Tumor migration/invasion is the main cause of tumor progression and STAT3 is needed to enhance tumor migration/invasion by up-regulating MMP-9. Thus, agents that inhibit STAT3 activation may be used as an anticancer drug. We present herein that 6-methyl-2-propylimino-6, 7-dihydro-5H-benzo [1, 3]-oxathiol- 4-one (LYR71) , a derivative of trimeric resveratrol, has an anticancer activity through inhibition of STAT3 activation. We found that LYR71 suppressed STAT3 activation and inhibited the expression and activity of MMP-9 in RANTES-stimulated breast cancer cells. In addition, LYR71 reduced RANTES-induced MMP-9 transcripts by blocking STAT3 recruitment, dissociating p300 and deacetylating histone H3 and H4 on the MMP-9 promoter. Furthermore, LYR71 inhibited tumor migration/invasion in RANTES-treated breast cancer cells and consequently blocked tumor progression in tumor-bearing mice. Taken together, the results of this study suggest that LYR71 can be therapeutically useful due to the inhibition effect of STAT3-mediated MMP-9 expression in breast cancer cells.
Animals ; Antineoplastic Agents/chemistry/*pharmacology ; Bicyclo Compounds, Heterocyclic/chemistry/*pharmacology ; Blotting, Western ; Breast Neoplasms/genetics/metabolism/pathology ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Survival/drug effects ; Chromatin Immunoprecipitation ; Female ; Gene Expression/drug effects ; Humans ; Imines/chemistry/*pharmacology ; Immunohistochemistry ; Mammary Neoplasms, Experimental/pathology/prevention & control ; Matrix Metalloproteinase 9/genetics/*metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Molecular Structure ; Phosphorylation/drug effects ; Reverse Transcriptase Polymerase Chain Reaction ; STAT3 Transcription Factor/genetics/*metabolism ; Stilbenes/chemistry ; Xenograft Model Antitumor Assays/methods

PURPOSE: Because vascular endothelial cells play a pivotal role in the vascular diseases, damage of vascular endothelial cells lead to progression of vascular disease. Apoptotic damage of cells is an important mechanism in vascular disease. Therefore, several growth factors that have antiapoptotic effect may have a protective role in maintaining a cell function in apoptotic cell injury. In this study, we examined the effects of adrenomedullin on apoptosis in iopromide-induced endothelial cell injury. METHODS: Human umbilical vein endothelial cells were incubated with nonionic radiocontrast agent, iopromide and/or adrenomedullin. Apoptosis was assessed quantitatively using FACScan after annexin V-FITC and propidium iodide staining, and by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) stain. Signaling pathway was evaluated by Western blot analysis of phospho-Akt and Akt. RESULTS: Iopromide-induced apoptosis in human umbilical vein endothelial cells was increased in a dose-dependent manner. Adrenomedullin prevented iopromide-induced apoptosis in human umbilical vein endothelial cells in a dose dependent manner. Wortmannin, phosphatidylinositol 3-kinase inhibitor, decrease the adrenomedullin-induced antiapoptotic effect. CONCLUSION: These results suggest that adrenomedullin protects vascular endothelial cells from iopromide-induced apoptosis by regulating the activity of Akt.
Adrenomedullin ; Androstadienes ; Apoptosis ; Blotting, Western ; Contrast Media ; Endothelial Cells ; Human Umbilical Vein Endothelial Cells ; Intercellular Signaling Peptides and Proteins ; Iohexol ; Phosphatidylinositol 3-Kinase ; Propidium ; Vascular Diseases

BACKGROUND: Dynorphin A (1-17) is conceived as an endogenous opioid peptide with a high degree of selectivity forkappa- opioid receptor even though it has been reported to sometimes act like amicro- opioid agonist. The aim of this study was to investigate [35S] GTPgammaS binding stimulated activation by dynorphin A (1-17) in the cerebral and thalamic membranes of a rhesus monkey. METHODS: The rhesus monkey (Macaca mulatta, male, n = 1) was euthanized for the preparation of the cerebral and thalamic membranes. Protein concentrations were determined by the Bradford method. In the dynorphin A (1-17)-stimulated [35S] GTPgammaS binding dose-response curve, EC50 (effective concentration 50 nM) and maximum stimulation (% over basal) were determined in the absence or presence of themicro-andkappa-opioid receptor antagonists naloxone (20 nM) and norbinaltorphimine (nor-BNI, 3 nM), respectively. E2078-stimulated [35S] GTPgammaS binding was also determined in the absence or presence ofmicro-andkappa-opioid receptor antagonists in the cortical membrane and compared with dynorphin A (1-17). RESULTS: Values of EC50 and maximum stimulation of dynorphin A (1-17)-stimulated [35S] GTPgammaS binding were as follows: cortex (474 nM/32.0%) and thalamus (423 nM/45.3%). Nor-BNI (3 nM) did not antagonize dynorphin A (1-17)-stimulated [35S] GTPgammaS binding at all in cortical or thalamic membrane, but naloxone (20 nM) produced a 12.2 fold rightward shift of the dynorphin A (1-17)-stimulated [35S] GTPgammaS binding dose-response curve in the thalamic membrane. The EC50 and the maximum stimulation of E2078-stimulated [35S] GTPgammaS binding were 65.6 nM and 22.7%, respectively. In E2078-stimulated [35S] GTPgammaS binding, the dose-response curve was antagonized not by nor-BNI but by naloxone but in the cortical membrane (a 14.2 times rightward shift). CONCLUSIONS: Dynorphin A (1-17) is selective formicro-opioid receptor in agonist-stimulated [35S] GTPgammaS binding in the cortical and thalamic membranes of rhesus monkey.
Dynorphins* ; Guanosine 5'-O-(3-Thiotriphosphate)* ; Haplorhini* ; Humans ; Macaca mulatta ; Male ; Membranes* ; Naloxone ; Opioid Peptides ; Receptors, Opioid ; Thalamus

PURPOSE: The of this study was to describe the changes of airway inflammation in children with stable, steriod naive asthma after inhaling fluticasone by using serial induced sputum. We sought to investigate the role of neutrophils, interleukin-8(IL-8), and myeloperoxidase(MPO) in asthma. METHOD: To examine the change of neutrophil and their products in childhood asthma after inhaling fluticasone, we assessed the cell counts, IL-8, and MPO in the sputum at each visit. Also, the daily symptom scores, FEV1, peak expiratory flow variability, and methacholin airway responsiveness were checked and their relationships were analyzed. RESULT: There was a significant improvement in asthma severity, as measured by symptom score, and FEV1. There were significant reductions in IL-8 and MPO after 3 weeks treatment, and significant increase in the total sputum cell counts. Significant increase in total lymphocyte and alvelor macrophage cell counts with no increase in neutrophil and eosinophil counts were found. Airway responsiveness was significantely correlated with total eosinophil counts before inhaling fluticasone and it was correlated with IL-8 after the treatment. CONCLUSION: This study highlight, the probable importance of IL-8 and myeloper-oxidase within the asthmatic airways and the beneficial modulatory effect of inhaled fluticasone treatment upon them.
Asthma ; Cell Count ; Child ; Eosinophils ; Humans ; Inflammation ; Inhalation ; Interleukin-8* ; Lymphocytes ; Macrophages ; Neutrophils ; Peroxidase* ; Sputum* ; Fluticasone*

PURPOSE: The aim of this study is to investigate the effects of high humidification of nearly 100% on insensible water loss and total fluid requirement in very low birth weight infants during their first week of life. METHODS: We retrospectively compared twenty-five infants (GA 28.1+/-1.7 wk, and BW 970+/-186 g) who were cared for in a double walled incubator with high humidification with 24 infants (GA 27.6+/-2.2 wk, and BW 972+/-186 g) who were in a double walled incubator without raised humidity during the first week of their life. We analyzed the changes in body weight, total fluid intake, insensible water loss, urine output, input of sodium and potassium, serum levels of sodium and potassium, and the incidence of complications during the hospitalization in the high humidified group and the control group. RESULTS: High humidification during the first week of life in very low birth weight infants reduced insensible water loss and total fluid requirement. However the imbalance of serum electrolyte or oliguria did not increase. The high humidification group (n=25) acquired more physiologic weight loss during the first two weeks of life than the control group (n=24) but gained more weight than the control group (n=24) on the third month of life. Infants nursed with high humidification showed an increased tendency toward spontaneous closure of the patent ductus arteriosus and a decreased tendency toward surgical ligation of the patent ductus arteriosus and intraventricular hemorrhage without the evidence of an increase in infection. No significant differences were noted in the incidence of patent ductus arteriosus, bronchopulmonary dysplasia and retinopathy of prematurity. CONCLUSION: The high humidification of nearly 100% and fluid restriction therapy during the first week of life were effective in the fluid and electrolyte management of very low birth weight infants.
Body Weight ; Bronchopulmonary Dysplasia ; Ductus Arteriosus, Patent ; Hemorrhage ; Hospitalization ; Humans ; Humidity ; Incidence ; Incubators ; Infant ; Infant, Newborn ; Infant, Very Low Birth Weight* ; Ligation ; Oliguria ; Potassium ; Retinopathy of Prematurity ; Retrospective Studies ; Sodium ; Water Loss, Insensible ; Weight Loss

OBJECTIVES: This study was conducted to identify the factors influencing the mortality of Koreans over the age of 40 by a nested case-control study. METHODS: The cohort consisted of the beneficiaries of Korea Medical Insurance Corporation for Government Employees & Private School Teachers and Staff(KMIC) who received health examinations of KMIC in 1992 and 1993 retrospectively. At that time, they were more than 40 years old. The cases were 19,258 cohort members who had died until December 31, 1997. The controls were 19,258 cohort members who were alive until December 31, 1997. Controls were matched with age and sex distribution of the cases. The data used in this study were the funeral expenses requesting files, and the files of health examinations and health questionnaires gathered in 1992 and 1993. To assess the putative risk factors of death, student t-test, chi-square test, multiple logistic regression analysis were used. RESULTS: In multiple logistic regression analysis, independent risk factors of death were as follows; systolic blood pressure, diastolic blood pressure, blood glucose, AST, urine glucose, urine protein, alcohol drinking(frequency), cigarette smoking and perceived health status, intake of restoratives and blood transfusion showed positive associations with death; coffee consumption showed negative associations with death; and body mass index and serum total cholesterol showed J-shaped association with death. CONCLUSIONS: Regarding the direction of association, the result of analysis on the data restricted to '96-'97 was same as that of '93-'97. But in some variables such as obesity, serum cholesterol, the odds ratios of death in the data of '96-'97 were higer than those of '93-'94, which suggested that the data of '93-'94 was bearing effect-cause relationship. We concluded that it suggested further researches using long-term follow-up data to be needed in this area.
Adult ; Asian Continental Ancestry Group ; Blood Glucose ; Blood Pressure ; Blood Transfusion ; Body Mass Index ; Case-Control Studies ; Cholesterol ; Coffee ; Cohort Studies ; Glucose ; Humans ; Insurance ; Korea ; Logistic Models ; Mortality* ; Obesity ; Odds Ratio ; Surveys and Questionnaires ; Retrospective Studies ; Risk Factors ; Sex Distribution ; Smoking

No abstract available.
Humans

Carcinoma of lung is classified by histologic cell type, this is based on predominant major cell population by tissue specimen. But in fact a range of 13% to 63% of lung cancer has been appeared to be heterogeneous cell type at the light microscopic level. After treatment of the mixed lung cancer and/or with time there are reports that cell type is changed. Because it is possible that the tumor were pleomorphic and that the antitumor therapy eliminated the more sensitive cell population and permitted the subsequent emergence of the more resistant cell population. The authors reported here, a case of 32 year old female patient with mixed lung cancer composed of three cell type, and this is the first case in Korea.
Adult ; Female ; Humans ; Korea ; Lung ; Lung Neoplasms ; Population Characteristics

The tumorous type of endobronchial tuberculosis was reported to be 5 to 10% in the bronchoscopic examination. It was protruding mass that tuberculous mediastinal lymph node ruptured into the bronchial lumen. Generally histologic examination has been performed for purpose of differentiation, because the tumorous type of endobronchial tuberculosis simulate lung cancer in bronchoscopic finding. A case considering operation similar to bronchial adenoma in the bronchoscopic finding was confirmed to endobronchial tuberculosis by positive AFB and disapperance of mass after antituberculosis medication. Case history was presented and reviewed.
Adenoma* ; Bronchoscopy ; Lung Neoplasms ; Lymph Nodes ; Tuberculosis*

No abstract available.
Appointments and Schedules* ; Hepatitis B Vaccines* ; Hepatitis B virus* ; Hepatitis B* ; Hepatitis* ; Humans ; Infant, Newborn* ; Vaccination*