40, and 80mg/kg of extracts of persimmon leaves were intraperitoneally injected to experimental groups respectively and several toxicological parameters and induction of metallothionein were measured from the rats that inhaled cadmium aerosol in air. The results of this study were as follows. Cadmium concentration that cadmium control and experimental groups were inhaled was 0.980±0.061 mg/㎥. Mass median diameter of cadmium aerosol for inhalation exposure was 4.93±0.483㎛. Cadmium content of normal group in lung was 0.088㎍/g and the highest cadmium content in lung, 55.492㎍/g was from 80mg/kg dose group. Cadmium concentration of normal group in blood was 0.348㎍/100㎖ and the highest cadmium concentration in blood, 2.642㎍/100㎖ was from cadmium control. Cadmium concentration of normal group in liver was 0.010㎍/g and the highest cadmium concentration in liver, 31.100㎍/g was from 20mg/kg dose group. Cadmium concentration of normal group in kidney was 0.030㎍/g and the highest cadmium concentration in kidney, 2.526㎍/g was from cadmium control. Cadmium concentration of normal group in intestine was O.064㎍/g and the highest cadmium concentration in intestine, 0.300㎍/g was from 80mg/kg dose group. The highest cadmium concentration in urine by week was 6.080㎍/day from 20mg/kg dose group in the fouth week and the highest cadmium concentration in feces by week was 341.731㎍/day from 20mg/kg dose group in the fouth week. Metallothionein concentration of normal group in lung was 5.769㎍/g and the highest in lung, 30.986㎍/g was from 80mg/kg dose group. Metallothionein concentration of normal group in liver was 38.856㎍/g and the highest in liver, 169.378㎍/g was from 40mg/kg dose group. Metallothionein concentration of normal group in kidney was 22.228㎍/g and the highest in kidney, 47.898㎍/g was from 80mg/kg dose group. Metallothionein concentration of normal group in intestine was 2.170㎍/g and the highest in intestine, 13.642㎍/g was from 80mg dose group.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.3 no.1
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• pp.85-98
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• 1997

Oriental medicine as a candidate for effective cancer treatment recently gain positive concerns in fields of therapeutic oncology. that is why some herbal medicines have been empirically safer in toxicity than anticancer drugs used in western medicine, and to show excellent therapeutic efficacy in human trial. Thus, these effects by clinically applied-herbs have not yet fully demonstrated in experimental tumor model. This study was initiated to evaluate the antitumor effect of Insambaekhaptang as candidate of antitumor-herbal agent against B16 melanoma metastasized into C57BL/6 mice lung. In experiment to test whether Insambaekhaptang can directly kill cancer cells in vitro or not, Insambaekhaptang showed direct killing action in concentration or higher against B16 melanoma cells using MTT assay, and showed lower IC50. Another experiment to know whether Insambaekhaptang can inhibit growth and metastasis of cancer cell or not, Insambaekhaptang significantly inhibited Solid tumor by intraperiperal injected-melanoma and lung metastasis induced by intravenous injected-melanoma in inbred C57BL/6 mice. When quantitative survival time increasing, we could obtain results that increased 113% in treated by Insambaekhaptang. These results show that Insambaekhaptang can inhibit growth of B16 melanoma cells through various biological mechanisms.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2909-2912
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• 2012

Aim: To evaluate efficacy and tolerability of topotecan treatment for recurrent small cell lung carcinoma. Patients and Methods: A total of 62 patients were evaluated retrospectively. Statistical analysis was performed using GraphPad Instat (version 3.05). Results: DFifty five of patients (89%) were male and 7 (11%) were female. Median age was $56.7{\pm}9.3$ (34-75). Forty eight of patients (80%) were extensive stage (ES) at the time of diagnosis. Fifty of the patients (80.6 Medical Oncology Clinic) were given median 5.36 cycles of cisplatin-etoposide (2-8 cycles). Time to recurrence was $15.6{\pm}6.13$ weeks in patients with limited stage (LS) and $6.3{\pm}3.82$ weeks in extensive stage (ES) (p<0.0001). Overall survival was $14.0{\pm}6.08$ months in ES and $17.9{\pm}6.88$ months in LS. The difference between two groups was statistically meaningful (p=0.0447). The overall survival of the patients was $14.8{\pm}6.43$ months (4.5-40 months). In terms of survival, there was no difference between males and females (p=0.1171). In 17 (27%) patients who were refractory to topotecan or in whom progression occurred other chemotherapies were used. Conclusion: Small cell lung cancer is chemosensitive, but recurrences occur in short time. Other chemotherapy regimens are used in progression. Topotecan is one of them. Patients who were young and in whom recurrences occur late had given better response to topotecan. Because of the retrospective nature of the study, we couldn't reach the records exactly and consequently, rate and duration of response couldn't be calculated. In recurrent SCLC topotecan is one of the treatment choices. But both hematological and non hematological side effects should be taken into consideration.

• Toxicological Research
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• v.21 no.4
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• pp.347-353
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• 2005

Eukaryotic initiation factor 4E (elF4E) is a key element for cap-dependent protein translation controlled by affinity between elF4E and 4E-binding protein 1 (4E-BP1). Rapamycin can also affect protein translation by regulating 4E-BP1 phosphorylation. Tobacco-specific nitrosamine, 4(N-methyl-N-nitrosamino )-1-(3-pyridyl)-1-butanone (NNK) is a strong lung carcinogen, but its precise lung cancer induction mechanism remains unknown. Relative roles of cap-dependent and -independent protein translation in terms of NNK-induced lung carcinogenesis were elucidated using normal human bronchial epithelial cells. NNK concentrations applied in this study did not decrease cell viability. Addition of NNK restored rapamycin-induced decrease of protein synthesis and rapamycin-induced phosphorylation of 4E-BP1, and increased expression levels of mTOR, ERK1/2, p70S6K, and Raf-1 in a concentration-dependent manner. NNK also caused perturbation of normal cell cycle progression. Taken together, NNK might cause toxicity through the combination of restoration of 4E-BP1 phosphorylation and increase of elF4E as well as mTOR protein expression, interruption of Raf1/ERK as well as the cyclin G-associated p53 network. Our data could be applied towards elucidation of the molecular basis for lung cancer treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7303-7307
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• 2014

Objective: To explore the clinical efficacy of gemcitabine concomitant with nedaplatin and drug resistance in the treatment of non-small cell lung cancer (NSCLC) and associated molecular predicators. Materials and Methods: A total of 68 patients diagnosed with NSCLC by histology served as the study objects and were randomly divided into an observation group treated with gemcitabine concomitant with nedaplatin and a control group with cisplatin concomitant with gemcitabine, 34 cases for each group. Short-term and long-term efficacies, adverse responses as well as the expression of nucleotide excision repair cross complementing 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1) and lung resistance-related protein (LRP) in NSCLC tissues in both groups were assessed. Results: The short-term objective response rate (ORR) and disease control rate (DCR) were 35.3% (12/34) and 76.5% (26/34) in the observation group and 38.2% (13/34) and 85.3% (29/34) in the control group, respectively, the differences not being statistically significant. The time to progression (TTP) in both groups were 1~12 months, while the median TTP was 135 d and 144 d, respectively. Though the survival was slightly higher in the control group, there were no significant differences in TTP and survival time. The rates of decreased hemoglobin, vomiting and nausea as well as renal toxicity were evidently lower in the observation group, while other adverse responses demonstrated no significant difference. The positive expression rates of ERCC1, RRM1 and LRP were 47.1% (16/34), 61.8% (21/34) and 64.7% (22/34) in the observation group, respectively. Compared with negative ERCC1 expression, ORR had decreasing trend and the overall survival time (OS) decreased significantly in patients with positive ERCC1 expression, which were markedly decreased by the positive expressions of RRM1 and LRP. Conclusions: Gemcitabine concomitant with nedaplatin has significant effects in the treatment of NSCLC, with an adverse response rate obviously lower than for cisplatin concomitant with gemcitabine, suggesting that wider use in the clinic is warranted. Additionally, the positive expressions of ERCC1, RRM1 and LRP may increase patient drug resistance, so they can be applied as the chemotherapeutic predicators to guide individualized therapy of NSCLC patients.

• Journal of Preventive Medicine and Public Health
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• v.27 no.1 s.45
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• pp.84-106
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• 1994

Hyperbaric oxygen (HBO) therapy for carbon monoxide (CO) poisoning eventually inducing the hypoxia-reoxygenation condition, may produce oxygen free radicals, which forms 8-hydroxydeoxyguanosine (8-OH-dG) by attacking C-8 position of deoxyguanosine (dG) in DNA. Effects of oxygen partial pressure or duration of HBO therapy with or without CO poisoning on the tissue 8-OH-dG formation were investigated. Male Sprague-Dawley rats were grouped and exposed to air (control group), 4000 ppm of CO for 10 to 30 minutes (CO only group), air for 30 minutes after 30 minute exposure to 4000 ppm of CO(CO-air exposure group), HBO after 30 minute exposure to 4000 ppm of CO(CO-HBO group), or HBO therapy fo. $10{\sim}120$ minutes(HBO only group). The 8-OH-4G concentrations in the brain and the lung tissues were measured with high performance liquid chromatography and electrochemical detector (ECD). Average concentrations of the 8-OH-dG of each group were statistically compared. In the brain tissues, 8-OH-dG concentrations of the CO only group, the CO-air exposure group, and the CO-HBO group did not significantly differ from those of the control group. Similar insignificance was also found between the CO-HBO group and the HBO only groups. No appreciable dose-response relationship was observed between the 8-OH-dG concentration and the oxygen partial pressure or the duration of HBO. However, the 8-OH-dG concentrations of the 30 minute CO only group were higher than those of the CO-air exposure group (p-value<0.05). In the lung tissues, there were no significant differences between the 8-OH-dG concentrations of the control group and those of the CO only group, the CO-air exposure group, and the CO-HBO group. However, mean 8-OH-dG concentration of the CO-air exposure group was significantly higher than that of the CO only group under the same CO exposure condition(p-value<0.05). With the duration of CO exposure, the 8-OH-dG concentrations of the lung tissues decreased significantly (p-value<0.05). The concentrations of 8-OH-dG in the lung tissues proportionally increased with the duration of HBO, but no such relation was observed with the oxygen partial pressure. These results suggest that the brain may be more resistant to oxygen free radicals as compared with the lungs, and that oxygen toxicity following HBO may be affected by factors other than oxygen free radicals.

• Journal of Environmental Health Sciences
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• v.47 no.2
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• pp.111-122
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• 2021

Objectives: There was a judgment of acquittal for the manufacturer SK Chemical and the vendor Aekyung regarding humidifier disinfectant (HD) containing 5-chloro-2-methylisothiazol-3(2H)-one/2-methylisothiazol-3(2H)-one (CMIT/MIT). The rationale used in this judgement is discussed here in the light of scientific consideration. Methods: The sentencing document for the judgements was obtained from the Korea Supreme Court Service. In particular, the judgements made by the court related to the risk of HD and external and internal exposure to CMIT/MIT are discussed based on scientific evidence. Results: Rendering a determination in a criminal trial of insufficient evidence of causation, the court dismissed the prosecution's motion that humidifier disinfectant-associated lung injuries (HDLI) and asthma were associated with the utilization of these products. However, CMIT/MIT, a strong sensitizing and corrosive substance, has been reported to be associated with brain toxicity, allergic contact dermatitis, and asthma. Furthermore, the judgment did not consider total consumption amounts or the cumulative dose of CMIT/MIT in the humidifier. Lastly, there are several cases supporting the fact that exposure to water-soluble substances including CMIT/MIT can cause lower respiratory tract diseases. In addition to cases of asthma among the workers exposed to CMIT/MIT, we identified lung injury victims who were exposed to HDs exclusively containing CMIT/MIT. Conclusions: We conclude that there is sufficient evidence supporting the assertion that HDs containing CMIT/MIT cause lung injuries, including asthma, contrary to the court's judgement.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.15 no.4
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• pp.2189-2198
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• 2014

Paraquat (PQ) is a very effective and widely used herbicide that was commercially introduced in 1962. In this study, instead of using antioxidants like in the past, to inhibit the formation of PQ-induced ROS, we attempted to reduce the oxygen concentration by using non-lethal hypoxia therapy. Therefore, we studied the toxicity of PQ in vivo, analyzed the major effects of ROS on the targeted lung tissue and compared the results with the gross histological changes after the cell protective effect of non-lethal hypoxia therapy. In vivo studies demonstrated that low-concentration oxygen therapy (i.e., 10-12% oxygen) in rats administered with PQ was associated with a higher survival rate than in rats that received only PQ. In vivo non-lethal hypoxia treatment showed better survival and less lung tissue damage. Using a hypoxic/anaerobic incubator with integrated multifaceted molecular analysis, including MDA assay, glutathione assay, and SOD assay, we established an optimal, significantly reduced in vivo non-lethal hypoxia treatment by exploiting the PQ-induced cytotoxicity responses.

• Environmental Mutagens and Carcinogens
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• v.26 no.3
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• pp.77-85
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• 2006

2,3,7,8-Tetrachlorodibenzo-$\rho$-dioxin(TCDD) displays high toxicity in animals and has been implicated in human carcinogenesis. Although TCDD is recognized as potent carcinogens, relatively little is known about their role in the tumor promotion and carcinogenesis. It is known that TCDD can increase of cancer risk from various types of tissue by a mechanism possibly involving the aryl hydrocarbon receptor (AhR) activation. In this study, effects of TCDD on cellular proliferation of normal human skin and lung fibroblasts, Detroit551 and WI38 cells were investigated. In addition, to enhance our understanding of TCDD-mediated carcinogenesis, we have investigated process in which expression of Erk1/2, cyclinD1, oncogene such as Ha-ras and c-myc, and their cognate signaling pathway. TCDD that are potent activators of AhR-mediated activity was found to induce significant increase of cytochrome P4501A1 mRNA expression, suggesting a presence of functional AhR. These results support that CYP1A1 enzyme may be involved in the generation of TCDD-induced toxicity. Moreover mitogen-activated protein kinases (MARKs) phosphorylation and cyclin D1 overexpression are induced by TCDD, which corresponded with the progression of cellular proliferation. However, TCDD did not affected Ha-ras and c-myc mRNA expression. Taken together, it seems that TCDD are could be a part of cellular proliferation in non-tumorigenic normal human cells such as Detroit551 and WI38 cells through the upregulation of MAPKs signaling pathway regulating growth of cell population. Therefore, AhR-activating TCDD could potentially contribute to tumor promotion and Detroit551 and WI38 cells have been used as a detection system of tumorigenic effects of TCDD.