• The Korean Journal of Air & Space Law and Policy
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• v.35 no.1
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• pp.33-62
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• 2020

The current air transportation industry is facing a lot of changes not only in the quantitative growth of the market, but also in the legal aspects. For many years, the Warsaw Convention has contributed to the uniform discipline of civil carriers' legal liabilities arising from international aviation accident and has fulfilled the duties of legal guardians for the development of the air transport industry. In the process, however, the consumer interests of the air transport industry did not have much protection compared to other industries. In response, the Montreal Convention has effected for protecting the interests of aviation consumers, and there are numerous legal changes around the world to protect aviation consumers like passengers. The mental damages of airline passengers arising from the accident can also be understood as part of the protection of air consumers. Considering that the US Federal Court has dealt with the recognition of mental damages for air passengers since the early 1990s. However, Korean judicial precedent still excludes mental anguishes from the scope of damage compensation. From this point of view, it is considered academically meaningful to analyze the latest case of the US federal court. Recently, the United States Court of Appeal for the Sixth Circuit in Doe v Etihad Airways applied a different interpretation against the traditional opinion: passengers could not recover for mental distress unless that mental distress resulted from a bodily injury sustained in an airplane accident. The background of the court's conclusions can be explained in many ways, among other things, unlike the Warsaw Convention the new international rule, Montreal Convention is recognizing the importance of ensuring protection of the interests of consumers in international carriage by air and the need for equitable compensation based on the principle of restitution.

• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.229-240
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• 1999

Background: The impact of the immune response on cancer gene therapy using viral vectors to deliver a "suicide gene" is currently unclear. A vigrous immune response targeted at viral proteins or transgene may enhance the efficacy of tumor destruction and even augment responses to tumor antigens. These responses may involve the release of cytokines and stimulation of tumor specific cytotoxic T-lymphocytes that enhance therapeutic efficacy. On the other hand, a vigorous rapid cellular immune response may destroy cells expressing the therapeutic gene and attenuate the response to therapy. Furthermore, development of neutralizing antibody responses may prevent readministration of virus, a potentially significant limitation. Evaluating the significance of these limitations in animal models and developing solutions are therefore of obvious importance. Methods: After retroviral transduction of mouse mesothelioma cell line(AB12) with Herpes Simplex Virus thymidine kinase (HSVtk) gene in vitro, subcutaneous flank tumors were established. To study the effect of intact immune system on efficacy of tumor erradication, the ability of the HSVtk/ganciclovir system to inhibit tumor growth was compared among normal Balb/c mice, immunodeficient Balb/c-nude and SCID mice, and Balb/c mice immunosuppressed with cyclosporin. Results: Ganciclovir treatment resulted in greater inhibition of tumor growth in Balb/c mice compared with immunodeficient Balb/c-nude mice and SCID mice(in immunodeficient mice, there were no growth inhibition by ganciclovir treatment). Ganciclovir treatment resulted in greater inhibition of tumor growth in noncyclosporin (CSA) treated Balb/c mice compared with CSA treated Balb/c mice. On day 8, mean ganciclovir-treated tumor volume were 65% of control tumor volume in Balb/c mice versus 77% control tumor volume in CSA-treated Balb/c mice. This effect was still evident during therapy (day 11 and 13). On day 13, non-CSA treated tumor volume was 35% of control tumor volume versus 60% of control tumor volume in CSA treated Balb/c mice. Duration of expression of HSVtk was not affected by the immunosuppression with CSA. Conclusion: These results indicate that the immune responses against retrovirally transduced cells enhance the efficacy of the HSVtk/ganciclovir system. These findings have important implications for clinical trials using currently available retrovirus vectors as well as for future vector design.

• Tuberculosis and Respiratory Diseases
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• v.48 no.5
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• pp.757-765
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• 2000

Background : Angiogenesis plays a critical role in human tumor growth and metastasis. Microvessel count as a measure of tumor angiogenesis, has been significantly correlated with invasive and metastatic patterns in breast. prostate and cutaneous carcinomas. Materials and Methods : Fifty patients with curatively resected non-small cell lung cancer were evaluated. Tumor tissues embedded in paraffin block were stained by anti CD 31 (PECAM, platelet endothelial cellular adhesion molecule) using immunohistochemical method to assess microvessel count. Microvessels were counted in the most active areas of neovascularization(microscopy, 200$\times$). Results: 1) Mean microvessel count was 47.1$\pm$17.7(per 200$\times$field) in total 50 cases. 2) Mean microvessel count of adenocarcinoma (54.4$\pm$19.9) was significantly higher than that of squamous cancer (43.9$\pm$16.2) (p<0.05), but there were no relationship between microvessel count and TNM stages. 3) Median survival time, 2-year and 5-year survival rates of the low microvascular group (microvessel count<45, 22 cases) were 61 months, 80% and 40%, respectively, and those of the high microvascular group(microvessel count$\geq$45, 28 cases) were 46 months, 75% and 12%, respectively. As results, prognosis of low microvascular group is statistically significantly superior to that of the high microvascular group (p=0.0162, Kaplan-Meier, log-rank). Conclusion : Angiogenesis assessed by microvessel count can be used as one of the significant prognostic factors in non-small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.58 no.5
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• pp.473-479
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• 2005

Background : Gefitinib targets the epidermal growth factor receptor r(EGFR), and Gefitinib has antitumor activity in patient with non-small cell lung cancer (NSCLC). However, only 10 to 20 percent of patients show a clinical response to this drug, and the molecular mechanisms underlying patient sensitivity to gefitinib are unknown. PTEN (Phosphatase and tensin homolog deleted on chromosome Ten) plays a role for the modulation of the phosphatidylinositol 3-kinase pathway (PI3K), which is involved in cell proliferation and survival, so that it can inhibit cell cycle progression and induce G1 arrest. Therefore, we analyzed the relationship between PTEN expression and gefitinib's responsiveness in patients having advanced non small cell lung cancer that had progressed after previous chemotherapy. Methods : The expression of PTEN was studied by immunohistochemistry in paraffin-embedded tumor blocks that were obtained from 22 patients who had been treated with gefitinib from JAN, 2001 to AUG. 2004. For the evaluation of the relationships between the PTEN expression, the clinical stage and the basal characteristics, those cases that showed the respective antigen expression in >50% of the tumor cells were considered positive. Results : The positive rate of PTEN staining was 55% of the total of 22 patients. There was a significant relationship between the increased expression of PTEN and the response group (p=0.039). However, there was no significant relationship between the expression of PTEN and other clinicopathologic characteristics. Conclusion: The expression of PTEN in patients with advanced non small cell lung cancer that has progressed after previous chemotherapy may play a role in gefitinib's responsiveness.

• Korean Journal of Environmental Biology
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• v.26 no.3
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• pp.252-263
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• 2008

The purpose of this study was to determine trophic state, based on nutrients (TN, TP), transparency (SD), and chlorophyll-${\alpha}$ (Chl) and identify their empirical relations of TN-Chl, TP-Chl and Chl-SD depending on the dataset used along with dynamics of conductivity and suspended solids. Analysis of trophic states showed that more than half of 36 reservoirs were judged as eutrophic-hypertrophic conditions depending on the trophic variables. Seasonal values of TP varied by nearly 500% and showed greater in August than any other months. In contrast, TN varied within less than 90% and all monthly mean values of TN were never fall less than 1.2 mg L$^{-1}$ indicating low seasonal variations and high ambient concentrations (eutrophic-hypertrophic state). Analysis of empirical relations in the trophic variables showed that transparency had greater functional relations with Chl (R$^2$=0.31, p<0.001) than TP (R$^2$=0.15, p<0.001) and TN (R$^2$=0.20, p<0.001). Ratios of TN : TP in the ambient water indicated that most reservoirs showed a potential phosphorous limitation on the algal growth. Thus, algal biomass, based on Chl values, was more regulated by phosphorous than nitrogen. Analysis of linear regression model, based on log-transformed annual mean values, showed that only 30% in the variation of Chl was explained by TP (R$^2$=0.295, p=0.001, n=36) and 15% by TN (R$^2$=0.151, p=0.019, n=36). However, linear regression model, based on individual system, showed that Chl-TP model had strong positive relations (R$^2$=0.62, p=0.002, n=12), whereas the model had no any relations (p=0.892, n=12). Overall, our data suggested that averaging effect in the empirical model developments may influence the significance in the statistical analysis.

• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.298-309
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• 2000

Background : The antitumor effects of herpes simplex virus thymidine kinase (HSV-tk) and ganciclovir (GCV) strategies for cancer gene therapy have a the following advantages : 1) a direct cytotoxicity to HSV-tk modified cancer cells by GCV 2) a cell death by the local transfer of toxic metabolites from the HSV-tk modified cells to nearby unmodified tumor cells (bystander effect), and 3) in vivo bystander effect such as antitumor-immunity. Retroviral and adenoviral sequences can silence transgene expression in cells and mice. In this study, we investigated the above described advantages of HSV-tk/GCV strategy in Lewis lung cell and mouse lung cancer model using retroviral vector and adenoviral vector. Also, we observed whether the expression of a silenced gene can be reactivated by treating cells with butyrate. Methods : Retrovirus-HSV-tk and adenovirus-HSV-tk vectors were used for the transduction of Lewis lung carcinoma (LLC) cells. The change of HSV-tk expression by butyrate was measured by Western blol The antitumor activities containing bystander effect were observed in vivo (by MTT assay) and in vivo tumor models of various combinations of LLC and LLC-tk. Results : 1. Butyrate induced the enhancement of HSV-tk expression from adenovirally transduced cells but not from retrovirally transduced cells. 2. Both retrovirus-HSV-tk and adenovirus-HSV-tk vectors with GCV treatment were effective for killing of tumor cell in vitro and suppression of LLC tumorigenicity. Bystander effect was responsible for killing of mixture of LLC-tk and LLC in vitro and in vivo-tumorigenicity model. Conclusion : Butyrate could augment adenovirus-mediated HSV -tk gene expression. Cancer gene therapy with HSV-tk suicide gene by retroviral and adenoviral vector seems to be an effective approach for lung cancer therapy.

• Tuberculosis and Respiratory Diseases
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• v.66 no.2
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• pp.110-115
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• 2009

Background: A forceps-biopsy is performed to acquire tissue from patients with an endobronchial carcinoma using a flexible bronchoscope. Recently, a cryo-biopsy has also been used to acquire tissue samples. Cryo-biopsy is the diagnostic application of extreme cold for the local destruction of abnormal living tissue. This technique is safe, with no radiation danger, no risk of electrical accidents, and a little risk of bleeding. This study compared a forceps-biopsy with a cryo-biopsy using a flexible bronchoscope, and examined the chemosensitivity and level of VEGF (vascular endothelial growth factor) in the specimens obtained from the cryo-biopsy. Methods: We present a prospective study of 30 consecutive patients who underwent a forceps-biopsy between January 2007 and October 2007 with a mean age of 62.1 years and a male:female ratio of 5 : 1. A flexible bronchoscope was inserted to the area of the abnormal lesions, and a cryo-probe was then applied through the working channel of the flexible bronchoscope. A temperature of approximately -h80 was delivered to the tumor site for 8 seconds. The cryo-biopsy was performed after destroying the tumor mass. Results: The mean size of the tissue from the forceps-biopsy and cryo-biopsy were 2.0${\pm}$1.2 mm and 6.0${\pm}$3.0 mm. A chemosensitivity test was performed on 5 specimens obtained using cryo-biopsy and the level of VEGF was examined in 2 specimens obtained from a cryo-biopsy. There were no side effects in either group. Conclusion: Cryo-biopsy using a flexible bronchoscope is a safe and effective technique for acquiring tissue samples.

• Tuberculosis and Respiratory Diseases
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• v.66 no.4
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• pp.280-287
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• 2009

Background: The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), became an attractive therapeutic option for advanced non-small-cell lung cancer (NSCLC). Several studies suggested that there might be some different efficacy or response predictors between gefitinib and erlotinib. We compared the efficacy and toxicity of gefitinib and erlotinib in Korean patients with advanced NSCLC and evaluated specific predictors of response for both gefitinib and erlotinib. Methods: We collected the clinical information on patients with advanced NSCLC, who were treated with gefitinib or erlotinib at the Ewha Womans University Hospital, between July 2003 and February 2009. Median survival times were calculated using the Kaplan-Meier method. Results: Eighty-six patients (52 gefitinib vs. 34 erlotinib) were enrolled. Patient median age was 64 years; 53 (62%) subjects were male. Out of the 86 patients treated, 83 received response evaluation. Of the 83 patients, 35 achieved a response and 12 experienced stable disease while 36 experienced progressive disease, resulting in a response rate of 42% and a disease control rate of 57%. After a median follow-up of 502 days, the median progression-free and overall survival time was 129 and 259 days, respectively. Comparing patients by treatment (gefitinib vs erlotinib), there were no significant differences in the overall response rate (44% vs. 39%, p=0.678), median survival time (301 days vs. 202 days, p=0.151), or time to progression (136 days vs. 92 days, p=0.672). Both EGFR-TKIs showed similar toxicity. In a multivariate analysis using Cox regression model, adenocarcinoma was an independent predictor of survival (p=0.006; hazard ratio [HR], 0.487; 95% confidence interval [CI], 0.292-0.811). Analyses of subgroups did not show any difference in response predictors between gefitinib and erlotinib. Conclusion: Comparing gefitinib to erlotinib, there were no differences in the response rate, overall survival, progression-free survival, or toxicity. No specific predictor of response to each EGFR-TKI was identified.

• Tuberculosis and Respiratory Diseases
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• v.66 no.1
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• pp.20-26
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• 2009

Background: $^{18}F$-Fluorodeoxyglucose positron emission tomography (FDG-PET) is widely used for the diagnosis and staging of non-small cell lung cancer (NSCLC). The aim of this study is to determine whether the bone marrow hypermetabolism seen on FDG-PET predicts a response to chemotherapy in patients with NSCLC. Methods: We evaluated the patients with advanced NSCLC and who were treated with combination chemotherapy. For determination of the standardized uptake value (SUV) of the bone marrow (BM SUV) on FDG-PET, regions of interest (ROIs) were manually drawn over the lumbar vertebrae (L1, 2, 3). ROIs were also drawn on a homogenous transaxial slice of the liver to obtain the bone marrow/ liver SUV ratio (BM/L SUV ratio). The response to chemotherapy was evaluated according to the Response Evaluation Criteria in Solid Tumor (RECIST) criteria after three cycles of chemotherapy. Results: Fifty-nine NSCLC patients were included in the study. Multivariate analysis was performed using a logistic regression model. The BM SUV and the BM/L SUV ratio on FDG-PET were not associated with a response to chemotherapy in NSCLC patients (p=0.142 and 0.978, respectively). Conclusion: The bone marrow hypermetabolism seen on FDG-PET can not predict a response to chemotherapy in NSCLC patients.

• Journal of Yeungnam Medical Science
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• v.24 no.1
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• pp.24-40
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• 2007

Background : Accumulating evidence shows that interleukin(IL)-1 plays a critical role in inflammation and connective tissue destruction observed in both osteoarthritis and rheumatoid arthritis. IL-1 induces gene expression related to cytokines, chemokines and matrix metalloproteinases by activation of many different transcription factors. Materials and Methods : The chondrosarcoma cell line, SW1353, is known to be a valuable in vitro system for investigating catabolic gene regulation by IL-$1{\beta}$ in chondrocytic cells. To explore and analyze the changes in gene expression by IL-1 responsible for arthritis, SW1353 was treated with IL-1 for 1, 6 and 24 h and then total RNAs were purified for each time. The changes in gene expression were analyzed with 17k human cDNA microarrays and validated by semi-quantitative RT-PCR. Results : Greater than a two-fold change was observed in 1,200 genes including metallothioneins, matrix metalloproteinases, extracellular matrix proteins, antioxidant proteins, cytoskeleton proteins, cell cycle regulatory proteins, proteins for cell growth and apoptosis, signaling proteins and transcription factors. These changes appeared to be correlate with the pathophysiological changes observed in early osteoarthritis. Conclusion : cDNA microarray analysis revealed a marked variability in gene expression, and provided insight into the overall molecular changes. The result of this study provide initial information for further studies to identify therapeutic targets in osteoarthritis pathogenesis.