• Tuberculosis and Respiratory Diseases
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• v.56 no.3
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• pp.289-296
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• 2004

Background : Mucus hypersecretion in the patients with airway diseases represents poor prognosis as well as discomfort. However, there is no known therapy for its effective control. One important component of mucus is mucin, a glycosylated protein, which endows mucus with viscosity. We studied whether a proteinase has a role in mucin secretion and if so, which. Methods : (1) Inhibition of mucin secretion Group-specific proteinase inhibitors were tested to evaluate whether a proteinase belonging to a group of proteinases plays a role in mucin secretion. Phenylmethylsulfonyl fluoride(PMSF, a serine proteinase inhibitor), E-64(a cysteine proteinase inhibitor), Pepstatin(an aspartic proteinase inhibitor) and 1, 10-Phenanthroline(a metalloproteinase inhibitor) were treated into the Calu-3 cell line for 24 hours. The enzyme linked immunoabsorbant assay(ELISA) for MUC5AC was performed to evaluate the amount of mucin secretion and to compare with a control. (2) Stimulation of mucin secretion Matrix metalloproteinase-9(MMP-9), MMP-12 and TACE(TNF-alpha converting enzyme), which are known to be related with airway diseases, were used to be treated into Calu-3 for 24 hours. ELISA for MUC5AC was performed to evaluate the amount of mucin secretion and to compare with the controls. Results : (1) PMSF($10^{-4}M$), E-64($10^{-4}M$), Pepstatin($10^{-6}M$) and 1, 10-Phenanthroline($10^{-4}M$) reduced the MUC5AC secretion by $1{\pm}4.9%$(mean${\pm}$standard deviation; P=1.0 compared with the control), $-6{\pm}3.9%$(P=0.34), $-13{\pm}9.7%$(P=0.34) and $41{\pm}8.2%$(P=0.03), respectively. (2) The amounts of MUC5AC secretion stimulated by MMP-9(250ng/ml), MMP-12(100ng/ml) and TACE(200ng/ml) were $103{\pm}6%$(P=0.39), $102{\pm}8%$(P=1.0) and $107{\pm}13%$(P=0.39), respectively, compared with the controls. Conclusion : Metalloproteinase(s) is (are) suggested to play a role in mucin secretion. It appears that metalloproteinases, other than MMP-9, MMP-12 or TACE, affect the mucin secretion in this in vitro model.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.785-789
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• 2016

A key drug for treatment of EGFR mutation-positive non-small cell lung cancer is epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). While the dosage of many general anti-tumor drugs is adjusted according to the patient body surface area, one uniform dose of most TKIs is recommended regardless of body size. In many cases, dose reduction or drug cessation is necessary due to adverse effects. Disease control, however, is frequently still effective, even after dose reduction. In this study, we retrospectively reviewed the characteristics of 26 patients at Fukuoka University Hospital between January 2004 and January 2015 in whom the EGFR-TKI dose was reduced with respect to progression free survival and overall survival. There were 10 and 16 patients in the gefitinib group and the erlotinib group, respectively. The median progression-free survival in the gefitinib group and the erlotinib group was 22.4 months and 14.1 months, respectively, and the median overall survival was 30.5 months and 32.4 months, respectively. After stratification of patients by body surface area, the overall median progression-free survival was significantly more prolonged in the low body surface area (<1.45 m2) group (25.6 months) compared to the high body surface area (>1.45 m2) group (9.7 months) (p=0.0131). These results indicate that low-dose EGFR-TKI may sufficiently control disease without side effects in lung cancer patients with a small body size.

• YAKHAK HOEJI
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• v.56 no.2
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• pp.136-143
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• 2012

Type 2 Diabetes Mellitus (T2DM) is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and dietary modification. As the condition progresses, medications may be needed such as oral sulfonylurea or others. Recently, dipeptidyl peptidase 4 (DPP- 4) Inhibitor is new drug which can control blood glucose by increasing the active levels of incretin hormone in the body. However, researches have been carried out for mostly Caucasian and Japanese, not for Koreans at all. Therefore, this study was to evaluate the efficacy and safety of DPP-4 inhibitor (Sitagliptin, Vildagliptin) in patients with T2DM in Koreans. This study was carried out retrospectively with reviewing of medical records from the 141 patients who received sitagliptin or vildagliptin over 24 week periods from January 2009, to December 2009. Information including demographics, concomitant medication, disease duration, and exercise was evaluated. $HbA_{1c}$, random blood glucose, post prandial 2 hour glucose, blood pressure, AST, ALT, serum creatinine, total cholesterol, triglyceride levels were also collected at baseline and endpoint (at 24 weeks). In each post-treatment group, $HbA_{1c}$, random blood glucose and post prandial 2 hour glucose levels were decreased significantly from baseline in the sitagliptin group (-0.82%, -28.76 mg/dl, -46.65 mg/dl) and vildagliptin group(-1.22%, -27.96 mg/dl, -67.2 mg/dl). Greater $HbA_{1c}$ mean reductions from baseline to 24 weeks were seen in patients with higher baseline values (>7.0%), with shorter disease durations (${\leq}1$ year) compared with those with lower baseline values (<7.0%), with longer disease durations (>1 year) in both sitagliptin and vildagliptin groups. The incidences of hypoglycemia, headache and upper respiratory infection were 0%, 8.7%, 5.8% in sitagliptin group and 2.8%, 8.3%, 6.9% in vildagliptin group. In conclusion, our results showed DPP-4 inhibitor provided similar efficacy compared with sulfonylurea after 24 weeks of treatment and were safer than sulfonylurea in hypoglycemia for Korean T2DM. Also vildagliptin was associated with significant improvement in $HbA_{1c}$ reduction in Korean patient with subgroup (body mass index<25 $kg/m^2$, metformin dose${\geq}$1000 mg, p<0.05) compared to sitagliptin. Therefore, even though DPP-4 inhibitor use for Korean needs to be studied more consistently in the future, DPP-4 inhibitor is a safe and effective drug for Korean T2DM based on our result.

• Tuberculosis and Respiratory Diseases
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• v.70 no.3
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• pp.206-217
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• 2011

Background: Transcription factor FOXP3 characterizes the thymically derived regulatory T cells. FOXP3 is expressed by cancer cell itself and FOXP3 expression was induced by TGF-${\beta}$ treatment in pancreatic cancer cell line. However, the expression of FOXP3 expression is not well known in patients with lung cancer. This study was conducted to investigate the expression of FOXP3 in patients with lung cancer and to investigate the regulation of FOXP3 expression by the treatment of TGF-${\beta}$ and DNA methyltransferase inhibitor in lung cancer cell lines. Methods: FOXP3 expression in the tissue of patients with resected non-small cell lung cancer (NSCLC) was evaluated by immunohistochemistry. The regulation of FOXP3 expression was investigated by Western blot and RT-PCR after lung cancer cell lines were stimulated with TGF-${\beta}1$ and TGF-${\beta}2$. The regulation of FOXP3 expression was also investigated by RT-PCR and flow cytometry after lung cancer cell lines were treated with DNA methyltransferase inhibitor (5-AZA-dC). Results: FOXP3 expression was confirmed in 27% of patients with NSCLC. In NCI-H460 cell line, TGF-${\beta}2$ decreased FOXP3 mRNA and protein expressions. In A549 cell line, both TGF-${\beta}1$ and TGF-${\beta}2$ decreased FOXP3 mRNA and protein expressions. 5-AZA-dC increased FOXP3 mRNA expression in NCI-H460 and A549 cell lines. Moreover, 5-AZA-dC increased intracellular FOXP3 protein expression in A549 cell lines. Conclusion: It was shown that FOXP3 is expressed by cancer cell itself in patients with NSCLC. Treatment of TGF-${\beta}2$ and DNA methyltransferase inhibitor seems to be associated with the regulation of FOXP3 expression in lung cancer cell lines.

• Tuberculosis and Respiratory Diseases
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• v.75 no.4
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• pp.140-149
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• 2013

Background: Plasminogen activator inhibitor type 1 (PAI-1), an important regulator of plasminogen activator system which controls degradation of extracellular membrane and progression of tumor cells, and PAI-1 gene polymorphic variants have been known as the prognostic biomarkers of non-small cell lung cancer patients. Recently, experimental in vitro study revealed that transforming growth factor-${\beta}1$ initiated PAI-1 transcription through epithelial growth factor receptor (EGFR) signaling pathway. However, there is little clinical evidence on the association between PAI-1 A15T gene polymorphism and prognosis of Korean population with pulmonary adenocarcinoma and the influence of activating mutation of EGFR kinase domain. Methods: We retrospectively reviewed the medical records of 171 patients who were diagnosed with pulmonary adenocarcinoma and undergone EGFR mutation analysis from 1995 through 2009. Results: In all patients with pulmonary adenocarcinoma, there was no significant association between PAI-1 A15T polymorphic variants and prognosis for overall survival. However, further subgroup analysis showed that the group with AG/AA genotype had a shorter 3-year survival time than the group with GG genotype in patients with EGFR mutant-type pulmonary adenocarcinoma (mean survival time, 24.9 months vs. 32.5 months, respectively; p=0.015). In multivariate analysis of 3-year survival for patients with pulmonary adenocarcinoma harboring mutant-type EGFR, the AG/AA genotype carriers had poorer prognosis than the GG genotype carriers (hazard ratio, 7.729; 95% confidence interval, 1.414-42.250; p=0.018). Conclusion: According to our study of Korean population with pulmonary adenocarcinoma, AG/AA genotype of PAI-1 A15T would be a significant predictor of poor short-term survival in patients with pulmonary adenocarcinoma harboring mutant-type EGFR.

• Tuberculosis and Respiratory Diseases
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• v.59 no.5
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• pp.517-521
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• 2005

Background : The balances of the proteinases and antiproteinases system have been implicated in the pathogenesis of various exudative pleural effusions. The aim of this study was to examine the matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels in exudative pleural effusions. Methods : The study included 33 tuberculous effusions, 17 malignant, and 5 transudates. The pleural levels of MMP-1 and TIMP-1 were determined using a commercially available ELISA assay. Results : The group of tuberculous effusions showed higher pleural MMP-1 levels than the malignant and transudates. The pleural TIMP-1 levels of the tuberculous and malignant effusions were higher than the transudates. Conclusion : Elevated pleural MMP-1 and TIMP-1 levels were found in tuberculous effusions.

• Tuberculosis and Respiratory Diseases
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• v.76 no.1
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• pp.8-14
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• 2014

Non-small cell lung cancer harboring epidermal growth factor receptor (EGFR) sensitizing mutations has a distinct disease entity. Patients with this cancer have better prognosis, and frequently achieve long-term survival. EGFR-tyrosine kinase inhibitor (TKI) is the drug of choice for this cancer; but the disease inevitably progresses, after durable response. The tumor is a mixture of EGFR-TKI sensitive clones and resistant clones, regardless of their molecular mechanisms. EGFR-TKI sensitive clones are very susceptible to this drug, but rarely eradicated; so, withdrawal of the drug permits rapid regrowth of drug sensitive clones, possibly causing "disease flare." Re-administration or continuation of EGFR-TKI can effectively suppress the expansion of drug sensitive clones, even when the total tumor volume continuously increases. Chemotherapy can definitely prolong the survival of patients experiencing EGFR-TKI failure. Prospective clinical trials are warranted to compare efficacies of chemotherapeutic agents. A few retrospective studies suggested that a taxanebased regimen may be superior to others. Here, we reviewed therapeutic options and clinical evidence about this unique disease entity.

• Applied Biological Chemistry
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• v.34 no.1
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• pp.43-48
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• 1991

New quinoline compounds were designed, synthesized, and examined with submitochondria. Most compounds showed high activity against NADH-ubiquinone oxidoreductase. Inhibition activity was mainly affected by the length of the lipophilic part, regardless of bulkiness or location of a phenyl group in the side chain. The $\beta-methyl$ group was demons)rated to be the optimal functionality on the nuclei of the quinoline derivatives so 4hat either deletion or insertion of a methylene on the group eliminated its activity.

• Tuberculosis and Respiratory Diseases
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• v.71 no.3
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• pp.210-215
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• 2011

Imatinib mesylate, a selective inhibitor of BCR-ABL kinase activity, has demonstrated significant clinical efficacy in the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GISTs). It has become the standard of treatment for these diseases. Although the toxicity profile of imatinib is superior to that of interferon or other cytotoxic agents, some adverse events including edema, gastrointestinal toxicities and hematologic toxicities are commonly observed in the patients treated by imatinib. We present two cases of imatinib induced interstitial pneumonitis during the treatment of a chronic phase of CML.

• Tuberculosis and Respiratory Diseases
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• v.76 no.3
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• pp.127-130
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• 2014

The risk of dying from a pulmonary embolism (PE) is estimated to be about 30% if inotropic support is required and no cardiopulmonary arrest occurs. Fibrinolysis in massive PE is regarded as a life-saving intervention, unless there is a high risk of bleeding following the use of the fibrinolytic therapy. Rivaroxaban is an oral factor Xa inhibitor, however its anticoagulation effects before or after administration of fibrinolytics in massive PE are still unknown. Two patents were admitted: 61-year-old woman with repeated syncope, and a 73-year-old woman was admitted with dyspnea and poor oral intake. Systemic arterial hypotension with radiologic confirmation led to a diagnosis of massive PE in both patients. Rivaroxaban was administered before in one, and after firbrinolytic therapy in the other. One showed similar efficacy of rivaroxaban with currently used anticoagulants after successful fibrinolysis, and the other one without antecedent administration of the fibrinolytic agent showed unfavorable efficacy of rivaroxaban.