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PDF file - 49K, The expression of hc-smR-S2-5 in hc-smR-S2-5-transfected cells: The expression of hc-smR-S2-5 in A549 cells transfected with hc-smR-S2-5 or a negative control was determined by TaqMan miRNA Assay. (bars, SD; *, P < 0.05)

PDF file - 131K, The expression of c-Met in lung cells and tissues: (A) The expression of c-Met in various lung-derived cells was determined by quantitative RT-PCR analysis. (B) The expression of c-Met was compared between lung cancer tissue and normal lung tissue. Experiments were repeated three times. (bars, SD; *, P < 0.05)

MicroRNAs (miRNA) are small noncoding RNAs that regulate gene expression in human diseases, including lung cancer. miRNAs have oncogenic and nononcogenic functions in lung cancer. In this study, we report the identification of a novel miRNA, miR-7515, from lung cancer cells. The novel miR-7515 was characterized using various predictive programs and experimental methods. miR-7515 was able to forming a stem-loop structure and its sequence was conserved in mammals. The expression level of miR-7515 in lung cancer cells and tissues was profiled using TaqMan miRNA assays. miR-7515 was downregulated in lung cancer compared with normal human lung cells and tissues. The target of miR-7515 was determined using a dual luciferase reporter assay. Expression of the target gene was determined by quantitative RT-PCR and Western blot analysis after transfection with miR-7515. miR-7515 directly suppressed human mesenchymal–epithelial transition factor (c-Met) by binding to the 3′ untranslated region (UTR). Overexpression of miR-7515 significantly decreased cell-cycle–related proteins downstream of c-Met through c-Met inhibition. Cell proliferation and migration were examined using the XTT proliferation assay and the Transwell migration assay. miR-7515 led to decreased cell proliferation, migration and invasion in a lung cancer cell line. These results suggest that miR-7515 plays an important role in the proliferation and migration of lung cancer cells through c-Met regulation. Mol Cancer Res; 11(1); 43–53. ©2012 AACR.

PDF file - 80K, The expression of hc-smR-S2-5 in Dicer knock-down cells: (A) Dicer mRNA expression in Dicer knock-down cells was determined by RT-PCR analysis. (B) The expression of hc-smR-S2-5 in Dicer knock-down cells was determined by TaqMan miRNA Assay. let-7a, a known miRNA, was used as a positive control. Experiments were repeated three times. (bars, SD; *, P < 0.05)

PDF file - 69K, The expression of hc-smR-S2-5 in various cell types: The expression of hc-smR-S2-5 in various cell types was determined by poly A-tailed RT-PCR

PDF file - 47K, Lung cancer patient tissues: Information of 10 human lung tissue samples

// Sun Min Lim 1, 2 * , Hye Ryun Kim 1 * , Eun Kyung Cho 3 , Young Joo Min 4 , Jin Seok Ahn 5 , Myung-Ju Ahn 5 , Keunchil Park 5 , Byoung Chul Cho 1 , Ji-Hyun Lee 6 , Hye Cheol Jeong 6 , Eun Kyung Kim 6 , Joo-Hang Kim 2 1 Department of Internal Medicine, Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea 2 Department of Internal Medicine, Division of Medical Oncology, CHA Bundang Medical Center, CHA University, Seongnam, Korea 3 Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea 4 Department of Oncology, Asan Medical Center, University of Ulsan college of Medicine, Seoul, Korea 5 Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 6 Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea * These authors have contributed equally to this work Correspondence to: Joo-Hang Kim, email: kim123@cha.ac.kr Keywords: primary resistance, epidermal growth factor, next-generation sequencing, tyrosine kinase inhibitor Received: March 01, 2016 Accepted: April 05, 2016 Published: April 21, 2016 ABSTRACT Background: Non-small-cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor ( EGFR ) mutations may exhibit primary resistance to EGFR tyrosine kinase inhibitor (TKI). We aimed to examine genomic alterations associated with de novo resistance to gefitinib in a prospective study of NSCLC patients. Methods: One-hundred and fifty two patients with activating EGFR mutations were included in this study and 136 patients’ tumor sample were available for targeted sequencing of genomic alterations in 22 genes using the Colon and Lung Cancer panel (Ampliseq, Life Technologies). Results: All 132 patients with EGFR mutation were treated with gefitinib for their treatment of advanced NSCLC. Twenty patients showed primary resistance to EGFR TKI, and were classified as non-responders. A total of 543 somatic single-nucleotide variants (498 missense, 13 nonsense) and 32 frameshift insertions/deletions, with a median of 3 mutations per sample. TP53 was most commonly mutated (47%) and mutations in SMAD4 was also common (19%), as well as DDR2 (16%), PIK3CA (15%), STK11 (14%), and BRAF (7%). Genomic mutations in the PI3K/Akt/mTOR pathway were commonly found in non-responders (45%) compared to responders (27%), and they had significantly shorter progression-free survival and overall survival compared to patients without mutations (2.1 vs . 12.8 months, P =0.04, 15.7 vs. not reached, P

Myocarditis is an inflammatory disease of the myocardium caused by various infectious or noninfectious triggers. Although viral infections are important causes of myocarditis, some drugs or toxins can also cause myocarditis. We report a case of life-threatening fulminant myocarditis which followed an extensive coffee diet program. Despite medical treatment, the patient was not able to maintain hemodynamic stability. She was supported by extracorporeal membrane oxygenation and completely recovered 3 months later.

MicroRNAs (miRNA) are small noncoding RNAs that regulate gene expression in human diseases, including lung cancer. miRNAs have oncogenic and nononcogenic functions in lung cancer. In this study, we report the identification of a novel miRNA, miR-7515, from lung cancer cells. The novel miR-7515 was characterized using various predictive programs and experimental methods. miR-7515 was able to forming a stem-loop structure and its sequence was conserved in mammals. The expression level of miR-7515 in lung cancer cells and tissues was profiled using TaqMan miRNA assays. miR-7515 was downregulated in lung cancer compared with normal human lung cells and tissues. The target of miR-7515 was determined using a dual luciferase reporter assay. Expression of the target gene was determined by quantitative RT-PCR and Western blot analysis after transfection with miR-7515. miR-7515 directly suppressed human mesenchymal–epithelial transition factor (c-Met) by binding to the 3′ untranslated region (UTR). Overexpression of miR-7515 significantly decreased cell-cycle–related proteins downstream of c-Met through c-Met inhibition. Cell proliferation and migration were examined using the XTT proliferation assay and the Transwell migration assay. miR-7515 led to decreased cell proliferation, migration and invasion in a lung cancer cell line. These results suggest that miR-7515 plays an important role in the proliferation and migration of lung cancer cells through c-Met regulation. Mol Cancer Res; 11(1); 43–53. ©2012 AACR.

Primary effusion lymphoma (PEL) is a rare type of lymphoma that arises in the body cavity without detectable masses. It is associated with human herpes virus-8 (HHV-8), Epstein-Barr virus (EBV), and human immunodeficiency virus (HIV). Recently, PEL unrelated to viral infection has been reported and it has been termed HHV-8 unrelated primary effusion lymphoma-like lymphoma (HHV-8 unrelated PEL-like lymphoma). Here, we report a case of HHV-8 unrelated PEL-like lymphoma in an 80-year-old woman. Chest X-ray and computed tomography revealed left-sided pleural effusion. Pleural effusion analysis and mediastinoscopic biopsy showed atypical cells that had originated from the B cells. The cells were positive for CD20 and bcl-2, but negative for CD3, CD5, CD21, CD30, CD138, epithelial membrane antigen, and HHV-8. Serological tests for HIV and EBV were negative. Considering the patient's age, further treatments were not performed. She has shown good prognosis without chemotherapy for more than 18 months.

Purpose: Because evasion of tumor suppression is a critical step in cancer development, cancer cells have developed a variety of mechanisms to circumvent the influence of tumor suppressive pathways. Thus, genes that negatively regulate tumor suppressors could be considered novel types of oncogenes such as Bmi-1 repressing p16Ink4a and inhibiting p53 and were found to be frequently up-regulated in a variety of cancers. p38 mitogen-activated protein kinase (MAPK), which reportedly plays a crucial role as a tumor suppressor, is activated in number of lung adenocarcinomas, which is seemingly at odds with its role as a tumor suppressor. Methods: We examined 10 lung adenocarcinomas and corresponding normal tissues and determined the expression levels of a variety of tumor suppressor proteins through real-time polymerase chain reaction and immunohistochemistry and measured p38 MAPK activity by immunoblotting or immunohistochemistry analysis. In the in vitro cellular model, p38 activation by H-Ras and consequent senescence induction was achieved through retro-viral gene transduction. Similarly, the suppression of p16Ink4a by Bmi-1 after the introduction of H-Ras was achieved through transient transfection with cationic liposome. Results: We detected several lung adenocarcinomas that were positive for activated p38 MAPK but evidenced reduced levels of p16Ink4a expression. The suppression of p16Ink4a occurred in parallel with an increase in Bmi-1 and/or p16Ink4a promoter hypermethylation. Consistent with these observations, the H-Ras-stimulated induction of p16Ink4a was suppressed significantly through the coexpression of Bmi-1 in vitro. Discussion: These results demonstrate that the suppression of p16Ink4a by either the induction of Bmi-1 or the hypermethylation of p16Ink4 may be an important step in avoiding tumor surveillance by p38 MAPK during the development of lung cancer.

Myasthenia gravis (MG) is often complicated by respiratory failure, known as a myasthenic crisis. However, most of the patients who develop respiratory symptoms do so during the late course of disease and have other neurological signs and symptoms. However, in some patients respiratory failure is the initial presenting symptom. We report the case of a 68-year-old woman with MG who presented with isolated respiratory failure as her first presenting symptom. As illustrated by this case, it is important to consider neuromuscular disorders in cases of unexplained respiratory failure.

Summary A 56-year-old woman presented with bile-tinged sputum for one year. Five years ago, she was diagnosed with hepatocellular carcinoma. She was treated with five hepatic arterial chemotherapies, two radiofrequency ablations, four chemoembolizations, and a right lobectomy of the liver. Two years ago, a liver abscess with biliary stricture occurred and was treated with endoscopic biliary drainage and balloon dilatation. On admission, bronchoscopy suggested a bronchobiliary fistula in the anterobasal segment of the right lower lobar bronchus. Fluorography showed a fistulous tract between the right lower lobar bronchus and the liver abscess pocket. We performed histoacryl embolization under bronchoscopic guidance and the bile-tinged sputum resolved. However, biliary obstruction and hepatic failure followed and the patient expired three months later. We report a case of a bronchobiliary fistula managed with a bronchoscopic approach.

Primary malignant fibrous histiocytoma (MFH) of the lung is a very rare neoplasm that usually presents as a parenchymal mass. Here we report an unusual case of primary MFH of the bronchus, showing relatively benign clinical features. We performed a palliative resection via flexible bronchoscopy, using a polypectomy snare. The patient has survived for over 2 years after being diagnosed with an endobronchial mass, later found to be MFH, and 14 months post-debulking. There is a possibility that endobronchial MFH has a more favorable prognosis than MFH of other origins. If this is true, interventional bronchoscopy can be a reasonable option for non-operable cases of MFH.

MicroRNAs (miRNAs) are a class of small noncoding RNAs that modulate target gene activity, and are aberrantly expressed in most types of cancer as well in lung cancer. A miRNA can potentially target a diverse set of mRNAs; further, it plays a critical role in lung tumorigenesis as well as affects patient outcome. Previous studies focused mainly on abnormal miRNAs expressions in lung cancer tissues. Interestingly, circulating miRNAs were identified in human plasma and serum in 2008. Since then, considerable effort has been directed to the study of circulating miRNAs as one of the biomarkers of lung cancer. miRNAs expression of tissues and blood in lung cancer patients is being analyzed by more researchers. Recently, to overcome the high false-positivity of low-dose chest computed tomography scan, miRNAs in lung cancer screening are being investigated. This article summarizes the recent researches regarding clinical applications of miRNAs in the diagnosis and management of lung cancer.

Pulmonary artery sarcoma (PAS) is a rare, poorly differentiated malignancy arising from the intimal layer of the pulmonary artery. Contrast-enhanced chest computed tomography (CT) is a good diagnostic modality that shows a low-attenuation filling defect of the pulmonary artery in PAS patients. An 18-year-old man was referred to our hospital for the evaluation and management of cavitary pulmonary lesions that did not respond to treatment. A contrast-enhanced CT of the chest was performed, which showed a filling defect within the right interlobar pulmonary artery. The patient underwent a curative right pneumonectomy after confirmation of PAS. Although lung parenchymal lesions of PAS are generally nonspecific, it can be presented as cavities indicate pulmonary infarcts. Clinicians must consider the possibility of PAS as well as pulmonary thromboembolism in patients with pulmonary infarcts. So, we report the case with PAS that was diagnosed during the evaluation of cavitary pulmonary lesions and reviewed the literatures.

Although the lung is the most common site of metastasis from extrapulmonary malignancies, endobronchial metastases (EBM) are relatively rare. EBM typically originate from breast, colorectal, or kidney cancer. EBM from uterine cervical cancer is relatively rare and is difficult to confirm. In this study, we report a case of EBM in a patient with previously treated uterine cervical cancer. In this case, differentiation of the EBM from primary bronchogenic carcinoma with clinical, radiological, and pathologic findings was difficult. As identical human papillomavirus (HPV)-16 DNA was detected in both the EBM and in previously resected tissues from the prior uterine cervical cancer, the patient was diagnosed with EBM from uterine cervical cancer. HPV genotyping may aid in discriminating EBM from primary bronchogenic carcinoma in patients with uterine cervical cancer.

Chronic obstructive pulmonary disease (COPD) is classified into emphysema and chronic bronchitis, which are thought to result from different pathophysiological pathways. Smoking-induced lung parenchymal destruction and inadequate repair are involved in the pathogenesis of emphysema. In addition, decreased expression of vascular endothelial growth factor and increased endothelial cell apoptosis in the lung may participate in emphysema pathogenesis. As stem cells, circulating endothelial progenitor cells (EPCs) may play a key role in the maintenance of vascular integrity by replacing and repairing the damaged endothelial cells in the tissues. To determine whether the lack of appropriate repair by circulating EPCs in cases of smoking-induced endothelial cell injury participates in emphysema pathogenesis, we determined the association between the colony-forming or migratory capacity of circulating EPCs and the presence of emphysema in 51 patients with COPD. The patients were divided into emphysema (n = 23) and non-emphysema groups (n = 28) based on high-resolution computed tomography. Twenty-two smokers with normal lung function and 14 normal non-smokers served as controls. Circulating EPCs isolated from patients with emphysema showed significantly lower colony-forming units (CFUs) than those from patients with non-emphysema group, smokers with normal lung function, and normal non-smokers. EPCs from patients with emphysema showed significantly lower migratory capacity than those from normal non-smoking controls (p < 0.05). On multivariate analysis, the EPC-CFU was independently associated with emphysema (OR 0.944, 95% CI = 0.903-0.987, p = 0.011). Thus, impaired functions of circulating EPCs may contribute to the development of emphysema.

Abnormal expression of let-7a microRNA (miRNA) in non-small cell lung cancer (NSCLC) cells and tissue has been previously reported. Our objective was to investigate whether let-7a miRNA is aberrantly expressed in the blood of NSCLC patients. Using real-time PCR (RT-PCR), we analyzed let-7a miRNA in archived whole blood from 65 participants, 35 of whom had NSCLC and 30 of whom did not. Using RT-PCR, we also investigated the expression of let-7a miRNA in NSCLC cell lines (A549 and HCC 1588), a normal human lung fibroblast cell line (WI-38) and in 40 human NSCLC tissues. The 2(-ddCt) of let-7a miRNA in the blood of normal subjects and those with NSCLC was 3242.49±355.28 and 747.85±177.74, respectively. The relative expression of let-7a miRNA in the A549 and HCC 1588 cancer cell lines was approximately 0.3 and 0.35, respectively, compared to WI-38 cells. The 2(-ddCt) of let-7a miRNA in the normal human lung tissues and human NSCLC tissues was 42.30±3.98 and 27.73±3.86, respectively. Let-7a miRNAs were under-expressed in the blood of NSCLC patients, as well as NSCLC cells and NSCLC tissues, compared to normal controls. The possibility of using let-7a miRNA as a serologic marker for lung cancer warrants further study.

Primary anaplastic large cell lymphoma (ALCL) of the lung is highly aggressive and quite rare. We report here a case of anaplastic lymphoma kinase-positive endobronchial ALCL, that was initially thought to be primary lung cancer. A 68-year-old woman presented with hemoptysis, dyspnea, and upper respiratory symptoms persisting since 1 month. The hemoptysis and and bronchial obstruction lead to respiratory failure, prompting emergency radiotherapy and steroid treatment based on the probable diagnosis of lung cancer, although a biopsy did not confirm malignancy. Following treatment, her symptoms resolved completely. Chest computed tomography scan performed 8 months later showed increased and enlarged intra-abdominal lymph nodes, suggesting lymphoma. At that time, a lymph node biopsy was recommended, but the patient refused and was lost to follow up. Sixteen months later, the patient revisited the emergency department, complaining of persistent abdominal pain since several months. A laparoscopic intra-abdominal lymph node biopsy confirmed a diagnosis of ALCL.

목적: 본 연구는 결핵 접촉자 조사에서 수집된 자료를 분석하고 그 결과를 평가하고자 계획되었다. 방법: 2012년 8월부터 2014년 7월까지 만 19세 이상의 배양검사 양성인 폐결핵 환자의 소아청소년접촉자들의 진료기록을 검토하였다. 결과: 배양검사 양성인 폐결핵 환자 79명과 그들의 소아청소년 접촉자 116명이 확인되었다. 확인된접촉자 116명 중 22%는 접촉자 검진을 중단하였다. 접촉자 검진을 완료한 90명 중 TST 음성이 42%이고 TST 양성이 58%였으며, 검진 기간 중 1%가 활동성 폐결핵으로 진단되었다. 항산균 도말 검사 음성 결핵 환자들의 접촉자 50명의 TST 양성률은 50%였다. 5세 이상의 연령(OR 8.3; 95% CI 2.3-30)과 남성(OR 3.9; 95% CI 1.5-9.9)이 접촉자 검진 중단과 유의하게 연관되었다. 결론: 활동성 폐결핵 환자들의 접촉자들을 확인하고 올바르게 검진하기 위해서 접촉자 검진 과정의 개선이 필요하다.

Anaphylaxis/anaphylactoid reaction is a medical emergency. In rare cases, acute respiratory distress syndrome (ARDS) can complicate this disorder. This is a case report of an anaphylactoid reaction complicated with ARDS that was successfully treated using extracorporeal membrane oxygenation (ECMO). A 52-year-old female patient developed sudden dyspnea immediately after she received gadolinium contrast injection and 80 mg of oral propranolol. She progressed rapidly to a state of shock and her chest radiograph showed pulmonary edema. The shock and pulmonary edema did not respond to epinephrine or steroid injection. On the next day, the permeability edema worsened and laboratory test revealed extreme hemoconcentration. The oxygenation goal was not achieved with mechanical ventilation alone, thus ECMO was applied as well. The patient showed clinical improvements on the 3rd day and was weaned from ECMO on the 4th day. She was completely recovered from shock and respiratory distress by day 5. The patient was discharged from hospital without further complications.

The fat-forming variant of solitary fibrous tumors (SFTs) is a rare soft tissue neoplasm that was previously referred to as a lipomatous hemangiopericytoma (L-HPC). The most common affected site is deep soft tissue. Here, we present the first case, worldwide, of a fat-forming variant of SFT of the pleura. A 74-year-old man presented with left lower chest pain. Chest radiographs showed a mass-like les ion at the left lower lung field and chest computed tomography revealed a 12 cm fat-containing enhancing mass that was well-separated, lobulated and inhomo-geneous. Radiology findings suggested a liposarcoma. Percutaneous needle biopsy was performed and pathological diagnosis of the mass was a fat-forming variant of SFT. Surgical resection was carried out and there has been no recurrence to date. So, a benign fat-forming variant of SFT must be considered as one of the differential diagnoses of lipomatous tumors of the pleura.Key Words: Solitary Fibrous Tumors; Pleura; Lipoma

A benign pulmonary metastasizing leiomyoma is a recognized clinical entity that has been infrequently reported in the medical literature. We report two cases of a benign pulmonary metastasizing leiomyoma. A 35-year-old woman who underwent myomectomy and a cesarean section approxima tely 6 years earlier visited our hospital for further evaluation of incidentally revealed multiple lung nodules. A diagnostic percutaneuous biopsy was performed. Finally she was diagnosed with a benign metastasizing leiomyoma. The patient then received LH-RH and has been followed up since. The other 44-year-old woman presented after an initial radiology evaluation revealed the presence of multiple, small-sized lung nodules. She underwent a right middle lung wedge resection to confirm the diagnosis. Finally she diagnosed with a benign metastasizing leiomyoma. The multiple lung nodules have been followed up closely.

Pulmonary arterial thrombosis develops during hypercoagulable states, intra-arterial tumorous conditions, and congenital heart disease accompanied by pulmonary hypertension. Thrombosis in the main pulmonary arterial stump after pneumonectomy can also occur. Herein, we report a very rare case of pulmonary arterial thrombosis in a patient with pulmonary hypertension and a lung destroyed by tuberculosis. He presented with aggravated dyspnea without fever or purulent sputum. His chest computerized tomography scan showed left main pulmonary arterial thrombosis as a convex shape, with the ipsilateral distal arteries and arterioles showing parenchymal destruction. After excluding pulmonary thromboembolism and hypercoagulable disorders, we diagnosed pulmonary arterial thrombosis and treated him with an anticoagulant.

Background: The currently available diagnostic markers for pleural effusion have a limited role. The soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is a molecule recently reported to play an important role in the myeloid cell mediated inflammatory response, and is up regulated in the body fluid by bacterial or fungal products. This study examined the expression of sTREM-1 in pleural effusion. Methods: Between April 2004 and December 2005, 48 patients with pleural effusions were enrolled in this study. The pleural fluids were taken and analyzed for the total protein, glucose, lactate dehydrogenase (LDH), adenosine deaminase (ADA), and sTREM-1. Bacterial cultures and cytology tests were also performed. Results: The clinical diagnoses were 17 parapneumonic, 14 tuberculous, and 13 malignant effusions. Four patients presented with transudates. The mean ages of the parapneumonic, tuberculous and malignant effusion groups were , , , and . respectively. The level of sTREM-1 expression was significantly higher in the parapneumonic effusions () than in the tuberculous effusions () and malignant effusions (). With a cut-off value of 55.4pg/ml, the sensitivity and specificity for a parapneumonic effusion was 70.6% and 74.1%. Conclusion: sTREM-1 expression is significantly higher in parapneumonic effusions, suggesting its potential role as an additional diagnostic marker for pleural effusions.

Background : Recently, there have been several studies showing that irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against extensive disease(ED) small cell lung cancer (SCLC). We conducted a phase II trial to evaluate the efficacy and toxicity of irinotecan plus cisplatin as a 1st line therapy for both limited and extensive disease SCLC. Methods : The study was conducted between January 2002 and June 2004. Patients were treated with irinotecan on day 1, 8, 15 and cisplatin on day 1, every 4 weeks. During concurrent thoracic irradiation for limited disease (LD)-SCLC patients, dose of irinotecan was reduced to . Prophylactic cranial irradiation was given to patients with complete remission (CR) after chemotherapy. Results : Median ages of LD- and ED- SCLC were 64 years and performance status (PS) was 0-2. In patients with LD-SCLC, the response rate after concurrent chemoradiotherapy was 85% (CR, 6; Partial response [PR], 11). The median survival was 20 months (95% CIs, 15.6 to 24.4) with 1-and 2-year survival rates of 85% and 35%, respectively. Median progression free survival (PFS) was 12 months (95% CIs, 6.2 to 18.1) with 1- year PFS of 36%. In ED-SCLC, the response rate was 83.4% (CR, 1; PR, 14). The median survival was 14.5 months (95% CIs, 8.8 to 20.1) with 1-year survival rates of 75%. Median PFS was 6.3 months (95% CIs, 5.6 to 7.1) with 1- year PFS of 20%. The major toxicities (grade 3 or 4) of this regimen included leukopenia, anemia, thrombocytopenia, nausea/vomiting, and diarrhea without life threatening complication. Conclusion : Our data shows that the combination of irinotecan plus cisplatin as a first line therapy is effective and tolerable in the treatment of both LD- and ED- SCLC.

Background : The role of combination therapy of inhaled corticosteroid (ICS) plus long-acting (LABA) in asthma is well established, but nor much is known about this treatment in COPD. Recent studies have revealed that combining therapy is associated with fewer acute exacerbations in COPD, but in most of the studies, high-dose combination therapies have been employed. The current study assessed the effect of moderate or high-dose combination therapy of ICS plus LABA on the frequency of acute exacerbations in COPD. Methods : Between January 1, 2001 and August 31, 2004, 46 patients with COPD (moderate, severe, very severe) were enrolled who received either fluticasone/salmeterol (flu/sal) twice a day (group A) or flu/sal twice a day (group B) for more than a year. We divided them into two groups depending on the dosage of ICS plus LABA. Effect of drugs was compared based on the factors such as symptom aggravation, number of admission, and time to first exacerbation during a year after use. Results : Eleven of twenty-six patients in group A (42.3%) experienced acute exacerbation and eleven of twenty patients in group B (55%) experienced acute exacerbation during 1 year. Mean exacerbation rate of Group A was 0.96 and Group B was 1.05. Mean admission rate was 0.15 and 0.30, respectively. There was no statistically significant difference of aggravation rate, number of administration and time to first exacerbation between the two treatment groups. Conclusion : There was no significant difference between moderate and high dose combined inhaler therapy to reduce acute exacerbation in COPD patients (moderate, severe, very severe). Hence, the effective dose of combination therapy needs further study in patients with COPD.

Backgroud : Lung cancer is the leading cause of cancer deaths in Korea and the number of lung cancer deaths is increasing. The higher response rates, decreased toxicity and improved performance status of the first-line treatments have resulted in an increased number of patients becoming candidates for second-line therapy. Several new antineoplastic agents, including gemcitabine, docetaxel and paclitaxel, have recently demonstrated second-line activity. This phase II study evaluated the efficacy and toxicity of gemcitabine and vinorelbine as combination chemotherapy for Korean patients with NSCLC as a second-line treatment. Methods : Sixty response-evaluable patients were enrolled from December 2000 to July 2003. We conducted a phase II study of a combination gemcitabine and vinorelbine chemotherapy for patients with histologically confirmed NSCLC that was stage IIIB and IV disease at the time of diagnosis, and the disease had progressed onward or the patients had relapsed after first-line platinum-based chemotherapy. They were treated with intravenous gemcitabine and intravenous vinorelbine on days 1 and 8. This chemotherapy regimen was repeated every 3 weeks. Results : A total of 215 cycles of treatment were given and the mean number of cycles was 3.6 cycles. All the patients were evaluable for the toxicity profile. The response rate was 10% according to the WHO criteria. The median progression free survival was 3.8 months and the median survival time was 10.1 months. The 1-year survival rate was 32.9%. Grade III and IV neutropenia were seen in 20 (33.3%) and 7 (11.7%) patients, respectively. Conclusion : The combination of gemcitabine and vinorelbine is active and well tolerated as a second-line therapy for patients with advanced nonsmall cell lung carcinoma.

Background : Idiopathic pulmonary fibrosis(IPF) is a devastating illness for which there is little effective treatment. The key cytokines currently implicated in the fibrotic process are the transforming growth factor-(TGF-), tumor necrosis factor-(TNF-), endothelin-1(ET-1) and interferon-(IFN-). The rat model for paraquat-induced pulmonary fibrosis was chosen to investigate the role of ET-1 in this disease. Both ET-1 and TGF- expression in lung lesions were examined using immunohistochemical staining. After administration, an orally active ET- and ET- receptor antagonist, the degree of pulmonary fibrosis and ET-1 and TGF- expression were analyzed. Method : Sprague-Dawley rats were divided into three groups, the control group, the fibrosis group, and the fibrosis--treated group. The animals were sacrificed periodically at 1, 3, 5, 7, 10, 14 days after administering saline or paraquat. The effects between groups were compared with the results of light microscopy and immunohistochemical staining for ET-1 and TGF-. The degree of fibrosis was evaluated by H&E and Masson's trichrome staining, which were graded by a computerized image analyzer. The degree of immunohistochemical staining was categorized by a semi-quantitative analysis method. Results : The lung collagen content had increased in the paraquat instillated animals by day 3, and continued to increase up to day 14. A daily treatment by gavage with (100mg/kg) did not prevent the increase in collagen deposition on the lung that was induced by paraquat instillation. There were increased immunohistochemical stains of ET-1 on the exudate, macrophages, vascular endothelial cells and pneumocytes in the paraquat instillated group. Furthermore, TGF- expression was higher on the exudate, macrophages, some inflammatory cells, pneumocytes( type I, and II), vascular endothelium and the respiratory epithelial cells around the fibrotic area. After Bosentan treatment, there were no definite changes in ET-1 and TGF- expression. Conclusion : Fibrosis of the Paraquat instillated group was more advanced when compared with the control group. In addition, there was increased ET-1 and TGF- expression around the fibrotic area. ET-1 is associated with lung fibrosis but there was little effect of the ET-1 receptor blocker() on antifibrosis.Background : Idiopathic pulmonary fibrosis(IPF) is a devastating illness for which there is little effective treatment. The key cytokines currently implicated in the fibrotic process are the transforming growth factor-(TGF-), tumor necrosis factor-(TNF-), endothelin-1(ET-1) and interferon-(IFN-). The rat model for paraquat-induced pulmonary fibrosis was chosen to investigate the role of ET-1 in this disease. Both ET-1 and TGF- expression in lung lesions were examined using immunohistochemical staining. After administration, an orally active ET- and ET- receptor antagonist, the degree of pulmonary fibrosis and ET-1 and TGF- expression were analyzed. Method : Sprague-Dawley rats were divided into three groups, the control group, the fibrosis group, and the fibrosis--treated group. The animals were sacrificed periodically at 1, 3, 5, 7, 10, 14 days after administering saline or paraquat. The effects between groups were compared with the results of light microscopy and immunohistochemical staining for ET-1 and TGF-. The degree of fibrosis was evaluated by H&E and Masson's trichrome staining, which were graded by a computerized image analyzer. The degree of immunohistochemical staining was categorized by a semi-quantitative analysis method. Results : The lung collagen content had increased in the paraquat instillated animals by day 3, and continued to increase up to day 14. A daily treatment by gavage with (100mg/kg) did not prevent the increase in collagen deposition on the lung that was induced by paraquat instillation. There were increased immunohistochemical stains of ET-1 on the exudate, macrophages, vascular endothelial cells and pneumocytes in the paraquat instillated group. Furthermore, TGF- expression was higher on the exudate, macrophages, some inflammatory cells, pneumocytes( type I, and II), vascular endothelium and the respiratory epithelial cells around the fibrotic area. After Bosentan treatment, there were no definite changes in ET-1 and TGF- expression. Conclusion : Fibrosis of the Paraquat instillated group was more advanced when compared with the control group. In addition, there was increased ET-1 and TGF- expression around the fibrotic area. ET-1 is associated with lung fibrosis but there was little effect of the ET-1 receptor blocker() on antifibrosis.

Background and Object : Immunostimulatory CpG-oligodeoxynucleotides (ISS CpG-ODN) up-regulate the -type immune response and down-regulate the -type response. This study was performed to investigate the immune response changes resulting from ISS CpG-ODN on bronchial hyperresponsiveness, eosinophilic inflammation and mucus hypersecretion in rat asthma. Materials and Methods : 10 normal controls(NC) and 26 asthmatic rats, which were generated by ovalbumin(OVA) sensitization and challenge, were studied. The asthmatic rats were randomized into 11 asthma controls(AC) and 15 in the asthma-CpG treatment group(CpG). The CpG group was administered ISS CpG-ODN intramuscularly and the AC group was administered a placebo(0.9% NaCl) on day 15 and 20. After CpG-ODN or placebo administration, we measured the IFN-(-type cytokine) and IL-4(-type cytokine) levels in the bronchoalveolar lavage fluid(BALF), the specific airway resistance(sRaw), eosinophilic fraction in BALF, eosinophilic infiltration, goblet cell dysplasia and MUC5AC gene expression in the lung tissue. Results : In the BALF of the CpG group, the IFN- concentration was significantly high and the IL-4 concentration was significantly low when compared with the AC group. Both the sRaw and eosinophilic fraction, and infiltration into the BALF and lung tissue significantly lower in the CpG group when compared with the AC group. However, little difference in goblet cell dysplasia and MUC5AC gene expression was observed between the CpG group and the AC group. Conclusion : ISS CpG-ODN decreases bronchial hyperresponsiveness and eosinophilic inflammation in the rat asthma model through the up-regulation of the -type immune response with the down-regulation of the -type response. However, the effect of these immune response changes on mucus hypersecretion was is not remarkable in this study.

Diffuse pulmonary nodular lesions have many causes. When they are caused by infection, the likely organisms are M. tuberculosis and various fungi. Silicosis, eosinophilic granuloma and pulmonary metastasis should be considered for differential diagnosis. Differential diagnosis needs detailed clinical history, physical examination and various laboratory tests. A case of persistent diffuse pulmonary nodular lesions which had persisted 5 years is reported. The patient was a 25 years old man with minimal pulmonary symptoms. Detailed past history and physical examination suggested thyroid tumor. Chest radiography showed numerous evenly sized well-defined nodules scattered in entire lung fields. Previous chest X-rays showed similar nodular lesions, which had lasted for 5 years. The number of nodules was slightly increased. Neck CT showed heterogenous mass in left lobe of thyroid gland and multiple lymphadenopathies along both internal jugular chains. Total thyroidectomy was performed. A case of lung metastasis which progressed slowly in papillary thyroid cancer is reported.

Background : The herbicide paraquat can cause severe lung injury and fibrosis in experimental animals. In this study we have investigated the changes in lung endothelin-1(Et-1) levels and immunohistochemical localization in relation to treatment with cyclophosphamide and methylprednisolone in paraquat induced pulmonary fibrosis in guinea pigs. Material and methods : 29 male Hartley guinea pigs were divided into 4 groups. Group I was normal control. Paraquat was instilled into the lung of guinea pig of group II, III and IV unilaterally. Group II was treated with cyclophosphamide and methylprednisolone. Group III was treated with methlprednisolone. Group IV was not treated. The degree of fibrosis was evaluated by H-E stains and Masson's trichrome stains and cell activity was assessed by Et-1 immunohistochemical stains. Statistical evaluation was performed using the Kruskawallis oneway analysis. Results : Paraquat induced an increase in numbers of fibroblasts and total amount of lung collagen in Group IV compared to the normal controls. There was no significant difference in total numbers of fibroblasts between any of paraquat instilled groups, but there was significant increase in total amount of collagen in Group IV compared to group II and III (p

Background: Persistent nonproductive cough is a major adverse effect encountered with ACE inhibitor treatment and the most frequent reason for withdrawal of the drug. The mechanism of cough was postulated to be associated with accumulation of bronchial irritants which are substrates of ACE. It has been speculated that occurrence of this adverse effect is genetically predetermined ; in particular, variants of the genes encoding ACE. To investigate this relationship, we determined ACE gene Insertion/Deletion polymorphism in subjects with and without a history of ACE inhibitor-induced cough. Methods: Among the 339 patients with ACE inhibitor treatment, subjects who developed cough that resolved when not taking medication were designated to cough group and other subjects who did not complain cough were designated to non-cough group. Clinical characteristics of the patients were collected by review of medical records. ACE genotypes were determined by PCR amplification of DNA from peripheral blood and agarose gel electrophoresis. Results: 37 patients complained of dry cough(cough group) and 302 patients did not complained of cough(non-cough group). The incidence of ACE inhibitor induced dry cough was 10.9%. There was a preponderance of females in the cough group (M : F=24.3% : 75.7%) compared to the non-cough group (M : F=49.7% : 50.3%, p=0.004). There was no significant difference in mean age, underlying diseases, and kinds and frequencies of ACE inhibitors and their mean dosage between the both groups. ACE genotypic frequencies were I/I : I/D : D/D=16.2% : 18.9% : 64.9% in the cough group and 18.9% : 18.2% : 62.9% in the non-cough group which showed no significant difference between the both groups(p=0.926). Allelic frequencies were I : D = 25.7% : 74.3% and 28.0% : 72.0% in the cough and non-cough group respectively and the difference was not significant(p = 0.676). Conclusion: The incidence of ACE inhibitor-induced cough are 10.9%, and women are more susceptible to ACE inhibitor-induced cough. ACE inhibitor-induced dry cough is not associated with ACE gene Insertion/Deletion polymorphism.

연구배경: 만성기침이란 기침이 적어도 3주 이상 지속되는 경우로, 원인으로는 후비루 증후군, 기관지천식, 위식도역류, 기관지 확장증, 만성기관지염, 안지오텐신 전환 효소 길항제 사용 등이 있다. 하지만 특별한 원인을 발견할 수 없고, 다른 증상 없이 단지 만성기침만 있는 경우에 대해서는 그 임상상과 조직병리소견이 아직도명확하게 규명되어 있지 않다. 이에 저자 들은 특별한 원인을 밝힐 수 없고, 다른 호흡기 증상이 없이 만성기침만을 호소하는 환자를 대상으로 임상상과 조직소견을 조사하여, 그 병인기전과 원인을 규명하고자 본 연구를 시행하였다. 방 법: 대상환자는 3주 이상 만성기침 외에 다른 호흡기 증상이 없는 25명의 환자들이었고, 후비루증후군, 위식도 역류, 약물 복용력 및 흉부질환, 심혈관 질환, 전신질환이 없었으며, 과거에 기관지 천식을 진단 받은 병력이 없었고, 폐기능 검사, 흉부 X-선 검사상 특이 소견이 없었다. 남자 10명 여자 15명으로 평균연령은 39.8세였고, 흡연가가 5명, 비흡연가가 20명이었다. 폐기능 검사, 메타콜린 유발검사, 알레르기 피부 단자 검사, 기관지 내시경하 점막 조직 생검을 시행하였고, 조직 비교를 위하여 정상 대조군 5명에 대해서도 기관지 내시경하 점막 조직 생검을 시행하였다. 모든 검사가 끝난 후, prednisolone 20~30 mg/일을 1~2주간 투여하였고, cough score로 치료반응 여부를 확인하였다. 결 과: 정상 대조군의 조직소견과 비교해 볼 때, 염증세포의 분포에 따라 대상군은 호산구 침윤이 저명한 경우(호산구 침윤군), 림프구 침윤이 저명한 경우(림프구 침윤군)의 두 군으로 구분이 되었다. 호산구 침윤군이 21예로, 호산구 수는 펑균 89.8 $cells/mm^2$ 였고, 정상 대조군은 평균 0.4 $cells/mm^2$ 였다 (P=0.005). 림프구 침윤군은 4예였으며, 림프구 수는 평균 84.3 $cells/mm^2$ 였고, 정상 대조군은 평균 28.4 $cells/mm^2$ 였다(P=0.026). 정상 대조군의 기저막 두께가 평균 $3.50\pm1.37\;{\mu}m$ 였던데 비하여, 대상군에서는 평균 $14.20\pm5.20{\mu}m$ 로 의미있게 두꺼운 소견을 보였다(p=0.001). 메타콜린 유발검사와 병리소견으로 대상군의 만성기침의 원인을 유추해보면, 호산구 침윤군 21예 중 메타콜린 유발검사 양성인 경우는 7예로, 기침형 천식으로 진단할 수 있었고, 14예는 메타콜린 유발검사가 음성으로, 호산구성 기관지염으로 진단할 수 있었다. 림프구 침윤균 4예는 모두 메타콜린 유발검사가 음성으로, 림프구 침윤에 의한 기관지염이었다. 호산구성 기관지염 14예 중 3예(21.4%)에서 아토피 양성이었다. 대상환자 25예중 22예(88.0%)에서 스테로이드 투여 후 증상지수가 호전되었다. 호산구성 기관지염 14예 중 12예(85.7%), 기침형 천식 7예 중 7예(100%), 림프구 침윤에 의한 기관지염 4예 중 3예(75.0%)에서 증상지수가 호전되었다. 병리소견으로 호산구 침윤군과 림프구 침윤군으로 구분했을 때, 증상지수가 호전된 경우가 각각 90.5%, 75.0%로 염증세포의 종류에 따른 차이는 없었다. 결 론: 흉부 X-선 및 폐기능 검사가 정상이며, 다른 증상이 없는 만성기침은 호산구 또는 림프구 침윤에 의한 기도염증과 연관이 있었다. 메타콜린 유발검사와 기관지 조직검사로 유추해 볼 때, 그 원인으로는 호산구성 기관지염, 기침형 천식, 림프구 침윤에 의한 기판지염이었다(이상 빈도순). 스테로이드 치료에 88%에서 증상지수가 호전되었다. 【Background: The purpose of this study was to examine the causes and pathologic process of chronic non-productive cough as an isolated symptom with a normal spirometry and chest radiograph by investigating clinicopathologic findings. Method: We studied 25 adults with chronic non-productive cough over a 3-week period with a normal chest radiograph and pulmonary function tests without any other symptoms. Clinical assessment, cough score, chest and sinus radiograph, pulmonary function tests, methacholine challenge, allergic skin prick test, and bronchoscopy for bronchial biopsies were performed. Subjects were then treated with prednesolone 20 to 30 mg/day for 1 to 2 weeks. Results: The experimental group was divided into two subgroups-those infiltrated with eosinophils, and those infiltrated with lymphocytes depending on eosinophil and lymphocyte counts, both of which were respectively higher than those of the control group. Eosinophils infiltrated group had mean numbers of eosinophil of 89.8 $cells/mm^3$ while control group's mean was 0.4 $cells/mm^2$ (p=0.005). Lymphocyte infiltrated group was 4 patients whose mean was 84.3 $cells/mm^2$ with 28.4 $cells/mm^2$ of control group(P=0.026). In addition, the mean thickness of the basement membrane of experimental group was $14.20{\pm}5.20{\mu}m$ in contrast of control group whose mean was $3.50{\pm}1.37{\mu}m$ (P=0.001). With the methacholine challenge test, 7 of the 21 eosinophil infiltrated subjects were diagnosed with cough variant asthma ; the other 14 with eosinophilic bronchitis. Three subjects with eosinophilic bronchitis were atopic positive (21.4%) with the skin prick test In the lymphocyte dominant group, all four subjects were diagnosed with lymphocytic bronchitis. Cough score was improved after steroid treatment in 22 of 25 subjects in the experimental group (88.0%). Conclusion: These results suggest chronic non-productive cough as an isolated symptom with a normal spirometry and chest radiograph was associated with airway inflammation by eosinophil and lymphocyte infiltration. The causes for chronic non-productive cough were eosinophilic bronchitis, cough variant asthma, and lymphocytic bronchitis(written in frequency). They further suggest that therapeutic treatment with steroids can provide effective symptomatic relief.】

Background : Leukotriene (LT) , , and , the main components of slow-reacting substance of anaphylaxis (SRS-A), have been suggested to play an important role in bronchial asthma such as antigen-induced bronchoconstriction, airway hyperreactivity, and pulmonary eosinophil accumulation. The purpose of this study was to evaluate the effects of treatment with the cysteinyl-LTs (cys-LTs) antagonist, pranlukast on allergen-induced guinea pig asthma model. Methods : Guinea pigs of treatment and placebo groups were sensitized by subcutaneous injection of ovalbumin(OVA) and challenged by inhalation of aerosolized OVA (1% weight/volume OVA). Normal control group did not sensitize with OVA. Oral ingestion of pranlukast and normal saline to the treatment and placebo groups was performed. In the treatment and placebo groups, airway resistance was measured before and after oral ingestion. Serum and eosinophilic infiltration of the bronchiolar and peribronchiolar tissues were measured after ingestion in the treatment and placebo groups. Results : Allergen-induced airway constriction developed in 20 (8 in treatment group, 12 in placebo group) among 35 guinea pigs. Airway resistance was significantly decreased at 3 and 6 minutes after OVA challenge in the pranlukast treatment group. In the placebo group, there was no difference of airway resistance between before and after saline ingestion. Serum levels showed 348.4 pg/ml in the treatment group, 373.9 pg/ml in the placebo group, and 364.4 pg/ml in the control group. There were no statistically significant difference between treatment and placebo group (p=0.232), and treatment and control group (p=0.501). Eosinophilic infiltrations in the peribronchiolar region per one-microscopic field (400 high power fields) demonstrated 7.06 in the treatment group, 19.2 in the placebo group, and 4.50 in the control group. There was significant decrement of eosinophilic infiltration in the treatment group which was compared with placebo group (p=0.001). Conclusion : These results demonstrate that pranlukast, a cys-LTs receptor antagonist, can attenuate allergen induced early-phase bronchoconstriction and eosinophilic infiltration in the bronchiolar tissues.

Background : The adrenergic receptor ( AR) polymorphisms occurring at amino acid position 16 (Arg to Gly), 27 (Gln to Glu), 34 (Val to Met), and 164 (Thr to Ile) are known to be functionally relevant and also disease-modifying in subjects with asthma. However the contribution of these polymorphisms to the development of the asthmatic phenotype or other markers for allergic disease remains to be established. Methods : 109 patients with bronchial asthma and 42 healthy person were included. Serum total IgE, allergen specific IgE, and skin prick test were performed to all of the subjects. AR polymorphisms were checked by mutated allele specific amplification (MASA) method. Results : The results were as follows. The frequencies of AR polymorphisms in asthmatic patients and healthy person were not statistically different(p>0.05). There was no association between AR polymorphisms of amino acid position 16, 27, 34 and the existence of atopy among asthmatic patients(p>0.05). Between asthmatic patients with or without elevated IgE level and AR polymorphisms of amino acid position 16, 27, 34, there was no statistically significant association(p>0.05). Conclusion : There was no difference in frequency of the AR polymorphism between asthmatic patients and healthy person. In the bronchial asthma, association of AR polymorphism and atopy/serum total IgE was not found.