• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10407-10412
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• 2015

Background: ${\beta}$-elemene, extracted from herb medicine Curcuma wenyujin has potent anti-tumor effects in various cancer cell lines. However, the activity of ${\beta}$-elemene against glioma cells remains unclear. In the present study, we assessed effects of ${\beta}$-elemene on human glioma cells and explored the underlying mechanism. Materials and Methods: Human glioma U87 cells were used. Cell proliferation was determined with MTT assay and colony formation assay to detect the effect of ${\beta}$-elemene at different doses and times. Fluorescence microscopy was used to observe cell apoptosis with Hoechst 33258 staining and change of glioma apoptosis and cell cycling were analyzed by flow cytometry. Real-time quantitative PCR and Western-blotting assay were performed to investigated the influence of ${\beta}$-elemene on expression levels of Fas/FasL, caspase-3, Bcl-2 and Bax. The experiment was divided into two groups: the blank control group and ${\beta}$-elemne treatment group. Results: With increase in the concentration of ${\beta}$-elemene, cytotoxic effects were enhanced in the glioma cell line and the concentration of inhibited cell viability ($IC_{50}$) was $48.5{\mu}g/mL$ for 24h. ${\beta}$-elemene could induce cell cycle arrest in the G0/G1 phase. With Hoechst 33258 staining, apoptotic nuclear morphological changes were observed. Activation of caspase-3,-8 and -9 was increased and the pro-apoptotic factors Fas/FasL and Bax were upregulated, while the anti-apoptotic Bcl-2 was downregulated after treatment with ${\beta}$-elemene at both mRNA and protein levels. Furthermore, proliferation and colony formation by U87 cells were inhibited by ${\beta}$-elemene in a time and does-dependent manner. Conclusions: Our results indicate that ${\beta}$-elemene inhibits growth and induces apoptosis of human glioma cells in vitro. The induction of apoptosis appears to be related with the upregulation of Fas/FasL and Bax, activation of caspase-3,-8 and -9 and downregulation of Bcl-2, which then trigger major apoptotic cascades.

• Clinical and Experimental Pediatrics
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• v.45 no.3
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• pp.362-369
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• 2002

Background : Anemia is still the most common nutrient deficiency worldwide, especially in adolescence because of an insufficient supply of iron, an increased iron requirement due to accelerated physical growth and blood loss due to menstruation in girls. This study was designed to assess the anemia and serum iron status of middle school girls. Methods : Hematologic examinations, physical examinations and questionnaires were performed for middle school girls in 1990, 1997, 1999 and 2000. Anemia was defined as a serum hemoglobin level of less than 11.5 g/dL. Iron deficiency was defined as a serum ferritin level of less than 10 ng/mL. Iron deficiency anemia was defined as anemia plus one of the following; MCV less than 78 fL, Ferritin level less than 10 ng/mL or Transferrin saturation rate less than 10%. Results : There was no significant difference in mean Hb between urban and rural areas and decreases in mean Hb as with age. The prevalence of anemia decreased by year; 13.5% in 1990, 6.9 % in 1997, 6.0% in 1999, and 5.7% in 2000. It was high in high school girls(10.1% in 1997 and 12.6% in 2000). The prevalence of iron deficiency decreased by year; 36.1% in 1990, 13.9% in 1997, 13.3% in 1999, and 23.2% in 2000. It was 21.3% in 1997 high school girls and 37.8% in 2000. The prevalence of iron deficiency anemia(IDA) decreased by year; 10.0% in 1990, 4.6% in 1997, 8.3% in 1999, and 6.1% in 2000. It was 11.6% in 1997 high school girls and 18.6% in 2000. Conclusion : Although the prevalence of iron deficiency decreased during this period, the prevalence of anemia in the elder adolescence girls was high. Two things are recommended; first, it is necessary to screen for anemia in middle school girls and high risk groups, second, it is important to evaluate the knowledge of nutrition and to enforce effective nutritional education, leading to subjects receiving adequate nutrition.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4603-4608
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• 2015

Background: To determine the potential value of serum tumor markers in predicting pCR (pathological complete response) during neoadjuvant chemotherapy. Materials and Methods: We retrospectively monitored the pro-, mid-, and post-neoadjuvant treatment serum tumor marker concentrations in patients with locally advanced breast cancer (stage II-III) who accepted pre-surgical chemotherapy or chemotherapy in combination with targeted therapy at Fudan University Shanghai Cancer Center between September 2011 and January 2014 and investigated the association of serum tumor marker levels with therapeutic effect. Core needle biopsy samples were assessed using immunohistochemistry (IHC) prior to neoadjuvant treatment to determine hormone receptor, human epidermal growth factor receptor 2(HER2), and proliferation index Ki67 values. In our study, therapeutic response was evaluated by pCR, defined as the disappearance of all invasive cancer cells from excised tissue (including primary lesion and axillary lymph nodes) after completion of chemotherapy. Analysis of variance of repeated measures and receiver operating characteristic (ROC) curves were employed for statistical analysis of the data. Results: A total of 348 patients were recruited in our study after excluding patients with incomplete clinical information. Of these, 106 patients were observed to have acquired pCR status after treatment completion, accounting for approximately 30.5% of study individuals. In addition, 147patients were determined to be Her-2 positive, among whom the pCR rate was 45.6% (69 patients). General linear model analysis (repeated measures analysis of variance) showed that the concentration of cancer antigen (CA) 15-3 increased after neoadjuvant chemotherapy in both pCR and non-pCR groups, and that there were significant differences between the two groups (P=0.008). The areas under the ROC curves (AUCs) of pre-, mid-, and post-treatment CA15-3 concentrations demonstrated low-level predictive value (AUC=0.594, 0.644, 0.621, respectively). No significant differences in carcinoembryonic antigen (CEA) or CA12-5 serum levels were observed between the pCR and non-pCR groups (P=0.196 and 0.693, respectively). No efficient AUC of CEA or CA12-5 concentrations were observed to predict patient response toward neoadjuvant treatment (both less than 0.7), nor were differences between the two groups observed at different time points. We then analyzed the Her-2 positive subset of our cohort. Significant differences in CEA concentrations were identified between the pCR and non-pCR groups (P=0.039), but not in CA15-3 or CA12-5 levels (p=0.092 and 0.89, respectively). None of the ROC curves showed underlying prognostic value, as the AUCs of these three markers were less than 0.7. The ROC-AUCs for the CA12-5 concentrations of inter-and post-neoadjuvant chemotherapy in the estrogen receptor negative HER2 positive subgroup were 0.735 and 0.767, respectively. However, the specificity and sensitivity values were at odds with each other which meant that improving either the sensitivity or specificity would impair the efficiency of the other. Conclusions: Serum tumor markers CA15-3, CA12-5, and CEA might have little clinical significance in predicting neoadjuvant treatment response in locally advanced breast cancer.

• Journal of the Korean Geographical Society
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• v.29 no.1
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• pp.46-64
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• 1994

Among every civilized people salt has been recognized as an essential foodstuff to the human society without which even man's survivor is unthinkable. The cultural-anthropological meaning of salt is estimated highly as well, and in geographical perspective salt itself symbolize regional interrelationship. Playing a decisive role in freeing innermost settlement from isolation, salt aiso made a contribution to expanding human habitats. This study tries to reconstruct historica geography of 18th and 19th century surrounding traditional salt-roasting (chayeom). The Joolpo Inlet area which is located on the mid-western coast in Honem Region is selected for study area. Established on the basis of optimum physical geographical conditions such as topography, climate and vegetation, salt-making of Joolpo Inlet area was run dynamically with the sudden turn of events in the 18-19th century which was chacterized as an age of transition from medieval society to modern one. In this paper the writer attempts to clarify mainly following three points: physical conditions and socio-economic background leading to the initiation and later development of roasting of salt in Joolpo Bay; distribution of saltworks; methods of saltmaking. Main points drawn from these analyses can be summarized as follows: of iron pan and cow-drawn tools rendered labour-saving and output growth. 1, Saltworks of Joolpo Inlet area in the 18-19th century were distributed evenly over Kobu, Puan, Mujang and Heungduck counties among which Kobu's was located in Puanmyon - a sort of exclave. All saltworks belonging to above four counties were clasified as most lucrative ones in Honam Region on government archives. In particular, Gumdang saltwork which belongs to Mujang county is noteworthy in that it was first introduced by one Paekje priest in 6th century and therefore it provides a clue to examine the history of salt-roasting of Joolpo Inlet area. In light of the fact that temple or monastery economy, regardless of East and West, has been closely connected with traditional industry, the case of Gumdang is not unusual. 2. The process of saltmaking follows this order: harrowing of salt field exposed to solar heat; construction of saltern mound with saline earth; acquiring of brine by leaching saline earth; roasting of salt. Salterns (saltworks) are consisted with various salt making facilities such as roasting shed, saltern mound, salt field, salt well) salt pit or brine pit) and seawater reservoir. Among them roasting shed which is constructed chiefly with hundreds of pieces of pine tree as a frame and with straw as roof and wall is customarily considered as an unit of saltwork. And inside it is saltpan made of two kinds of materials, that is iron pan or plaster pan. The area attached to one unit of roasting shed is approximately 1 ha, and that of saltern mound is a tenth of it.

• 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.40 no.1
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• pp.23-28
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• 1993

Background: Since an important component of carcinogenesis is unregulated growth, many investigators have reported the methods to detect cell proliferation in tissues including PCNA. PCNA is a 36 Kd intranuclear polypeptide and plays a critical role in cell proliferation. Thus progressive dysregulation of proliferation during carcinogenesis can be directly visualized in the paraffin embedded tissue using immunohistochemistry for PCNA which has an advantage of simplicity and maintenance of tissue architecture. The heterogeneity of PCNA expression is known to be related with proliferating fraction, histologic grade, DNA ploidy, and susceptibility of anticancer drugs, etc. We analyzed the biologic significance of the expression of PCNA in lung cancer tissues. Method: 43 lung cancer tissues, which were resected by surgery and were embedded in paraffin, were stained immunohistochemically by one hour MicroProbe System and the results were corelated with cell type, stage, site and survival. Result: 1) Suamous cell type showed high positivity (89%) than in adenocarcinoma (54%). 2) No significant difference related to tumor stage was noticed. 3) No significant difference between primary site and metastatic site was noticed. 4) No significant difference in 12-month survival between positive group and negative group was noticed. Conclusion: From this study, we concluded that imunohistochemistry for PCNA expression of routinely processed tissue is a simple technique for the assessment of proliferation in non-small cell lung cancer. Whether the labelling index has an independent prognostic value and deserves special attention in pathobiological evaluation in lung cancer remains to be investigated from large series with longer follow-up and to be correlated with multiple biological markers.

• Tuberculosis and Respiratory Diseases
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• v.42 no.2
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• pp.142-148
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• 1995

Background: Despite modern diagnostic, staging, and therapeutic advances, esp. with molecular biologic techniques, the 5-year survival rate of all cases of lung cancer does not exceed 15%. Also, the incidence of lung cancer of both sex in Korea is increasing year by year and the lung cancer is one of the leading causes of cancer death. Therefore, it is strongly needed to develop the new combination of treatment modalities including neoadjuvant chemotherapy and to identify tumor specific characteristics with staging or prognostic markers. Here we present the clinical significance of several biologic tumor markers to use as a prognostic markers in patients with non-small cell lung cancers. Method: The survival has correlated with the expressibility of proliferative cell nuclear antigen (PCNA), epidermal growth factor receptor(EGFR), p53 and/or blood group antigen A(BGAA) using immunohistochemistry in 46 patients with non-small cell lung cancers. Results: 1) The expression rates of PCNA, EGFR, p53 and BGAA were 80.6%, 61.3%, 45.9% and 64.3%, respectively and those were not correlated to cell types or clinical stges. 2) The expression of BGAA was correlated with better survival in median survival and in 2-year survival rate and that of PCNA was correlated with worse survival in median survival and 2-year survival rate. 3) The expression of EGFR or p53 was not valuable to predict prognosis in non-small cell lung cancers. 4) With simultaneous applications of PCNA, EGFR and p53 immunostain, the patients with 2 or more negative expressions showed better prognosis than the patients with 2 or more positive expressions. Conclusion: It is suggested that the expression of blood group antigen may be a positive prognostic factor and that of PCNA may be a negative prognostic factor. Also, the combination of expressions of PCNA, EGFR and p53 may be used as a negative prognostic factor.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.60 no.3
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• pp.304-313
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• 2006

Background : Heme oxygenase-1 (HO-1) is an inducible enzyme that catalyzes the oxidative degradation of heme to form biliverdin, carbon monoxide (CO), and free iron. The current evidence has indicated a critical role of HO-1 in cytoprotection and also in other, more diverse biological functions. It is known that the high expression of HO-1 occurs in various tumors, and that HO-1 has an important role in rapid tumor growth because of its antioxidative and antiapoptotic effects. Therefore, the role of HO-1 was analyzed in human lung cancer cell lines, and especially in the A549 cell line. Material and Methods : Human lung cancer cell lines, i.e., A549, NCI-H23, NCI-H157 and NCI-H460, were used for this study. The expression of HO-1 in the untreated state was defined by Western blotting. ZnPP, which is the specific HO inhibitor we used, and the viability of cells were tested for by conducting MTT assaysy. The HO enzymatic activity, as determined via the bilirubin level, was also indirectly measured. Moreover, the generation of intracellular hydrogen peroxide (H2O2) was monitored fluorimetrically with using a scopoletin-horse radish peroxidase (HRP) assay and 2',7'-dichlorofluorescein diacetate (DCFH-DA). We have also transfected small HO-1 interfering RNA (siRNA) into A549 cells, and the apoptotic effects were evaluated by flow cytometric analysis and Western blotting. Results : The A549 cells had a greater expression of HO-1 than the other cell lines, whereas ZnPP significantly decreased the viability of the A549 cells more than the viability of the other lung cancer cells in a dose-dependant fashion. Consistent with the viability, the HO enzymatic activity also was decreased. Moreover, intracellular H2O2 generation via ZnPP was induced in a dose-dependent manner. Apoptotic events were, then induced in the HO-1 siRNA transfected A549 cells. Conclusion : HO-1 provides new important insights into the possible molecular mechanism of the antitumor therapy in lung cancer.