• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7687-7692
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• 2014

Aim: To observe the effects of a novel all-trans retinoid acid (ATRA) derivative, N-(3-trifluoromethyl-phenyl)-retinamide (ATPR), on lung adenocarcinoma A549 cells and to explore the potential mechanism of ATPR inhibiting of A549 cell migration. Materials and Methods: The cytotoxicity of ATRA and ATPR on A549 cells was assessed using MTT assay. Wound healing assays were used to analyze the influences of ATRA, ATPR, ML-7 (a highly selective inhibitor of myosin light chain kinase (MLCK)), PMA (an activator of MAPKs) and PD98059 (a selective inhibitor of ERK1/2) on the migration of A549 cells. Expression of MLCK and phosphorylation of myosin light chain (MLC) were assessed by Western blotting. Results: ATRA and ATPR inhibited the proliferation of A549 cells in a dose- and time-dependent manner, and the effect of ATPR was much more remarkable compared with ATRA. Relative migration rate and migration distance of A549 cells both decreased significantly after treatment with ATPR or ML-7. The effect on cell migration of PD98059 combining ATPR treatment was more notable than that of ATPR alone. Moreover, compared with control groups, the expression levels of MLCK and phosphorylated MLC in A549 cells were both clearly reduced in ATRA and ATPR groups. Conclusions: ATPR could suppress the migration and invasion of A549 cells, and the mechanism might be concerned with down-regulating the expression of MLCK in the ERK-MAPK signaling pathway, pointing to therapeutic prospects in lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.65 no.2
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• pp.142-146
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• 2008

Small cell lung cancer is characterized by an aggressive clinical course and a high tendency for early dissemination in spite of a good chemotherapy response. Topotecan is a topoisomerase I inhibitor, and it is used as second-line treatment for small cell lung cancer. The reported dose-limiting adverse reactions to topotecan are mainly hematologic. Yet pulmonary toxicity associated with topotecan is known to be rare. We report here on a case that showed the development of acute respiratory distress syndrome during the 3rd cycle of topotecan chemotherapy in a patient with small cell lung cancer. He developed dyspnea and respiratory failure, and the chest CT scan revealed diffuse ground-glass opacity that was probably due to chemotherapy-related pulmonary toxicity. He finally died of acute respiratory distress syndrome.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8435-8440
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• 2014

Aims: Angiogenesis is important in malignant pleural effusion (MPE) formation and it is regulated by a number of pro- and anti-angiogenic cytokines. The purpose of this study was to evaluate the prognostic value of angiogenic factor vascular endothelial growth factor (VEGF) and angiogenesis inhibitor endostatin in lung cancer patients with MPE, and investigate the relationship between these two kinds of agent. Methods: Using enzyme-linked immunoadsorbent assay, the concentrations of VEGF and endostatin were measured in pleural effusions (PE) and serum from a total of 70 lung cancer patients with MPE and 20 patients with tuberculosis. Results: Compared to patients with tuberculosis, the levels of VEGF and endostatin in both PE and serum were significantly higher in patients with lung cancer. There were statistically significant correlations between VEGF levels in PE and serum (r=0.696, p<0.001), endostatin levels in PE and serum (r=0.310, p=0.022), and VEGF and endostatin levels in PE (r=0.287, p=0.019). Cox multivariate analysis revealed that elevated pleural VEGF and endostatin levels and serum endostatin level were independent predictors of shorter overall survival. Conclusion: Both pro- and anti-angiogenic factors are likely contributors to PE formation. Our results suggest that the levels of VEGF and endostatin in PE, together with endostatin in serum, may be potential prognostic parameters for lung cancer patients with MPE.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.1
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• pp.24-30
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• 2017

Gorham-Stout disease is a rare disorder characterized by lymphovascular proliferation and destruction of osseous matrix. The etiology of this condition remains poorly understood. Chylothorax as a consequence of lymphatic leakage in thoracic cage may cause a severe life-threatening complication, accompanying respiratory difficulty. Currently, there is no standard management for this extremely rare condition. Here we describe a patient affected by Gorham-Stout disease successfully managed by the combined treatment of mTOR inhibitor and beta-blocker. A previously healthy 11-year-old female developed dyspnea and chest pain with a massive pleural effusion. The ligation of right thoracic duct and bilateral pleurodesis temporarily decreased her pleural effusion, which was aggravated repetitively and required frequent admission and tube thoracotomies. Along with bilateral pleural adhesiolysis with thoracotomy, the combined treatment of oral beta-blocker and mTOR inhibitor was commenced. After 1 month of oral medication, her pleural effusion was not increased and she was free of respiratory difficulty on room air without chest tubes. Over eleven months of treatment, no serious adverse reaction was noted and her condition has been stable with no further admission required.

• Tuberculosis and Respiratory Diseases
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• v.61 no.2
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• pp.137-142
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• 2006

Background: Recent studies have suggested an association between chronic cough and gastroesophageal reflux. Our study aimed to assess the utility of a proton-pump inhibitor in unexplained chronic cough patients. Methods: Patients with chronic cough of unknown etiology were evaluated using a chest x-ray, methacholine challenge test, and an empirical trial of postnasal drip therapy. After excluding other potential causes of the cough, forty patients were included in the study and treated for 8 weeks with a proton-pump inhibitor. Results: Eleven and three patients in the first and second 4 weeks were lost to follow-up, leaving twenty-six patients finally included in the study. Of these patients, two were unimproved, eight partially responded to the proton-pump inhibitor and sixteen responded completely after the 8 week treatment. Conclusion: We suggest that empirical treatment with a proton pump inhibitor in all patients with persistent cough, which is not secondary to asthma or postnasal drip syndrome, represents a practical and simple approach to this ailment.

• The Journal of Internal Korean Medicine
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• v.28 no.2
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• pp.399-407
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• 2007

Angioedema is a localized transient swelling of sudden onset that can occur in the face, lips, tongue, hand, feet, respiratory system and gastrointestinal system. Angioedema is classified as allergy, hereditary, idiopathic or induced by medication as like aspirin, nonsteroidal anti-inflammatory agents, opiates, antibiotics, and angiotensin-converting enzyme. Angiotensin-converting enzyme inhibitors are widely prescribed for hypertension and heart failure. This drug is commonly associated with angioedema which may be potentially life threatening. We experienced a case of angioedema induced by ACE inhibitor (angiotensin-converting enzyme inhibitor) in a 74-year-old patient who took ACE inhibitor to control hypertension during hospitalization. We thought the angioedema in the face had relation to myenzhong (面腫, mienjong) in oriental medicine. Weiling-tang (Wiryung-tang) was effective for angioedema in the face. As a result the symptoms disappeared rapidly. After 6 days, the patient's symptoms had notably improved.

• Korean Journal of Clinical Laboratory Science
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• v.39 no.3
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• pp.249-255
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• 2007

While respiratory burst enhances neutrophil glucose utilization, many neutrophil functions are critically influenced by extracellular matrix interaction and phosphoinositide-3-OH kinase (PI3K) signaling. We thus evaluated the role of RGD integrin occupancy and PI3K inhibition on respiratory burst and [18F]FDG uptake of stimulated neutrophils. Human neutrophils were stimulated by 100 ng/mL phorbol-myristate-acetate (PMA), and respiratory burst was measured by cumulative luminescence with lucigenin. [18F]FDG uptake and total hexokinase activity was measured 20 min after PMA stimulation in the presence or absence of soluble RGD peptides (200 g/mL) and/or the PI3K inhibitor wortmannin (200 nM). PMA induced a 71.70.9 fold increase in neutrophil oxygen intermediate generation. [18F]FDG uptake was increased to $194.6{\pm} 3.7%$ and hexokinase activity to $145.0{\pm}2.0%$ of basal levels (both p<0.0005). RGD peptides attenuated respiratory burst activation to $35.6{\pm}0.2%$ (p<0.005), but did not inhibit stimulated [18F]FDG uptake or hexokinase activity. In contrast, without affecting respiratory burst activation, wortmannin inhibited PMA stimulated [18F]FDG uptake to $66.9{\pm}1.6%$ and hexokinase activity to $81.0{\pm}4.2%$ (both P<0.0005), demonstrating its dependence on PI3K activity. Neither RGD nor wortmannin reversed the other's inhibitory effect on stimulated [18F]FDG uptake and hexokinase activity or respiratory burst, which suggests the involvement of distinct signaling pathways. Neutrophil [18F]FDG uptake is enhanced by PMA through a mechanism that requires PI3K activity but is independent of integrin receptor occupancy or respiratory burst activation.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3471-3476
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• 2012

Background and Objective: Histone deacetylase (HDAC) inhibitors represent a promising class of potential anticancer agents for treatment of human malignancies. In this study, we investigated the effect of trichostatin A (TSA), one such HDAC inhibitor, in combination with docetaxel (TXT), a cytotoxic chemotherapy agent or erlotinib, a novel molecular target therapy drug, on lung cancer A549 cells. Methods: A549 cells were treated with TXT, erlotinib alone or in combination with TSA, respectively. Cell viability, apoptosis, and cell cycle distribution were evaluated using MTT (3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide) assay, Hochst33258 staining and flow cytometry. Moreover, immunofluorescent staining and Western blot analysis were employed to examine alterations of ${\alpha}$-tubulin, heat shock protein 90 (hsp90), epidermal growth factor receptor (EGFR), and caspase-3 in response to the different exogenous stimuli. Results: Compared with single-agent treatment, co-treatment of A549 cells with TSA/TXT or TSA/erlotinib synergistically inhibited cell proliferation, induced apoptosis, and caused cell cycle delay at the $G_2/M$ transition. Treatment with TSA/TXT or TSA/erlotinib led to a significant increase of cleaved caspase-3 expression, also resulting in elevated acetylation of ${\alpha}$-tubulin or hsp90 and decreased expression of EGFR, which was negatively associated with the level of acetylated hsp90. Conclusions: Synergistic anti-tumor effects are observed between TXT or erlotinib and TSA on lung cancer cells. Such combinations may provide a more effective strategy for treating human lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.62 no.2
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• pp.144-148
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• 2007

Gefitinib is an oral selective inhibitor that targets the tyrosine kinase of the epidermal growth factor receptor. The prevalence of interstitial lung disease is 2% in Japan and 0.3% in the USA with a mortality rate of up to one third. We describe two non-small cell lung cancer patients who developed acute respiratory failure after gefitinib, and suggest that clinicians take extreme caution when deciding to treat patients with gefitinib.

• Tuberculosis and Respiratory Diseases
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• v.68 no.5
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• pp.273-279
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• 2010

Background: Pulmonary hypertension is considered as a poor prognosis factor in patients with chronic obstructive pulmonary disease (COPD). There has been reported brain natriuretic peptide (pro-BNP) is related with increased right ventricular (RV) workloads. However, there are few studies that evaluate the relationship between BNP and pulmonary arterial pressure (PAP), RV function and St. George Respiratory Questionnaire (SGRQ) score in patients with COPD, and the effects of angiotensin converting enzyme inhibitor (ACEI) on these parameters. Methods: Pulmonary function test, echocardiography, blood BNP, and SGRQ score were evaluated in stabilized moderate degree COPD patients ($FEV_1$/FVC< 70%, $50%{\leq}FEV_1$ < 80%) aged 45 years and over, without worsening of symptoms within recent 3 months. After treating with ramipril 10 mg for 3 months, the same evaluation was repeated. Results: Twenty-two patients were included in this study. BNP was significantly correlated with PAP (Pearson coefficient ${\rho}=0.51$, p=0.02), but not with RV ejection fraction (EF) and predicted $FEV_1%$. The values for predicted $FEV_1%$ showed significant correlation with SGRQ total score and activity score, but not with BNP or PAP. After ramipril treatment, PAP showed significant decrease ($42.8{\pm}8.1$ vs. $34.5{\pm}4.5mm$ Hg p=0.0003), tricuspid annular plane systolic excursion significant increase ($21.5{\pm}3.3$ vs. $22.7{\pm}3.1mm$ p=0.009). BNP showed a tendency to decrease without statistical significance ($40.8{\pm}59.6$ vs. $18.0{\pm}9.1pg/mL$ p=0.55). SGRQ scores showed no significant change. Conclusion: BNP showed significant correlation with resting PAP, which means BNP could be used as markers for pulmonary hypertension. Treatment with ACEI didn't show significant change in the level of BNP, while pulmonary hypertension and RV function were improved.