• Tuberculosis and Respiratory Diseases
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• v.41 no.1
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• pp.11-19
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• 1994

Background: Mycobacterium tuberculosis is a facultative intracellular pathogen which persists and multiplies within macrophage. Competent cell mediated immunity by cooperation of both T lymphocyte and macrophage of the host is required to kill the Mycobacterium tuberculosis. But a precise understanding of the pathogenesis of tuberculosis infection in pulmonary alveolar macrophage has not been achived. Research on the macrophage's basic microbicidal mechanism has elucidated the importance of oxygen-dependent or oxygen-independent components. Oxygen dependent processing begins with the reduction of oxygen by NADPH oxidase and generation of superoxide. In this study, the oxidative metabolic status of blood monocyte and pulmonary alveolar macrophage in patients with active pulmonary tuberculosis was accessed and compared with that of healthy control subjects to know whether there was a basic difference in superoxide generation by mononuclear cells between two groups. Methods: Pulmonary alveolar macrophage was purified after performing BAL(bronchoalveolar lavage) through the bronchi of infected lesion by plastic adhesion method. Blood monocyte was purified by Ficoll-Hypaque method. Superoxide generation by blood monocyte and pulmonary alveolar macrophage was measured by ferricytochrome-C reduction method after either stimulated with PMA(phorbol myristate acerate) or non-stimulated states. We also measured the effect of pulmonary tuberculosis patient's serum on superoxide generation by monocyte. Results: 1) Generation of superoxide by alveolar macrophage obtained from patients with pulmonary tuberculosis was little higher than those of controls, and PMA enhanced the generation of 2) Generation of superoxide by blood monocyte obtained from patients with pulmonary tuberculosis was little higher than those of control(p>0.05), and PMA more enhanced the generation of superoxide in patientswith pulmonary tuberculosis than those in controls(p<0.02). 3) Patient's serum enhanced the generation of superoxide by blood monocyte obtained from patients with pulmonary tuberculosis and controls, but not in the case of PMA stimulated blood monocyte. Conclusion: The present study suggest that the phenomenon of M.tuberculosis escape the microbicidal action of macrophage was not result of suppressed superoxide generation by blood monocyte and pulmonary alveolar macrophage, rather there might be a factor to stimulate the generation of superoxide by blood monocyte in pulmonary tuberculosis patient serum, but the comparision with effect of control's serum on superoxide generation needs further elucidation.

• Radiation Oncology Journal
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• v.23 no.1
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• pp.51-60
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• 2005

Purpose : Selective inhibition of multiple molecular targets may improve the antitumor activity of radiation. Two specific inhibitors of selective cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) were combined with radiation on the HeLa cell line. To investigate cooperative mechanism with selective COX-2 inhibitor and EGFR blocker, in vitro experiments were done. Materials and Methods : Antitumor effect was obtained by growth inhibition and apoptosis analysis by annexin V-Flous method. Radiation modulation effects were determined by the clonogenic cell survival assay. Surviving fractions at 2 Gy ($SF_2$) and dose enhancement ratio at a surviving fraction of 0.25 were evaluated. To investigate the mechanism of the modulation of radiosensitivity, the cell cycle analyses were done by flow cytometry. The bcl-2 and bax expressions were analyzed by western blot. Results : A cooperative effect were observed on the apoptosis of the HeLa ceil line when combination of the two drugs, AG 1478 and NS 398 with radiation at the lowest doses, apoptosis of $22.70\%$ compare with combination of the one drug with radiation, apoptosis of $8.49\%$. In cell cycle analysis, accumulation of cell on $G_0/G_l$ phase and decrement of S phase fraction was observed from 24 hours to 72 hours after treatment with radiation, AG 1478 and NS 398. The combination of NS 398 and AG 1478 enhanced radiosensitivity on a concentration-dependent manner in HeLa cells with dose enhancement ratios of 3.00 and $SF_2$ of 0.12 but the combination of one drug with radiation was not enhanced radlosensitivity with dose enhancement ratios of 1.12 and SF2 of 0.68 (p=0.005). The expression levels of bcl-2 and bax were reduced when combined with AG 1478 and NS 398. Conclusion : Our results indicate that the selective COX-2 inhibitor and EGFR blocker combined with radiation have potential additive or cooperative effects on radiation treatment and may act through various mechanisms including direct inhibition of tumor cell proliferation, suppression of tumor cell cycle progression and inhibition of anti-apoptotic proteins.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.113-117
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• 2001

Purpose : To evaluate effect of postoperative radiotherapy on survival and local control for patients with non-small cell lung cancer (NSCLC). Materials and Methods : Ninety two NSCLC patients with N1or N2 involvement who were treated with postoperative radiotherapy following surgery with curative intent from May 1987 to October 1999 were retrospectively analyzed. Age of the patients was ranged from 32 to 78 years. According to TNM Stage, 35 patients had Stage II and 57 had Stage III disease. There were 49 patients with N1 involvement and 43 patients with N2 involvement. Fifty six patients were noted to have $T1\~2$ tumors and 36 patients to have $T3\~4$ tumors. Delivered total dose was ranged from 40 to 60 Gy. Majority of patients received 50 Gy or 50.4 Gy. Follow-up period was ranged from 9 month to 7 years with median follow-up of 26 months. Results : Overall survival rates at 3 and 5 years for entire group of patients were $46\%\;and\;38\%$, respectively. Corresponding disease free survival rates were $44\%\;and\;36\%$. There was significant difference in survival between patients with Stage II and Stage III disease ($50\%\;vs\;28\%$ at 5-year). Five year survival rates for N1 and N2 patients were $52\%\;and\;20\%$, respectively (p<0.05). These were $40\%\;and\;34\%$ for patients with $T1\~2$ tumors and $T3\~4$ tumors. There were documented local relapses in $13\%$ of the patients. For patients with N1 and N2 Stage, local relapse rates were $8\%\;and\;18\%$, respectively. Conclusion : Our study confirms that postoperative radiotherapy for patients with non-small cell lung cancer improves local control. However, influence of postoperative radiotherapy on long-term survival is less clear. More effective systemic treatment to prevent distant metastasis should be investigated in future study to improve long-term survival.

• Journal of Chest Surgery
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• v.43 no.1
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• pp.11-19
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• 2010

Background: The commercially used vascular xenografts have some problems such as calcification, fibrosis and tissue degeneration that are associated with inflammatory and immunologic reactions. We compared two methods of xenograft preservation (fresh cryopreservation versus acellularized cryopreservation) of goat aorta. Material and Method: Aortic valved xenografts were harvested from adult pigs, and these were preserved using fresh cryopreservation (FC group, n=4) or acellularized crypreservation (AC group, n=4). These xenografts were implanted into adult goats. There were 2 short-term survivors (less than 100 days) and 2 long-term survivors in each group. These xenografts were explanted and they underwent microscopic examination. Result: The goats survived 31, 40, 107 and 411 days in the FC group and the other goats survived 5, 40, 363 and 636 days in the AC group. All the short-term survivors in each group expired because of rupture at the proximal anastomosis site. Marked neutrophil infiltration was observed in the FC group FC and lymphocytes were observed in the AC group. There were no differences in the occurrence of calcification, fibrosis and thrombosis among the groups. Conclusion: Some goats survived more than 100 days after the xenograft implantation irrespective of the methods of preservation. Because severe tissue degeneration developed in both groups, we think these methods are not appropriate for xenograft preservation of aorta. It was worth a preliminary trial for improving the preservation method or to modify the processing of xenografts.

• Food Science and Preservation
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• v.30 no.6
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• pp.1095-1106
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• 2023

This study investigated the anti-oxidative and anti-inflammatory effects of Aster glehni (AG) extract in RAW 264.7 cells and Caenorhabditis elegans. The total polyphenol and flavonoid contents were higher in the ethanol extracts than in the hot water extracts. As a result of measuring the moisture contents (%) and extraction yields (%) of AG and drying A. glehni for processing (DAG), 70% ethanol, which has the highest percentage of extraction yield, was selected as the final solvent. DPPH radical scavenging activity showed higher antioxidant activity of ethanol extracts of DAG than AG. The cytotoxicity assay of the AG or DAG ethanol extracts was treated at different concentrations (25, 50, and 100 ㎍/mL), and cell viability rates were higher than 80% at all concentrations. The LPS-stimulated nitric oxide (NO) production in RAW 264.7 was significantly reduced at all concentrations of AG and DAG groups. As a result of measuring the gene expression of iNOS, which induces NO production, the AG or DAG group decreased by 33% and 32%, compared with the phosphate buffer saline (PBS) group. Under inflammatory stress conditions, the survival rate of C. elegans treated with AG or DAG ethanol extract with LPS showed concentration-dependent improvement in survival rate compared with the PBS group. Considering these results, AG could potentially be developed as an antioxidant and anti-inflammatory functional food material.

• Journal of Animal Science and Technology
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• v.46 no.4
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• pp.563-570
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• 2004

The insulin-like growth factor(IGF) system, consisting of IGFs-I and -II ligands and their receptors and six IGF-binding proteins(IGFBPs), plays an important role in survival, proliferation and differentiation of a variety of cell types. Lithium is a known modulator of survival and proliferation of many cell types in vitro. The present study was undertaken to investigate the relationship between LiCI-induced changes in cell survival and growth and the expression of the IGF system components in C6 rat glioma cell line which, besides IGF-I and its receptor, is known to express IGFBP-3 as its major IGF carrier. When C6 cells were cultured for 24h in the absence or presence of 2mM or 5mM LiCl in a 10% serwn-containing medium, the viability and the number of cells were not affected by added lithium. In 72-h culture, however, C6 cells clearly exhibited a dose-dependent response to added LiCl. The cells cultured for 72h in the presence of 0, 2mM and 5mM LiCl exhibited a typical mitotic, a growth-arrested and an apoptotic appearances, respectively. Moreover, the apoptotic cells were accompanied by reduced expression of IGF-I, IGF-I receptor and IGFBP-3 as examined by semi-quantitative reverse transcription-polymerase chain reaction. Interestingly, blockade of IGFBP-3 mRNA translation by addition of 101${\mu}M$ IGFBP-3 anti-sense oligodeoxyribonucleotide in serum-free, 24-h culture resulted in a decrease in the number of cells as well as relative abundance of the target mRNA. In summary, results suggest that the cytotoxic effect of lithium in C6 cell is likely to be mediated, in part, by suppression by this agent of the expression of the IGF system components. In this regard, IGFBP-3 may play at least a 'permissive' role in normal proliferation of this cell.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.4
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• pp.525-530
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• 2011

Pine needles have long been used as a traditional health-promoting medicinal food in Korea. This study was carried out to investigate the effects of pine needle extracts on the antioxidant activity, and proliferation of osteoclastic RAW 264.7 cells. Pine needle extracts were examined using hot water, ethanol, hexane, hot water-ethanol, and hot water-hexane. The effects of the pine needle extracts were examined by comparing the results with that of a commercial agents, proanthocyanidin. Analysis of each extract indicated that hot water-ethanol and ethanol extracts contained the highest total polyphenol concentrations. The hot water-ethanol and ethanol extracts also showed relatively the highest SOD-like activity. The proliferation of osteoclastic RAW 264.7 cells treated with pine needle extracts was decreased by lower than 70%. In addition, the hot water and ethanol extracts of pine needle significantly reduced the number of tartrate-resistant acid phosphatase-positive ($TRAP^+$) multinucleated cells from osteoclatic RAW 264.7 cells. These results indicate that pine needle extracts had an anabolic effect on bone through the promotion of osteoclast differentiation, suggesting that they could be used for the treatment of common metabolic bone diseases.

• Radiation Oncology Journal
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• v.29 no.1
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• pp.44-52
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• 2011

Purpose: To evaluate the outcomes and prognostic factors of postoperative radiotherapy (PORT) for patients with pathological stage III non-small-cell lung cancer (NSCLC) at a single institution. Materials and Methods: From 2000 to 2007, 88 patients diagnosed as having pathologic stage III NSCLC after curative resection were treated with PORT. There were 80 patients with pathologic stage IIIA and eight patients with pathologic stage IIIB in the AJCC 6th staging system. The majority of patients (n=83) had pathologic N2 disease, and 56 patients had single station mediastinal LN metastasis. PORT was administered using conventional technique (n=76) or three-dimensional conformal technique (n=12). The median radiation dose was 54 Gy (range, 30.6 to 63 Gy). Thirty-six patients received chemotherapy. Radiation pneumonitis was graded by the Radiation Therapy Oncology Group system, and other treatment-related toxicities were assessed by CTCAE v 3.0. Results: Median survival was 54 months (range, 26 to 77 months). The 5-year overall survival (OS) and disease free survival (DFS) rates were 45% and 38%, respectively. The number of metastatic lymph nodes was associated with overall survival (hazard ratio, 1.037; p-value=0.040). The 5-year locoregional recurrence free survival (LRFS) and distant metastasis free survival (DMFS) rates were 88% and 48%, respectively. Multiple stations of mediastinal lymph node metastasis was associated with decreased DFS and DMFS rates (p-value=0.0014 and 0.0044, respectively). Fifty-one relapses occurred at the following sites: 10 loco-regional, 41 distant metastasis. Grade 2 radiation pneumonitis was seen in three patients, and symptoms were well tolerated with anti-tussive medication. Grade 2 radiation esophagitis was seen in 11 patients. There were no grade 3 or more severe complications associated with PORT. Conclusion: Our retrospective data show that PORT for pathological stage III NSCLC is a safe and feasible treatment and could improve loco-regional control. The number of metastatic lymph nodes and stations of mediastinal lymph node metastasis were analyzed as prognostic factors. Furthermore, efforts are needed to reduce distant metastasis, which is a major failure pattern of advanced stage NSCLC.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.257-264
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• 2000

Purpose: For early stage non-small-cell lung cancer, surgical resection is the treatment of choice. But when the patients are not able to tolerate it because of medical problem and when refuse surgery, radiation therapy is considered an acceptable alternative. We report on the treatment results and the effect of achieving local control of primary tumors on survival end points, and analyze factors that may influence survival and local control. Materials and Method : We reviewed the medical records of 32 patients with medically inoperable non-small cell lung cancer treated at our institution from June, 1987 through June, 1997. All patients had a pathologic diagnosis of non-small cell lung cancer and were not candidate for surgical resection because of either patients refusal (4), old age (2), lung problem (21), chest wail invasion (3) and heart problems (3). In 8 patients, there were more than 2 problems. The median age of the patients was 68 years (ranging from 60 to 86 years). Histologic cell type included souamous (24), adenocarcinoma (6) and unclassiried squamous cell (2). The clinical stages of the patients were 71 in 5, 72 in 25, 73 in 2 patients. Initial tumor size was 3.0 cm in 11, between 3.0 cm and 5.0 cm in 13 and more than 5.0 cm in 8 patients. Ail patients had taken chest x-rays, chest CT, abdomen USG and bone scan. Radiotherapy was delivered using 6 MV or 10 MV linear accelerators. The doses of primary tumor were the ranging from 54.0 Gy to 68.8 Gy (median; 61.2 Gy). The duration of treatment was from 37 days through 64 days (median; 0.5 days) and there was no treatment interruption except 1 patient due to poor general status. In 12 patients, concomitant boost technique was used. There were no neoadjuvant or adjuvant treatments such as surgery or chemotherapy. The period of follow-up was ranging from 2 months through 93 months (median; 23 months). Survival was measured from the date radiation therapy was initiated. Results : The overall survival rate was 44.6$\%$ at 2 years and 24.5$\%$ at 5 years, with the median survival time of 23 months. of the 25 deaths, 7 patients died of intercurrent illness, and cause-specific survival rate was 61.0$\%$ at 2 years and 33.5$\%$ at 5 years. The disease-free survival rate was 38.9$\%$ at 2 years and 28.3$\%$ at 5 years. The local-relapse-free survival rate was 35.1$\%$, 28.1$\%$, respectively. On univariate analysis, tumor size was significant variable of overall survival (p=0.0015, 95$\%$ C.1.; 1.4814-5.2815), disease-free survival (P=0.0022, 95$\%$ C.1., 1.4707-5.7780) and local-relapse-free survival (p=0.0015, 95$\%$ C.1., 1.2910- 4.1197). 7 stage was significant variable of overall survival (p=0.0395, 95$\%$ C.1.; 1.1084-55.9112) and had borderline significance on disease-free survival (p=0.0649, 95$\%$ C.1.; 0.8888-50.7123) and local-relapse-free survival (p=0.0582, 95$\%$ C,1.; 0.9342-52.7755). On multivariate analysis, tumor size had borderline significance on overall survival (p=0.6919, 955 C.1., 0.9610-5.1277) and local-relapse-free survival ( p=0.0585, 95$\%$ C.1.; 0.9720-4.9657). Tumor size was also significant variable of disease-free survival (p=0.0317, 95% C.1.; 1.1028-8.4968). Conclusion : Radical radiotherapy is an effective treatment for small (71 or f3 cm) tumors and can be offered as alternative to surgery in elderly or infirmed patients. But when the size of tumor is larger than 5 cm, there were few long-term survivors treated with radiotherapy alone. The use of hypefractionated radiotherapy, endobronchial boost, radisensitizer and conformal or IMRT should be consider to improve the local control rate and disease-specific survival rate.

• Investigative Magnetic Resonance Imaging
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• v.16 no.1
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• pp.31-39
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• 2012

Purpose : To determine the optimal combination of commercially available superparamagnetic iron oxide (SPIO) nanoparticles with transfection agents (TA). Materials and Methods: Protamine sulfate (Pro) and poly-L-lysin (PLL) were incubated with ferumoxide and ferucarbotran in human mesenchymal stem cells at various concentrations, and cellular viability were evaluated. Cellular iron uptake was qualitatively and quantitatively evaluated. Cell visibility was assessed via MR imaging and the T2-relaxation time was calculated. Results: The cellular viabilities with ferucarbotran were more significantly decreased than those with ferumoxide (p < 0.05). Iron uptake with ferumoxide was significantly higher than that for those with with ferucarbotran. The T2-relaxation time was observed to be shorter with ferumoxide in comparison to those with ferucarbotran (p < 0.05). Ferumoxide at a concentration of 25 ${\mu}g$/ml in combination with either Pro or PLL at a concentration of 3.0 ${\mu}g$/ml did not adversely impact cell viability, maximized iron uptake, and exhibited a lower T2-relaxation time in comparison to other combinations. Conclusion: Stem cells with ferumoxide exhibited a higher cellular viability and iron uptake in comparison to ferucarbotran-treated stem cells. A 25 ${\mu}g$/ml of ferumoxide with a 3.0 ${\mu}g$/ml of TA is sufficient to label mesenchymal stem cells.