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So Ri Kim,
Lae Young Jung,
In-Jae Oh, Young-Chul Kim,
Kyeong-Cheol Shin,
Min Ki Lee,
Sei-Hoon Yang,
Hee Sun Park,
Mi-Kyung Kim,
Jin Young Kwak,
Soo-Jung Um,
Seung Won Ra,
Woo Jin Kim,
Seungsoo Kim,
Eu-Gene Choi,
Yong Chul Lee
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ABSTRACT: BACKGROUND: Pulmonary actinomycosis is a chronic pulmonary infection caused by Actinomyces. Both improving oral hygiene and early application of antibiotics to the case of suspicious pulmonary infections result in changes in incidences and presentations of pulmonary actinomycosis. However, there are little reports dealt with the recent clinical characteristics of pulmonary actinomycosis. This study aimed to review the characteristics of pulmonary actinomycosis occurred during the first decade of 21st century. METHODS: This retrospective study was performed on 94 subjects with pulmonary actinomycosis diagnosed pathologically from January 2000 to December 2010 in 13 hospitals in Korea. RESULTS: The data of the study showed that pulmonary actinomycosis occurs frequently in middle to old-aged males (mean age; 57.7 years old) and that the most common symptoms are cough, hemoptysis, and sputum production. Various radiologic features such as the consolidation with central low attenuation (74. 5%) and no regional predominance were also observed. Most of patients recovered completely with medical and/or surgical treatment, reaching approximately 98% cure rate. CONCLUSIONS: The results demonstrate that pulmonary actinomycosis is one of the cautious pulmonary diseases. More importantly, in cases of persistent hemoptysis or for differential diagnosis from lung malignancy, our data have revealed that surgical resection appears to be a useful intervention and that radiologic diagnosis may not provide decisive information. These findings indicate that it is important for the clinicians to include pulmonary actinomycosis as one of differential diagnoses for refractory pulmonary abnormal lesions to the current usual management.
BMC Infectious Diseases 05/2013; 13(1):216. · 3.12 Impact Factor
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ABSTRACT: The presence of epidermal growth factor receptor (EGFR) mutation is a prognostic and predictive marker for EGFR-tyrosine kinase inhibitor (TKI) therapy. However, inevitably, relapse occurs due to the development of acquired resistance, such as T790M mutation. We report a case of repeated responses to EGFR-TKIs in a never-smoked woman with adenocarcinoma. After six cycles of gemcitabine and cisplatin, the patient was treated by gefitinib for 4 months until progression. Following the six cycles of third-line pemetrexed, gefitinib retreatment was initiated and continued with a partial response for 6 months. After progression, she was recruited for an irreversible EGFR inhibitor trial, and the time to progression was 11 months. Although EGFR direct sequencing on the initial diagnostic specimen revealed a wild-type, we performed a rebiopsy from the progressed subcarinal node at the end of the trial. The result of peptide nucleic acid clamping showed L858R/L861Q.
Tuberculosis and Respiratory Diseases 03/2013; 74(3):129-33.
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Sung Yong Lee,
Hee Sun Park,
Kye Young Lee,
Hee Joung Kim,
Young June Jeon,
Tae Won Jang,
Kwan Ho Lee, Young Chul Kim,
Kyu Sik Kim,
In Jae Oh,
Sun Young Kim
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ABSTRACT: INTRODUCTION:: The development of paclitaxel-loaded polymeric micelle (PPM) has circumvented many of the infusion-related difficulties associated with standard solvent-based paclitaxel. PPM plus cisplatin combination chemotherapy showed significant antitumor activity in phase I and II studies. This prospective randomized controlled phase IIB study assessed the noninferiority of the efficacy and tolerability of high-dose PPM plus cisplatin to a standard dose of paclitaxel plus cisplatin. PATIENTS AND METHODS: Patients with stage IIIB/IV or recurrent non-small-cell lung cancer (NSCLC) who were chemonaive were eligible for participation. The patients were randomly assigned to receive PPM 230 mg/m(2) plus cisplatin 60 mg/m(2) or paclitaxel 175 mg/m(2) plus cisplatin 60 mg/m(2) once every 3-week cycle. The primary endpoint was to compare the response rate (RR) between the groups with coprimary analyses to assess noninferiority. Secondary endpoints included progression-free survival, overall survival, and safety. RESULTS: A total of 276 patients were randomized to PPM plus cisplatin (n = 140) or paclitaxel plus cisplatin (n = 136). RR was 43.6% in the PPM plus cisplatin group and 41.9% in the paclitaxel plus cisplatin group. Noninferiority of PPM plus cisplatin compared with paclitaxel plus cisplatin was confirmed for RR. There were no differences in progression-free survival and overall survival between the groups. Although there was a higher rate of grade 3 neutropenia in the PPM plus cisplatin group, the overall rate of adverse events was comparable between the 2 groups. CONCLUSION: PPM in combination with cisplatin was well tolerated, and its response rate was noninferior to that of paclitaxel plus cisplatin in patients with advanced NSCLC and who were chemonaive.
Clinical Lung Cancer 01/2013; · 2.94 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate the differences in clinical characteristics and treatment outcomes between older and younger tuberculosis (TB) patients in Korea.
We retrospectively analyzed the medical records of 271 younger (20-64 years old at diagnosis) and 199 older (≥65 years) TB patients who had been newly diagnosed and treated at Chonnam National University Hospital from May 2008 to August 2010.
Dyspnea and comorbid medical conditions were more frequent and positive TB culture rates were higher in older TB patients. In chest computed tomography (CT) scans of pulmonary TB patients, older patients were less likely to have micronodules (<7 mm in diameter), nodules (<30 mm in diameter), masses (>30 mm in diameter), and cavities compared with younger patients, but were more likely to have consolidations. Incidence of adverse drug reactions did not differ between the two groups, except for severe gastrointestinal disorders. There were no significant differences in favorable treatment outcomes between younger and older TB patients (97% vs. 94%, respectively; p = 0.251).
Older TB patients had more frequent dyspnea and less frequent active TB findings on chest CT. Treatment success and adverse drug reaction rates were similar in older and younger TB patients.
BMC Infectious Diseases 01/2013; 13:121. · 3.12 Impact Factor
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Kwan-Ho Lee,
Kye-Young Lee,
Young-June Jeon,
Maan-Hong Jung,
Choonhee Son,
Min-Ki Lee,
Jeong-Seon Ryu,
Sei-Hoon Yang,
Jae-Cheol Lee, Young-Chul Kim,
Sun-Young Kim
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ABSTRACT: This study was designed to analyze the efficacy of gefitinib as a second-line therapy, according to the clinical characteristics in Korean patients with non-small-cell lung cancer (NSCLC).
In this Phase IV observational study, we recruited patients, previously failed first-line chemotherapy, who had locally advanced or metastatic NSCLC, and who were found to be either epidermal growth factor receptor (EGFR) mutation-positive or satisfied 2 or more of the 3 characteristics: adenocarcinoma, female, and non-smoker. These patients were administered with gefitinib 250 mg/day, orally. The primary endpoints were to evaluate the objective response rate (ORR) and to determine the relationship of ORRs, depending on each patient's characteristics of modified intent-to-treat population.
A total of 138 patients participated in this study. One subject achieved complete response, and 42 subjects achieved partial response (ORR, 31.2%). The subgroup analysis demonstrated that the ORR was significantly higher in patients with EGFR mutation-positive, compared to that of EGFR mutation-negative (45.8% vs. 14.0%, p=0.0004). In a secondary efficacy variable, the median progression-free survival (PFS) was 5.7 months (95% confidence interval, 3.9~8.4 months) and the 6-month PFS and overall survival were 49.6% and 87.9%, respectively. The most common reported adverse events were rash (34.4%), diarrhea (26.6%), pruritus (17.5%), and cough (15.6%).
Gefitinib was observed in anti-tumor activity with favorable tolerability profile as a second-line therapy in these selected patients. When looking at EGFR mutation status, EGFR mutation-positive showed strong association with gefitinib by greater response and prolonged PFS, compared with that of EGFR mutation-negative.
Tuberculosis and Respiratory Diseases 12/2012; 73(6):303-11.
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Dae Hoon Kim, Young Chul Kim,
Woong Choi,
Hyo-Young Yun,
Rohyun Sung,
Hun Sik Kim,
Heon Kim,
Ra Young Yoo,
Seon-Mee Park,
Sei Jin Yun,
Young-Jin Song,
Wen-Xie Xu,
Sang Jin Lee
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ABSTRACT: This study was designed to elucidate high K(+)-induced relaxation in the human gastric fundus. Circular smooth muscle from the human gastric fundus greater curvature showed stretch-dependent high K(+) (50 mM)-induced contractions. However, longitudinal smooth muscle produced stretch-dependent high K(+)-induced relaxation. We investigated several relaxation mechanisms to understand the reason for the discrepancy. Protein kinase inhibitors such as KT 5823 (1 µM) and KT 5720 (1 µM) which block protein kinases (PKG and PKA) had no effect on high K(+)-induced relaxation. K(+) channel blockers except 4-aminopyridine (4-AP), a voltage-dependent K(+) channel (K(V)) blocker, did not affect high K(+)-induced relaxation. However, N(G)-nitro-L-arginine and 1H-(1,2,4)oxadiazolo (4,3-A)quinoxalin-1-one, an inhibitors of soluble guanylate cyclase (sGC) and 4-AP inhibited relaxation and reversed relaxation to contraction. High K(+)-induced relaxation of the human gastric fundus was observed only in the longitudinal muscles from the greater curvature. These data suggest that the longitudinal muscle of the human gastric fundus greater curvature produced high K(+)-induced relaxation that was activated by the nitric oxide/sGC pathway through a K(V) channel-dependent mechanism.
Korean Journal of Physiology and Pharmacology 10/2012; 16(5):297-303. · 0.96 Impact Factor
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Kyu-Sik Kim,
In-Jae Oh,
Hee-Jung Ban,
Hyun-Ju Cho,
Yong-Soo Kwon,
Yu-Il Kim,
Sung-Chul Lim,
Kook-Joo Na,
Sang-Yun Song,
Song Choi,
Yoo-Duk Choi, Young-Chul Kim
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ABSTRACT: A combination of docetaxel (D) and cisplatin (P) is one of the standard regimens for the initial treatment of advanced non-small cell lung cancer (NSCLC). Yet, the toxicity of D administered at 75 mg/m(2) in three weekly doses to patients is a concern. The aim of this study was to assess the efficacy of a lower combination dose, 60 mg/m(2) of D and 60 mg/m(2) of cisplatin (P), as a treatment for NSCLC. In this randomized, phase III trial, we compared the response rates (RRs) and toxicity profiles of two combination regimens, D/P 75/60 vs. 60/60 mg/m(2), to patients with stage IIIB or IV NSCLC. A total of 132 patients were randomized to the 75/60 (n=65) or 60/60 (n=67) dosage group. Non-inferiority of 60/60 group compared to the 75/60 group was confirmed by the RR (38.5% for the 75/60 group and 40.3% for the 60/60 group, 95% confidence interval -14.8 to 18.5, meeting the predefined non-inferiority criterion). The dose reduction rate and incidence of grade 3-4 neutropenia were significantly higher in the 75/60 group. The incidence of neutropenia was significantly higher in those with the non-expressing genotype (GG) compared to the AG or AA genotypes of CYP3A5. We determined that DP 60/60 was not inferior to DP 75/60 in RR, and that the reduced combination dosage provides a better safety profile for patients.
Experimental and therapeutic medicine 08/2012; 4(2):317-322.
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ABSTRACT: This study attempted to investigate the main causes of hemoptysis, the type of examinations used for diagnosis, the treatment modalities and outcomes.
A retrospective study was conducted on the medical records of 221 patients admitted to the Chonnam National University Hospital, between January 2005 and February 2010, with hemoptysis.
Bronchiectasis (32.6%), active pulmonary tuberculosis (18.5%), fungus ball (10.8%), and lung cancer (5.9%) accounted for most causes of hemoptysis. Computed tomography scan was the most sensitive diagnostic test when employed alone, with positive yield of 93.2%. There were 161 cases of conservative treatment (72.9%), 42 cases of bronchial artery embolization (BAE) (19.0%), and 18 cases of surgery (8.1%). Regarding the amount of hemoptysis, 70 cases, out of 221 cases, were mild (31.5%), 36 cases moderate (16.2%), and 115 cases massive hemoptysis (52.0%). Most of the patients were treated conservatively, but if there was more bleeding present, BAE or surgery was more commonly performed than the conservative treatment (p≤0.0001). In the multivariate model, severe hemoptysis and lung cancer were independently associated with short-term recurrence. BAE was independently associated with long-term recurrence, and lung cancer was associated with in-hospital mortality. The overall in-hospital mortality rate was 11.3%.
Hemoptysis is a common symptom with a good prognosis in most cases. However, patients exhibiting massive bleeding or those with malignancy had a poorer prognosis. In-hospital mortality was strongly related to the cause, especially in lung cancer.
Tuberculosis and respiratory diseases. 08/2012; 73(2):107-14.
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ABSTRACT: Temozolomide is an oral alkylating agent with clinical activity against glioblastoma multiforme (GM). It is generally well-tolerated and has few pulmonary side effects. We report a case of temozolomide-associated brochiolitis obliterans organizing pneumonia (BOOP) requiring very high-dose corticosteroid treatment. A 56-yr-old woman presented with a 2-week history of exertional dyspnea. For the treatment of GM diagnosed 4 months previously, she had undergone surgery followed by chemoradiotherapy, and then planned adjuvant chemotherapy with temozolomide. After the 1st cycle, progressive dyspnea was gradually developed. Chest radiograph showed diffuse patchy peribronchovascular ground-glass opacities in both lungs. Conventional dose of methylprednisolone (1 mg/kg/day) was begun for the possibility of BOOP. Although transbronchial lung biopsy findings were compatible with BOOP, the patient's clinical course was more aggravated until hospital day 5. After the dose of methylprednisolone was increased (500 mg/day for 5 days) radiologic findings were improved dramatically.
Journal of Korean medical science 04/2012; 27(4):450-3. · 0.84 Impact Factor
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ABSTRACT: Many studies which focus on the molecules and mechanisms related to the characteristics of the cancer have been performed. In particular, cell adhesion molecules (CAMs) are known to play a central role in the adhesion of cancer cells to vascular endothelial cells. In this study, the expression of CAMs in hepatocellular carcinoma (HCC) cell lines was analyzed and correlated with the characteristics of various HCC cell lines. Eight human HCC cell lines were used in this study. We analyzed the expression of ICAM-1, E-selectin and the integrin subunits of HCC cell lines by western blot analysis and ELISA kit. We estimated the expression of integrin-α5 using western blot analysis and RT-PCR to compare the expression at the gene level with the protein level. In addition, we determined the expression of TGF-β1, as one of the markers for the cellular activity compared to the levels of expression with the expression of integrin-α3 and -α5. ICAM-1 was highly expressed in all of the cell lines except SNU398 and Hep3B, which exhibit a more aggressive nature among the studied HCC cell lines. E-selectin and integrin subunits varied in all HCC cell lines. In particular, integrin-β2 was highly expressed on all HCC cell lines. In conclusion, the levels of expression of the CAMs may not affect cellular activity, morphology or tumorigenicity. However, most HCC cell lines show various expressions of CAMs, suggesting that HCC cell lines expressing the major CAMs remain candidates for molecular targeted therapy, which may need to be patient-tailored for therapy according to the molecular profile.
International Journal of Molecular Medicine 03/2012; 29(6):1158-64. · 1.98 Impact Factor
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ABSTRACT: Most patients with non-small-cell lung cancer (NSCLC) who initially respond to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) eventually experience progression of disease. Based on previous trials which showed second response after switching to another EGFR-TKI, we hypothesized that the reintroduction of gefitinib would lead to disease control rate (DCR) in more than 30% of patients. This was a single-arm, open-label, prospective, phase II trial of gefitinib for the treatment of advanced or metastatic NSCLC. Eligible patients had previously responded to, or had experienced disease stabilization with, initial gefitinib treatment for at least 3 months. Prior to retreatment, progressive disease (PD) should be observed, with at least one cytotoxic treatment following initial gefitinib failure. Twenty-three patients were recruited and defined as the intention to treat (ITT) group. Most of the enrolled patients were female (86.9%), never-smokers (91.3%), and adenocarcinoma patients (95.7%). Responses to initial gefitinib were partial response (PR) in 10 cases (43.5%) and stable disease (SD) in 13 cases (56.5%). PR and DCR were observed in 21.7% (5 patients) and 65.2% (15 patients) in the ITT group. Among 14 DNA samples, 13 cases had either exon 19 deletion or L858R point mutation, whereas one patient evidenced the wild-type EGFR gene. Re-initiation of EGFR-TKI can be considered as an option after failure of chemotherapy for those patients who previously controlled to EGFR-TKI treatment.
Lung cancer (Amsterdam, Netherlands) 02/2012; 77(1):121-7. · 3.14 Impact Factor
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ABSTRACT: We investigated whether the whole-body metabolic tumour volume (WBMTV) measured by (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) can improve the prediction of prognosis in patients with small cell lung cancer (SCLC).
We reviewed 106 consecutive patients (mean age 67 years, range 42-89 years, limited stage 45 patients, extensive stage 61 patients) with pathologically proven SCLC who underwent pretreatment FDG PET/CT. WBMTV and maximum standardized uptake value (SUV(max)) were measured in all malignant lesions. The Cox proportional hazards model was used with age, sex, performance status, lactate dehydrogenase (LDH), treatment, stage, SUV(max) and WBMTV to predict overall survival (OS) and progression-free survival (PFS). Subgroup analysis was performed using WBMTV combined with conventional staging and tumour node metastasis (TNM) staging.
The uni- and multivariate analyses showed that both stage and WBMTV were independent prognostic factors for death and progression. Patients with high WBMTV were associated with poor prognosis compared with patients with low WBMTV [hazard ratio = 2.11 (95% confidence interval 1.31-3.39) for death (p = 0.002) and 1.80 (95% confidence interval 1.16-2.80) for progression (p = 0.009)]. Incorporation of conventional staging and WBMTV could classify four subgroups with different prognoses (log-rank test, p < 0.001). Incorporation of TNM staging and WBMTV could classify six subgroups with different prognoses (log-rank test, p < 0.001).
WBMTV is an independent predictor for progression and death in patients with SCLC. Incorporation of WBMTV with TNM staging can provide a more detailed prediction of prognosis than WBMTV with conventional staging as well as tumour staging alone.
European Journal of Nuclear Medicine 01/2012; 39(6):925-35. · 4.53 Impact Factor
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ABSTRACT: Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are elevated in patients with secondary pulmonary hypertension and chronic lung disease with right ventricular overload. The aim of the present study was to investigate the use of plasma NT-proBNP levels as a prognostic marker of severe COPD with chronic respiratory failure and latent pulmonary hypertension.
Plasma NT-proBNP levels were measured in 61 patients with stable COPD. Plasma NT-proBNP levels, pulmonary function, PaO(2), and PaCO(2) levels and systolic pulmonary artery pressure were compared according to COPD severity. In addition, we examined correlations between plasma NT-proBNP levels and pulmonary function, PaO(2), PaCO(2), and systolic pulmonary artery pressure.
The levels of plasma NT-proBNP significantly increased in patients with stage IV and stage III COPD compared to individuals with stage II COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. The area under the receiver-operating characteristic curve of plasma NT-proBNP for severe to very severe COPD (FEV(1) <50%) was 0.707 (95% confidence interval [CI] 0.566-0.847, P=0.008). Plasma NT-proBNP levels significantly correlated with %FEV(1) (r= -0.557; P < 0.001), arterial blood gas parameters such as PaCO(2) (r = 0.476; P < 0.001) and PaO(2) (r = -0.347; P = 0.031), and systolic pulmonary artery pressure (r = 0.435; P = 0.001).
Plasma NT-proBNP levels increased significantly with disease severity, progression of chronic respiratory failure, and secondary pulmonary hypertension in patients with stable COPD. These results suggest that plasma NT-proBNP can be a useful prognostic marker to monitor COPD progression and identify cases of secondary pulmonary hypertension in patients with stable COPD.
Beiträge zur Klinik der Tuberkulose 01/2012; 190(3):271-6. · 1.90 Impact Factor
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Tae-Jin Song,
Yuman Fong,
Sung-Jin Cho,
Mithat Gönen,
Michael Hezel,
Scott Tuorto,
Sang-Yong Choi, Young-Chul Kim,
Sung-Ock Suh,
Bum-Hwan Koo,
Yang-Seok Chae,
William R Jarnagin,
David S Klimstra
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ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Although some epidemiologic and etiologic differences between Asian and Western HCC are known, detailed comparative studies with pathologic correlations have not been performed.
Paraffin sections of resected HCC specimens from Memorial Sloan-Kettering Cancer Center and Korea University Medical Center were used to construct tissue microarrays. Immunohistochemical staining of microarray sections was performed using antibodies against markers of proliferation and regulators of cell cycle. Patient data were correlated with staining results.
When comparing both cohorts, significant differences were found in expression of p53 and MDM2. In the Asian group, more frequent positive staining for p53 (24%) was observed compared with the American group (9%; P = 0.037). For MDM2, 26% of American cases stained positive compared with 2% of Asian cases (P = 0.0003). No significant differences were found in expression of Ki67, p21, p27, cyclin D1, or bcl2. Female gender, vascular invasion, and lack of viral hepatitis infection correlated with positive MDM2 staining.
These data likely correlate with differences in molecular pathogenesis of HCC based on racial and regional differences. These findings may have implications in choice of molecular targeted therapies based on patient ethnicity.
Journal of Surgical Oncology 01/2012; 106(1):84-8. · 2.10 Impact Factor
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Young Chul Kim,
Woong Choi,
Hyo-Young Yun,
Rohyun Sung,
Ra Young Yoo,
Seon-Mee Park,
Sei Jin Yun,
Mi-Jung Kim,
Young-Jin Song,
Wen-Xie Xu,
Sang Jin Lee
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ABSTRACT: This study was designed to elucidate high-K(+)induced response of circular and longitudinal smooth muscle from human gastric corpus using isometric contraction. Contraction from circular and longitudinal muscle stripes of gastric corpus greater curvature and lesser curvature were compared. Circular smooth muscle from corpus greater curvature showed high K(+) (50 mM)-induced tonic contraction. On the contrary, however, longitudinal smooth muscle strips showed high K(+) (50 mM)-induced sustained relaxation. To find out the reason for the discrepancy we tested several relaxation mechanisms. Protein kinase blockers like KT5720, PKA inhibitor, and KT5823, PKG inhibitor, did not affect high K(+)-induced relaxation. K(+) channel blockers like tetraethylammonium (TEA), apamin (APA), glibenclamide (Glib) and barium (Ba(2+)) also had no effect. However, N(G)-nitro-L-arginine (L-NNA) and 1H-(1,2,4) oxadiazolo (4,3-A) quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC) and 4-AP (4-aminopyridine), voltage-dependent K(+) channel (K(V)) blocker, inhibited high K(+)-induced relaxation, hence reversing to tonic contraction. High K(+)-induced relaxation was observed in gastric corpus of human stomach, but only in the longitudinal muscles from greater curvature not lesser curvature. L-NNA, ODQ and K(V) channel blocker sensitive high K(+)-induced relaxation in longitudinal muscle of higher portion of corpus was also observed. These results suggest that longitudinal smooth muscle from greater curvature of gastric corpus produced high K(+)-induced relaxation which was activated by NO/sGC pathway and by K(V) channel dependent mechanism.
Korean Journal of Physiology and Pharmacology 12/2011; 15(6):405-13. · 0.96 Impact Factor
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ABSTRACT: Invariant natural killer T (iNKT) cells may play an important role in regulating the innate and acquired immune systems in chronic obstructive pulmonary disease (COPD). However, there is little information regarding the potential role of iNKT cells in the pathogenesis of COPD. To investigate whether iNKT cells have an important role in COPD, the frequency of iNKT cells in peripheral blood of patients with COPD was analysed.
This was a comparative study of 28 patients with COPD and 19 age-matched healthy control subjects. Blood iNKT cells were stained with 6B11 mAb, anti-T cell receptor Vα24 mAb, anti-T cell receptor Vβ11 mAb or α-galactosylceramide-loaded CD1d-tetramer, and analysed by flow cytometry.
The frequency of CD4(+) 6B11(+) iNKT, CD4(+) Vα24(+) iNKT, CD4(+) Vβ11(+) iNKT and CD3(+) 6B11(+) iNKT cells was significantly lower in peripheral blood of patients with COPD than in that of healthy control subjects. The frequency of CD4(+) 6B11(+) iNKT cells was significantly lower in patients with exacerbations of COPD compared with those with stable COPD.
The frequency of iNKT was decreased in peripheral blood of patients with COPD. These results strongly suggest that iNKT cells may play an important role in the pathogenesis of COPD.
Respirology 11/2011; 17(3):486-92. · 2.42 Impact Factor
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Hee Joung Kim,
Kye Young Lee, Young-Chul Kim,
Kyu-Sik Kim,
Sung Yong Lee,
Tae Won Jang,
Min Ki Lee,
Kyeong-Cheol Shin,
Gwan Ho Lee,
Jae Chol Lee,
Jeong Eun Lee,
Sun Young Kim
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ABSTRACT: EGFR tyrosine kinase inhibitors (EGFR-TKIs) are recommended as first-line therapy in patients with advanced, recurrent, or metastatic non-squamous non-small cell lung cancer (NSCLC) that have active EGFR mutations. The importance of rapid and sensitive methods for the detection of EGFR mutations is emphasized. The aim of this study is to examine the EGFR mutational status by both direct DNA sequencing and peptide nucleic acid (PNA)-mediated real-time PCR clamping and to evaluate the correlation between the EGFR mutational status and the clinical response to EGFR-tyrosine kinase inhibitors. Clinical specimens from 240 NSCLC patients were analyzed for EGFR mutations in exons 18, 19, 20 and 21. All clinical data and tumor specimens were obtained from 8 centers of the Korean Molecular Lung Cancer Group (KMLCG). After genomic DNA was extracted from paraffin-embedded tissue specimens, we performed PNA-mediated real-time PCR clamping and direct DNA sequencing for the detection of EGFR mutations. Of 240 tumor samples, PNA-mediated PCR clamping was used to detect genomic alterations in 83 (34.6%) samples, including 61 identified by sequencing and 22 additional samples (10 in exon 19, 9 in exon 21, and 3 in both exons); direct DNA sequencing was used to identify a total of 63 (26.3%) mutations that contained 40 deletion mutations in exon 19 (63.5%) and 18 substitution mutations (28.6%) in exon 21. PNA-mediated PCR clamping was used to identify more mutations than clinical direct sequencing, whereas clinical outcomes were not significantly different between the groups harboring activating mutations detected by each method. These data suggest that PNA-mediated real-time PCR clamping exhibits high sensitivity and is a simple procedure relative to direct DNA sequencing that is a useful screening tool for the detection of EGFR mutations in clinical settings.
Lung cancer (Amsterdam, Netherlands) 09/2011; 75(3):321-5. · 3.14 Impact Factor
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Manaljav Tseden-Ish,
Yoo-Duk Choi,
Hyun-Ju Cho,
Hee-Jung Ban,
In-Jae Oh,
Kyu-Sik Kim,
Sang-Yun Song,
Kook-Joo Na,
Sung-Ja Ahn,
Song Choi, Young-Chul Kim
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ABSTRACT: Expression of excision repair cross-complementation group 1 (ERCC1) is recognized as a favourable prognostic marker in patients who have undergone surgical resection of non-small cell lung cancer (NSCLC). However, in patients treated with adjuvant chemotherapy after surgical resection, ERCC1 correlated with poor prognosis. Class III beta tubulin (TUBB3) is also known to be a predictive marker of the efficacy of treatment with taxanes or vinorelbine.
Tumour tissues (n = 363) from patients with surgically resected NSCLC were analysed retrospectively. Tissue sections were labelled with ERCC1- and TUBB3-specific antibodies. Using genomic DNA from 262 patients, single nucleotide polymorphisms of the ERCC1 gene (T19007C and C8092A) were genotyped by PCR-restriction fragment length polymorphism analysis.
Only 5.9% of patients with stage I disease (14/238) and 61.6% of patients with stages II-III disease (77/125) received adjuvant chemotherapy. Relapses were noted in 30.6% (111) of patients, and among these, 31 ultimately succumbed. The relapse rate (RR) was 24.8% for stage I disease, and 41.6% for stages II-III disease. The RR was significantly lower in ERCC1-positive (24.3%) as compared with ERCC1-negative patients (36.3%, P = 0.014) and was lower in patients with the AA/CA genotype at the ERCC1 C8092A locus (29.5%) compared with those with the CC genotype (42.1%, P = 0.034). The median disease-free survival (DFS) time was 62.3 months. DFS was significantly greater in ERCC1-positive patients (62.3 months) than in ERCC1-negative patients (48.0 months, P = 0.042). In a multivariate analysis, ERCC1 expression and the C8092A polymorphism were independent prognostic factors in patients with stage I disease who were naïve to chemotherapy.
ERCC1 expression and the AA/CA genotype at the C8092A locus were correlated with a good prognosis in patients who had undergone surgical resection of NSCLC.
Respirology 09/2011; 17(1):127-33. · 2.42 Impact Factor
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Hyun Wook Kang,
Tae Ok Kim,
Bo Ram Lee,
Jin Yeong Yu,
Su Young Chi,
Hee Jung Ban,
In Jae Oh,
Kyu Sik Kim,
Yong Soo Kwon,
Yu Il Kim, Young Chul Kim,
Sung Chul Lim
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ABSTRACT: A reduction in diaphragm mobility has been identified in patients with chronic obstructive pulmonary disease (COPD) and has been associated with a decline in pulmonary function parameters. However, little information exists regarding the potential role of diaphragm mobility on hypercapnia in COPD. A new method of assessing the mobility of the diaphragm, using ultrasound, has recently been validated. The purpose of the present study was to investigate the relationship between diaphragm mobility and pulmonary function parameters, as well as that between arterial blood gas values and diaphragm mobility, in COPD patients. Thirty seven COPD patients were recruited for pulmonary function test, arterial blood gas analysis and diaphragm mobility using ultrasound to measure the craniocaudal displacement of the left branch of the portal vein. There were significant negative correlations between diaphragmatic mobility and P(a)CO(2) (r = -0.373, P = 0.030). Diaphragmatic mobility correlated with airway obstruction (FEV(1), r = 0.415, P = 0.011) and with ventilatory capacity (FVC, r = 0.302, P = 0.029; MVV, r = 0.481, P = 0.003). Diaphragmatic mobility also correlated significantly with pulmonary hyperinflation. No relationship was observed between diaphragm mobility and P(a)O(2) (r = -0.028, P = 0.873). These findings support a possibility that the reduction in diaphragm mobility relates to hypercapnia in COPD patients.
Journal of Korean medical science 09/2011; 26(9):1209-13. · 0.84 Impact Factor
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ABSTRACT: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways and progressive destruction of lung parenchyma. Apoptosis is critical for the maintenance of normal tissue homeostasis and is in equilibrium with proliferation and differentiation. This study was undertaken to investigate relationship between apoptosis of peripheral blood lymphocytes during exacerbation of COPD and inflammatory response that characterizes this condition.
Seventeen patients with COPD exacerbation, 21 stable COPD, and 12 control subjects were included. T lymphocytes were isolated from peripheral blood using MACS. Apoptosis of T lymphocytes was assessed with FACS using annexin V and 7-aminoactinomycin. Serum levels of interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-α were determined by an immunoassay technique.
There was significantly increased percentage of apoptotic lymphocytes, CD 4+, and CD 8+ T cells in the peripheral blood of patients with exacerbation of COPD compared with stable COPD. Serum levels of IL-6, IL-8, and TNF-α were significantly increased in patients with exacerbation of COPD compared with stable COPD. Only TNF-α presented a positive correlation with apoptotic lymphocytes in patients with exacerbation of COPD.
Increased apoptotic lymphocytes may be associated with upregulation of TNF-α in the peripheral blood of patients with acute exacerbation of COPD.
Yonsei medical journal 07/2011; 52(4):581-7. · 0.77 Impact Factor
