Young Whan Kim

Pusan National University, Tsau-liang-hai, Busan, South Korea

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Publications (205)551.51 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background/aims: In assigning patients with chronic obstructive pulmonary disease (COPD) to subgroups according to the updated guidelines of the Global Initiative for Chronic Obstructive Lung Disease, discrepancies have been noted between the COPD assessment test (CAT) criteria and modified Medical Research Council (mMRC) criteria. We investigated the determinants of symptom and risk groups and sought to identify a better CAT criterion. Methods: This retrospective study included COPD patients seen between June 20, 2012, and December 5, 2012. The CAT score that can accurately predict an mMRC grade ≥ 2 versus < 2 was evaluated by comparing the area under the receiver operating curve (AUROC) and by classification and regression tree (CART) analysis. Results: Among 428 COPD patients, the percentages of patients classif ied into subgroups A, B, C, and D were 24.5%, 47.2%, 4.2%, and 24.1% based on CAT criteria and 49.3%, 22.4%, 8.9%, and 19.4% based on mMRC criteria, respectively. More than 90% of the patients who met the mMRC criteria for the 'more symptoms group' also met the CAT criteria. AUROC and CART analyses suggested that a CAT score ≥ 15 predicted an mMRC grade ≥ 2 more accurately than the current CAT score criterion. During follow-up, patients with CAT scores of 10 to 14 did not have a different risk of exacerbation versus those with CAT scores < 10, but they did have a lower exacerbation risk compared to those with CAT scores of 15 to 19. Conclusions: A CAT score ≥ 15 is a better indicator for the 'more symptoms group' in the management of COPD patients.
    The Korean Journal of Internal Medicine 09/2015; 30(5):629-37. DOI:10.3904/kjim.2015.30.5.629 · 1.43 Impact Factor
  • Journal of Critical Care 08/2015; 30(4):845-846. DOI:10.1016/j.jcrc.2015.04.076 · 2.00 Impact Factor
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    Bin Ahn · Joohae Kim · Chul-Gyu Yoo · Young Whan Kim · Sung Koo Han · Jae-Joon Yim
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    ABSTRACT: Diagnostic methods for pulmonary tuberculosis (TB) have recently advanced. The aim of this study was to evaluate the changes in TB diagnostic tests that prompted the initiation of anti-TB treatment over time in South Korea, an industrialized country with an intermediate TB burden. Patients diagnosed with pulmonary TB in the first halves of 2005 and 2013 at a tertiary referral hospital were included. Diagnostic methods that prompted the initiation of anti-TB treatment were compared between the 2 groups of patients. A greater proportion of patients were diagnosed with pulmonary TB using bronchoscopy in 2013 than in 2005 (26.7% vs. 6.6%, respectively; p<0.001), while the proportion of patients clinically diagnosed with pulmonary TB was lower in 2013 than in 2005 (24.7% vs. 49.0%, respectively; p<0.001). Additionally, more patients started anti-TB treatment based on positive polymerase chain reaction (PCR) results for Mycobacterium tuberculosis DNA in 2013 than in 2005 (47.3% vs. 7.9%, respectively; p<0.001). The initiation of treatment for pulmonary TB in South Korea has become more frequently based on PCR and the use of bronchoscopic specimens.
    Tuberculosis and Respiratory Diseases 07/2015; 78(3):227-31. DOI:10.4046/trd.2015.78.3.227
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    ABSTRACT: Because anaplastic lymphoma kinase (ALK) is dependent on Hsp90 for protein stability, Hsp90 inhibitors are effective in controlling growth of lung cancer cells with ALK rearrangement. We investigated the mechanism of acquired resistance to 17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), a geldanamycin analogue Hsp90 inhibitor, in H3122 and H2228 non-small cell lung cancer cell lines with ALK rearrangement. Resistant cell lines (H3122/DR-1, H3122/DR-2 and H2228/DR) were established by repeated exposure to increasing concentrations of 17-DMAG. Mechanisms for resistance by either NAD(P)H/quinone oxidoreductase 1 (NQO1), previously known as a factor related to 17-DMAG resistance, or P-glycoprotein (P-gp; ABCB1/MDR1) were queried using RT-PCR, western blot analysis, chemical inhibitors, the MTT cell proliferation/survival assay, and cellular efflux of rhodamine 123. The resistant cells showed no cross-resistance to AUY922 or ALK inhibitors, suggesting that ALK dependency persists in cells with acquired resistance to 17-DMAG. Although expression of NQO1 was decreased in H3122/DR-1 and H3122/DR-2, NQO1 inhibition by dicumarol did not affect the response of parental cells (H2228 and H3122) to 17-DMAG. Interestingly, all resistant cells showed the induction of P-gp at the protein and RNA levels, which was associated with an increased efflux of the P-gp substrate rhodamine 123 (Rho123). Transfection with siRNA directed against P-gp or treatment with verapamil, an inhibitor of P-gp, restored the sensitivity to the drug in all cells with acquired resistance to 17-DMAG. Furthermore, we also observed that the growth-inhibitory effect of 17-DMAG was decreased in A549/PR and H460/PR cells generated to over-express P-gp by long-term exposure to paclitaxel, and these cells recovered their sensitivity to 17-DMAG through the inhibition of P-gp. P-gp over-expression is a possible mechanism of acquired resistance to 17-DMAG in cells with ALK rearrangement.
    BMC Cancer 07/2015; 15(1):553. DOI:10.1186/s12885-015-1543-z · 3.36 Impact Factor
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    Keunhee Oh · Myung Won Seo · Young Whan Kim · Dong-Sup Lee
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    ABSTRACT: Lung fibrosis is a life-threatening disease caused by overt or insidious inflammatory responses. However, the mechanism of tissue injury-induced inflammation and subsequent fibrogenesis remains unclear. Recently, we and other groups reported that Th17 responses play a role in amplification of the inflammatory phase in a murine model induced by bleomycin (BLM). Osteopontin (OPN) is a cytokine and extracellular-matrix-associated signaling molecule. However, whether tissue injury causes inflammation and consequent fibrosis through OPN should be determined. In this study, we observed that BLM-induced lung inflammation and subsequent fibrosis was ameliorated in OPN-deficient mice. OPN was expressed ubiquitously in the lung parenchymal and bone-marrow-derived components and OPN from both components contributed to pathogenesis following BLM intratracheal instillation. Th17 differentiation of CD4(+) αβ T cells and IL-17-producing γδ T cells was significantly reduced in OPN-deficient mice compared to WT mice. In addition, Th1 differentiation of CD4(+) αβ T cells and the percentage of IFN-γ-producing γδ T cells increased. T helper cell differentiation in vitro revealed that OPN was preferentially upregulated in CD4(+) T cells under Th17 differentiation conditions. OPN expressed in both parenchymal and bone marrow cell components and contributed to BLM-induced lung inflammation and fibrosis by affecting the ratio of pathogenic IL-17/protective IFN-γ T cells.
    Immune Network 06/2015; 15(3):142-9. DOI:10.4110/in.2015.15.3.142
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    ABSTRACT: Mammalian target of rapamycin complex (mTORC) regulates various cellular processes including proliferation, growth, migration and differentiation. In this study, we showed that mTORC1 regulates platelet-derived growth factor (PDGF)-induced phenotypic conversion of vascular smooth muscle cells (VSMCs). Stimulation of contractile VSMCs with PDGF significantly reduced the expression of contractile marker proteins in a time- and dose-dependent manner. In addition, angiotensin II (AngII)-induced contraction of VSMCs was completely blocked by the stimulation of VSMCs with PDGF. PDGF-dependent suppression of VSMC marker gene expression was significantly blocked by inhibition of phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinase (ERK), and mTOR whereas inhibition of p38 MAPK had no effect. In particular, inhibition of mTORC1 by rapamycin or by silencing of Raptor significantly blocked the PDGF-dependent phenotypic change of VSMCs whereas silencing of Rictor had no effect. In addition, loss of AngII-dependent contraction by PDGF was significantly retained by silencing of Raptor. Inhibition of mTORC1 by rapamycin or by silencing of Raptor significantly blocked PDGF-induced proliferation of VSMCs. Taken together, we suggest that mTORC1 plays an essential role in PDGF-dependent phenotypic changes of VSMCs. Copyright © 2015. Published by Elsevier Inc.
    Biochemical and Biophysical Research Communications 05/2015; 464(1). DOI:10.1016/j.bbrc.2015.05.097 · 2.30 Impact Factor
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    ABSTRACT: Hemodynamic forces causing mechanical stretch (MS) of vascular smooth muscle cells (VSMC) play an important role in vascular remodeling, but the underlying mechanism involved is not fully understood. Thus, this study investigated whether osteopontin (OPN) expression in VSMC was induced by MS, and identified the intracellular signaling pathways involved in OPN production. The plasma level of OPN and its expression in aortic tissue were increased in various animal models of hypertension including spontaneous hypertensive rats and hypertensive mice induced by angiotensin II or L-NAME. When aortic VSMC was stimulated with MS, OPN production was increased, which was markedly attenuated in VSMC treated with PI3K/Akt inhibitor as well as in Akt1-depleted cells, but not in Akt2-depleted cells, suggesting a pivotal role of Akt1 isoform in OPN expression in VSMC. In the promoter assay, MS increased OPN promoter activity, which was attenuated when the region harboring AP-1 binding sites was mutated. The MS-enhanced promoter activity and OPN expression were also decreased in cells treated with AP-1 siRNA or inhibitor. Moreover, MS-induced MMP-2 production was attenuated in cells treated with OPN siRNA or anti-OPN antibody as well as in OPN-deficient VSMC cultured from aorta of OPN deficient mice. In in vivo experiments, the expressions of OPN and MMP-2 were increased in the aortic tissues from hypertensive mice, but these increases were markedly attenuated in OPN-deficient mice with hypertension. In conclusion, these results suggested that OPN expression in the hypertensive vasculature was increased via signaling pathways that involve Akt1/AP-1, leading to vascular remodeling by increasing the production of MMP-2. Copyright © 2015. Published by Elsevier Ltd.
    Journal of Molecular and Cellular Cardiology 05/2015; 85. DOI:10.1016/j.yjmcc.2015.05.006 · 4.66 Impact Factor
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    ABSTRACT: History of treatment for tuberculosis (TB) is a risk factor for obstructive lung disease. However, it has been unclear whether the clinical characteristics of patients with destroyed lung by TB differ according to the presence or absence of airflow limitation. The objective of the study was to evaluate differences in acute exacerbations and forced expiratory volume in 1 second (FEV1) decline in patients with destroyed lung by TB according to the presence or absence of airflow limitation. We performed a retrospective cohort study and enrolled patients with destroyed lung by TB. The presence of airflow limitation was defined as FEV1/forced vital capacity (FVC) < 0.7. One hundred and fifty-nine patients were enrolled, and 128 (80.5%) had airflow limitation. The proportion of patients who experienced acute exacerbation was higher in patients with airflow limitation compared to those without (89.1 vs. 67.7%, respectively; P = 0.009). The rate of acute exacerbation was higher in patients with airflow limitation (IRR, 1.19; 95% CI, 1.11-1.27). Low body mass index (X vs. X + 1; HR, 0.944; 95% CI, 0.895-0.996) in addition to airflow limitation (HR, 1.634; 95% CI, 1.012-2.638), was an independent risk factor for acute exacerbation. The annual decline of FEV1 was 2 mL in patients with airflow limitation and 36 mL in those without (P < 0.001). In conclusion, the presence of airflow limitation is an independent risk factor for acute exacerbation in patients with the destroyed lung by TB.
    Journal of Korean Medical Science 05/2015; 30(6):737-742. DOI:10.3346/jkms.2015.30.6.737 · 1.27 Impact Factor
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    ABSTRACT: Androgen receptor (AR) signaling is important for prostate cancer (PCa) cell proliferation. Here, we showed that proliferation of hormone-sensitive prostate cancer cells such as LNCaP was significantly enhanced by testosterone stimulation whereas hormone-insensitive prostate cancer cells such as PC3 and VCaP did not respond to testosterone stimulation. Blocking of AR using bicalutamide abolished testosterone-induced proliferation of LNCaP cells. In addition, knockdown of AR blocked testosterone-induced proliferation of LNCaP cells. Basal expression of low-density lipoprotein receptor-related protein 6 (LRP6) was elevated in VCaP cells whereas stimulation of testosterone did not affect the expression of LRP6. However, expression of LRP6 in LNCaP cells was increased by testosterone stimulation. In addition, knockdown of LRP6 abrogated testosterone-induced proliferation of LNCaP cells. Given these results, we suggest that androgen-dependent expression of LRP6 plays a crucial role in hormone-sensitive prostate cancer cell proliferation.
    Korean Journal of Physiology and Pharmacology 05/2015; 19(3):235-40. DOI:10.4196/kjpp.2015.19.3.235 · 1.38 Impact Factor
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    ABSTRACT: Lung cancer is the leading cause of cancer death in many countries, including Korea. The majority of patients are inoperable at the time of diagnosis because symptoms are typically manifested at an advanced stage. A recent large clinical trial demonstrated significant reduction in lung cancer mortality by using low dose computed tomography (LDCT) screening. A Korean multisociety collaborative committee systematically reviewed the evidences regarding the benefits and harms of lung cancer screening, and developed an evidence-based clinical guideline. There is high-level evidence that annual screening with LDCT can reduce lung cancer mortality and all-cause mortality of high-risk individuals. The benefits of LDCT screening are modestly higher than the harms. Annual LDCT screening should be recommended to current smokers and ex-smokers (if less than 15 years have elapsed after smoking cessation) who are aged 55 to 74 years with 30 pack-years or more of smoking-history. LDCT can discover non-calcified lung nodules in 20 to 53% of the screened population, depending on the nodule positivity criteria. Individuals may undergo regular LDCT follow-up or invasive diagnostic procedures that lead to complications. Radiation-associated malignancies associated with repetitive LDCT, as well as overdiagnosis, should be considered the harms of screening. LDCT should be performed in qualified hospitals and interpreted by expert radiologists. Education and actions to stop smoking must be offered to current smokers. Chest radiograph, sputum cytology at regular intervals, and serum tumor markers should not be used as screening methods. These guidelines may be amended based on several large ongoing clinical trial results.
    Journal of the Korean Medical Association 04/2015; 58(4):291. DOI:10.5124/jkma.2015.58.4.291 · 0.18 Impact Factor
  • Seo Yeon Jin · Jung Min Ha · Young Whan Kim · Hye Sun Lee · Sun Sik Bae
    02/2015; 25(2):231-236. DOI:10.5352/JLS.2015.25.2.231
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    ABSTRACT: Despite being a major public health problem, chronic obstructive pulmonary disease (COPD) remains underdiagnosed, and only 2.4% COPD patients are aware of their disease in Korea. The objective of this study was to estimate the prevalence of COPD detected by spirometry performed as a preoperative screening test and to determine the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group distribution and self-awareness of COPD. We reviewed the medical records of adults (age, ≥40 years) who had undergone spirometry during preoperative screening between April and August 2013 at a tertiary hospital in Korea. COPD was defined as a postbronchodilator forced expiratory volume in 1 s/forced vital capacity ratio of <0.7. We analyzed self-administered COPD questionnaires for the assessment of the frequency of acute exacerbation over the previous year and dyspnea severity using the modified Medical Research Council dyspnea scale and COPD assessment test. Among 3029 patients aged >40 years who had undergone spirometry as a preoperative screening test, 474 (15.6%; 404 men; median age, 70 years; range, 44-93 years) were diagnosed with COPD. Only 26 (5.5%) patients reported previous diagnosis of COPD (2.1%), emphysema (0.8%), or chronic bronchitis (2.5%). The GOLD group distribution was as follows: 63.3% in group A, 31.2% in group B, 1.7% in group C, and 3.8% in group D. The prevalence of COPD diagnosed by preoperative spirometry was 15.6%, and only 5.5% patients were aware of their disease. Approximately one-third of the COPD patients belonged to GOLD groups B, C, and D, which require regular treatment.
    PLoS ONE 01/2015; 10(1):e0115787. DOI:10.1371/journal.pone.0115787 · 3.23 Impact Factor
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    ABSTRACT: Background: Multiple comorbidities related to chronic obstructive pulmonary disease (COPD) make it a difficult disease to treat. The relationship between these comorbidities and COPD has not been fully investigated. We aimed to determine whether COPD was independently associated with various comorbidities. Methods: This was a cross-sectional study, which used data from the Korean National Health and Nutrition Examination Survey (KNHANES) V conducted between 2010 and 2012. Survey design analysis was employed to determine the association between COPD and 15 comorbidities. A COPD patient was defined as a smoker with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < 0.7 and comorbidities were defined based on objective laboratory findings and questionnaires. Results: Of a total of 9488 patient who underwent spirometry, 744 (7.84%) COPD cases and 3313 non-COPD controls were included in the analyses. Although the prevalence rates of the majority of the comorbidities were high among the COPD patients, only hypertension (adjusted odds ratio [aOR], 1.63; 95% CI, 1.13-2.33 in Stage 1 COPD group; aOR, 1.92; 95% CI, 1.36-2.72 in Stage 2-4 COPD group) and a history of pulmonary tuberculosis (aOR, 3.38; 95% CI, 1.90-5.99 in Stage 2-4 COPD group) were independently associated with COPD after adjustment for age, smoking status, and confounders. Conclusions: Only hypertension and a history of pulmonary tuberculosis were independently associated with COPD after adjustment for confounders among 15 comorbidities. The results suggest that majority of COPD patients might have similar risk factors with its comorbidities, including age and smoking status.
    Respiratory Medicine 11/2014; 109(1). DOI:10.1016/j.rmed.2014.10.015 · 3.09 Impact Factor
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    ABSTRACT: In this study, we investigated the role of Akt1 isoform in phenotypic change of vascular smooth muscle cells (VSMCs) and neointima formation. Laminin-induced conversion of synthetic VSMCs into contractile VSMCs was measured by expression of marker proteins for contractile VSMCs and collagen gel contraction assay. Culture of synthetic VSMCs on laminin-coated plates induced expression of marker proteins for contractile VSMCs and showed contraction in response to angiotensin II (AngII) stimulation. Silencing integrin-linked kinase attenuated activation of Akt1 and blocked phenotypic conversion of VSMCs resulting in the loss of AngII-dependent contraction. Laminin-induced phenotypic conversion of VSMCs was abrogated by phosphatidylinositol 3-kinase inhibitor or in cells silencing Akt1 but not Akt2. Proliferation of contractile VSMCs on laminin-coated plate was enhanced in cells silencing Akt whereas silencing Akt2 did not affect. Promoter activity of myocardin and SM22 alpha was enhanced in contractile phenotype and overexpression of myocardin stimulated promoter activity of SM22 alpha in synthetic phenotype. Promoter activity of myocardin and SM22 alpha was reduced in cells silencing Akt1 and promoter activity of SM22 alpha was restored by overexpression of myocardin in cells silencing Akt1. However, silencing of Akt2 affected neither promoter activity of myocardin nor SM22 alpha. Finally, neointima formation in carotid artery ligation and high fat-diet-induced atherosclerosis was facilitated in mice lacking Akt1. This study demonstrates that Akt1 isoform stimulates laminin-induced phenotypic conversion of synthetic VSMCs by regulating the expression of myocardin. VSMCs become susceptible to shifting from contractile to synthetic phenotype by the loss of Akt1 in pathological conditions.
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 11/2014; 1842(11). DOI:10.1016/j.bbadis.2014.08.014 · 4.88 Impact Factor
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    ABSTRACT: Background Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown causes. Three proteins (mammalian target of rapamycin, mTOR; zinc finger E-box-binding homeobox 1, ZEB1; Rho-associated, coiled-coil containing protein kinase 1, ROCK1) may be related to pulmonary fibrosis. However, they have not been assessed in human pulmonary fibrosis. We assessed the clinical significance of mTOR, ZEB1, and ROCK1 expression in human pulmonary fibrosis of usual interstitial pneumonia (UIP) pattern. Methods The mTOR, ZEB1, and ROCK1 expression was evaluated by immunohistochemical staining of 30 surgical lung biopsy tissues from 26 IPF and 4 UIP pattern connective tissue disease related interstitial lung disease (CTD-ILD) patients. The expression scores correlated with the clinical features. Results The mTOR, ZEB1 and ROCK1 mainly expressed in alveolar epithelial cells of UIP lungs. The histological fibrosis scores and lung function decline in the strong mTOR expression group were higher than those in the weak and intermediate expression group. Patients with positive ZEB1 expression had higher fibrosis scores and greater decline in carbon monoxide diffusion capacity (DLCO) than patients with negative ZEB1 expression. Patients with positive mTOR or ZEB1 expression had poorer prognosis than that of patients with negative mTOR or ZEB1 expression, although it was not statistically significant. ROCK1 was not associated with the studied clinicopathological features. Conclusions The mTOR and ZEB1 expression in pulmonary fibrosis patients significantly correlated with the fibrosis score and lung function decline, indicating that it may be related to the prognosis of pulmonary fibrosis. Further studies involving large numbers of homogeneous IPF patients are warranted.
    BMC Pulmonary Medicine 10/2014; 14(1):168. DOI:10.1186/1471-2466-14-168 · 2.40 Impact Factor
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    ABSTRACT: Objective While several prognostic models have been presented in NSCLC patients with brain metastasis, none of these models have included molecular markers as an index. The aim of our study was to evaluate the prognostic value of EGFR mutations and to integrate these EGFR mutations into the prognostic index in NSCLC patients with brain metastasis. Materials and Methods We analyzed retrospectively 292 lung adenocarcinoma patients with brain metastasis. Clinico-pathological features and overall survival (OS) were compared between patients with EGFR mutations and patients with EGFR wild type. EGFR mutation status was integrated with lung specific Graded Prognostic Assessment (GPA) score. Results Among 292 patients, EGFR mutation status was tested in 183 patients. One hundred and five patients (57.4%) had EGFR activating mutations, 14 (7.7%) had EGFR non-activating mutations and 64 (35.0%) had EGFR wild type. OS was significantly longer in patients with EGFR activating mutations than in those with EGFR wild type patients (20.4 vs. 10.1 months, p = 0.002). However, patients with EGFR non-activating mutations did not show superior OS compared with EGFR wild type patients (14.6 vs. 10.1 months, p = 0.83). Multivariate analysis revealed that the presence of EGFR activating mutation is an independent positive prognostic factor for OS (adjusted hazard ratio 0.56, p = 0.002). Conclusions EGFR activating mutations have a prognostic role in lung adenocarcinoma patients with brain metastasis that is independent of other known prognostic factors. The frequency of EGFR mutation was higher than expected. The presence of EGFR activating mutations should be included as an index in the prognostic models for lung adenocarcinoma patients with brain metastasis.
    Lung Cancer 10/2014; 86(3). DOI:10.1016/j.lungcan.2014.10.001 · 3.96 Impact Factor
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    ABSTRACT: Background: Previous studies have investigated the relationship between occupational and environmental agents and idiopathic pulmonary fibrosis (IPF). However, there have been few studies regarding the prognosis of patients with IPF according to patient occupation. Methods: We investigated whether occupational dust exposure was associated with clinically decreased lung function and poor prognosis. The Korean Interstitial Lung Disease Research Group conducted a national survey to evaluate the clinical, physiologic, radiologic, and survival characteristics of patients with IPF. A total of 1,311 patients with IPF were stratified into five groups according to their occupation: (1) unemployed or homemakers (n = 628); (2) farmers, fishers, or ranchers (n = 230); (3) sales or service personnel (n = 131); (4) clerical or professional personnel (n = 151); and (5) specific dust-exposed workers (n = 171). Results: The mean age of subjects at diagnosis, was 67.5 ± 9.7 years. Current smokers were 336 patients, 435 were exsmokers, and 456 were never smokers. Dust-exposed workers showed early onset of IPF (61.3 ± 8.6 years; P < .001) and a longer duration of symptoms at diagnosis (17.0 ± 28.2 months; P = .004). Aging (P = .001; hazard ratio [HR], 1.034; 95% CI, 1.014-1.054), FVC % predicted at diagnosis (P = .004; HR, 0.984; 95% CI, 0.974-0.995), and dust-exposure occupation (P = .033; HR, 1.813; 95% CI, 1.049-3.133) were associated with mortality. Conclusions: These findings indicate that occupational dust may be an aggravating factor associated with a poor prognosis in IPF.
    Chest 10/2014; 147(2). DOI:10.1378/chest.14-0994 · 7.48 Impact Factor
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    ABSTRACT: Objective To assess whether measuring the solid portion of adenocarcinomas appearing as part-solid ground-glass nodules (GGNs) can predict a patient’s prognosis accurately and how the prognosis corresponds to that of solid nodules. Methods 501 patients (solid nodule group, 304; part-solid GGN group, 197) underwent curative surgery for stage I adenocarcinomas. Maximal diameters of the whole lesion including ground-glass opacities (D whole ) and solid components only (D solid ) were measured on CT. Disease-free survival (DFS) and overall survival (OS) were calculated from the date of surgery. Results D solid was a significant prognostic factor in the part-solid GGN group, while D whole was not. Part-solid GGNs with D solid ≤2 cm showed significantly better DFS (P = 0.016) and OS (P = 0.004) than solid nodules; however, those with D solid >2 cm did not show a significant difference. Hazard ratio (HR) for increase in D solid was significantly greater in part-solid GGNs than in solid nodules (P = 0.009). For OS, HR for increase in D solid was greater in part-solid GGNs than in solid nodule, which was marginally not significant (P = 0.060). Conclusion D solid was better than D whole for prognosis prediction of adenocarcinomas appearing as part-solid GGNs. In addition, the influence of D solid on prognosis in the part-solid GGN group was greater than in the solid nodule group. Key points • Dsolidis a better prognosis indicator than Dsolidin part-solid GGN adenocarcinomas • Part-solid GGN adenocarcinoma show better prognosis than solid adenocarcinomas when Dsolid≤2 cm • Dsolidhas greater prognostic influence in part-solid GGN adenocarcinomas than solid adenocarcinomas
    European Radiology 10/2014; 25(2). DOI:10.1007/s00330-014-3441-1 · 4.01 Impact Factor
  • Chest 10/2014; 146(4_MeetingAbstracts):588A. DOI:10.1378/chest.1991270 · 7.48 Impact Factor
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    ABSTRACT: Reactive oxygen species (ROS) are chemically reactive molecules containing oxygen and associates with multiple cellular functions such as cell proliferation, differentiation, and apoptosis. In the present study, we showed that Insulin-like growth factor-1(IGF-1) modulates SKOV-3 ovarian cancer cell by regulation of generation of ROS. Akt mediates cellular signaling pathways in association with mammalian target of rapamycin complex (mTOR) and Rac small G protein. Insulin-like growth factor-1 (IGF-1)-induced generation of ROS was completely abolished by phosphatidylinositol 3-kinase (PI3K) (LY294002, 10?µM) or Akt inhibitors (SH-5, 50?µM), whereas inhibition of extracellular-regulated kinase by an ERK inhibitor (PD98059, 10?µM) or inhibition of mammalian target of rapamycin complex 1 (mTORC1) by an mTORC1 inhibitor (Rapamycin, 100?nM) did not affect IGF-1-induced generation of ROS. Inactivation of mTORC2 by silencing Rapamycin-insensitive companion of mTOR (Rictor), abolished IGF-1-induced SKOV-3 cell migration as well as activation of Akt. However, inactivation of mTORC1 by silencing of Raptor had no effect. Silencing of Akt1 but not Akt2 attenuated IGF-1-induced generation of ROS. Expression of PIP3-dependent Rac exchanger1 (P-Rex1), a Rac guanosine exchange factor and a component of the mTOR complex. Silencing of P-Rex1 abolished IGF-1-induced generation of ROS. Finally, inhibition of NADPH oxidase system completely blunted IGF-1-induced generation of ROS, whereas inhibition of xanthine oxiase,cyclooxygenase, and mitochondrial respiratory chain complex was not effective. Given these results, we suggest that IGF-1 induces ROS generation through the PI3K/Akt/ mTOR2/NADPH oxidase signaling axis.

Publication Stats

2k Citations
551.51 Total Impact Points


  • 2011–2015
    • Pusan National University
      • • Medical Research Center for Ischemic Tissue Regeneration
      • • Department of Pharmacology
      Tsau-liang-hai, Busan, South Korea
  • 1992–2015
    • Seoul National University Hospital
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea
  • 2011–2014
    • Keimyung University
      • College of Medicine
      Sŏul, Seoul, South Korea
  • 1996–2014
    • Seoul National University
      • • Department of Internal Medicine
      • • Department of Medicine
      • • Institute on Aging
      • • College of Medicine
      Sŏul, Seoul, South Korea
  • 2009
    • Korea University
      • Department of Earth and Environmental Sciences
      Seoul, Seoul, South Korea
    • Cancer Research Institute
      New York, New York, United States
  • 2008
    • Inje University Paik Hospital
      Sŏul, Seoul, South Korea
    • Inje University
      • College of Medicine
      Kŭmhae, Gyeongsangnam-do, South Korea
  • 2006
    • Korea Medical Research Institute
      Sŏul, Seoul, South Korea