Characterization of Cigarette Smoke Extract (CSE)-induced Cell Death in Lung Epithelial Cells / 결핵및호흡기질환

Emphysema is characterized by air space enlarge?ment and alveolar destruction. The mechanism responsible for the development of emphysema was thought to be protease/antiprotease imbalance and oxidative stress. A very recent study shows that alveolar cell apoptosis causes lung destruction and emphysematous changes. Thus, this study was per?formed to support the evidence for the role of apoptosis in the development of emphysema by characterizing cigarette smoke extract (CSE)-induced apoptosis in A549 (type II pneumocyte) lung epithelial cells. CSE induced apoptosis at low concentration (10% or less) and both apoptosis and necrosis at high concentration (20%). Apoptosis was demonstrated by DNA fragmentation using FACScan for subG1 fraction. Discrimination between apoptosis and necrosis was done by morphologic analysis using fluorescent microscopy with Hoecst 33342/propium iodide double staing and electron microscopy. Cy?tochrome c release was confirmed by using immuno?fluorescence with monoclonal anti-cytochrome c antibody. However, CSE-induced cell death did not show the activation of caspase 3 and was not blocked by caspase inhibitors. This suggests that CSE-induced apoptosis might be caspase-independent apoptosis. CSE-induced cell death was near com?pletely blocked by N-acetylcystein and bcl-2 over?expression protected CSE-induced cell death. This results suggests that CSE might induce apoptosis through intracellular oxidative stress. CSE also activated p53 and functional knock-out of p53 using stable overexpression of HPV-E6 protein inhibited CSE-induced cell death. The characterization of CSE-induced cell death in lung epithelial cells could support the role of lung cell apoptosis in the patho?genesis of emphysema.

Concurrent Chemoradiation with Weekly Paclitaxel in Locally Advanced Non-small Cell Lung Cancer / 결핵및호흡기질환

BACKGROUND: Paclitaxel is highly beneficial anticancer drug for the treatment of non-small cell lung cancer and has shown remarkable radiosensitizing effect in vitro. We evaluated whether concurrent chemoradiation therapy with weekly paclitaxel (60 mg/m2) could be tolerated and effective in the treatment of locally advanced non-small cell lung cancer (NSCLC). METHODS: Twenty-two stage III (IIIA:6, IIIB:16) NSCLC patients were treated with weekly administration of paclitaxel (60 mg/m2) on days 1, 8, 15, 22, 29, and 36 in addition to concurrent radiation therapy of 54 Gy. After the initial phase of concurrent chemoradiation, patients received additional two cycles of consolidation chemotherapy with paclitaxel (175mg/m2)/cisplatin (75 mg/m2) or paclitaxel (175 mg/m2)/carboplatin (6AUC) every 3 weeks. RESULTS: Overall response rate was 81.8% (18/22) with 9.1% (2/22) of complete response and 72.7% (16/22) of partial response rate. Two patients (9.1%) died of chemoradiation-induced pneumonitis after completion of therapy. In total, grade 3 toxicities included pneumonitis (22.7%), esophagitis (22.7%), neuropathy (13.6%), and neutropenia (13.6%). The median survival time was 15 months and 2-year overall survival were 31.8%. CONCLUSION: Concurrent chemoradiation therapy with weekly paclitaxel in locally advanced NSCLC showed good local response, but survival rate was not completely satisfactory due to potentially fatal chemoradiati1on-induced pneumonitis.

A Case of Hantavirus Pulmonary Syndrome / 결핵

Hantavirus pulmonary syndrome(HPS) is a systemic disease that is caused by a newly discorved and characterized virus of the Hantavirus genus, which is most frequently referred to as the sin nombre virus. The clinical syndrome resembles other hantavirus syndromes worldwide, except that it is characterized by a brief prodromal illness followed by rapidly progressive, noncardiogenic edema, and that it is more deadly than any previously recognized hantavirus infection. The clinical manifestations of HPS are characterized by four clinical phases prodrome, pulmonary edema and shock, diuresis, and convalescence. Mortality is greatest in the first 24 hours of the pulmonary edema and shock phase of the illness. These phases are strikingly similar to the clinical phases of Hemorrhagic fever with renal syndrome(HFRS) induced by Hantaan virus, except that HPS has not been associated with renal failure and Disseminated intravascular coagulation(DIC). We here report a case of hantavirus pulmonary syndrome developed in a 58 year-old man. He had a flu-like illness followed by the rapid onset of respiratory failure due to noncardiogenic pulmonary edema. HPS was diagnosed by clinical manifestations, identification of high titer antibody to Hantaan virus antigen and histologic finding of transbronchial lung biopsy (TBLB) specimen. The patient was treated with mechanical ventilation and initial corticosteroid pulse therapy resulting in successful outcome.