• Journal of Chest Surgery
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• v.34 no.2
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• pp.138-147
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• 2001

배경: 폐암발생에 EGF의 자가 분비는 암의 성장과정에 직, 간접적인 영향을 주고 있으며, TNF-$\alpha$는 면역 반응의 급성체로서 폐암의 발생을 억제하고 이미 발생한 폐암종의 치료에도 이용되고 있는 실정이다. 폐암 조직과 혈장에서 epidermal growth factor(EGF)와 tumor necrosis factor-$\alpha$(TNF-$\alpha$)를 면역 방사선 분석법을 이용하여 정량분석 하여 발현 정도를 분석해보고자 하였다. 대상 및 방법: 폐암환자 20례와 양성종양 및 육아종 환자 4례에 대해서 AJCCS에 의한 조직학적 분류와 TNM 분류에 따라 구분하여 절제수술을 받은 환자를 대상으로 수술전 혈액을 채취하고 수술직후 적출한 표본을 암이 없는 건강하다고 판단되는 대조조직과 폐암조직에서 일정량의 조직을 절취하여 액화질소 내에 실험시까지 급속 냉동보관 하였다. 수술후 혈액을 재 채취하여 혈장을 분리하여 냉동고에 검사시까지 보관하였다. EGF의 정량은 Human Epidermal Growth Factor kit(Amersham Phamacia Biotech, England)를 사용하였으며, TNF-$\alpha$ 정량은 TNF-$\alpha$ IRMA kit(Biosouce, Belgium)을 사용하여 IRMA 방법으로 각각 정량분석하여 표현유무를 연구한 결과 다음과 같은 결론을 얻었다. 결과: 1. 대조조직, 양성종양 및 육아종과 폐암 수술전후의 조직과 혈청 모두에서 EGF와 TNF-$\alpha$가 발현되었다. 2. EGF와 TNF-$\alpha$의 농도는 대조조직과 양성종양(0.11$\pm$0.06 ng/ml, 20,3$\pm$9.08 pg/ml)에 비하여 폐암조직(0.13$\pm$0.05 ng/ml, 34.34$\pm$47.74pg/ml)에서 유의하게 높은 농도가 발현되고 있었다. 3. 폐암중 선암조직에서 특히 TNF-$\alpha$(80.92$\pm$104.08 ng/ml)의 발현이 강하게 나타났다. 4. 혈청내의 EGF와 TNF-$\alpha$의 발현되는 양이 조직내의 양보다도 높았다. EGF는 5.7배정도 TNF는 1.3배정도 강하게 표현되었다. 5. 폐암의 조직학적 종류에 따라서 EGF는 거의 차이가 없었으나 TNF-$\alpha$ 정량치에는 차이가 있었다. 6. TNM stage가 진행함에 따라 EGF는 농도가 증가하였고 TNF-$\alpha$는 오히려 감소하는 반대되는 교차현상이 있었다. 7. 수술직후 EGF는 증가하였으나 TNF-$\alpha$는 오히려 감소하였다. 결론: 결론적으로 저자는 암조직과 대조조직간에 EGF와 TNF-$\alpha$의 표현량의 차이가 있음을 관찰하였으며 또한 조직과 혈청사이에도 표현량에 차이가 있으며 조직보다도 오히려 혈청내의 농도가 높다는 사실을 관찰하였다. EFG와 TNF-$\alpha$는 정상조직이나 양성조직과 폐암조직 모두에서 분비작용되는 cytokines으로 세포기능에 따라 다양하게 표현이 되며 계속적인 연구로서 밝혀야만 할 과제라고 판단된다.

• Journal of Chest Surgery
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• v.42 no.2
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• pp.141-147
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• 2009

Background: We performed this study to identify the tumor suppressor genes located in the long arm of chromosome 21 in non-small cell lung cancer. Material and Method: The genes of USP25 in 21q11.2, NCAM2, ADAMTS1 in 21q21.2, and Claudin-8 (CLDN8), Claudin-17 (CLDN17) and TIAM1 in 21q22.1 were investigated for their gene expressions, genetic alterations and promoter methylation. Result: The expressions of CLDN8 and CLDN17 were significantly decreased in 7 (L132, H157, H358, H522, H1299, H1703 and HCC2108) of 13 cell lines, and the expression of ADAMTS1 was also significantly reduced in 6 cell lines (A549, SW900, H1299, H1373, H1703 and H1793). There were no genetic alterations by PCR-SSCP and cDNA cloning in the cell lines with a decreased gene. In the cell lines with a decreased gene expression, the mRNA expression was increased significantly with treatment of 5-Aza-CdR. Conclusion: These results suggest that the ADMTS1, CLDN8 and CLDN17 may act as tumor suppressor genes.

• Journal of Chest Surgery
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• v.43 no.5
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• pp.499-505
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• 2010

Background: There have been several reports using animal experiments that CD1-restricted T-cells have a key role in tumor immunity. To address this issue, we studied the expression of markers for CD1c+ myeloid dendritic cells (DCs) isolated from peripheral blood in the clinical setting. Material and Method: A total of 24 patients with radiologically suspected or histologically confirmed lung cancer who underwent pulmonary resection were enrolled in this study. The patients were divided according to histology findings into three groups: primary adenocarcinoma of lung (PACL), primary squamous cell carcinoma of lung (PSqCL) and benign lung disease (BLD). We obtained 20 mL of peripheral venous blood from patients using heparin-coated syringes. Using flow-cytometry after labeling with monoclonal antibodies, data acquisition and analysis were done. Result: The ratio of CD1c+CD19- dendritic cells to CD1c+ dendritic cells were not significantly different between the three groups. CD40 (p=0.171), CD86 (p=0.037) and HLA-DR (p=0.036) were less expressed in the PACL than the BLD group. Expression of CD40 (p=0.319), CD86 (p=0.036) and HLA-DR (p=0.085) were less expressed in the PACL than the PSqCL group, but the differences were only significant for CD86. Expression of co-stimulatory markers was not different between the PSqCL and BLD groups. Expression of markers for activated DCs were dramatically lower in the PACL group than in groups with other histology (CD40 (p=0.005), CD86 (p=0.013) HLA-DR (p=0.004). Conclusion: These results suggest the possibility that CD1c+ myeloid DCs participate in control of the tumor immunity system and that low expression of markers results in lack of an immune response triggered by dendritic cells in adenocarcinoma of the lung.

• Journal of Chest Surgery
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• v.43 no.6
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• pp.588-595
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• 2010

Background: Base on types of tumor, the types of expressed tumor is diverse and the difference in its expression rate is even more various. Due to such reasons an animal model is absolutely needed for a clinical research of lung cancer. The author attempted oncogenesis by cultivating a cell line of non-small cell carcinoma and then injecting it inside thoracic cavities of nude mice. The author conducted quantitative analyses of HER2/neu tumor gene - an epidermal growth factor receptor (EGFR) related to lung cancer, and TGF-${\beta}_1$, which acts as a resistance to cell growth inhibition and malignant degeneration. In order to investigate achievability of the oncogenesis, histological changes and the expression of cancer gene in case of orthotopic lung cancer is necessary. Material and Method: Among 20 immunity-free male BALB/c, five nude mice were selected as the control group and rest as the experimental group. Their weights ranged from 20 to 25 gm (Orient, Japan). After injection of lung cancer line (SW900 G IV) into the pleural cavity of nude mice, They were raised at aseptic room for 8 weeks. HER2/neu was quantitatively analyzed by separating serum from gathered blood via chemiluminiscent immunoassay (CLIA), and immunosandwitch method was applied to quantitatively analyze TGF-${\beta}_1$. SPSS statistical program (SPSS Version 10.0, USA) was implemented for statistical analysis. Student T test was done, and cases in which p-value is less than 0.05 were considered significant. Result: Even after lung cancer was formed in the normal control group or after intentionally injected lung cancer cell line, no amplification of HER2/neu gene showed reaction. However, the exact quantity of TGF-${\beta}_1$ was $28,490{\pm}8,549pg/mL$, and the quantity in the group injected with lung cancer cell was $42,362{\pm}14,449pg/mL$, meaning 1.48 times highly Significant (p<0.483). It proved that HER2/neu gene TGF-${\beta}_1$ had no meaningful interconnection. Conclusion: TGF-${\beta}_1$ gene expressed approximately 1.48 times amplification in comparison to the control group. The amplification of TGF-${\beta}_1$ meant somatic recuperation inhibition mechanism due to carcinogenesis in nude mice was definitely working. It may be implemented as a quantitative analysis that allows early detection of lung cancer in human body.

• Tuberculosis and Respiratory Diseases
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• v.75 no.3
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• pp.95-103
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• 2013

Background: Small cell lung cancer (SCLC) transformation during epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in lung cancer has been suggested as one of possible resistance mechanisms. Methods: We evaluated whether SCLC transformation or neuroendocrine (NE) differentiation can be found in the cell line model. In addition, we also investigated its effect on responses to conventional chemotherapeutic drugs of the SCLC treatment. Results: Resistant cell lines to various kinds of EGFR-TKIs such as gefitinib, erlotinib, CL-387,785 and ZD6474 with A549, PC-9 and HCC827 lung adenocarcinoma cell lines were established. Among them, two resistant cell lines, A549/GR (resistant to gefitinib) and PC-9/ZDR (resistant to ZD6474) showed increased expressions of CD56 while increased synaptophysin, Rb, p16 and poly(ADP-ribose) polymerase were found only in A549/GR in western blotting, suggesting that NE differentiation occurred in A549/GR. A549/GR cells were more sensitive to etoposide and cisplatin, chemotherapeutic drugs for SCLC, compared to parental cells. Treatment with cAMP and IBMX induced synaptophysin and chromogranin A expression in A549 cells, which also made them more sensitive to etoposide and cisplatin than parental cells. Furthermore, we found a tissue sample from a patient which showed increased expressions of CD56 and synaptophysin after development of resistance to erlotinib. Conclusion: NE differentiation can occur during acquisition of resistance to EGFR-TKI, leading to increased chemosensitivity.

• Journal of Chest Surgery
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• v.29 no.1
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• pp.43-51
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• 1996

From march 1989 to October 1993, 57 patients were diagnosed and operated for primary non-small cell lung cancer, and evaluated clinically. 1. There were 45 males and 12 females (M:F=3.8:1), and the peak incidence of age was 6th decade of life (45.6%). In the preoperative diagnostic methods and their positive rate, sputum cytology was 11%, bronchial washing cytology 50%, bronchoscopic biopsy 73%, and CT guided percutaneous needle aspiration biopsy 83%. 3. Histopathologically, squamous cell carcinoma was 56.1%, adenocarcinoma 22.8%, bronchioloal veolar cell carcinoma 1%, and undifferentiated large cell carcinoma 1.8%. 4. In the operation, pneumonectomy was 35.1%, lobectomy 38.6%, bilobectomy 3.5%, segmentec tony 7%, and exploratory thoracotomy 15.8%, and overall resectability was 84.2%. 5. In postoperative stagings, stage I was 28.1%, st ge II 22.8%, stage IIIa 31.6% and stage IIIb 17.5%. 6. Postoperative complications were developed in 11 cases (19.3%) and operative mortality was none. 7. One year survival rate in rejectable cases was 87.0%, 2 year 61.6% and 5 year 44.9%. According to stage, 3 year survival rate was 75.8% in stage I, 16.9% in stage II, 60.9% in stage IIIa, 50% in stage IIIb.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.505-515
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• 1997

Background : We assessed the accuracy of staging in evaluation of bronchial invasion, thus found the role of CT in patients who underwent resective surgery in primary lung cancer. Materials and Methods : Authors retrospectively analized the preoperative CT scans of 156 patients receiving pneumonectomy(n = 95) and lobectomy(n = 61). Among lobectomy patients, 7 patients subsequently performed pneumonectomy because of positive resection margin of bronchus in frozen biopsy. We also retrospectively analized CT scans of non-operated 60 patients who performed sufficient bronchoscopic biopsy. Bronchial wall thickness more than 3mm, irregular wall thickening and reduction of diameter by CT were defined as bronchial invasion. The pathologic examination of resection margin were positive in 20, stump recurrence occurred in 6 of the operated group, and the pathologic examination of biopsy of bronchial wall were positive in 34 of the non operated group, and these were an regarded as bronchial invasion. Results : The CT assessment of bronchial invasion revealed low sensitivity (11.5%), low positive predictability(38%), but high specificity(96%) and relatively high accuracy (84%) in the operated group and higher sensitivity (62%), higher positive predictability(95%) in non-operated group. Conclusion : In lung cancer patients who underwent operation, CT showed very low sensitivity and positive predictability in evaluation of bronchial invasion. Because the usefulness of CT in evaluation of bronchial invasion is limited, therefore aggressive fiberoptic bronchoscopic biopsy is thought to be necessary before surgical attempt.

• Journal of Chest Surgery
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• v.44 no.1
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• pp.32-38
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• 2011

Background: Surgical treatment of stage I non-small cell lung cancer (NSCLC) can be performed either by thoracotomy or by employing video-assisted thoracic surgery (VATS). The aim of this study was to evaluate the feasibility of VATS lobectomy for pathologic stage I NSCLC. Material and Methods: Between December 2003 and December 2007, 529 patients with pathologic stage I NSCLC underwent lobectomies (373 thoracotomy, 156 VATS). Patients in both groups were selected after being matched by age, gender and pathologic stage using propensity score method, to create two comparable groups: thoracotomy and VATS groups, and the overall survival, recurrence-free survival, complication and length of hospitalization were compared between these two groups. Results: After the patients were matched by age, gender and pathologic stage, 272 patients remained eligible for analysis, 136 in each group (mean age of 59.5 years; 70 men, 66 women; 80 stage IA, 56 stage IB). There was no statistical difference in other preoperative clinical characteristics between the two groups. No hospital mortality was observed in both groups. Overall 3-year survival rate was 97.4% in thoracotomy group and 96.6% in VATS groups (p=0.76). During the follow-up, 20 patients (14.7%) developed recurrence in thoracotomy group, including loco-regional recurrence in 7, distant metastasis in 13. In VATS group, 13 patients (9.6%) developed recurrence, including loco-regional recurrence in 4, distant metastasis in 9. Three-year recurrence-free survival rate was 81.8% in thoracotomy group and 85.3% in VATS groups (p=0.43). There was no significant difference in postoperative complications between thoracotomy and VATS groups (30 cases in 22 patients vs. 19 cases in 17 patients, p=0.65, odds ratio=1.19). The mean hospital stay of VATS group was 2 days shorter than that of thoracotomy group ($8.8{\pm}6.5$ days vs. $6.3{\pm}3.3$ days, p<0.05). Conclusion: VATS lobectomy for pathologic stage I lung cancer is a feasible operation with shorter hospitalization, while surgical outcome is comparable to thoracotomy lobectomy.

• Korean Journal of Radiology
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• v.23 no.3
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• pp.370-380
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• 2022

Objective: To compare pneumonic-type invasive mucinous adenocarcinoma (pIMA) confined to a single lobe with clinical T2, T3, and T4 stage lung cancer without pathological node metastasis regarding survival after curative surgery and to identify prognostic factors for pIMA. Materials and Methods: From January 2010 to December 2017, 41 patients (15 male; mean age ± standard deviation, 66.0 ± 9.9 years) who had pIMA confined to a single lobe on computed tomography (CT) and underwent curative surgery were identified in two tertiary hospitals. Three hundred and thirteen patients (222 male; 66.3 ± 9.4 years) who had non-small cell lung cancer (NSCLC) without pathological node metastasis and underwent curative surgery in one participating institution formed a reference group. Relapse-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Cox proportional hazard regression analysis was performed to identify factors associated with the survival of patients with pIMA. Results: The 5-year RFS and OS rates in patients with pIMA were 33.1% and 56.0%, respectively, compared with 74.3% and 91%, 64.3% and 71.8%, and 46.9% and 49.5% for patients with clinical stage T2, T3, and T4 NSCLC in the reference group, respectively. The RFS of patients with pIMA was comparable to that of patients with clinical stage T4 NSCLC and significantly worse than that of patients with clinical stage T3 NSCLC (p = 0.012). The differences in OS between patients with pIMA and those with clinical stage T3 or T4 NSCLC were not significant (p = 0.11 and p = 0.37, respectively). In patients with pIMA, the presence of separate nodules was a significant factor associated with poor RFS and OS {unadjusted hazard ratio (HR), 4.66 (95% confidence interval [CI], 1.95-11.11), p < 0.001 for RFS; adjusted HR, 4.53 (95% CI, 1.59-12.89), p = 0.005 for OS}. Conclusion: The RFS of patients with pIMA was comparable to that of patients with clinical stage T4 lung cancer. Separate nodules on CT were associated with poor RFS and OS in patients with pIMA.

• Journal of Chest Surgery
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• v.11 no.2
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• pp.129-134
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• 1978

Two hundred and seventeen patients underwent diagnostic rigid bronchoscopy or bionchofiberscopy to evaluate the cytologic diagnosis in the lung cancer patient at the department of chest surgery of Yon-Sei university, college of the medicine from 1971 to 1977 year. One hundred and twenty cases of these patients were taken rigid bronchoscopy and ninety four cases of these patient were taken bronchofiberscopy. Cytologic examination of the sputum was done in 214 cases and sputum cytology was positive in 50 cases [23.4%]. Rigid bronchoscopy was made in 120 cases and this bronchoscopic cytology including bronchial washing and bronchial biopsy was positive in 34 cases [28.5%]. Bronchofiberscopy was performed in 94 cases and was positive in 45 cases [47.5%]. Histopathologically, 41 cases [43.6%] were epidermoid cell carcinoma, 8 cases [8.5%]of undifferentiated cell type, 12 cases [12.8%]of adenocarcinoma, 8 cases [8.5%]of alveolar cell type, and the 25 cases were undetermined. Cytologic examination of the sputum lacks the accuracy of the bronchoscopies in terms of both localization and accurate histologic indentification of the type of neoplasm. Rigid bronchoscope has the advantage of permitting identification of a tumor in a central location and of providing a sufficient amount of biopsy material for accurate diagnosis of carcinoma. However, it has the disadvantage of limiting examination to the larger, more central portions of the tracheobronchial tree. Bronchofiberscope had the advantage of examine upper lobe as well as other portions of the tracheobronchial tree which could not be visualized with the rigid bronchoscopy. A positive diagnosis in bronchofiberscopy was obtained in the highest rate, 47. 8% [45 cases]. A1 last, if a bronchogenic carcinoma is suspected on the basis of either symptoms of an abnormality on the chest film the diagnostic work-up-sputum cytology, bronchial washing, bronchoscopic biopsy, scalene node biopsy, thoracentesis and mediastinoscopy explothoracotomy etc-should precede in an attempt not only to obtain the higher positive diagnosis but also to obtain a tissue diagnosis and to evaluate the stage of the disease and to ascertain the appropriate mode of therapy.