• Tuberculosis and Respiratory Diseases
• /
• v.52 no.5
• /
• pp.485-496
• /
• 2002

Background : The NF-${\kappa}B$ transcription factors control various biological processes including the immune response, acute phase reaction and cell cycle regulation. NF-${\kappa}B$ complexes are retained in the cytoplasm in the basal state and various stimuli cause a translocation of the NF-${\kappa}B$ complexes into the nucleus where they bind to the ${\kappa}B$ elements and regulate the transcription of the target genes. Recent reports also suggest that NF-${\kappa}B$ proteins are involved in oncogenesis, tumor growth and metastasis. High expression of NF-${\kappa}B$ expression was reported in many cancer cell lines and tissues. The constitutive activation of NF-${\kappa}B$ was also reported in several cancer cell lines supporting its role in cancer development and survival. The anti-apoptotic action of NF-${\kappa}B$ is important for cancer survival. NF-${\kappa}B$ also controls the expression of several proteins that are important for cellular adhesion (ICAM-1, VCAM-1) suggesting a role in cancer metastasis. In lung cancer, high expression levels of the NF-${\kappa}B$ subunit p50 and c-Rel were reported. In fact, high expression does not mean a high activity, and the activation pattern of NF-${\kappa}B$ in lung cancer has not been reported. Materials and Methods : In this study, the NF-${\kappa}B$ nuclear binding activity in the basal and TNF-${\alpha}$ stimulated states were exmined in various lung cancer cell lines and compared with the normal bronchial epithelial cell line. Twelve lung cancer cell lines including the non-small cell and small cell lung cancer cell lines (A549, NCI-H358, NCI-H441, NCI-H552, NCI-H2009, NCI-H460, NCI-H1229, NCI-H1703, NCI-H157, NCI-H187, NCI-H417, NCI-H526) and BEAS-2B bronchial epithelial cell line were used. To evaluate the NF-${\kappa}B$ expression and DNA binding activity, western blot analysis and an electrophoretic mobility shift assay with the nuclear protein extracts. Results : The basal expressions of the p65 and p50 subunits were observed in the BEAS-2B cell line and all lung cancer cell lines except for NCI-H358 and NCI-H460. The expression levels of p65 and p50 were increased 30 minutes after stimulation with TNF-${\alpha}$ in BEAS-2B and in 10 lung cancer cell lines. In the NCI-H358 and NCI-H460 cell lines, p65 expression was not observed in the basal and stimulated states and the two p50 related protein levels were higher after stimulation with TNF-${\alpha}$ These new proteins were smaller than p50 and are thought to be variants of p50. In the basal state, NF-${\kappa}B$ was nearly activated in the BEAS-2B and all lung cancer cell lines. The DNA binding activity of the NF-${\kappa}B$ complexes was markedly higher after stimulation with TNF-${\alpha}$ In the BEAS-2B and all lung cancer cell line except for NCI-H358 and NCI-H460, the activated NF-${\kappa}B$ complex was a p65/p50 heterodimer. In the NCI-H358 and NCI-H460 lung cancer cell lines, the NF-${\kappa}B$ complex was variant of a p50/p50 homodimer. Conclusion : The NF-${\kappa}B$ activation pattern in the lung cancer cell lines and the normal bronchial epithelial cell lines was similar except for the activation of a variant of the p50/p50 homodimer in some lung cancer cell linse.

• Tuberculosis and Respiratory Diseases
• /
• v.66 no.6
• /
• pp.444-450
• /
• 2009

Background: Biomarkers for cancer have several potential clinical uses, including the following: early cancer detection, monitoring for recurrence prognostication, and risk stratification. However, no biomarker has been shown to have adequate sensitivity and specificity. Many investigators have tried to validate biomarkers for the early detection and recurrence of lung cancer. To evaluate plasma G-CSF as such a biomarker, protein levels were measured and were found to correlate with the clinicopathological features of primary lung tumors. Methods: Between December 2006 and May 2008, 100 patients with histologically-validated primary lung cancer were enrolled into this study. To serve as controls, 127 healthy volunteers were enrolled into this study. Plasma G-CSF levels were measured in lung cancer patients using the sandwich ELISA system (R & D inc.) prior to treatment. Results: The mean plasma G-CSF levels were 12.2$\pm$0.3 pg/mL and 46.0$\pm$3.8 pg/mL (mean$\pm$SE) in the normal and in the cancer groups, respectively. In addition, plasma G-CSF levels were higher in patients with early lung cancer than in healthy volunteers (p<.001). Plasma G-CSF levels were higher in patients who were under 65 years old or smokers. Within the cancer group, plasma G-CSF levels were higher in patients with non small cell lung cancer than in patients with small cell lung cancer (p<.05). Overall, plasma G-CSF levels were shown to increase dependent upon the type of lung cancer diagnsosed. In the order from highest to lowest, the levels of plasma G-CSF tended to decrease in the following order: large cell carcinoma, squamous cell carcinoma, adenocarcinoma, and bronchioloalveolar carcinoma. Plasma G-CSF levels tended to be higher in patients with advanced TNM stage than in localized TNM stage (I, II

• Journal of Chest Surgery
• /
• v.31 no.2
• /
• pp.134-141
• /
• 1998

Primary lung cancer has recently increased progressively in its incidence in Korea. It is clearly evident that surgical resection offers the best offortunity for cure of non-small cell carcinoma. This study was designed to analyse the clinical data of 100 primary non-small cell carcinoma patients who underwent lung resection surgery from January 1992 to July 1995 at the department of Thoracic and Cardiovascular Sugery, Kyungpook National University Hospital. There were 86 males and 14 females(6:1). In the age distribution, the peak incidence was recorded in the seventh decade(43%). The methods of tissue diagnosis were bronchoscopic biopsy in 53 patients(50.5%), percutaneous needle aspiration in 17 patients(16.2%), transbronchial lung biopsy in 11 patients(10.5%), mediastinoscopic biopsy in 2 patients (1.9%), sputum cytology in 2 patients(1.9%), and thoracotomy in 20 patients(19.0%). Fifty-five lobectomies, 22 pneumonectomies, 15 bilobectomies, 2 segmentectomies, 4 sleeve lobectomies, a sleeve pneumonectomy, and a wedge pneumonectomy were performed. Operative mortality occured in 4 cases(sepsis in 2 cases, respiratory failure in 1 case, and acute myocardiac infarction in 1 case). The histologic types of tumor were 67 squamous cell carcinomas, 26 adenocarcinomas, 6 large cell carcinomas, and an adenosquamous cell carcinoma. Eighteen patients with N2 mediastinal lymph node metastases had 8 squamous cell carcinomas(11.9%), 9 adenocarcinomas(34.6%), and a large cell carcinoma(16.7%). The primary tumors in these patients were in the right upper lobe in 4 patients, the right middle and lower lobe in 9 patients, the left upper lobe in 3 patients, and the left lower lobe in 2 patients. With regard to pathologic stages, 45 patients had stage I disease; 13 patients, stage II; 36 patients, stage IIIa; 5 patients, stage IIIb; and 1 patient, stage IV. The overall actuarial survival rate was 77.5% at 12 months, 56.1% at 24 months and 43.7% at 43 months. The actuarial survival rates at 43 months were 81.3% in Stage I, 20.8% in Stage II, 27.9% in Stage IIIa, 25.0% in Stage IIIb and 33.3% in Stage IV. These facts suggest that early detection and surgical resection are recommended for favorable postoperative survival in non-small cell lung cancer.

• Journal of Chest Surgery
• /
• v.32 no.6
• /
• pp.536-542
• /
• 1999

Background: The purpose of this study is to improve the quality of the diagnostic procedures in the preoperative evaluation so as to reduce the unnecessary thoracotomy and to ensure resectability in non-small cell lung cancer. Material and Method: Of 616 patients who underwent thoracotomy for primary lung cancer from January 1990 to December 1996, 59 patients(9.6%) turned out to have inoperable lesions after the thoracotomy. We reprospectively reviewed the bronchoscopic findings, methods of tissue diagnosis, CT scans, pulmonary function test and lung perfusion scan, reasons for nonresectability, and adjuvant therapy, and then followed up on the survival rate after exploratory thoracotomy. Result: The cell types were squamous cell carcinoma in 38, adenocarcinoma in 15, large cell carcinoma in 3 and others in 3. Primary loci were RUL in 20, RML in 6, RLL in 8, LUL in 13, LLL in 4 and others in 8. The reasons for non-resectability were various; direct tumor invaison to mediastinal structures(n=41), seeding on pleural cavity(n=8), poor pulmonary function(n=2), invasions to extranodal mediastinal lymph node(n=2), technical non- resectability due to extensive chest wall invasion (n=3), small cell carcinoma (n=1), malignant lymphoma(n=1), and multiple rib metastases(n=1). In the follow-up of 58 patients, 1-year survival rate was 55.2% and 2-year survival rate was 17.2% and the mean survival time was 14 months. When compared according to cell types or postoperative adjuvant therapeutic modalities, no significant difference in the survival rates were found. The squamous cell carcinoma was frequently accompanied by local extension to contiguous structures and was the main cause of non-resectability. In adenocarcinoma, pleural seeding with malignant effusion was frequently encountered, and was the major reason for non-resectability. Conclusion: These data revealed that if appropriate preoperative diagnostic tools had been available, many unnecessary thoracotomies could have been avoided. Both the use of thoracoscopy in selected cases of adenocarcinoma and the more aggressive surgical approach to the locally advanced tumor could reduce the incidence of unnecessary thoracotomies for non-small cell lung cancers.

• Tuberculosis and Respiratory Diseases
• /
• v.39 no.1
• /
• pp.15-23
• /
• 1992

Background: The prognosis of lung cancer remains poor and early detection and curative surgery is still the most effective treatment for many. In the early detection of lung cancer, sputum cytology and simple chest x-ray are used, but both of these tests are far from being perfect. So we studied the characteristics of patients diagnosed as lung cancer without demonstrable mass lesion on simple chest x-ray to help in the early diagnosis of lung cancer. Methods: We conducted a retrospective study on 11 subjects who were diagnosed as lung cancer at Seoul National University Hospital between August 1986 and June 1989 and had no demonstrable mass lesion on simple chest x-rays. Results: Ten of 11 patients were male, 8 had a history of smoking, most frequent symptoms were sputum, cough, and hemoptysis, and 3 patients either had wheezing or stridor. In 3 of the cases, although there were no mass lesion, there were ill-defined infiltration, major fissure thickening, and fibrostreaky density mimiking tuberculosis where the tumor was eventually found and in one patient tumor was masked by a rib shadow. Also in one case, lateral chest film demonstrated a retrocardiac mass. Both bronchoscopy and computed tomogram were useful in the localization of the tumor. Seven of 11 had relatively early disease (less than StageII). Four of 11 are still alive without any evidence of recurrence between 2 and a half and 4 years after the operation. Conclusion: We conclude that in patients with respiratory symtoms in whom cancer cannot be ruled out, sputum cytology and lateral chest x-rays should be taken and that if necessary further studies like computed tomogram and bronchoscopy should be done to aid in the early diagnosis of lung cancer.

• Tuberculosis and Respiratory Diseases
• /
• v.40 no.5
• /
• pp.495-500
• /
• 1993

Background: For the relief of the occlusion of major bronchi, laser therapy, radiation therapy or combined therapy is generally used. But the effect of radiation therapy is very slow and not consistent and laser therapy requires expensive equipments and technical expertise with occasional serious side effects. Direct ethanol injection has been widely used for the control of bleeding in gastrointestinal lesion, esophageal varices or renal cell carcinoma with good results. So we tried direct injection of ethanol into the tumor to relieve the obstruction of major bronchus in 11 patients. Method: All procedures were done under the fiberoptic bronchoscopy with continuous oxygen supplement and aliquoted 0.5-1.0 ml of absolute ethanol directly into the tumor through the endobronchial aspiration needle. The tumor was endoscopically removed with a biopsy forceps immediately after ethanol injection. The whole procedure was repeated 3-4 days interval until the lumen opens. Usually after 2-3 trials of ethanol injection, the lumen opened up. Results: The immediate effect of ethanol injection was whitening of the mucosa and prompt cessation of bleeding. The late effect was necrosis of the tumor. The final results of this procedure were improvement of symptoms and reexpnasion of the lung in all patients. $FEV_{1.0}$ and FVC were improved and $PaO_2$ was increased from $68.1{\pm}9.2$ mmHg to $83.9{\pm}8.1$ mmHg, $SaO_2$: from $94{\pm}8.5%$ to $96.6{\pm}1.1%$, and $AaDO_2$ was reduced from $26.5{\pm}8.5$ mmHg to $10.9{\pm}9.1$ mmHg. Conclusion: Direct ethanol injection into the tumor tissue is a rapid, cheap and relatively safe method of relieving the complete occlusion of major bronchus.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.4
• /
• pp.760-765
• /
• 1998

Background: Glucose uptake has been found to be increased in cancer cells, and FDG-PET imaging is used for diagnosis of cancer using this phenomenon. However, the exact mechanism of increased glucose uptake in cancer cells has not been clarified. Recent studies demonstrated the presence of glucose transporter(GLUT) mRNA expression in gastrointestinal cancer and head and neck cancer, and suggested that GLUT may be associated with glucose uptake in cancer cells. In lung cancer cells, glucose metabolism is also known to be increased. We evaluated GLUT mRNA expression in human lung cancer cell lines in order to find out the mechanism of increased glucose uptake in lung cancer. Method: Total RNA was isolated from 15 human lung cancer cell lines and immortalized bronchial epithelial cell line(BEAS-2B). After electrophoresis of $20{\mu}g$ total RNA, Northern blot analysis was done using GLUT1 cDNA and GLUT3 cDNA as probes. Results: Thirteen of 14 human lung cancer cell lines expressed GLUT1 mRNA and 10 of 14 human lung cancer cell lines expressed GLUT3 mRNA. Eight human lung cancer cell lines expressed both GLUT mRNAs. BEAS-2B expressed GLUT1 mRNA and did not express detectable GLUT3 mRNA. Conclusion: The increase of glucose metabolism in lung cancer may be associated with GLUT1 and GLUT3 expression.

• Journal of Chest Surgery
• /
• v.30 no.6
• /
• pp.591-597
• /
• 1997

Cardiopulmonary bypass in children is associated with capillary leak which results in an increase in total body water after open heart surgery The purpose of these studies was to assess the cardiopulmonary effects of modified ultrafiltration after pediatric open heart surgery Study h: Twenty-six consecutive children aged 0.1 ~ 10 years(median 7 months) underwent cardiac operation inc rporating modified ultrafiltration. After completion of cardiopulmonary bypass, modified ultrafiltration was commenced at the flow rate of 100~ 15011min for 3 ~ 14 min. After modified ultrafiltration, elevation of hematocrit(28.3% $\pm$ 3.6% vs. 33.8olo $\pm$ 4.Ooloi p < 0.001), increased systolic 1)loots Pressure(66.7 $\pm$ 11.2mmHg vs. 76.2$\pm$ 11.BmmHg, p < 0.02), and decreased central venous pressure(7.8 $\pm$ 3.7mmHg vs. 6.9$\pm$ 2.gmmHg, p<0.001) were observed. Study B: Twenty-six children who underwent cardiac operation with the diagnosis of VSD under 2 years were assigned to control(n= 14) or modified ultrafiltration(n= 12). Peak inspiratory pressure checked immediately after operation was significantly lower in modified ultrafiltration group than in control group(20.0$\pm$ 2.4 cmH20 vs.22.4$\pm$ 2.3cmH20, p < 0.03). Modified ultrafiltration after cardiopillmonary bypass in children improves early homodynamics and pulmonary mechanics, and represents an excellent option for perioperative managemen of accumulation of fluid in the tissues. We will continually employ the modified ultrafiltration technique in pediatric cardiac operations.

• Journal of Chest Surgery
• /
• v.31 no.3
• /
• pp.271-278
• /
• 1998

In order to access the value of computed tomography in mediastinal LN staging of NSCLCa, 581 LN stations of 77 patients were selected from 552 patients who were diagnosed as Lung Ca and operated in Seoul National University Hospital from 1992 to 1995. The selection criteria were as follows ; the patients 1) whose preoperative chest CTs were available; 2) underwent curative resection (lobectomy or more) with complete lymph node dissection; 3) whose final pathologic diagnosis were proven to be non-small cell lung cancer. We adopted Receiver Operating Characteristic curve method to determine a proper size criterion for diagnosing malignant mediastinal adenopathy. From curve analysis, we decided the size criterion of lymph node to 1 cm in their short axis. Using this size criterion, it's sensitivity was 43.9%, specificity was 87.4%, and accuracy was 83.1%. Eventhough we couldn't determine the precise size criterion for the adenoca, it seemed that shorter than 1 cm size criterion should be applied in that particular cell type. Lymph node stations associated with the tuberculosis or bronchiectasis tend to be overestimated in nodal staging and have relatively high false positive rate. The low sensitivity of CT scan suggest that radical and complete dissection or precise mediastinal lymph node evaluation through the surgical approach is mandatory.

• Journal of Chest Surgery
• /
• v.39 no.12 s.269
• /
• pp.949-952
• /
• 2006

Spontaneous pneumothorax is rarely occurred as an initial sign of primary lung cancer. As a lot of these cases have already advanced, even then surgical resection is performed, the prognosis is often undesirable, We happened to find a ruptured cavity on a 65-year-old male patient who had suffered from pulmonary tuberculosis in the past, while performing VATS bullectomy for simple spontaneous pneumothorax, Then, as a result of frozen biopsy, it was diagnosed as squamous cell cancer Because the tumor was infiltrated from the upper lobe into the lower lobe passing by fissure, we should remove by pneumonectomy and the pathologic stage was found stage I(T2N0M0). When we made an follow-up observation for one year and a half, there was neither relapse nor complication. When there appears spontaneous pneumothorax to the high risk group for lung cancer who were smokers over forty-year old, with chronic bronchitis or pulmonary emphysema, it needs to have a closer observation on a base lung disease such as lung cancer through chest CT, and it is also necessary to make more active approach by performing the surgical operation through a thoracoscopy when there is a continued air release.