• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.3
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• pp.401-408
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• 2011

Type 2 diabetes mellitus (NIDDM) is a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. In order to control the type 2 diabetes mellitus, anti-hyperglycemic effect of Triticum aestivum L. water extracts (TAWE) was investigated in 7 week old male diabetic C57BL6/J-ob/ob mice. For the experiments, the diabetic animal model ob/ob mice and non-diabetic animal model lean mice were divided into 3 groups: non-treatment control group (Control), and two experimental groups orally treated with 25 or 100 mg/kg/day dose of TAWE (TAWE-25 and TAWE-100, respectively). The lean mice were used as the non-diabetic normal control. TAWE was orally administrated for 6 weeks and the diabetic clinical markers, including blood glucose level, body weight, organs weight and insulin level were determined. The oral administration of TAWE-100 in ob/ob diabetic mice significantly decreased blood glucose level (78.4%) and body weight (11.9%) compared with diabetic control group. The weights of organs, including spleen, liver, kidneys, heart and lung were not different among groups, while the treatments of TAWE-100 in ob/ob diabetic mice significantly reduced blood total cholesterol (24.35%) and triglyceride (23.97%) levels compared with the diabetic control group. The levels of serum insulin and glucose tolerance were improved after TAWE-100 treatment in ob/ob diabetic mice. Moreover, the immunohistochemical staining for insulin detection in pancreatic islet $\beta$-cells expressed high level of insulin in TAWE-100 treated ob/ob mice. From the above results, the intake of TAWE may be effective in anti-hyperglycemia by the attenuation of glucose and lipid levels. TAWE-containing diets or drugs may be beneficial for controlling diabetes mellitus type 2 in human.

• The korean journal of orthodontics
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• v.31 no.1 s.84
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• pp.107-120
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• 2001

Nitric oxide(NO) has been reported to be one of the mediators relating to bone remodelling. Nitric oxide is synthesized from L-arguinine by nitric oxide synthetase(NOS), which is largely divided Into two groups. One group which is composed of $NOS_1\;and\;NOS_3$, is dependent of calcium or calmodulin. The other consisted of $NOS_2$, which is independent of calcium or calmodulin. NOS is thought to be a possible intermediate affecting in the course of tooth movement. This study was designed to evaluate the expression of nitrous oxide synthetase(NOS) in periodontal tissue during the experimental movement of rat incisors, by LSAB(labelled streptavidine biotin) immunohistochemical staining for $NOS_2\;and\;NOS_3$. Twenty seven Sprague-Dawley rats were divided into a control group(3 rats), and 6 experimental groups(24 rats), to which 75g of force was applied, with helical springs across the maxillary incisors. Rats of experimental groups were sacrificed at 12 hours, 1, 4, 7, 14 and 28 days after force application, respectively. After that, the tissues of the control group and experimental groups were studied immunohistochemically. The results were as follows: 1. In control group, the expression of $NOS_3$ was rare in gingiva, dentin, periodontal ligament and alveolar bone, and was mild in the capillaries of pulp and intermaxillary suture. And the expression of $NOS_2$ showed similar pattern to that of $NOS_3$. 2. There were no differences in the expression of $NOS_2\;or\;NOS_3$ in dentin, gingiva, cementum, cementoblast and odontoblast, between control and experimental groups, regardless of the duration of the force application. 3. The expression of $NOS_3$ began to increase at 4 days and showed to the highest degree at 7 days after force application, in the apical region of pressure side of periodontal ligament in experimental groups. 4. The expression of $NOS_3$ in alveolar bone was rare until 7 days, after which it increased to mild degree at 14 days through 28 days in experimental group. But there was no difference between pressure and tension side of periodontal ligament. 5. The expression of $NOS_2$ in periodontal ligament was mild from 7 days after force application, regardless of the side of periodontium, which was generally more evident than that of $NOS_3$. 6. The expression of $NOS_2$ in alveolar bone increased to mild degree at 14 days after force application, and it was evident in osteoblasts, osteoclasts and osteocytes. And the expression of $NOS_2$ was little more stronger in the tension side than that of pressure side of alveolar bone.

• Tuberculosis and Respiratory Diseases
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• v.47 no.3
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• pp.347-355
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• 1999

Background: Phospholipase C(PLC) plays a central role in cellular signal transduction and is important in cellular growth, differentiation and transformation. There are currently ten known mammalian isozymes of PLC reported to this date. Hydrolysis of phosphatidylinositol 4,5-bisphosphate($PIP_2$) by PLC produces two important second messengers, inositol 1,4,5-trisphosphate($IP_3$) and diacylglycerol. PLC-${\gamma}1$, previously, was known to be activated mainly through growth factor receptor tyrosine kinase. Other mechanisms of activating PLC-yl have been reported such as activation through tau protein in the presence of arachidonic acid in bovine brain and activation by $IP_3$, phosphatidic acid, etc. Very recently, another PLC-${\gamma}1$ activator protein such as tau has been found in bovine lung tissue, which now is considered to be AHNAK protein. But there has been no report concerning AHNAK and its associated disease to this date. In this study, we examined the expression of the PLC-${\gamma}1$ activator, AHNAK, in lung cancer specimens and their paired normal. Methods: From surgically resected human lung cancer tissues taken from twenty-eight patients and their paired normal counterparts, we evaluated expression level of AHNAK protein using immunoblot analysis of total tissue extract Immunohistochemical stain was performed with primary antibody against AHNAK protein. Results: Twenty-two among twenty-eight lung cancer tissues showed overexpression of AHNAK protein (eight of fourteen squamous cell lung cancers, all of fourteen adenocarcinomas). The resulting bands were multiple ranging from 70 to 200 kDa in molecular weight and each band was indistinct and formed a smear, reflecting mobility shift mainly due to proteolysis during extraction process. On immunohistochemistry, lung cancer tissues showed a very heavy, dense staining with anti-AHNAK protein antibody as compared to the surrounding normal lung tissue, coresponding well with the results of the western blot Conclusion: The overexpression of PLC-${\gamma}1$ activator protein, AHNAK in lung cancer may provide evidence that the AHNAK protein and PLC-${\gamma}1$ act in concerted manner in carcinogenesis.

• Tuberculosis and Respiratory Diseases
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• v.50 no.5
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• pp.557-567
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• 2001

Background : Tumor angiogenesis is required for tumor growth and metastasis. In this study, we investigated the correlation between the intensity of angiogenesis and stage, nodal status, histologic type, metastasis and survival rate of non-small cell lung cancer. Method : Formalin fixed, paraffin embedded surgical specimens of 45 patients who had surgically resected primary non-small cell lung cancers without pre or post operative adjuvant chemotherapy or radiotherapy were examined. The microvessel count(MVC) was demonstrated by immunohistochemical staining for CD31(platelet endothelial cell adhesion molecule, PECAM). Results : Microvessel counts(MVCs) in stage IIIA and IIIB were higher than in stage I and II(p<0.05). The MVC in patients with lymph node metastasis was higher than that in patients without lymph node metastasis, although the difference was not statistically significant(p>0.05). However, in adenocarcinoma, the MVC in patients with lymph node metastasis was significantly higher than that seen in patients without lymph node metastasis(p<0.05). The MVC in adenocarcinoma was higher than that in squamous cell carcinoma(p<0.05). The difference between the MVCs of adenocarcinoma and squamous cell carcinoma was not statistically significant in stage I and II or N0 stage(p>0.05). However, in stage IIIA and IIIB or N1~3 stage, the MVC in adenocarcinoma was higher than that in squamous cell carcinoma(p<0.05). MVC was more increased when metastasis developed within 12 months. In the same histologic type and stage, the duration of survival time in patients with high MVC was shorter than in patients with low MVC, however the difference was not statistically significant(p>0.05). The survival rate in patients with high MVCs was lower than that in patients with low MVCs(P<0.05). Conclusion : In non-small cell lung cancer, MVC correlated relatively well with pathologic stage, nodal status(limited in patients with adenocarcinoma), histologic type, postoperative metastasis and survival rate. However, in the same histologic type and stage, MVC was not significantly related to the duration of survival. Therefore the assessment of the intensity of angiogenesis in non-small cell lung cancer may be helpful in predicting prognosis and in selecting patients for systemic adjuvant therapy of potential metastasis according to the results.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.776-784
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• 1998

Background: The cyclin D1 gene is one of the most frequently amplified chromosomal regions(11q13) in human carcinomas. In laryngeal and head and neck carcinomas, its overexpression has been shown to be associated with advanced local invasion and presence of lymph node metastases. Cyclin D1 may therefore playa key role in cell growth regulation and tumorigenesis. Lung cancer is a worldwide problem and in many contries it is the most lethal malignancy. As relapse is frequent after resection of early stage non-small cell lung cancer, there is an urgent need to define prognostic factors. Purpose: This study was undertaken to evaluate the prognostic value of the cyclin D1, that is one the G1 cyclins which control cell cycle progression by allowing G1 to S phase transition, on the patients in radically resected non-small cell lung cancer. Method: Total 81 cases of formalin-fixed paraffin-embedded blocks from resected primary non-small cell lung cancer from January 1, 1983 to July 31, 1995 at Hanyang University Hospital were available for both clinical follow-up and immunohistochemical staining using monoclonal antibodies for cyclin D1. Results : The histologic classification of the tumor was based on WHO criteria, and the specimens included 45 squamous cell carcinomas, 25 adenocarcinomas and 11 large cell carcinomas. Cyclin D1 overexpression was noted in 26 cases of 81 cases tested (30.9%). Cyclin D1 expression was not significantly associated with cell types of the tumor, pathological staging and the size of the tumor. But cyclin D1 overexpression was significantly correlated with positive lymph node metastasis(p=0.035). The mean survival duration was $22.76{\pm}3.50$ months in cyclin D1 positive group and $45.38{\pm}5.64$ months in eyclin D1 negative group. There was a nearly significant difference in overall survival between cyclin D1 positive and negative groups(p=0.0515) in radically resected non-small cell lung cancer. Conclusion: Based on this study, cyelin D1 overexpression appears an important poor prognostic indicator in non-small cell lung cancer and may have diagnostic and prognostic importance in the treatment of resectable non-small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.40 no.6
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• pp.659-668
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• 1993

Background: p53 is currently considered as a tumor suppressive gene product, and its alterations are suggested to be involved in several human malignancies, including non-small cell lung cancers. p53 expression rates are variable in many reports and among cell types. Also, whether the phase of p53 expression is early or late during carcinogenesis is not certain. Thus, We have investigated to evaluate p53 expression rates of the various cell types and tissues and identify expression phase (early or late). Method: We obtained 71 tissue from 50 non-small cell lung cancer patients and performed the simple immunohistochemical staining using nonspecific monoclonal antibody(NCL-p53DO7). Results: 1) In non-small cell lung cancer patients. the expression rate of lungs(46.5%) is higher than that(25.0%) of lymph nodes. But, there is no significant difference between two groups. 2) Among the various cell types, p53 expression rates in squamous cell carcinoma and adenocarcinoma are 58.3% and 50.0% respectively without significant difference. 3) p53 expression rates in various stages are 33.3%, 60.0%, 40.0%, 60.0% and 66.7% in stage I, II, IIIa, IIIb and IV, respectively with no significant difference. 4) p53 expression rates in the various T parameters are 33.3%, 50.0%, 16.7% and 100% in T1, T2, T3 and T4, respectively and p53 expression rates in the various N parameters are 27.3%, 22.2% and 25.0% in N1, N2 and N3, respectively. There are no significant differences in the expression rates among varous T & N parameters. 5) p53 expression rates of lymph nodes in patients who have positive stains in lungs are 12.5% and 50.0% in N1 and N2. 6) p53 expression rates of all lymph nodes in patients who have negative stains in lungs are 0.0%. Conclusion: The above results show that p53 expression rate in non-small cell lung cancers is not correlated with cell type and progression of stage and it is thought to need further investigations about at what phase p53 expression influences the development and progression of lung cancers.

• Tuberculosis and Respiratory Diseases
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• v.52 no.2
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• pp.117-127
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• 2002

Backgroud : MUC1 mucin is a heavily glycosylated large glycoprotein and is expressed aberrantly in carcinoma. CD44 is polymorphic family of cell surface glycoproteins participating in cell-cell adhesion and modulation of the cell-matrix interaction. MUC1 mucin and CD44 expression have been implicated in a tumor invasion and metastasis in certain malignancies. In this study, the expression of MUC1 and the standard form of CD44 (CD44s) was examined in non-small cell lung cancer (NSCLC). Methods : Immunohistochemical staining using monoclonal antibodies including MUC1 glycoprotein and CD44s was performed on 80 NSCLC surgical specimens. The association between MUC1 and CD44s expression and the histological type and tumor stage was investigated. Results : Depolarized MUC1 expression in more than 10% of cancer cells was found in 12 (27.9%) out of 43 squamous cell carcinomas (SCCs) and 12 (32.4%) out of 37 adenocarcinomas (ACs). It was not associated with the tumor histological type and the TNM-stage in SCCs. Depolarized MUC1 expression correlated with the N-stage in ACs (p=0.036). CD44s was expressed in 36 (83.7%) out of 43 SCCs and 14 (37.8%) out of 37 ACs. Reduced CD44s expression correlated with the N-stage (p=0.031) and the TNM-stage (p=0.006) in SCCs. Conclusions : Depolarized MUC1 expression was related to the nodal stage in NSCLC adenocarcinoma. Reduced CD44s expression was related to nodal involvement and the TNM-stage in squamous cell carcinoma. This suggests that MUC1 and CD44s expression in NSCLC might play important roles in tumor progression and cap be used as prognostic variables.

• Tuberculosis and Respiratory Diseases
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• v.54 no.6
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• pp.610-620
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• 2003

Background : 3p deletion has been shown to be the most frequently occurring change in lung cancers, suggesting the presence of a tumor suppressor gene in this region. Recent attention has focused on a candidate 3p14.2 tumor suppressor gene, FHIT. Therefore, the association of the expression of FHIT, with apoptosis, cell proliferation cycle and the clinicopathological features, including survival, were investigated Materials and Methods : 83 patients with non-small cell lung cancer, who underwent curative operation, between Jan. 1996 and Aug. 2000, at the Wonkwang university hospital, were analyzed. The expression of the FHIT was identified by immunohistochemical staining, and rate of apoptosis and cell proliferation cycle by flow cytometry. Results : 43% (36/83) of patients exhibited no FHIT expression. The rates of FHIT loss were 52% (28/54), 22% (5/23), 50% (3/6); 30% (11/37), 48% (16/33), 69% (9/13); 54% (30/56) and 22% (6/27), in squamous cell cancers, adenocarcinomas, large cell cancers, TNM stages I, II and III, smokers and non-smokers, respectively. All the differences in FHIT loss rates, according to the histopathology, TNM stages and smoking habits, were statistically significant. The median survival time and 2-year survival rate of the FHIT(-) group were 24 months and 44%, and those of the FHIT(+) group were 25 months and 51% (p>0.05), respectively. The apoptotic rate of the FHIT(-) and FHIT(+) groups were 50.72 (${\pm}13.93$) and 59.38 (${\pm}14.33$)%, respectively (p=0.01). The S- and G1-phase fractions of the FHIT(-) and FHIT(+) groups were 13.93 (${\pm}7.35$) and $51.50({\pm}23.15$)% and 15.65(${\pm}6.59$) and 54.16 (${\pm}20.25$)%, respectively (p>0.05). Conclusion : The loss of FHIT expression was increased to a greater extent with advancing TNM stage, smoking habits and squamous cell cancer compared to the adenocarcinomas. However, no survival differences were found according to the expression of FHIT. The apoptotic rate of the FHIT(+) group was greater than in the FHIT(-) group, but differences in the S- and G1-phase fractions, according to the expression of the FHIT, were not found.

• Journal of Gastric Cancer
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• v.6 no.4
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• pp.250-256
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• 2006

Purpose: Recently, interest in peroxisome-proliferator-activated receptors (PPAR) has increased, although clinical studies of the effect of $PPAR-{\gamma}$ expression on gastric cancer have not been reported yet. In this study, we investigated the role of $PPAR-{\gamma}$ expression in gastric cancer patients. Materials and Methods: One hundred twenty-eight (128) samples of both gastric cancer and normal tissues were obtained from 128 patients who had undergone at a curative gastrectomy at Seoul Medical Center from Jan. 2001 to Dec. 2005. $PPAR-{\gamma}$ expression was determined by using immunohistochemical staining, and the results were analyzed. The statistical analysis was based on clinicopathological findings and the differences in survival rates. Results: The mean age of the patients was 6n, and the male : female ratio was 1.9 : 1. $PPAR-{\gamma}$ expression was significantly higher in cancer tissues than in normal tissue (81.3% vs. 57.0%, p<0.001). There was insignificant difference between well and moderately differentiated types and poorly differentiated types in terms of the expression of $PPAR-{\gamma}$ (87.0% vs. 74.6%, P=0.074). In the univariate analysis the survival rate was significantly increased when $PPAR-{\gamma}$ was expressed in normal tissue (P=0.003). In the multivariate analysis, only the UICC TNM staging had significance related to the survival rate. Conclusion: The rate of $PPAR-{\gamma}$ expression was higher in cancer tissue than it was in normal tissue from gastric cancer patients. In the univariate analysis, $PPAR-{\gamma}$ expression in normal tissue had significance with respect to survival, but the multivariate analysis showed no such significance. Thus, we should further evaluate more cases to determine whether or not such a significance exists.

• Journal of Gastric Cancer
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• v.8 no.4
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• pp.176-181
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• 2008

Purpose: The adipocyte-derived cytokine leptin plays a major role in the control of stable body weight by suppressing food intake and increasing energy metabolism. Leptin regulates the cell proliferation of various epithelial cells and it may be involved in the promotion of cancer. Leptin and its receptor are highly expressed in gastric adenocarcinoma, but the association between the serum leptin level and the tissue expression of leptin is uncertain. We evaluated the serum leptin level and the expressions of leptin and leptin receptor in gastric cancer, and we explore the possible mechanism and role of leptin in the carcinogenesis of gastric cancer. Materials and Methods: 72 carcinomas that were curatively resected at our hospital from October 2005 to March 2007 were included in this study. By immunoassay and immunohistochemical staining, we evaluated the serum leptin level and the expressions of leptin and its receptor, and we analyzed their relationship together with the clinicopathological variables. Results: The serum leptin level was increased as the patient's BMI increased and it was decreased in H. pylori infected patients. The expression of leptin was increased as the TNM stage increased (P=0.014), and the expression of leptin receptor in the intestinal type gastric adenocarcinoma was higher than that in the diffuse type gastric adenocarcinoma (71.4% vs 28.6%, respectively, P=0.033). Conclusion: There was no significant correlation between the serum leptin level and expression of leptin in gastric cancer patients. The expression of leptin was associated with the TNM stage, but its role in the pathogenesis of gastric cancer has to be elucidated.