• Tuberculosis and Respiratory Diseases
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• v.57 no.3
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• pp.257-264
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• 2004

Background : There are many combinations of treatment for locally advanced non-small cell lung cancer (NSCLC). Recent studies have showed the efficacy of concurrent chemoradiotherapy (CCRT) in NSCLC. At present, however, there is no consensus about the optimal dosages and timing of radiation and chemotherapeutic agents. The aims of study were to determine the feasibility, toxicity, response rate, and survival rate in locally advanced NSCLC patients treated with doxetaxel and cisplatin based CCRT. Method : Sixteen patients with unresectable stage III NSCLC were evaluated from May 2000 until September 2001. Induction chemoradiotherapy consisted of 3 cycles of docetaxel (75 $mg/m^2/IV$ on day 1) and cisplatin (60 $mg/m^2/IV$ on day 1) chemotherapy every 3 weeks and concomitant hyperfractionated chest irradiation (1.15 Gy/BID, total dose of 69 Gy) in 6 weeks. Patient who had complete or partial response, and stable disease were applied consolidation chemotherapy of docetaxel and cisplatin. Results : All patients showed response to CCRT. Four patients achieved complete response (25%), partial responses in 12 patients (75%). The major common toxicities were grade III or more of neutropenia (87.3%), grade III esophagitis (68.8%), pneumonia (18.8%) and grade III radiation pneumonitis (12.5%). Thirteen patients were ceased during follow-up period. Median survival time was 19.9 months (95% CI; 4.3-39.7 months). The survival rates in one, two, and three years are 68.7%, 43.7%, and 29.1%, respectively. Local recurrence was found in 11 patients (66.8%), bone metastasis in 2, and brain metastasis in 1 patient. Conclusion : The response rate and survival time of CCRT with docetaxel/cisplatin in locally advanced NSCLC were encouraging, but treatment related toxicities were high. Further modification of therapy seems to be warranted.

• Tuberculosis and Respiratory Diseases
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• v.46 no.1
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• pp.36-43
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• 1999

Background : Tumor growth is the net result of intrinsic proliferation and escape from active cell death. bcl-2 is a member of a new category of oncogenes that is not involved in influencing cell proliferation but is involved in regulating cell death(apoptosis). Based on this information, it seems to be reasonable to expect that there may be clinical prognostic significance of bcl-2 expression in non-small cell lung cancer. But its prognostic significance is not established. Methods: To investigate the role of bcl-2 in lung cancer, we performed immunohistochemical stain of bcl-2 on 57 biopsy specimens from resected primary non-small cell lung cancer. Thereafter, flow cytometric cell cycle analysis was done. And we analyzed the correlation between bcl-2 expression, clinical parameters, S-, $G_1$-phase fraction and survival. Results: bcl-2 were detected in 43.8% of total 57 patients(according to histology, squamous cancer 47%, adenocarcinoma 32%, according to TNM stage, I 28.6%, II 52.3%, III 45.5%. both differences were insignificant). By using the flow cytometric analysis, mean S-phase fraction of bcl-2(+) and (-) group were 14.1($\pm7.8$)%, 24.7($\pm10.5$)% (p<0.005), mean $G_1$-phase fraction of bcl-2(+) and bcl-2(-) group were 75.5($\pm10.8$)%, 65.5($\pm11.4$)%(p<0.05). 2yr, 3yr and 5yr survival and median survival time of bcl-2(+) group were 65%, 54%, 41%, 53 months, and those of bcl-2(-) group were 71%, 52%, 46%, 37 months. (p>0.05, Kaplan-Meier, log rank) Conclusion: bcl-2 was detected in 43.8% of primary non-small cell lung cancer. The S-phase fraction of bcl-2(+) group was less than bcl-2(-) group, and G1-phase fraction of bcl-2(+) group was more than bcl-2(-) group. But, expression of bcl-2 could not be a prognostic factor.

• Tuberculosis and Respiratory Diseases
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• v.55 no.6
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• pp.589-596
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• 2003

Background : The solitary pulmonary nodule(SPN) presents a diagnostic dilemma to the physician and the patients in the our nation with high incidence of tuberculoma. We could not exclude whether the SPN was benign or malignant by the change of the size at chest radiograph and findings of chest CT. Recently, positron emission tomography(PET) have been tried as the differential diagnostic method of SPN. We evaluated the efficacy of PET for differentiating malignant from benign SPN and the relationship between standardized uptake values(SUV) of PET and serum glucose. Method : Between January 2001 and July 2002, sixty-one patients with pulmonary nodule were examined by the chest CT and PET. The SPN has been finally diagnosed by the transthorasic needle aspiration and biopsy, bronchoscopic biopsy, and open lung biopsy. Results : Forty eight patients had a malignant nodule(23 squamous cell lung carcinoma, 16 adenocarcinoma, 9 small cell lung cancer) and thirteen patients had a benign nodule(3 tuberculoma, 9 inflammatory granuloma, 1 cryptococcosis). The mean size of malignant and benign nodule was 40.6 mm and 20.0 mm, respectively. All malignant nodules showed a marked increase in 18 fluorodeoxyglucose (FDG) uptake. Mean SUV of malignant was $9.52{\pm}5.20$ and benign nodule was $1.61{\pm}3.60$. There were false positive cases with an increase in 18-FDG uptake (2 tuberculoma, 1 inflammatory granuloma). The SUV of malignant nodule in diabetes patients has no difference in non diabetes patients($9.10{\pm}4.51$ vs $9.65{\pm}5.46$). The sensitivity and specificity of the PET scan for SPN were 100%, 77%, respectively. The positive and negative predictive values were 94% and 100%. Conclusion : PET scanning showed highly accurate result in differentiating the malignant and benign SPN. There were no significant differences between the SUV and serum glucose in the patients with lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.62 no.4
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• pp.318-322
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• 2007

Although reports of multiple primary malignant tumors have increased recently, cases of synchronous double primary tumors of lung and liver are rare. A 73-year-old man suffered from chronic cough. His chest x-ray showed segmental atelectasis of the right upper lobe. Bronchoscopy revealed a mass occluding the orifice of the anterior segmental bronchus of the right upper lobe, and a biopsy showed a squamous cell carcinoma. A synchronous hepatic mass was found by ultrasonography. However, F18-FDG-PET showed no evidence of a distant metastasis. The liver biopsy revealed a hepatocellular carcinoma. A right upper lobe lobectomy and a sleeve resection were performed for the lung cancer, and radiofrequency ablation was performed for the hepatocellular carcinoma.

• Journal of Chest Surgery
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• v.40 no.1 s.270
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• pp.37-44
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• 2007

Background: It is known that long-term survival rate in patients underwent bronchial sleeve lobectomy for primary lung cancer is at least equal to that in patients underwent pneumonectomy, and bronchial sleeve lobectomy is performed in patients with suitable tumor location even in patients have adequate pulmonary function. Sleeve pneumonectomy is performed when carina was invaded by tumor or tumor location was near to the carina. We performed this study to know our results of sleeve resection for primary lung cancer. Material and Method: We analyzed retrospectively the medical records of 45 patients who underwent sleeve lobectomy or sleeve pneumonectomy for primary lung cancer by one thoracic surgeon from May 1990 to July 2003 in Department of Thoracic & Cardiovascular Surgery, College of Medicine, Kyung Hee University. Follow-up loss was absent and last follow-up was performed in April 5, 2005. Kaplan-Meyer method and log-lank test were used to know long-term survival rate and p-value. Result: Mean age was 60 years old and male to female ratio 41:1. Histologic types were squamous cell carcinoma were 39, adenocarcinoma were 4, and others were 2 patients. Pathologic stages were I 14, II 14, and III 17 patients. Nodal stages were N0 23, N1 13, and N2 9 patients. Types of operation were sleeve lobectomy 40 and sleeve pneumonectomy 5 patients. Operative mortality was 3 patients and its cause was respiratory complications. Early complications were pneumonia 4, atelectasis 8, air leakage more than 7 days 6, and atrial fibrillation 4 patients. In 19 patients tumor was recurred. Local recurrence was 10 and systemic metastasis was 9 patients. Overall 5, 10-year survival rate were 54.2%, 42.5%. The 5, 10-year survival rates according to the pathologic stage were 83.9%, 67.1% in stage I, 55%, 47.1% in II, 33.3%, 25% in III, and significance difference was present between stage I and III. The 5, 10-year survival rate according to the lymph node involvement were 63.9%, 54.6% in N0, 53,8%, 46.5% in N1, 28.5%, 14.2% in N2, and significance difference was present between N0 and N2. Conclusion: Because bronchial sleeve lobectomy for primary lung cancer could be performed safely and shows acceptable long-term survival rate, it could be considered primary in case of suitable tumor location if complete resection is possible. Although sleeve pneumonectomy for primary lung cancer shows somewhat high operative mortality rate, it could be considered in view of curative treatment.

• Journal of Life Science
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• v.29 no.4
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• pp.499-508
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• 2019

Cancer stem cells (CSCs), which are primarily responsible for metastasis and recurrence, have self-renewal, differentiation, therapeutic resistance, and tumor formation abilities. Numerous studies have demonstrated the signaling pathways essential for the acquisition and maintenance of CSC characteristics, such as WNT/${\beta}$-catenin, Hedgehog, Notch, B lymphoma Mo-MLV insertion region 1 homolog (BMI1), Bone morphogenetic protein (BMP), and TGF-${\beta}$ signals. However, few therapeutic strategies have been developed that can selectively eliminate CSCs. Recently, neutralizing antibodies against Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1), immune checkpoint inhibitors (ICIs), have shown promising outcomes in clinical trials of melanoma, lung cancer, and pancreatic cancer, as well as in hematologic malignancies. ICIs are considered to outperform conventional anticancer drugs by maintaining long-lasting anti-cancer effects, with less severe side effects. Several studies reported that ICIs successfully blocked CSC properties in head and neck squamous carcinomas, melanomas, and breast cancer. Together, these findings suggest that novel and effective anticancer therapeutic modalities using ICIs for selective elimination of CSCs may be developed in the near future. In this review, we highlight the origin and characteristics of CSCs, together with critical signaling pathways. We also describe progress in ICI-mediated anticancer treatment to date and present perspectives on the development of CSC-targeting ICIs.

• Tuberculosis and Respiratory Diseases
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• v.64 no.3
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• pp.200-205
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• 2008

Background: Tumor angiogenesis plays an important role in tumor growth, maintenance and metastatic potential. Tumor tissue produces many types of angiogenic growth factors. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have both been implicated to have roles in tumor angiogenesis. In this study, the expression of tissue VEGF and bFGF from non-small cell lung cancer (NSCLC) patients were analyzed. Methods: We retrospectively investigated 35 patients with a histologically confirmed adenocarcinoma or squamous cell carcinoma of the lung, where the primary curative approach was surgery. An ELISA was employed to determine the expression of VEGF and bFGF in extracts prepared from 35 frozen tissue samples taken from the cancer patients. Results: VEGF and bFGF concentrations were significantly increased in lung cancer tissue as compared with control (non-cancerous) tissue. The VEGF concentration was significantly increased in T2 and T3 cancers as compared with T1 cancer. Expression of VEGF was increased in node-positive lung cancer tissue as compared with node-negative lung cancer tissue (p=0.06). VEGF and bFGF expression were not directly related to the stage of lung cancer and patient survival. Conclusion: Expression of VEGF and bFGF were increased in lung cancer tissue, and the expression of VEGF concentration in lung cancer tissue was more likely related with tumor size and the presence of a lymph node metastasis than the expression of bFGF. However, in this study, expression of both VEGF and bFGF in tissue were not associated with patient prognosis.

• Radiation Oncology Journal
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• v.12 no.2
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• pp.175-184
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• 1994

From March 1983 through January 1990, two hundred sixty six patients with non-small cell lung cancer were treated with external radiation therapy at the Department of Therapeutic Radiology, Kangnam St. Mary's Hospital, Catholic University Medical College. A retrospective analysis was performed on eligible 116 patients who had been treated with radiation dose over 40 Gy and had been able to be followed up. There were 104 men and 12 women. The age ranged from 33 years to 80 years (median ; 53 years). Median follow up period was 18.8 months ranging from 2 months to 78 months. According to AJC staging system, there were 18($15.5\%$) patients in stage II, 79($68.1\%$) patients in stage III and 19($16.4\%$) patients in stage IV. The Pathologic classification showed 72($62.8\%$) squamous cell carcinomas, 16($13.8\%$) adenocarcinomas, 7($6\%$) large cell carcinomas, 5($4\%$) undifferentiated carcinomas, and 16($13.8\%$) un-known histology. In Karnofsky performance status, six ($5.2\%$) patients were in range below 50, 12($10.4\%$) patients between 50 and 60, 46($39.6\%$) patients between 60 and 70, 50($44.0\%$) patients between 70 and 80 and only one ($0.8\%$) patient was in the range over 80. Sixty ($51.7\%$) patients were treated with radiation therapy (RT) alone. Thirty three ($28.4\%$) patients were treated in combination RT and chemotherapy, twenty three ($19.8\%$) patients were treated with surgery followed by postoperative adjuvant RT and of 23 Patients above, five ($4.3\%$) patients, were treated with postoperative RT and chemotherapy. Overall response according to follow-up chest X-ray and chest CT scans was noted in $92.5\%$ at post RT 3 months. We observed that overall survival rates at 1 year were $38.9\%$ in stage II, $27.8\%$ in stage III, and $11.5\%$ in stage IV, and 2 year overall survival rates were $11.1\%$ in stage II, $20.8\%$ in stage III and $10.5\%$ in stage IV, respectively. We evaluated the performance status, radiation dose, age, type of histology, and the combination of chemotherapy and/or surgery to see the influence on the results fellowing radiation therapy as prognostic factors. Of these factors, only performance status and response after radiation therapy showed statistical significance (P<0.05)

• Tuberculosis and Respiratory Diseases
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• v.54 no.5
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• pp.563-569
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• 2003

Background : Pleural effusions with high amylase levels are reported frequently in patients with pancreatic diseases, a rupture of the esophagus and a malignancy. However, there is no data available on the clinical features of an amylase-rich pleural effusion in Korea. This report describes the causes of the high amylase levels in a pleural effusion and analyzes its association with malignancy. Methods : The records of patients with an amylase-rich pleural effusion who were assessed at the Gyeongsang National University Hospital from January 1998 to August 2002 were examined retrospectively, and the distribution of amylase levels in those patients, the causative diseases, and the histological type in the case of a malignancy were analyzed. Among the 532 patients whose pleural effusion was evident on a chest X-ray, there were 36 cases with an amylase-rich pleural effusion. The amylase levels were determined by an enzyme method (Hitach 747 autoanalyzer). Results : Of the 36 patients with an amylase-rich pleural effusion, there were 18 patients(50%) associated with a malignancy, 8 patients(22%) with a parapneumonic effusion, 7 patients(19%) with pancreatic disease, and 3 patients with other causes. The amylase level in a pleural effusion due to pancreatic disease was much higher than that due to other causes(p<0.01). Among the malignant pleural effusions with high amylase levels, the origin of the malignancy was a primary lung cancer in 13 cases and metastatic lung cancer in 5 cases. The histological types of malignant causes were adenocarcinoma in 10 cases(56%), squamous cell carcinoma in 2 cases(11%) and unknown type of carcinoma in 6 cases. The amylase level in the adenocarcinoma cases was much higher than that in the other cell type carcinomas(p<0.01). There was no significant association between the amylase level and the glucose level among the malignant cases with amylase-rich pleural effusion(p=0.21). Conclusion : The most frequent cause of an amylase-rich pleural effusion was a malignancy. Primary lung cancer and adenocarcinoma were the most common malignancies and histological types associated with a malignant pleural effusion with high amylase levels. The amylase level in a pleural effusion secondary to pancreatic disease was much higher than from any other causes.

• Tuberculosis and Respiratory Diseases
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• v.59 no.3
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• pp.286-297
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• 2005

Background : Non-small cell lung cancer (NSCLC) is a common cause of cancer-related death in North America and Korea, with an overall 5-year survival rate of between 4 and 14%. The TNM staging system is the best prognostic index for operable NSCLC . However, epidermal growth factor receptor (EGFR), matrix metalloproteinase-9(MMP-9), and C-erbB-2 have all been implicated in the pathogenesis of NSCLC and might provide prognostic information. Methods : Immunohistochemical staining of 81 specimens from a resected primary non-small cell lung cancer was evaluated in order to determine the role of the biological markers on NSCLC . Immunohistochemical staining for EGFR, MMP-9, and C-erbB-2 was performed on paraffin-embedded tissue sections to observe the expression pattern according to the pathologic type and surgical staging. The correlations between the expression of each biological marker and the survival time was determined. Results : When positive immunohistochemical staining was defined as the extent area>20%(more than Grade 2), the positive rates for EGFR, MMP-9, and C-erbB-2 staining were 71.6%, 44.3%, and 24.1% of the 81 patients, respectively. The positive rates of EGFR and MMP-9 stain for NSCLC according to the surgical stages I, II, and IIIa were 75.0% and 41.7%, 66.7% and 47.6%, and 76.9% and 46.2%, respectively. The median survival time of the EGFR(-) group, 71.8 months, was significantly longer than that of the EGFR(+) group, 33.5 months.(p=0.018, Kaplan-Meier Method, log-rank test).. The MMP-9(+) group had a shorter median survival time than the MMP-9(-) group, 35.0 and 65.3 months, respectively (p=0.2). The co-expression of EGFR and MMP-9 was associated with a worse prognosis with a median survival time of 26.9 months, when compared with the 77 months for both negative-expression groups (p=0.0023). There were no significant differences between the C-erbB-2(+) and C-erbB-2 (-) groups. Conclusion : In NSCLC, the expression of EGFR might be a prognostic factor, and the co-expression of EGFR and MMP-9 was found to be associated with a poor prognosis. However, C-erbB-2 expression had no prognostic significance.