• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5033-5036
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• 2012

Objective: To study the relationship between expression of $p57^{KIP2}$ and prognosis and other clinicopathological parameters in invasive breast cancers. Methods: We assessed the expression of $p57^{KIP2}$ in 89 cases of invasive breast cancer and 20 cases of normal breast tissue by immunohistochemical methods and analyzed the results with SPSS software (ver. 16.0). Result: The positive expression rates of $p57^{KIP2}$ protein in the invasive breast cancers and surrounding normal tissue were 30.3% (27/89) and 65% (13/20), respectively. Cases with no $p57^{KIP2}$ expression exhibited a significantly higher post-operative distant metastasis rate than those with $p57^{KIP2}$ expression (37.9% vs. 14.8%; P = 0.01). DFS analysis showed that $p57^{KIP2}$-/C-erbB-2+ tumors also exhibited a significantly higher post-operative distant metastasis rate than the other groups (66.7% vs. 29.2%; P = 0.007), as did $p57^{KIP2}$-/p53+ tumors (64.3% vs. 22.7%; P = 0.001). Survival analysis revealed that $p57^{KIP2}$ was associated with breast cancer-specific survival overall (P = 0.045, log-rank test). Subgroup analysis demonstrated that individuals with $p57^{KIP2}$-/C-erbB-2+tumors experienced significantly worse post-operative survival than those with $p57^{KIP2}$-/C-erbB-2- or other tumors (P = 0.006, log-rank test). $p57^{KIP2}$-/p53+ tumors were associated with significantly worse post-operative survival than $p57^{KIP2}$-/p53- or other tumors (P = 0.001, log-rank test). Cox regression analysis showed that $p57^{KIP2}$ was a non-independent prognostic factor for breast cancer (P = 0.303). Conclusions: $p57^{KIP2}$ is expressed at low levels in invasive breast cancer and is associated with better overall survival rate and disease-free survival in breast cancer patients, but it was a non-independent prognostic factor for breast cancer. Thus, the connection between $p57^{KIP2}$/p53 and $p57^{KIP2}$/C-erbB-2 may provide biomarkers for breast cancer.

• Tuberculosis and Respiratory Diseases
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• v.49 no.4
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• pp.474-485
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• 2000

Background : Current studies on multimodal strategy for N2 non-small cell lung cancer are being high interest, have drawn much attention. N2 lung cancer, however, is composed of is divided into several sub groups with that have different prognoses. The prognostic factors still remain controversial. Methods : Between January 1990 and June 1999, 180 patients with N2 lung cancer who underwent surgical resection were investigated, excluding 10 of these for surgical mortality. All patients underwent mediastinal lymph node dissection. 20 clinicopathologic factors were investigated by univariable and multivariable analyses to identify significant prognostic factors among resected N2 disease. Results : The overall 5-year survival rate was 20.6%. Multivariable analyses among overall patients revealed 3 significant prognostic factors : Age, Histologic type, Vascular invasion. Based on the result, 49 patients with both age more than 60 and pathologic Non-squamous cell showed a 5-year survival of 5.0%, whereas 37 patients with neither of the factors showed a 5-year survival of 56.6%(p<0.001). And 12 patients with both vascular invasion and pathologic Non-squamous cell showed a 5-year survival of 11.9%, whereas 67 patients with neither of the factors showed a 5-year survival of 33.6%(p=0.01). Conclusion : The prognosis of surgically resected N2 disease varies according to the 3 significant prognosis factors. Tumor size may be an additional influencing factor in the prognosis of N2 disease.

• Journal of Chest Surgery
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• v.36 no.7
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• pp.489-496
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• 2003

To clarify the prognostic implication of the location and number of the metastatic mediastinal nodes in resected stage IIIA N2 non-small cell lung cancer. Material and Method: One hundred and seventy-four patients with resected non-small cell lung cancer who eventually proved to have pathologic stage IIIA N2 disease were studied. Patients who received preoperative induction therapy, non-curative operation or defined as operative mortality were excluded from this study. Result: In upper lobe tumors, there was no difference in 5-year survival according to the involvement of lower mediastinal nodes (32.3% vs 25.6%, p＝0.86). In lower lobe tumors, no difference was found in 5-year survival according to the involvement of upper mediastinal nodes (25.1% vs 14.1%, p＝0.33). There was no significant difference in 5-year survival between patients with or without metastatic subcarinal node (20.9% vs 25.6%, p＝0.364). In terms of the number of metastatic mediastinal nodes, 5-year survival was better in single station group (26.3%) than multiple station group (18.3%) (p＝0.048). In multiple station N2 group, the patients who received postoperative chemotherapy and radiation therapy had better 5-year survival (34.2%) (p＝0.01). Cox's proportional hazards model revealed that the age $\geq$60 (O.R: 1.682, p＝.006), multiple station N2 (O.R: 1.503. p＝0.021), pneumonectomy (O.R: 1.562, p＝0.018), postoperative chemotherapy and radiation therapy (O.R: 0.625, p＝0.012) were the factors affecting the postoperative survival. Conclusion: Multiple station N2 disease was the important prognostic factor for postoperative survival in resected stage IIIA N2 non-small cell lung cancer. Postoperative chemotherapy and radiotherapy were thought to improve the survival in case of multiple station N2 disease.

• Tuberculosis and Respiratory Diseases
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• v.57 no.1
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• pp.37-46
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• 2004

Background : Lung pericytes are important constituent cells of blood-air barrier in pulmonary microvasculature. These cells take part in the control of vascular contractility and permeability. In this study, it was hypothesized that change of lung pericytes might be attributable to pathologic change in microvasculature in acute lung injury. The purpose of this study was how hypoxia change proliferation and genetic expression in lung pericytes. Methods : From the lungs of several Sprague-Dawley rats, performed the primary culture of lung pericytes and subculture. Characteristics of lung pericytes were confirmed with stellate shape in light microscopy and immunocytochemistry. 2% concentration of oxygen and $200{\mu}M$ $CoCl_2$ were treated to cells. Tryphan blue method and reverse transcription-polymerase chain reaction were done. Results : 1. We established methodology for primary culture of lung pericytes. 2. Hypoxia inhibited cellular proliferation in pericytes. 3. Hypoxia could markedly induce vascular endothelial growth factor(VEGF) and smad-2. 4. Hypoxia-inducible factor-$1{\alpha}$(HIF-$1{\alpha}$) was also induced by 2% oxygen. Conclusion : Viability of lung pericytes are inhibited by hypoxia. Hypoxia can stimulate expression of hypoxia-responsive genes. Pericytic change may be contributed to dysfunction of alveolar-capillary barrier in various pulmonary disorders.

• Tuberculosis and Respiratory Diseases
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• v.59 no.1
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• pp.30-38
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• 2005

Background : Arsenic trioxide ($As_2O_3$) has been used to treat acute promyelocytic leukemia, and it induces apoptosis in a variety of solid tumor cell lines including non-small cell lung cancer cells. However, nonsteroidal antiinflammatory drugs (NSAID) can enhance tumor response to chemotherapeutic drugs or radiation. It was previously demonstrated that a combination treatment with $As_2O_3$ and sulindac induces the apoptosis of NCI-H157 human lung carcinoma cells by activating the caspase cascade. This study aimed to determine if a combination treatment augmented its apoptotic potential through other pathways except for the activation of the caspase cascade. Material and Methods : The NCI-H157 cells were treated with $As_2O_3$, sulindac and antioxidants such as glutathione (GSH) and N-acetylcysteine (NAC). The cell viability was measured by a MTT assay, and the level of intracellular hydrogen peroxide ($H_2O_2$) generation was monitored fluorimetrically using a scopoletin-horse radish peroxidase (HRP) assay. Western blotting and mitochondrial membrane potential transition analysis were performed in order to define the mechanical basis of apoptosis. Results : The viability of the cells was decreased by a combination treatment of $As_2O_3$ and sulindac, and the cells were protected using antioxidants in a dose-dependent manner. The increased $H_2O_2$ generation by the combination treatment was inhibited by antioxidants. The combination treatment induced changes in the mitochondrial transmembrane potential as well as the expression of the Bcl-2 family proteins, and increased cytochrome c release into the cytosol. However, the antioxidants inhibited the effects of the combination treatment. Conclusion : Combination treatment with $As_2O_3$ and sulindac induces apoptosis in NCI-H157 human lung carcinoma cells via ROS generation with a mitochondrial dysfunction.

• Journal of Life Science
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• v.29 no.11
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• pp.1218-1226
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• 2019

The white-spotted flower chafer Protaetia brevitarsis seulensis is a medicinally beneficial and important edible insect species. We previously performed an in silico analysis of the Protaetia brevitarsis seulensis transcriptome to identify putative antimicrobial peptides and then tested their antimicrobial and hemolytic activities. These peptides had potent antimicrobial activities against bacteria and yeast without inducing hemolysis. In the present study, the cationic antimicrobial peptide, protaetiamycine 2, was selected for further assessment of its anti-inflammatory properties in mouse macrophage Raw264.7 cells. Protaetiamycine 2 treatment of Raw264.7 cells suppressed LPS-induced nitric oxide production and reduced the expression of inducible nitric oxide synthase and cyclooxygenase-2, as determined by real-time PCR and western blotting. The expression of proinflammatory cytokines ($TNF-{\alpha}$, IL-6, and $IL-1{\beta}$) was also attenuated through the MAPKs and $NF-{\kappa}B$ signaling. We also confirmed that protaetiamycine 2 bound to bacterial cell membranes by a specific interaction with LPS. Collectively, these data obtained from LPS-induced Raw264.7 cells indicated that protaetiamycine 2 could have both antimicrobial and anti-inflammatory properties.

• Journal of Preventive Medicine and Public Health
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• v.37 no.4
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• pp.359-365
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• 2004

Objectives : This study was performed to determine whether an increase in abdominal obesity is an independent risk factor for impaired fasting glucose and type 2 DM. Methods : Among 24,212 adults over 30 years who undertook comprehensive medical screening examinations from Jan to Dec 1999, in a university hospital in Seoul, a total of 11,183 subjects were selected who had no DM at baseline and who were followed up more than once by Dec 2002. The average follow up period was 2.4 (${\pm}0.5$) years. DM was defined as having a fasting glucose level $\geq$ 126mg/dl, and impaired fasting glucose as showing a fasting glucose level between 110 and 125 mg/dl. Body weight, height and waist circumference (WC) were simultaneously measured with blood sampling. The relative risks (RRs) for DM and impaired fasting glucose by WC were calculated using Cox proportional hazard model. Ageadjusted rates were estimated by direct standardization using a reference population of 2000 from 30 to 80 years. Results : The average age of the subjects was 41.7 (${\pm}7.0$) years; males 41.2 (${\pm}6.5$) and females 45.6 (${\pm}9.2$). RRs for type 2 DM by WC with the reference group of WC < 80cm were as follows: 2.66 (95%, CI $0.55{\sim}12.8$) for WC of $80{\sim}89cm$ in men, 5.92 (95%, CI $1.08{\sim}32.3$) for WC $\geq$ 90 cm in men, and 2.64 (95%, CI $0.23{\sim}29.8$) for WC of $80{\sim}89cm$ in females. RRs for impaired fasting glucose by WC were 3.03 (95%, CI $2.18{\sim}4.22$) for WC $80{\sim}89cm$ in men, 6.10 (95%, CI $4.25{\sim}8.75$) for WC $\geq$ 90cm in men, and 1.56 (95%, CI $0.43{\sim}5.67$) for WC $80{\sim}89cm$ in women, and 8.08 (95%, CI $2.22{\sim}29.4$) for WC $\geq$ 90cm in females. These results remained significant after adjustment for age, BMI and fasting glucose concentrations at baseline in both sexes. Annual increment of more than 1 cm in WC was associated with the development of DM and impaired fasting glucose independently of age, sex, BMI, or presence of abdominal obesity. Conclusion : In Korean adults, abdominal obesity increased the risk for the development of type 2 diabetes and impaired fasting glucose. This result supports many other prospective studies suggesting abdominal obesity as a risk factor for type 2 diabetes.

• Radiation Oncology Journal
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• v.14 no.3
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• pp.181-189
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• 1996

Purpose : To find the more effective treatment methods that improving the survival of patients with glioblastoma multiforme(GBM), we analyze the prognostic factors and the outcome of therapy in patients with GBM. Materials and Methods : One hundred twently-one patients with a diagnosis of GBM treated at Severance Hospital between 1973 and 1993 were analyzed for survival with respect to patients characteristics, that is, duration of symptom, age, and Karnofsky performance status, as well as treatment related variables such as extent of surgery and radiotherapy. Results : The median survival time(MST) and 2-year overall survival rate (OSR) of the patients with GBM were 13 months and $20.8\%$, respectively. Duration of symptom, age, Karnofsky performance status(KPS), radiotherapy, and extent of surgical resection were associated with improved survial in a univariate analysis. Patients whose duration of symptom was longer than 3 months, had the 2-year OSR of $47.2\%$(p=0.0082), who were younger than age 50, $32.9\%$(p=0.0003) In patients with a KPS of 80 or higher, the 2-rear OSR was $36.9\%$(p=0.0422). Patients undergoing radiotherapy had the 2-year OSR of $22.9\%$(p=0.0030), and surgical resection of $23.3\%$ (p<0.000). A Cox regression model confirmed a significant correlation of duration of symptom, age, radiotherapy, and extent of surgical resection with survival, excluding KPS(P=0.8823). The 2-year OSR were $22.3\%$ and $19.4\%$, combined with chemotherapy or without, respectively(p=0.6028). The duration of symptom of 3 months or shorter, 50 years of age or older, and undergoing stereotactic biopsy only were considered as risk factors, then patients without any risk factors had the MST of 29 months and 2-year OSR of $53.9\%$ compared to 4 months and $0\%$ for Patients who had all 3 risk factors. Most of all treatment failures occurred in the primary tumor site($80.4\%$). Conclusion : The duration of symptom, age, radiotherapy, and extent of surgical resection were a prognostically significant indeuendent variables. To get a better survival, it seems to be reasonable that the study design which improves the local control rates is warranted.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.2
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• pp.227-233
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• 2004

Chronic exposure to solar radiation, particularly ultraviolet (UV) light, causes a variety of adverse reactions on human skin, such as sunburn, photoaging and photocarcinogenesis. Free radicals and reactive oxygen species (ROS) caused by UV exposure or other environmental facts play critical roles in cellular damage. And, repeated-UV irradiation activated the expression of the matrix metalloproteinase (MMP) and induced skin irritation. Therefore, the development of effective and safe photoprotectants that can reduce and improve the skin damage has been required. The purpose of this study was to investigate the photo-protective effect of several chinese medical plants (Juniperus chinensis) on the UV -induced skin cell damages. We tested free radical and superoxide scavenging effect in vitro. Fluorometric assays of the proteolytic activities of MMP-1 (collagenase) were performed using fluorescent collagen substrates. UVA induced MMP-1 synthesis and activity were analyzed by enzyme-linked immunosorbent assay (ELISA) and gelatin-based zymography in skin fibroblasts. We also examined anti-inflammatory effects by the determination test of proinflammatory cytokine, interleukin 6 in HaCaT keratinocytes. Expression of prostaglandin E$_2$ (PGE$_2$) after UVB irradiation was measured by competitive enzyme immunoassay(EIA) using PGE$_2$ monoclonal antibody. In the human skin we tested anti-irritation effect on the SLS-induced damage skin after appling the extract containing emulsion. We found that Juniperus chinensis extract had potent radical scavenging effect by 98% at 100$\mu\textrm{g}$/mL. The extract of Juniperus chinensis showed strong inhibitory effect on MMP-1 activities by 97% at 100 $\mu\textrm{g}$/mL and suppressed the UVA induced expression of MMP-1 by 79% at 25$\mu\textrm{g}$/mL. This extract also showed strong inhibition on MMP-2 activity in UVA irradiated fibroblast by zymography. In the test of proinflammatory cytokines of human keratinocytes Juniperus chinensis extract decreased expression of interleukin 6 about 30%. The amount of PGE$_2$ by HaCaT keratinocytes was significantly increased at the doses of above 10 mJ/$\textrm{cm}^2$ of UVB (p < 0.05). At the concentrations of 3.2-25$\mu\textrm{g}$/mL of this extract, the production of PGE$_2$ by HaCaT keratinocytes (24 h after 10mJ/$\textrm{cm}^2$ UVB irradiation) was significantly inhibited in culture supernatants (p < 0.05). In SLS-induced skin irritation model in vivo, we found to reduce skin erythema and improve barrier recovery after appling Juniperus chinensis extract containing emulsion when compared to irritated non-treated and placebo-treated skin. Our results suggest that Juniperus chinensis extract can be effectively used for the prevention of UV and SLS-induced adverse skin reactions and applied as anti-aging and anti-irritation cosmetics.

• Journal of Chest Surgery
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• v.42 no.2
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• pp.206-213
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• 2009

Background: Previous series have suggested that younger patients with primary lung cancer exhibit a more aggressive disease course with a worse prognosis, as compared to older patients, although this issue is still debatable. Material and Method: We reviewed the medical records of 79 patients (32 patients 50 years and younger (Group I) and 47 patients 70 years and older (Group II)) who underwent curative resection for primary lung cancer between July 2000 and June 2008. Result: The median age of the patients was 46.5 years in Group I and this was 73 years in Group II. The older patients were more likely to have major comorbidities (44% versus 77%, respectively; p=0.003). Histological examinations identified that the minor histological types (excluding non-small cell lung cancer (NSCLC)) were predominantly found in the Group I patients (16% versus 2%, respectively; p=0.037). For the TNM staging of the NSCLC, with excluding the minor histologic types, a higher proportion of patients had stage III disease in Group I (33% versus 13%, respectively; p=0.038). There was no significant difference in major morbidity (16% versus 30%, respectively; p=0.148) and operative mortality (0% versus 4.3%; p=0.512) between the groups. The mean follow-up interval was 33 months (range: $1{\sim}98$ months) for patients in both groups. For the patients with NSCLC, the five-year overall survival rate was 52.3% for Group I and 53.7% for Group II (p=0.955). The rate of freedom from recurrence at five years was significantly lower for the Group I patients than for the Group II patients (39.4% versus 70.4%, respectively; p=0.027), and only being a member of Group I impacted recurrence, based on the Cox proportional hazard analysis (p=0.034). Of the patients who had recurrence, four patients in Group I underwent aggressive surgical treatment. All of these patients exhibited long-term survival (range: $46{\sim}87$ months). Conclusion: In our study, the early outcome and long-term survival were similar for the younger and older patients after curative resection of primary lung cancer. However, we think that younger patients require meticulous follow-up as they had a tendency to proceed to surgery with advanced stage disease, a higher recurrence rate than did the older patients and the survival rates were improved, even for the recurred cases, with early aggressive treatment.