Biomedical subjects

Jae Jeong Shim

Publications and source records attributed to Jae Jeong Shim.

16 recordsLinked to original sources

PubMed2006

Phase II study of irinotecan plus cisplatin with concurrent radiotherapy for the patients with limited-disease small-cell lung cancer.

BACKGROUND: A recently conducted randomized, phase III study that compared irinotecan plus cisplatin (IP) with etoposide plus cisplatin for the patients with extensive disease SCLC revealed a superior median survival rate and a superior 2-year survival rate for the IP combination therapy. Yet there have been few such reports on the patients suffering with limited disease SCLC (LD-SCLC). We conducted a phase II trial to evaluate the efficacy and toxicity of administering IP with concurrent radiotherapy for the patients with LD-SCLC. PATIENTS AND METHODS: Twenty chemotherapy-naïve patients with LD-SCLC were enrolled in our study. The patients were treated with 40 mg/m(2) irinotecan on days 1, 8 and 15 and with 60 mg/m(2) cisplatin on day 1 every 4 weeks until a maximum of six cycles was delivered. Once-daily radiotherapy included the administration of 50.4 Gy in 28 fractions. After completion of the radiation therapy, the dose of irinotecan was increased to 60 mg/m(2). RESULTS: The response rate was 85% (CR: 6; partial response, PR: 11). The median survival was 20.0 months (95% CI: 15.6-24.4 months) with 1-year and 2-year overall survival rates of 85 and 35%, respectively. The median progression free survival (PFS) was 12 months (95% CI: 6.2-18.1 months) with a 1-year PFS of 36%. The major hematologic toxicities of this regimen were neutropenia (60%), leukopenia (55%), anemia (20%) and thrombocytopenia (10%). The non-hematologic toxicities were nausea/vomiting (55%), diarrhea (35%) and dysphagia (15%). CONCLUSIONS: Our data show that IP with concurrent radiotherapy is an effective and tolerable regimen for the treatment of LD-SCLC and these findings warrant further investigation.

Adolescent↗

PubMed2006

Inhibition of matrix metalloproteinase-9 prevents neutrophilic inflammation in ventilator-induced lung injury.

Neutrophils are considered to play a central role in ventilator-induced lung injury (VILI). However, the pulmonary consequences of neutrophil accumulation have not been fully elucidated. Matrix metalloproteinase-9 (MMP-9) had been postulated to participate in neutrophil transmigration. The purpose of this study was to investigate the role of MMP-9 in the neutrophilic inflammation of VILI. Male Sprague-Dawley rats were divided into three groups: 1) low tidal volume (LVT), 7 ml/kg of tidal volume (VT); 2) high tidal volume (HVT), 30 ml/kg of VT; and 3) HVT with MMP inhibitor (HVT+MMPI). As a MMPI, CMT-3 was administered daily from 3 days before mechanical ventilation. Degree of VILI was assessed by wet-to-dry weight ratio and acute lung injury (ALI) scores. Neutrophilic inflammation was determined from the neutrophil count in the lung tissue and myeloperoxidase (MPO) activity in the bronchoalveolar lavage fluid (BALF). MMP-9 expression and activity were examined by immunohistochemical staining and gelatinase zymography, respectively. The wet-to-dry weight ratio, ALI score, neutrophil infiltration, and MPO activity were increased significantly in the HVT group. However, in the HVT+MMPI group, pretreatment with MMPI decreased significantly the degree of VILI, as well as neutrophil infiltration and MPO activity. These changes correlated significantly with MMP-9 immunoreactivity and MMP-9 activity. Most outcomes were significantly worse in the HVT+MMPI group compared with the LVT group. In conclusion, VILI mediated by neutrophilic inflammation is closely related to MMP-9 expression and activity. The inhibition of MMP-9 protects against the development of VILI through the downregulation of neutrophil-mediated inflammation.

Animals↗

PubMed2006

Peroxisome proliferator-activated receptor-gamma inhibits cigarette smoke solution-induced mucin production in human airway epithelial (NCI-H292) cells.

The main etiologic factor for chronic bronchitis is cigarette smoke. Exposure to cigarette smoke is reported to induce goblet cell hyperplasia and mucus production. Mucin synthesis in airways has been reported to be regulated by the EGFR system. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the ligand-activated nuclear receptor superfamily. PPAR-gamma is implicated in anti-inflammatory responses, but mechanisms underlying these varied roles remain ill-defined. Recently, reports have shown that upregulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) might be one of the mechanisms through which PPAR-gamma agonists exert their anti-inflammatory actions. However, no data are available on the role of PPAR-gamma in smoke-induced mucin production. In this study, we investigated the effect of PPAR-gamma agonist (rosiglitazone) on smoke-induced mucin production in NCI-H292 cells. Exposure to cigarette smoke causes a significant decrease in PTEN expression and increases dose-dependent EGFR-specific tyrosine phosphorylation, resulting in MUC5AC mucin production in NCI-H292 cells. PPAR-gamma agonists or specific inhibitors of phosphoinositide 3-kinase exert inhibition of cigarette smoke-induced mucin production, with the upregulation of PTEN signaling and downregulation of Akt expression. This study demonstrates that PPAR-gamma agonist functions as a regulator of epithelial cell inflammation that may result in reduction of mucin-producing cells in airway epithelium.

Carcinoma, Mucoepidermoid↗

PubMed2006

Successful removal of a slowly growing mediastinal cavernous haemangioma after vascular embolization.

Mediastinal haemangioma is a rare disease. We report a 23-year-old male patient with a posterior mediastinal cavernous haemangioma. The CXR revealed a progressively enlarging mediastinal mass which on chest CT and angiography appeared to be a well-enhanced hypervascular tumour. Angiographic gel foam embolization of the feeding vessels was undertaken prior to the surgical removal of the mass. The mass lesion following surgical removal was shown to be a cavernous haemangioma on histological examination.

Adult↗

PubMed2005

PPAR-gamma agonist increase gefitinib's antitumor activity through PTEN expression.

Gefitinib exhibits antitumor activity in patient with non-small cell lung cancer (NSCLC). However, only 10-20% of patients exhibit clinical response to this drug. The molecular mechanisms underlying gefitinib sensitivity remain unknown. Peroxisome proliferators-activated receptor-gamma (PPAR-gamma) plays roles in the regulation of cellular differentiation and growth. This regulation was mediated by increasing Phosphatase and tensin homologue deleted on chromosome Ten (PTEN) levels. PTEN plays a role in the modulation of the phosphatidylinositol 3-kinase pathway (PI3K), which is involved in cell proliferation and survival. This study investigated the effects of PPAR-gamma agonist (rosiglitazone) on the expression of PTEN, as well as EGFR tyrosine kinase inhibitor (gefitinib)'s antitumor activity in A549 cells. The treatment of A549 cells with rosiglitazone reduced the growth of A549 cells in a dose-dependent manner, and facilitated the anti-proliferative effects of gefitinib. PPAR-gamma and PTEN expression were found to have increased in the gefitinib- and rosiglitazone-treated cells. This suggests that PPAR-gamma agonist (rosiglitazone) potentiated gefitinib's anti-proliferative effects by increased of PTEN expression, and suggest that PPAR-gamma ligands may serve as potential therapeutic agents for NSCLC.

Antineoplastic Agents↗

PubMed2005

The inhibitory effects of rebamipide on cigarette smoke-induced airway mucin production.

Cigarette smoke may be the main cause of chronic bronchitis. Exposure of cigarette smoke induces the recruitment of inflammatory cells in the airway epithelium, and release of the tumor necrosis factor alpha (TNFalpha) from airways. Previous reports have shown that cigarette smoke induces goblet cell metaplasia by activating an epidermal growth factor receptor (EGFR) cascade, and that this results in mucin production. Rebamipide (2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid, OPC-12759) directly inhibits the production of superoxide (O2-) and inhibits proinflammatory cytokines (such as TNFalpha and IL-8). In the present study, we aimed to analyze the inhibitory effects of rebamipide on TNFalpha and EGFR activation after cigarette smoke treatment in vitro and in vivo. NCl-H292 cells and Sprague-Dawley rats were used for in vitro and in vivo studies. In vitro studies, cigarette smoke solution was found to increase TNFalpha secretion, and EGFR-specific tyrosine phosphorylation, and to elevate MUC5AC production. These effects were inhibited dose-dependently by pretreatment with rebamipide (MUC5AC protein levels were inhibited from 44% to 17%, P<0.05). In vivo studies, cigarette smoke was found to cause inflammatory cell recruitment and to increase the secretion of TNFalpha in bronchoalveolar lavage (BAL) fluids (from 198+/-78 to 2270+/-158 pg/ml, P<0.01). Moreover, the pretreatment of rats with rebamipide inhibited goblet cell metaplasia and TNFalpha secretion, dose-dependently (from 2270+/-158 to 1377+/-112 pg/ml, P<0.05). In conclusion, the exposure of airway epithelium to cigarette smoke-induced TNFalpha production, neutrophil recruitment, activated EGFR, and caused MUC5AC mucin synthesis. Moreover, rebamipide was found to prevent this cigarette smoke-induced TNFalpha release, and mucin production.

Alanine↗

PubMed2005

Prevalence of chronic obstructive pulmonary disease in Korea: a population-based spirometry survey.

RATIONALE: Although chronic obstructive pulmonary disease is a leading cause of mortality and morbidity worldwide, there are only limited data on its prevalence, especially in Asia. OBJECTIVES: A population-based epidemiologic survey of chronic obstructive pulmonary disease in a representative national sample was conducted using spirometry. METHODS: A stratified multistage clustered probability design was used to select a nationally representative sample. The survey was performed in conjunction with the second Korean National Health and Nutrition Examination Survey of 9,243 adults over the age of 18 years. The participation rate was 88.8% for questionnaires and 52.1% for spirometry. RESULTS: The prevalence of chronic obstructive pulmonary disease based on Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (a ratio of FEV1 to FVC of less than 0.7) was 17.2% (men, 25.8%; women, 9.6%) among subjects older than 45 years. Among adults of all ages (age>18 years), the prevalence of airflow obstruction was 7.8% (10.9% in men, 4.9% in women). The majority of these cases were found to be mild in degree, and only a minority of these subjects had received physician diagnosis or treatment. Multivariate analysis revealed that age over 65 years, male sex, smoking more than 20 pack-years, and low income were independent predictors for chronic obstructive pulmonary disease. CONCLUSIONS: Seventeen percent of Korean adults over the age of 45 years have mild chronic obstructive pulmonary disease.

Aged↗

PubMed2005

Behçet disease complicated by diffuse alveolar damage.

We report an extremely rare case of Behçet disease complicated by diffuse alveolar damage, which was fatal in this patient. It manifested as progressive diffuse ground-glass attenuation in both lungs on chest radiographs and high-resolution CT. Ground-glass attenuation was confirmed histopathologically as diffuse alveolar damage without identified etiology by open lung biopsy.

Behcet Syndrome↗

PubMed2005

[Expression of epidermal growth factor receptor, ErbB2 and matrix metalloproteinase-9 in hepatolithiasis and cholangiocarcinoma].

BACKGROUND/AIMS: Hepatolithiasis is a common disease in East Asia and presents as a histological feature of proliferative glands containing mucin. 5-10% of hepatolithiasis is known to be associated with cholangiocarcinoma. Recent studies reported that epidermal growth factor receptor (EGFR) could be activated through heparin binding- EGF cleavage by metalloproteinases. Matrix metalloproteinases (MMPs) which digest the extracellular matrix are required for cancer cell invasion and the expression of MMP-9 is known to be increased in cholangiocarcinoma. However, there has been few studies on the expressions and roles of EGFR and MMP in hepatolithiasis. This study was performed to clarify and compare the expressions of EGFR, erbB2 and MMP-9 in hepatolithiasis and cholangiocarcinoma. METHODS: Surgically resected liver tissues with hepatolithiasis (n = 14), cholangiocarcinoma (n = 20) and trauma (n = 2 as controls) were included. The expressions of EGFR, erbB2 and MMP-9 in tissue samples were examined by immunohistochemistry using respective monoclonal antibodies. RESULTS: In traumatic livers, the expressions of EGFR, erbB2 and MMP-9 were all negative. The expression of EGFR was increased in hepatolithiasis group (79%, 11/14) compared with cholangiocarcinoma group (25%, 5/20) (p < 0.05). The expression of erbB2 was detected only in cholangiocarcinoma (25%, 5/20). MMP-9 was increased in both hepatolithiasis (79%, 11/14) and cholangiocarcinoma (95%, 19/20) (p > 0.05). CONCLUSIONS: EGFR expression appears to be the dominant component in periductular hyperplasia of hepatolithiasis and MMP-9 is upregulated not only in cholangiocarcinoma but also in hepatolithiasis. This study suggests that EGFR and MMP-9 are associated with cholangiocarcinoma and hepatolithiasis.

Adult↗

PubMed2004

Effects of matrix metalloproteinase inhibitor on LPS-induced goblet cell metaplasia.

Bacterial infections of the lung are known to induce inflammatory responses, which lead to mucus hypersecretion. Moreover, mucin synthesis in the airways has been reported to be regulated by neutrophilic inflammation-induced epidermal growth factor receptor (EGFR) expression and its activation. Furthermore, matrix metalloproteinases (MMPs), especially MMP-9, have been reported to promote the transmigration of activated neutrophils. In this study, we investigated the associations between lipopolysaccharide (LPS)-induced goblet cell (GC) metaplasia and EGFR expression and the effects of MMP inhibitor (MMPI). Various concentrations of LPS were instilled into the tracheas of pathogen-free Sprague-Dawley rats, and airways were examined at different times after LPS instillation. To examine the role of MMP-9, we treated rats 3 days before LPS instillation and daily thereafter with MMPI. Neutrophilic infiltration, Alcian blue/periodic acid-Schiff (AB/PAS) staining, and immunohistochemical staining for MUC5AC, EGFR, and MMP-9 were performed. The instillation of LPS increased AB/PAS and MUC5AC staining in time- and dose-dependent manners, and treatment with MMPI significantly prevented GC metaplasia. The instillation of LPS into the trachea also induced neutrophilic infiltration and EGFR and MMP-9 expression in the airway epithelium, and MMPI was found to significantly prevent neutrophil recruitment, GC metaplasia, and EGFR and MMP-9 expression. This study demonstrates that the MMP-9 and EGFR cascades are associated with LPS-induced mucus hypersecretion.

Animals↗

PubMed2003

Prevalence and correlates of airway obstruction in a community-based sample of adults.

BACKGROUND: Virtually all the information available on the prevalence of obstructive airway disease is from Western countries. There are no data from Korea, and reports from other regions of Asia are poorly documented. OBJECTIVES: To evaluate the prevalence and correlates of airway obstruction in a community-based setting in Korea. DESIGN: A cross-sectional, population-based study. SETTING: Ansan City, near Seoul, South Korea. PARTICIPANTS: A sample of 1,160 community-dwelling men and women aged >or= 18 years (73.1% of the men and 4.1% of the women were either current or former smokers). MEASUREMENTS: Subjects underwent physical examinations following a standardized protocol. Data on demographic and health-related factors also were collected. Pulmonary function testing was administered according to American Thoracic Society (ATS) recommendations. RESULTS: The prevalence of airway obstruction was 10.3% (men, 17%; women, 5.6%) by ATS criteria. Ninety percent of the cases of airway obstruction were mild in degree. Twenty percent of male current smokers had airway obstruction. After adjusting for age, gender, and alcohol consumption, the odds of disease was 3.2 times greater in subjects who had smoked for >or= 20 pack-years vs never smokers (95% confidence interval [CI], 1.7 to 6.2). The adjusted odds of disease were 4.3-fold higher in subjects >or= 45 years of age vs those who were younger (95% CI, 2.6 to 7.0). CONCLUSIONS: Since airway obstruction is strongly related to age and smoking, the prevalence of obstructive airway disease in countries like Korea, where the population is rapidly aging and cigarette smoking is on the rise among younger individuals (particularly among women), can be expected to increase. Further efforts to diagnose early obstructive airway disease and to prevent or delay its onset should be emphasized as a major public health concern.

Adolescent↗

PubMed2003

[Expression of MUC3, MUC5AC, MUC6 and epidermal growth factor receptor in gallbladder epithelium according to gallstone composition].

BACKGROUND/AIMS: Gallbladder (GB) mucin is one of the key factors in the gallstone formation. However, there is little information about the diversity of mucin secretion according to the stone composition. Epidermal growth factor receptor (EGFR) functions in proliferation including mucin secreting goblet cell hyperplasia. We compared the expressions of MUC3, MUC5AC, MUC6 and EGFR in the GB epithelium with cholesterol gallstones (GB-chol) group and pigment gallstones (GB-pig group). METHODS: GBs from elective laparoscopic cholecystectomy for the gallstone disease were studied. Stone composition was analyzed by the spectrophotometer. Immunohistochemical stain was performed using each monoclonal antibody. The percentage of stained proportion was scored by the NIH image program and the results were compared between both groups. RESULTS: Total 20 patients were enrolled (10 patients with cholesterol gallstones, 10 patients with pigment gallstones). The percentages of stained proportion for MUC3, MUC5AC, and MUC6 were 42 +/- 27%, 31 +/- 15%, and 17 +/- 9%, respectively in GB-chol group and 32 +/- 22%, 33 +/- 23%, and 15 +/- 10%, respectively in GB-pig group (p>0.05). The expression of EGFR was 50% (5/10) in the GB-chol group and 80% (8/10) in the GB-pig group respectively. CONCLUSIONS: There was no difference in the expressions of MUC3, MUC5AC, and MUC6 between the two groups. Further studies are needed to elucidate the role of EGFR in the gallstone formation.

Bile Pigments↗

PubMed2002

Utility of polymerase chain reaction for detecting Mycobacterium tuberculosis in specimens from percutaneous transthoracic needle aspiration.

PURPOSE: To determine the clinical utility of polymerase chain reaction (PCR) for detecting Mycobacterium tuberculosis in specimens from percutaneous transthoracic needle aspiration (PTNA). MATERIALS AND METHODS: PCR for M tuberculosis detection in specimens from PTNA was performed prospectively in addition to cytologic and histologic analyses in 45 patients. On computed tomographic (CT) scans, tuberculosis (TB) versus malignant neoplasm or other infection was diagnosed in 28 patients; possible malignancy was diagnosed in 11, but TB was considered clinically because of young patient age or presence of tuberculous lesions in other areas of the lungs. In six of these patients, TB was diagnosed, but bacteriologic results were negative. PTNA was performed with a 21-gauge needle by one chest radiologist by using CT (n = 25), ultrasonographic (n = 5), or fluoroscopic guidance (n = 15). Final diagnoses were malignant neoplasm (n = 19), hamartoma (n = 1), TB (n = 17), and pneumonia (including actinomycosis and aspergillosis) (n = 8). Sensitivity, specificity, and positive predictive values of PCR in PTNA specimens for diagnosis of TB were calculated. RESULTS: In 17 patients with TB, PCR results were positive in 11 and negative in six. PCR results were negative in all cases of malignant neoplasm, hamartoma, and pneumonia. Cytologic and histologic analysis of PTNA specimens resulted in a specific diagnosis of TB in two (12%) of 17 patients. By adding the PCR results, diagnosis of TB was established in 12 (71%) of 17 patients. Sensitivity, specificity, and positive and negative predictive values of PCR for diagnosis of TB in PTNA specimens were 65% (11 of 17), 100% (28 of 28), 100% (11 of 11), and 82% (28 of 34), respectively. CONCLUSION: PCR for detection of M tuberculosis in PTNA specimens is a useful adjuvant to cytologic and histologic analysis for diagnosis of TB.

Adult↗

PubMed2002

IL-13-induced Clara cell secretory protein expression in airway epithelium: role of EGFR signaling pathway.

Previous work showed that the Th2 cytokine interleukin (IL)-13 induces goblet cell metaplasia via an indirect mechanism involving the expression and subsequent activation of epidermal growth factor receptor (EGFR). Because Clara cell secretory protein (CCSP) expression has been reported in cells that express mucins, we examined the effect of IL-13 on CCSP gene and protein expression in pathogen-free rat airways and in pulmonary mucoepidermoid NCI-H292 cells. Intratracheal instillation of IL-13 induced CCSP mRNA in epithelial cells without cilia within 8-16 h, maximal between 24 and 48 h; CCSP immunostaining increased in a time-dependent fashion, maximal at 48 h. The CCSP immunostaining was localized in nongranulated secretory cells and goblet cells and in the lumen. Pretreatment with the selective EGFR tyrosine kinase inhibitor BIBX1522, cyclophosphamide (an inhibitor of bone marrow leukocyte mobilization), or a blocking antibody to IL-8 prevented CCSP staining. Treatment of NCI-H292 cells with the EGFR ligand transforming growth factor-alpha, but not with IL-13 alone, induced CCSP gene and protein expression. Selective EGFR tyrosine kinase inhibitors, BIBX1522 and AG1478, prevented CCSP expression in NCI-H292 cells, but the platelet-derived growth factor receptor tyrosine kinase inhibitor AG1295 had no effect. These findings indicate that IL-13 induces CCSP expression via an EGFR- and leukocyte-dependent pathway.

Animals↗

PubMed2002

Association of asthma severity and bronchial hyperresponsiveness with a polymorphism in the cytotoxic T-lymphocyte antigen-4 gene.

OBJECTIVES: Cytotoxic T-lymphocyte antigen (CTLA)-4 is a homolog of CD28, which is expressed only on activated T cells. It binds to accessory molecule B7 and mediates T-cell-dependent immune response. Signaling through CTLA-4 may down-regulate type 1 T-helper cell proliferation; moreover, some studies suggest that CTLA-4 might also deliver a positive signal to type 2 T-helper cell activation. Disruption of this delicate balance of immune regulation may lead to autoimmune diseases or atopic diseases. To evaluate the possible role of CTLA-4 polymorphisms in bronchial asthma, we investigated the association between polymorphisms (exon 1 +49 A/G, promoter -318 C/T) and atopy, asthma severity, and bronchial hyperresponsiveness in bronchial asthma patients and a group of healthy control subjects. PATIENTS: Eighty-eight asthmatic patients and 88 healthy control subjects were studied. MEASUREMENTS AND RESULTS: Asthma severity assessment, methacholine challenge, allergy skinprick test, and serum total IgE measurements were performed. The genotypes of the CTLA-4 promoter (-318 C/T) and exon 1 (+49 A/G) in all subjects were determined using the polymerase chain reaction and restriction fragment length polymorphism. The CTLA-4 promoter (-318 C/T) polymorphism was shown to be associated with asthma severity, but not with asthma, atopy, or bronchial hyperresponsiveness. A significant association was found between severe asthma and the T allele (p = 0.037). The CTLA-4 exon 1 (+49 A/G) polymorphism was shown to be associated with bronchial hyperresponsiveness, but not with asthma, atopy, or asthma severity. Asthmatic patients of the GG genotype had more hyperresponsive airways than those with the AG or AA genotype (p = 0.019). CONCLUSIONS: The CTLA-4 promoter (-318 C/T) T allele may serve as a clinically useful marker of severe asthma. The CTLA-4 exon 1 (+49 A/G) polymorphism may have a disease-modifying effect in asthmatic airways.

Abatacept↗

PubMedDate not supplied

Substance P-immunoreactive nerves in endobronchial biopsies in cough-variant asthma and classic asthma.

BACKGROUND: Unlike classic asthma, cough-variant asthma does not show any evidence of airway obstruction. The main symptom is a dry cough with little known pathophysiology. Hypersensitivity of the cough receptors in cough-variant asthma and an increase in the sensory nerve density of the airway epithelium in persistent dry cough patients have been reported. Therefore, it is possible that there is a higher sensory nerve density in cough-variant asthma patients than in classic asthma patients. OBJECTIVES: This study was undertaken to compare the substance P (SP)-immunoreactive nerve density in mucosal biopsies of cough-variant asthma patients, classic asthma patients, and in control subjects. METHODS: Bronchoscopic biopsies were performed in 6 cough-variant asthma patients, 14 classic asthma patients, and 5 normal controls. The tissues obtained were stained immunohistochemically. The SP-immunoreactive nerve density was measured in the bronchial epithelium using a light microscope at 400 x magnification. RESULTS: SP- immunoreactive nerve density for the cough-variant asthma group was significantly higher than that of the classic asthma group (p = 0.001), and of the normal control group (p = 0.006). CONCLUSIONS: It is possible that a sensory nerve abnormality within the airway may be related to hypersensitivity of the cough receptor, and that this may be one of the pathophysiologies of cough-variant asthma.

Adult↗