• Journal of Gastric Cancer
• /
• v.1 no.2
• /
• pp.92-99
• /
• 2001

Purpose: E-cadherin is an adhesion molecule essential for tight connection between cells, forming the cadherin/catenin complex. Truncated $\beta$-catenin disrupts the interaction between E-cadherin and $\alpha$-catenin, leading to the loss of intercellular adhesion. Met protein, the hepatocyte growth factor receptor, plays important roles in signal transduction. We investigated the relationships between the expressions of E-cadherin, $\beta$-catenin, and c-met protein and the clinicopathological and prognostic parameters in gastric adenocarcinomas. Materials and Methods: The patterns of E-cadherin, $\beta$-catenin, and c-met protein expression were studied using immunohistochemistry in formalin-fixed, paraffin-embedded archival tissues from 76 surgically resected gastric adenocarcinomas. Results: Increased expressions of E-cadherin, $\beta$-catenin, and c-met were more significantly correlated in early gastric cancers (EGC) than in advanced gastric cancers (AGC) (P=0.002, P=0.003 and P=0.026). The positive immunoreactivities of all three markers were markedly lower in signet ring-cell type and poorly differentiated type lesions than in intestinal-type lesions. Decreased expression of the $\beta$-catenin protein correlated well with increased tumor invasion depth (P=0.039), and increased lymph node metastasis correlated well with reduced expression of c-met (P=0.046). Conclusion: In gastric cancers, reduced expressions of the E-cadherin, $\beta$-catenin, and c-met proteins may play some role in poorer tumor differentiation, deeper tumor invasion, and increased lymph node metastasis. Also, the c-met gene is thought to play a specific role in the mechanism of the yet unknown catenin action.

• Journal of Life Science
• /
• v.26 no.9
• /
• pp.1027-1032
• /
• 2016

Antigen is substance causing disease derived from pathogen. Living organism has the immune system in terms of defense mechanism against antigen. Antigen is processed through several pathways such as phagocytosis, antibody action, complement activation, and cytotoxins by NK or cytotoxic T lymphocyte via MHC molecule. Lymph node (LN) is comprised of the complicated 3 dimensional network and several stromal cells. Fibroblastic reticular cells (FRC) are distributed in T zone for interaction with T cells. FRC produces the extra cellular matrix (ECM) into LN for ECM reorganization against pathogen infections and secretes homing chemokines. However, it has not so much been known about the involvement of the antigen process of FRC. The present report is for the function of FRC on antigen process. For this, FRC was positioned with several infected situations such as co-culture with macrophage, T cell, lipopolysaccharide (LPS) and TNFα stimulation. When co-culture between FRC with macrophage and T cells was performed, morphological change of FRC was observed and empty space between FRCs was made by morphological change. The matrix metallo-proteinase (MMP) activity was up-regulated by Y27632 and T cells onto FRC. Furthermore, inflammatory cytokine, TNFα regulated the expression of adhesion molecules and MHC I antigen transporter in FRC by gene chip assay. NO production was elevated by FRC monolayer co-cultured with macrophage stimulated by LPS. GFP antigen was up-taken by macrophage co-cultured with FRC. Collectively, it suggests that FRC assists of the facilitation of antigen process and LN stroma is implicated into antigen process pathway.

• Tuberculosis and Respiratory Diseases
• /
• v.47 no.2
• /
• pp.161-171
• /
• 1999

Background: Interleukin-12 (IL-12) can induce antitumor effects in vivo. This antitumor effect is associated with T cell infiltration but the effect of IL-12 on the steps of T cell migration into the tumor tissue has not been fully elucidated. This study focused on the effect of IL-12 on the tumor growth and the metastasis and on the expression of E-selectin, an adhesion molecule which is activated endothelial specific in its expression. In addition, we studied whether the expression of E-selectin is associated with the TNF-$\alpha$, a cytokine that its production is increased by IL-12 and has functions inducing a variety of adhesion molecules. Methods: Mice of C57BL/6 strain were injected with Lewis lung cancer cells followed by either IL-12, TNF-$\alpha$, or normal saline by intraperitoneal route. Twenty eight days after tumor cell inoculation, metastatic nodules of lung were enumerated and immunohistochemical staining of the subcutaneous tumors were performed with monoclonal antibodies to CD4, CD8, CD16, and E-selectin. In IL-12 treated mice, the subcutaneously implanted Lewis lung tumors were decreased in size and the metastases were also decreased in number compared to control mice. On tumor tissues, increased infiltration of CD4+, CD8+, and CD16+ cells were oberved in IL-12 treated mice compared to control mice. In control mice, E-selectin was absent on tumor vessels, but the expression of E-selectin was increased on tumor vessels of IL-12 treated mice. Administration of TNF-$\alpha$ increased not only the expression of E-selectin but also infiltrations of CD4+, CD8+, and CD16+ cells on tumor tissues. Conclusions: These results demonstrate that IL-12 inhibits tumor growth and metastases through infiltrations of inflammatory cells in mouse model of Lewis lung carcinoma and E-selectin may playa role in inflammatory cell recruitment on tumor tissue following IL-12 administration. Also, TNF-$\alpha$ may have a role as a mediator responsible for the IL-12 induced expression of E-selectin.

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

• Anatomy & Biological Anthropology
• /
• v.31 no.4
• /
• pp.143-149
• /
• 2018

Leucocyte extravasation has been known to play an important role in inflammatory reactions including contact dermatitis. Previous studies suggested that CD99 regulates ${\beta}1$ integrin activity and may be a novel therapeutic target molecule for inflammatory diseases. In this study, the effects of CD99-derived peptide, CD99CRIII3, on inflammatory reactions in contact dermatitis mouse model were investigated. CD99CRIII3 decreased ${\beta}1$-integrin activity in human monocytic U937 cells. CD99CRIII3 inhibited the adhesion of U937 monocytes to human umbilical vein endothelial cells and their extravasation through human umbilical vein endothelial cells. CD99CRIII3 reduced inflammation in the phorbol myristate acetate-induced contact dermatitis mice in a dose-dependent manner. These results indicate that CD99CRIII3 suppresses the extravasation of monocytes and inflammatory reactions in the animal model of the contact dermatitis, suggesting that CD99CRIII3 could be a new drug candidate against inflammatory skin diseases.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.43 no.4
• /
• pp.498-506
• /
• 2014

The objective of this study was to investigate the beneficial effects of mulberry extract (MBE) on blood flow improvement. The $SC_{50}$ value for the DPPH radical scavenging activity of MBE was $89.36{\pm}5.46{\mu}g/mL$. Analysis of the cellular toxicity of MBE on RAW 264.7 and HepG2 cells showed no toxicity under a concentration of 2,500 ${\mu}g/mL$. We found that MBE inhibited the enzyme activity of cyclooxygenase (COX)-2 as well as oxidation of human LDL. Western blotting analysis showed that MBE inhibited protein expression of COX-2 and 5-lipoxygenase in RAW 264.7 cells. In addition, MBE inhibited protein expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in human umbilical vein endothelial cells. Furthermore, MBE reduced the serum levels of total cholesterol and C-reactive protein in a concentration-dependent manner. These results both in vitro and in vivo suggest that MBE can be employed for the improvement of blood flow.

• Tuberculosis and Respiratory Diseases
• /
• v.42 no.4
• /
• pp.569-583
• /
• 1995

Background: The expression of the adhesion molecules on the cell surface is important in the movement of cells and the modulation of immune response. DILD starts as an alveolitis and progresses to pulmonary fibrosis. So adhesion molecules in these patients is expected to be increased. There are several reports about adhesion molecules in DILD in terms of the percentage of positive cells in immuno-stain, in which the interpretation is subjective and the data were variable. Methods: So we measured the relative median fluorescence intensity(RMFI) which is the ratio of the FI emitted by bound primary monoclonal antibody to FI emitted by isotypic control antibody of the cells in BALF of 28 patients with DILD(IPF:10, collagen disease:7, sarcoidosis:9, hypersensitivity pneumonitis:2) and 9 healthy control. Results: RMFI of the ICAM-1 on AM($3.30{\pm}1.16$) and lymphocyte($5.39{\pm}.70$) of DILD were increased significantly than normal control($0.93{\pm}0.18$, $1.06{\pm}0.21$, respectively, p=0.001, P=0.003). RMFI of the CD18 on lymphocyte was also higher($24.9{\pm}14.9$) than normal($4.59{\pm}3.77$, p=0.0023). And there was a correlation between RMFI of ICAM on AM and the % of AM(r=-0.66, p=0.0001) and lymphocyte(r=0.447, p=0.0116) in BALF. Also RMFI of ICAM on lymphocyte had a significant (r=0.593, p=0.075) correlation with the % of IL-2R(+) lymphocyte in BALF. The soluble ICAM(sICAM) in serum was also significantly elevated in DILD($499.7{\pm}222.2\;ng/ml$) compred to normal($199.0{\pm}38.9$) (p=0.00097) and sICAM in BAL fluid was also significantly higher than normal control group($41.8{\pm}23.0\;ng/ml$ vs $20.1{\pm}13.6\;ng/ml$). There was a Significant correlation between sICAM level in serum and the expression of ICAM-l on AM(r=0.554, p=0.0259).Conclusion: These data suggest that in DILD the expression of adhesion molecules is increased in the AM and BAL lymphocytes with elevated serum sICAM, and these parameter may be useful in determining disease activity.

• Journal of Gastric Cancer
• /
• v.4 no.3
• /
• pp.156-163
• /
• 2004

Purpose: While E-cadherin in normal cells induces calciumdependent cell-cell adhesion, in malignant cell, it plays a role in invasion and metastasis with a reduction of adhesion. Serum soluble E-cadherin is a result of the reduction of the cellular E-cadherin molecule and is found in the circulation of normal individuals, but it is particularly known to be increased in patients with malignancies. Accordingly, through checking the level of serum soluble E-cadherin in patients with gastric cancer and analyzing it in the view of clinicopathology, we investigated whether serum soluble E-cadherin could be translated into a clinicopathologic esult and used as a tumor marker. Materials and Methods: The investigation targeted 88 patients who had been diagnosed as having gastric cancer by the Department of Surgery, St. Mary's Hospital, from October 1, 2002, to July 30, 2003, and who had under gone performed surgery. We measured the level of preoperative serum E-cadherin in the 88 patients by unsing ELISA. Among them, we collected gastric cancer tissues from 54 patients and executed immunohistochemistry for E-cadherin. The samples were compared with normal tissues in terms of both serum E-cadherin level and immunohistochemistry level, as well as with other clinicopathologic factors. Result: The mean serum E-cadherin level of the 88 patients was 4368.7 ng/ml and was significantly higher than the level in 12 normal control patients, 3335.5 ng/ml (P=0.016). In terms of clinicopathology, the serum level of E-cadherin was significantly correlated with increasing age (P=0.0006) and was higher in positive venous invasion patients (P=0.0005). When the E-cadherin immunohistochemical stain was compared with the serum E-cadherin level in 54 patients, no significant statistically meaningful result was obtained (P=0.2881). However, 4 patients with serum E-cadherin levels about 6000 ng/ml were classified into the lower expression group ($<80\%$ of E-cadherin immunohistochemicals stain. In the analysis for 36 patients who were early gastric cancer patients, the serum E-cadherin level in lymph-node-metastatic patients was higher than it was in the other patients (P=0.0442). Conclusion: The serum E-cadherin level in gastric cancer patients was higher than the level in normal control patients. In advanced gastric cancer patients, that the difference was increased. Also, since the E-cadherin level correlated with the serum E-cadherin level with venous invasion, it can be used as an effective tumor marker for gastric cancer. Particularly, in that the serum E-cadherin level correlated with lymph node metastasis in early gastic cancer, it can be used when a therapeutic method for early gastric cancer is selected.

• Tuberculosis and Respiratory Diseases
• /
• v.43 no.1
• /
• pp.75-87
• /
• 1996

Background: Lung cancer is the second most frequent malignancy in man in Korea. Surgery is the best treatment modality for non-small cell lung cancer, but most patients were presented in far advanced stage. So radiation therapy(RT) with or without chemotherapy is the next choice and radiation-induced pneumonitis and pulmonary fibrosis is the major limiting factor for the curative RT. Radiation pneumonitis is manifested with fever, cough and dyspnea, 2~3 months after the termination of radiotherpy. Chest X ray shows infiltration, typically limited to the radiation field, but occasionally bilateral infiltration was reported. Also Gibson et al reported that BAL lymphocytosis was found in both lungs, even though the radiation was confined to one lung. The aim of this study is to investigate the change of adhesion molecules expression on BAL cells and serum soluble ICAM-1(sICAM-1) level after the RT and its relationship to the development of radiation pneumonitis. The second aim is to confirm the bilaterality of change of BAL cell pattern and adhesion molecule expression. Subjects: BAL and the measurement of sICAM level in serum and BALF were done on 29 patients with lung cancer who received RT with curative intention. The BAL was done before the RT in 16 patients and 1~2 month after RT in 18 patients. 5 patients performed BAL before and after RT. Result: Clinically significant radiation pneumonitis developed in 7 patients. After RT, total cell count in BAL was significantly increased from $(20.2{\pm}10.2){\times}10^6\;cells/ml$ to $(35.3{\pm}21.6){\times}10^6\;cells/ml$ (p=0.0344) and %lymphocyte was also increased from $5.3{\pm}4.2%$ to $39.6{\pm}23.4%$ (p=0.0001) in all patient group. There was no difference between ipsilateral and contraleteral side to RT, and between the patients with and without radiation-pneumonitis. In whole patient group, the level of sICAM-1 showed no significant change after RT(in serum: $378{\pm}148$, $411{\pm}150\;ng/ml$, BALF: $20.2{\pm}12.2$, $45.1{\pm}34.8\;ng/ml$, respectively), but there was a significant difference between the patients with pneumonitis and without pneumonitis (serum: $505{\pm}164$ vs $345{\pm}102\;ng/ml$, p=0.0253, BALF: $67.9{\pm}36.3$ vs $25.2{\pm}17.9\;ng/ml$, p=0.0112). The expression of ICAM-1 on alveolar macrophages (AM) tends to increase after RT (RMFI: from $1.28{\pm}0.479$ to $1.63{\pm}0.539$, p=0.0605), but it was significantly high in patients with pneumonitis ($2.10{\pm}0.390$) compared to the patients without pneumonitis ($1.28{\pm}0.31$, p=0.0002). ICAM-1 expression on lymphocytes and CD 18 (${\beta}2$-integrin) expression tended to be high in the patients with pneumonitis but the difference was statiastically not significant. Conclusion: Subclinical alveolitis on the basis of BAL finding developed bilaterally in all patients after RT. But clinically significant pneumonitis occurred in much smaller fraction and the ICAM-1 expression on AM and the sICAM-1 level in serum were good indicator of it.

• Tuberculosis and Respiratory Diseases
• /
• v.43 no.6
• /
• pp.936-944
• /
• 1996

Background: Neutrophils or monocytes separated in vitro by the adherence to plastic surface are known to be activated by surface adherence itself and subsequent experimental data might be altered by surface adherence. Adhesion molecules and gene transcription of the inflammatory mediators are known to be associated in this process. To evaluate whether adhesion molecule and transcriptional activation of the inflammatory substances are also involved in the activation of human alveolar macrophage by the adherence procedure, we designed this experiment. Method : Bronchoalveolar lavage was performed in the person whose lung of either side was confirmed to be nonnal by chest cr and alveolar macrophage was harvested. To measure the expression of Interleukin-8(IL-8) mRNA, manganese superoxide dismutase(SOD) mRNA and CD11/CD18 mRNA in human alveolar macrophage of both adherence state and suspension state, Northern blot analysis was done at 0, 2, 4, 8 and 24hrs after the adherence to plastic surface and during suspension state. Then, phorbol myristate acetate(pMA) and N-formyl-methionyl-leucyl-phenylalanine(fMLP) were added respectively in the same experimental condition. Result : 1) Human alveolar macrophages in the adherent state induced IL-8 mRNA and SOD mRNA expression which was maximal at 8 hours after the adherence to plastic surface. But we could not observe the upregulation of CD18 mRNA by surface adherence. 2) PMA induced these mRNA expression both in the adherent cell and the nonadherem cells, but the induction of mRNA expression by fMLP occurred only in the adherent cells. Conclusion: These results suggest that adherence of huamn alveolar macropahge is an important cell-activating event that may play a critical role in the modulation of lung inflammatory respones.