Chan Kwon Park

Catholic University of Korea, Sŏul, Seoul, South Korea

Are you Chan Kwon Park?

Claim your profile

Publications (15)38.24 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and objectivePeptide nucleic acid (PNA)-mediated real-time polymerase chain reaction clamping was recently developed to improve mutation detection sensitivity. Pleural effusion could be a good sample candidate for mutation analysis. To establish if PNA clamping could be used to detect KRAS mutation in particular in pleural effusion, we analysed its diagnostic performance.Methods We studied 57 patients with malignant effusion. KRAS mutation was evaluated in samples of matched tumour tissue, cell block, pleural effusion and serum using PNA clamping and direct sequencing.ResultsThe detection rate of KRAS mutation using pleural effusion was 14% for PNA clamping and 10.5% for direct sequencing. The κ coefficient between the two methods was 0.76 (P value < 0.0001), 1.00 (P value < 0.0001) and 0.87 (P value < 0.0001) in pleural effusion, tissue and cell block, respectively. The diagnostic performance of KRAS mutation detection from pleural effusion compared with the results obtained for all samples combined showed that the sensitivity, specificity, positive predictive value and negative predictive value were as follows: 89, 100, 100 and 98%, respectively for PNA clamping; 67, 100, 100 and 94%, respectively for directing sequencing.Conclusions The current study suggests that PNA clamping had a good concordance with direct sequencing for the detection of KRAS mutation in patients with malignant effusion. Furthermore, the good diagnostic performance obtained from pleural effusion samples provides evidence that pleural effusion can be a useful source for detecting KRAS mutation in a clinical setting, in which the collection of tumour tissues is challenging.
    Respirology 11/2014; · 2.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: ABSTRACT Objective: The tyrosine kinase inhibitor nilotinib has potent inhibitory activity against the stem cell growth factor receptor c-Kit and platelet-derived growth factor receptor (PDGFR). The present study aimed to determine whether nilotinib suppresses airway remodeling and whether its effect is associated with the c-Kit and PDGFR pathways. We also aimed to compare the effect of nilotinib and imatinib on remodeling. Methods: We developed a mouse model of airway remodeling, which includes smooth muscle thickening, in which ovalbumin (OVA)-sensitized mice were repeatedly exposed to intranasal OVA administration twice a week for 3 months. Mice were treated with nilotinib or imatinib during the OVA challenge. Results: Compared with control mice, the mice chronically exposed to OVA developed sustained eosinophilic airway inflammation, airway hyperresponsiveness (AHR), and exhibited features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Administration of nilotinib significantly inhibited eosinophilic inflammation, AHR, and remodeling in mice chronically exposed to OVA. Nilotinib showed a trend of more potent effect than imatinib on attenuating remodeling in hydroxyproline assay and smooth muscle staining. Nilotinib treatment significantly reduced the expression of phosphorylated (p)-c-Kit, p-PDGFRβ, and p-extracellular signal-regulated kinase 1/2. The expression levels of the genes encoding c-Kit and PDGFRβ were also reduced by nilotinib treatment. Treatment with nilotinib did not affect significantly the level of OVA-specific IgE and IgG1 in serum. In vitro, nilotinib significantly inhibited cell proliferation of fibroblast. Conclusions: These results suggest that nilotinib administration can prevent airway inflammation, AHR, and airway remodeling associated with chronic allergen challenge.
    Experimental Lung Research 05/2014; · 1.47 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Simultaneous genotyping has advantages in turnaround time and detecting the real mutational prevalence in unresectable non-small-cell lung cancer (NSCLC), a group not previously genetically characterized.Methods We developed simultaneous panel of screening EGFR and KRAS mutations by direct sequencing or PNA clamping, and ALK rearrangement by fluorescent in situ hybridization (FISH) in multicenter manner.ResultsOf 510 NSCLC Korean patients, simultaneous genotyping identified mutations of EGFR (29.0%) and KRAS (8.6%) and rearrangement of ALK (9.2%). Seven patients had overlaps in mutations. Although several well-known associations between genotypes and clinical characteristics were identified, we found no relationship between ALK rearrangement and sex or smoking history. Unlike the other genotype mutations, ALK rearrangement was associated with advanced disease. Among the ALK-negative group, patients with 10–15% of ALK FISH split shared characteristics, such as younger age and advanced stage disease, more with the ALK-positive group (>15% ALK FISH split) than <10% ALK FISH split group.Conclusions Simultaneous panel genotyping revealed more prevalent ALK rearrangements than reported in previous studies and their strong association with advanced stage irrespective of sex or smoking history. ALK rearrangement seems to be a marker for aggressive tumor biology and should be assessed in advanced disease. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 05/2014; · 2.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Conventional biomarkers cannot always establish the cause of pleural effusions; thus, alternative tests permitting rapid and accurate diagnosis are required. The primary aim of this study is to assess the ability of pentraxin-3 (PTX3) in order to diagnose the cause of pleural effusion and compare its efficacy to that of other previously identified biomarkers. We studied 118 patients with pleural effusion, classified as transudates and exudates including malignant, tuberculous, and parapneumonic effusions (MPE, TPE, and PPE). The levels of PTX3, C-reactive protein (CRP), procalcitonin (PCT) and lactate in the pleural fluid were assessed. The levels of pleural fluid PTX3 were significantly higher in patients with PPE than in those with MPE or TPE. PTX3 yielded the most favorable discriminating ability to predict PPE from MPE or TPE by providing the following: area under the curve, 0.74 (95% confidence interval, 0.63-0.84), sensitivity, 62.07%; and specificity, 81.08% with a cut-off point of 25.00 ng/mL. Our data suggests that PTX3 may allow improved differentiation of PPE from MPE or TPE compared to the previously identified biomarkers CRP and PCT.
    Tuberculosis and Respiratory Diseases 12/2013; 75(6):244-9.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Lower respiratory tract infection is one of the most common infectious diseases. However, conventional methods for detecting infectious pathogens are time-consuming, and generally have a limited impact on early therapeutic decisions. We previously reported a rapid and sensitive method for detecting such pathogens using stuffer-free multiplex ligation-dependent probe amplification coupled with high-resolution CE-SSCP. In this study, we report an application of this method to the detection of respiratory pathogens. As originally configured, this method was capable of simultaneously detecting seven bacterial species responsible for lower respiratory tract infections, but its detection limit and assay time were insufficient to provide useful information for early therapeutic decisions. To improve sensitivity and shorten assay time, we added a target-specific preamplification step, improving the detection limit from 50 pg of genomic DNA to 500 fg. We further decreased time requirements by optimizing the hybridization step, enabling the entire assay to be completed within 7 h while maintaining the same detection limit. Taken together, these improvements enable the rapid detection of infectious doses of pathogens (i.e. a few dozen cells), establishing the strong potential of the refined method, particularly for aiding early treatment decisions.
    Electrophoresis 11/2013; · 3.26 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although the relationship between malignancy risk with systemic sclerosis (SSc) has been inconclusive, there are some previous studies for a positive correlation. Most patients with SSc have some degree of lung parenchymal involvement in the form of interstitial thickening and fibrosis. Interstitial lung disease is the most common pulmonary manifestation of SSc. Interstitial lung disease following chemotherapy (5-fluorouracil, leucovorin, and oxaliplatin [FOLFOX]) is an uncommon life-threatening complication and it is induced by oxaliplatin. We report a case of multiple cancers in a patient with SSc and aggravated interstitial lung disease by chemotherapy.
    Tuberculosis and Respiratory Diseases 09/2013; 75(3):111-115.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: ABSTRACT Thrombin activates protease-activated receptor (PAR)-1 and induces a myofibroblast phenotype in normal lung fibroblasts. The origins of myofibroblasts are resident fibroblasts, fibrocytes, and epithelial-mesenchymal transition (EMT). We investigated the effects of thrombin, an important mediator of interstitial lung fibrosis, on EMT in A549 human alveolar epithelial cells. We show that thrombin induced EMT and collagen I secretion through the activation of PAR-1, and PKC and ERK1/2 phosphorylation in A549 cells. These effects were largely prevented by a specific PAR-1 antagonist, short interfering RNA (siRNA) directed against PAR-1, or specific PKCα/β, δ, and ε inhibitors. These data indicated that interaction with thrombin and alveolar epithelial cells might directly contribute to the pathogenesis of pulmonary fibrosis through EMT. Targeting PAR-1 on the pulmonary epithelium or specific inhibitors to PKCα/β, δ, and ε might stop the fibrotic processes in human idiopathic pulmonary fibrosis by preventing thrombin-induced EMT.
    Experimental Lung Research 08/2013; · 1.47 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Peptide nucleic acid (PNA)-mediated real-time PCR clamping has higher sensitivity than conventional direct sequencing for detecting mutations. Pleural effusion and serum may provide good samples in which to detect epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) patients. We studied 37 NSCLC patients with malignant pleural effusion. EGFR mutations were assessed by PNA clamping and direct sequencing using tumor tissues, cell blocks, pleural effusion, and serum. Concordance between PNA clamping and direct sequencing results, and the diagnostic performance of pleural effusion were investigated. The κ coefficients for the two methods were 0.68 (p=0.0007), 0.91 (p<0.0001), 0.75 (p<0.0001) and -0.01 (p=0.8639) for tissues, cell blocks, pleural effusion, and serum, respectively. The diagnostic performance of pleural effusion compared with the combination of tumor tissue and cell blocks showed 89% sensitivity, 100% specificity, positive predictive value of 100%, and negative predictive value of 95% by PNA clamping, and 67% sensitivity, 90% specificity, positive predictive value of 75%, and negative predictive value of 86% by directing sequencing. A patient in whom an EGFR mutation was identified in pleural effusion only by PNA clamping showed a significant response to EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment. In contrast to the limited role of serum samples, pleural effusion had a diagnostic performance for the detection of EGFR mutations in NSCLC that was comparable to that of tumor tissues and cell blocks. The diagnostic performance of PNA clamping was good compared with that of direct sequencing. A more sensitive and accurate detection of EGFR mutations would benefit patients by allowing a better prediction of the response to EGFR-TKI treatment.
    Lung cancer (Amsterdam, Netherlands) 05/2013; · 3.14 Impact Factor
  • Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 01/2013; 8(1):126-7. · 4.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Oral tolerance (OT) is considered as a preventive and therapeutic strategy for treating asthma and allergic rhinitis (AR). We investigated the preventive effects of OT on allergic inflammation and remodeling in the upper and lower airways in a mouse model of allergy. BALB/c mice were divided into four groups: control, allergy, low-dose OT, and high-dose OT. To induce OT, mice were fed ovalbumin (OVA) before sensitization with OVA/Al(OH)(3) at a dose of 1 mg for 6 days in low-dose OT group and a single dose of 25 mg in high-dose OT group. After sensitization followed by OVA challenge, nasal symptoms, interleukin (IL)-13, interferon (IFN)-gamma, IL-10, and transforming growth factor (TGF) beta-1 levels in nasal lavage (NAL) and bronchoalveolar lavage (BAL) fluids were measured, and OVA-specific IgE, IgG1, and IgG2a levels were measured in the serum. The airway hyperresponsiveness (AHR) was measured by enhanced pause. The goblet cell hyperplasia and the thickness of lamina propria were observed in the upper and lower airways. In the allergy group, the allergic behavior scores, AHR, and OVA-specific IgE, IgG1, and IgG2a levels; inflammatory cells; IFN-gamma levels; and IL-13 levels in NAL/BAL fluids were elevated compared with the control group, low-dose OT group, and high-dose OT group. The allergy group had higher levels of IL-10 and TGF-beta-1 in BAL fluids when compared with the other groups. The goblet cell hyperplasia and the thickness of the lamina propria were attenuated in both OT groups compared with the allergy group. OT may effectively prevent AHR, allergic inflammation, and airway remodeling in the upper and lower airways.
    American Journal of Rhinology and Allergy 01/2013; 27(1):11-6.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Direct sequencing remains the most widely used method for the detection of epidermal growth factor receptor (EGFR) mutations in lung cancer; however, its relatively low sensitivity limits its clinical use. The objective of this study was to investigate the sensitivity of detecting an epidermal growth factor receptor (EGFR) mutation from peptide nucleic acid-locked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamp and Ion Torrent Personal Genome Machine (PGM) techniques compared to that by direct sequencing. Furthermore, the predictive efficacy of EGFR mutations detected by PNA-LNA PCR clamp was evaluated. EGFR mutational status was assessed by direct sequencing, PNA-LNA PCR clamp, and Ion Torrent PGM in 57 patients with non-small cell lung cancer (NSCLC). We evaluated the predictive efficacy of PNA-LNA PCR clamp on the EGFR-TKI treatment in 36 patients with advanced NSCLC retrospectively. Compared to direct sequencing (16/57, 28.1%), PNA-LNA PCR clamp (27/57, 47.4%) and Ion Torrent PGM (26/57, 45.6%) detected more EGFR mutations. EGFR mutant patients had significantly longer progressive free survival (14.31 vs. 21.61 months, P = 0.003) than that of EGFR wild patients when tested with PNA-LNA PCR clamp. However, no difference in response rate to EGFR TKIs (75.0% vs. 82.4%, P = 0.195) or overall survival (34.39 vs. 44.10 months, P = 0.422) was observed between the EGFR mutations by direct sequencing or PNA-LNA PCR clamp. Our results demonstrate firstly that patients with EGFR mutations were detected more frequently by PNA-LNA PCR clamp and Ion Torrent PGM than those by direct sequencing. EGFR mutations detected by PNA-LNA PCR clamp may be as a predicative factor for EGFR TKI response in patients with NSCLC.
    PLoS ONE 01/2013; 8(12):e81975. · 3.53 Impact Factor
  • Chest 09/2012; 142(3):791-6. · 7.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent evidence suggests that acetylcholine acting through muscarinic receptors may play an inhibitory role in the mechanisms that drive the structural changes in the airways called airway remodeling. The novel anticholinergic drug tiotropium bromide, which selectively antagonizes muscarinic receptors, especially the M3 subtype, and is long acting, could be beneficial in attenuating airway remodeling in chronic asthma. To investigate the effect of tiotropium bromide on parameters of airway remodeling, including smooth muscle hypertrophy and peribronchial thickening, in a mouse model of chronic asthma. To develop the murine models of acute and chronic asthma, BALB/c mice were sensitized and challenged to ovalbumin for 1 and 3 months, respectively. The effect of tiotropium bromide (0.1mM in 50 μL of phosphate-buffered saline) on pulmonary inflammation and remodeling was evaluated. The expression of muscarinic receptors M2 and M3 was analyzed. In the chronic asthma model, the tiotropium-treated group significantly decreased smooth muscle thickening and peribronchial collagen deposition. As for pulmonary inflammation, the chronic asthma model had a reduction of inflammatory cells and T(H)2 cytokines by tiotropium bromide, but the effects in the asthma acute model were reversed. In the chronic asthma model, expression of the M3 receptor was inhibited and that of the M2 receptor was elevated by the administration of tiotropium bromide. This study suggests that tiotropium bromide might have an inhibitory effect on airway remodeling in a murine model of chronic asthma. Differential effects on muscarinic receptor subtypes may explain why tiotropium bromide has different effects on acute and chronic asthma.
    Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 07/2012; 109(1):29-35. · 3.45 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a lethal parenchymal lung disease characterized by myofibroblast proliferation. Alveolar epithelial cells (AECs) are thought to produce myofibroblasts through the epithelial to mesenchymal transition (EMT). Receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface receptors whose activation is associated with renal fibrosis during diabetes and liver fibrosis. RAGE is expressed at low basal levels in most adult tissues except the lung. In this study, we evaluated the interaction of ligand advanced glycation end products (AGE) with RAGE during the epithelial to myofibroblast transition in rat AECs. Our results indicate that AGE inhibited the TGF-β-dependent alveolar EMT by increasing Smad7 expression, and that the effect was abolished by RAGE siRNA treatment. Thus, the induction of Smad7 by the AGE-RAGE interaction limits the development of pulmonary fibrosis by inhibiting TGF-β-dependent signaling in AECs.
    Experimental and Molecular Medicine 07/2011; 43(9):517-24. · 2.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Asthma is characterized by airway hyperresponsiveness (AHR), inflammation and remodeling. The tyrosine kinase inhibitor imatinib mesylate was developed to inhibit BCR-ABL kinase activity; however, it also has potent inhibitory activity against the c-Kit and platelet-derived growth factor receptors. The present study aimed to determine whether imatinib suppresses airway smooth muscle (ASM) remodeling and whether its effect is associated with growth factors such as transforming growth factor (TGF)-β1 and stem cell factor (SCF). We developed a mouse model of airway remodeling, which includes smooth muscle thickening, in which ovalbumin (OVA)-sensitized mice were repeatedly exposed to intranasal OVA administration twice a week for 3 months. Mice were treated with imatinib during the OVA challenge. Mice chronically exposed to OVA developed sustained eosinophilic airway inflammation and AHR compared with control mice. In addition, the mice chronically exposed to OVA developed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Administration of imatinib significantly inhibited the development of AHR, eosinophilic inflammation and, importantly, ASM remodeling in mice chronically exposed to OVA. Imatinib treatment significantly reduced the levels of interleukin-4, -5 and -13. In addition, TGF-β1 and SCF were significantly reduced in the imatinib-treated animals. These results suggest that imatinib administration can prevent not only airway inflammation, but also airway remodeling associated with chronic allergen challenge. Imatinib may provide a clinically attractive therapy for chronic severe asthma.
    International Archives of Allergy and Immunology 02/2011; 155(3):243-51. · 2.25 Impact Factor