• CELLMED
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• v.3 no.2
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• pp.10.1-10.8
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• 2013

Cancer is one of the major dreaded diseases causing high mortality. Lung cancer is second in position of all cancer related deaths and mainly divided into two morphologic sub-types: small-cell lung cancer and non-small cell lung cancer (NSCLC). NSCLC is an aggressive neoplasm which hardly responds to any conventional chemotherapy. Epidermal growth factor receptor (EGFR) belongs to the ErbB family of receptor tyrosine kinase that is mainly over-expressed in NSCLC. EGFR is mainly involved in the pathogenesis and progression of different carcinoma. In vivo and in vitro studies suggest that EGFR and EGF like peptides are often over-expressed in human NSCLC and these proteins are able to induce cell transformation. The conventional therapies mostly inhibit the EGFR activity and expression level in human NSCLC with the use of some EGFR-inhibitors like HKI-272, EKB569, CL-387785 etc. and some synthetic chemotherapeutic drugs like erlotinib, gefitinib, plumbagin, docetaxel, cisplatin etc., alone or in combination of two or more drugs. These therapies selectively act by competitive inhibition of the binding of adenosine triphosphate to the tyrosine kinase domain of the EGFR, resulting in inhibition of the EGFR signaling pathway. But these chemotherapeutic drugs have some cytotoxic activities to the normal cells and have some adverse side-effects. Recent studies on some traditional alternative therapies including some herbal and plant extracts, active ingredients like curcumin, different homeopathic drugs, etc. can target EGFR-signalling in NSCLC with less toxic side-effects are being currently developed.

• Tuberculosis and Respiratory Diseases
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• v.38 no.3
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• pp.250-254
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• 1991

This article reviews the clinical characteristics of seven synchronous multiple primary lung cancer cases seen at the Seoul National University Hospital between the July of 1986 and the December of 1989. All seven patients were male with the mean age of 64. All were smokers, most of them were heavy smokers with the mean of 66.7 pack-years of smoking history. The tumors were of the same histologic type in five cases (all were squamous cell carcinoma). different in one case (squamous cell carcinoma and small cell carcinoma), and undetermined in one case (squamous cell carcinoma and non-small cell carcinoma). Fiberoptic bronchoscopy was a very useful tool in diagnosing multiple primary lung cancer. Surgical resection could be done in only one case.

• Journal of Chest Surgery
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• v.41 no.1
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• pp.68-73
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• 2008

Background: The presence of infiltrated mediastinal lymph nodes is a crucial factor for the prognosis of lung cancer. The aim of our study is to investigate the pattern of metastatic non-small cell lung cancer that spreads to the mediastinal lymph nodes, in relation to the primary tumor site, in patients who underwent major lung resection with complete mediastinal lymph node dissection. Material and Method: We retrospectively. studies 293 consecutive patients [mean age $63.0{\pm}8.3$ years (range $37{\sim}88$) and 220 males (75.1%)] who underwent major lung resection due to non-small cell lung cancer from January 1998 to December 2005. The primary tumor and lymph node status was classified according to the international TNM staging system reported by Mountain. The histologic type of the tumors was determined according to the WHO classification. Fisher's exact test was used; otherwise the chi-square test of independence was employed. A p-value < 0.05 was considered significant. Result: Lobectomy was carried out in 180 patients, bilobectomy in 50, sleeve lobectomy in 10 and pnemonectomy in 53. The pathologic report revealed 124 adenocarcinomas, 138 squamous-cell tumors, 14 adenosquamous tumors, 1 carcinoid tumor, 8 large cell carcinomas, 1 carcinosarcoma, 2 mucoepidermoid carcinomas and 5 undifferentiated tumors. The TNM stage was IA in 51 patients, IB in 98, IIB in 41, IIIA in 71, IIIB in 61 and IV in 6. 25.9 % of the 79 patients had N2 tumor. Most common infiltrated mediastinal lymph node was level No.4 in the right upper lobe, level No. 4 and 5 in the left upper lobe and level No. 7 in the other lobes, but no statistically significant difference was observed. Thirty-six patients (12.3%) presented with skip metastasis to the mediastinum. Conclusion: Mediastinal lymph node dissection is necessary for accurately determining the pTNM stage. It seems that there is no definite way that non-small cell lung cancer spreads to the lymphatics, in relation to the location of the primary cancer. Further, skip metastasis to the mediastinal lymph nodes was present in 12.3% of our patients.

• Journal of Chest Surgery
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• v.39 no.9 s.266
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• pp.668-673
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• 2006

Background: Docetaxel has been effectively used as an anti-cancer chemotherapuetic agent for various tumor treatments including lung cancer. However, the cell death induction mechanism(s) involved with docetaxel treatment in lung cancer cells has not been known yet. Material and Method: In the present study, the cellular and biochemical changes of NCI-H1703 cells (non-small cell lung cancer cell line, p53-mutant) after docetaxel treatment have been monitored by flow cytometry, fluorescence microscopy and western blot. Result: Docetaxel treatment significantly resulted in decrease of S phase as well as increase of G2 phase, and consequently evoked an increase of cell death in NCI-H1703 cells. After docetaxel exposure the activations of caspase-3 and caspase-9 were detected. Conclusion: Take together, it is suggested that the docetaxel induces NCI-H1703 cell death by caspase-9 and caspase-3 dependent mitochondrial apoptotic pathway.

• Tuberculosis and Respiratory Diseases
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• v.74 no.4
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• pp.181-186
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• 2013

We report a rare synchronous presentation of primary lung cancer and adrenal pheochromocytoma. A 59-year-old woman was diagnosed with right upper lobe non-small cell lung carcinoma measuring 2.8 cm and a right adrenal gland mass measuring 3.5 cm, which displayed increased metabolic activity on $^{18}F$-fluorodeoxyglucose positron emission tomography-computed tomography. The adrenal lesion was revealed to be asymptomatic. The patient underwent right adrenalectomy and histological examination revealed a pheochromocytoma. Ten days later, right upper lobectomy was performed for lung cancer. This case indicates that incidental adrenal lesions found in cases of resectable primary lung cancer should be investigated.

• Journal of Chest Surgery
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• v.37 no.8
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• pp.672-683
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• 2004

Background: The treatment results of the advanced lung carcinoma is not satisfactory with the present therapeutic modalities: surgical resection, anti-cancer chemotherapy, and radiotherapy or combination therapy. To predict the prognosis of the non-small-cell lung carcinoma, TNM classification has been was as the basic categorization; however, it has been not satisfactory. It is necessary to consider the causes and the prognosis of the lung carcinoma from another points of view rather the conventional methods. We intended to find out the relationship between the major apoptotic factor, p53 gene and the prognosis of the patient with lung carcinoma. Material and Method: Three hundreds and fifty-nine patients with lung carcinoma who underwent surgery were analysed. We observed p53 protein accumulated in the cellular nuclei. The p53 protein was detected by immuno-histo-chemical method. We collected information of the patient retrospectively. Result: p53 protein densities were observed in 40% in average as a whole. The protein density was 44 percent in man, 25 percent in woman, 49 percent in the squamous cell carcinoma, and 38 percent in the adenocarcinoma. There were significant correlations between the p53 protein density and the mortality in the squamous cell carcinoma (p=0.025), follow-up duration in TNM stage I group (p=0.010), and follow-up duration in the lobectomy patient group (p=0.043), and tumor cell differentiation (p=0.009). p53 protein densities were significantly different between the lobectomy and the pneumonectomy group (p=0.044). Conclusion: The authors found that p53 protein had some correlations with the prognosis of the lung cancer partially in some factors. We suggest the p53 protein density could be used as a marker of prognosis in the non-small-cell lung carcinoma.

• Tuberculosis and Respiratory Diseases
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• v.63 no.1
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• pp.31-41
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• 2007

Background: In pathogenesis and prognosis of lung cancer, significance of enormous types of genetic expression were very compounding and undetermined. We performed this study to search association between clinical characteristics and expression of COX-2, MMP-9 and p53 in non-small cell lung cancer. Methods: Ninety-one patients with adenocarcinoma or squamous cell carcinoma were enrolled. We had searched clinical data retrospectively and performed immunohistochemical staining for COX-2, MMP-9 and p53. We had analyzed significance of these three genes in clinical features and prognosis for survival. Results: 1) In squamous cell carcinoma, male was predominant and was significantly correlated with smoking. 2) Major prognostic determinants for overall survival were curative resection. 3) Expression of COX-2 was more frequent in adenocarcinoma than in squamous cell carcinoma. 4) Negative staining of COX-2, MMP-9 and p53 was more frequent in squamous cell carcinoma than adenocarcinoma. 5) Survival duration was longer in the group with positive expression of p53 and negative for COX-2 and MMP-9 (median duration of survival = 165.6 weeks) than groups with the other expressional patterns. 6) Significant correlation was found between expression of MMP-9 and COX-2. In squamous cell carcinoma, expression of MMP-9, COX-2 and mutant p53 were mutually correlated. 7) COX-2 expression was significant prognostic factor for survival in resected cancer group. In unresected inoperable non-small cell lung cancer group, MMP-9 was statistically significant prognostic factor for overall survival. Conclusion: COX-2 and MMP-9 might have some roles for progression or prognosis in some selected patients with non-small cell lung cancer. COX-2 and MMP-9 may have some roles for disease progression or prognosis in selected patients with NSCLC.

• 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.

• Radiation Oncology Journal
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• v.9 no.2
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• pp.221-225
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• 1991

Twenty five patients with unresectable non-small cell carcinoma of the lung have been treated with hyperfractionated radiotherapy with concomitant boost technique since September, 1989. Those patients with history of previous surgery or chemotherapy, pleural effusion or significant weight loss (greater than $10\%$ of body weight) were excluded from the study. Initially, 27 Gy were delivered in 15 fractions in 3 weeks to the large field. Thereafter, large field received 1.8 Gy and cone down boost field received 1.4 Gy with twice a day fractinations up to 49.4 Gy. After 49.4Gy, only boost field was treated twice a day with 1.8 and 1.4 Gy. Total tumor doses were 62.2 Gy for 12 patients and 65.4 Gy for remaining 13 patients. Follow up period was ranged from 6 to 24 month. Actuarial survival rates at 6, 12, and 18 month were $88\%,\;62\%,\;and\;38\%$, respectively. Corresponding disease free suwival rates were $88\%,\;41\%,\;and\;21\%$, respectively. Actuarial cumulative local failure rates at 9, 12 and 15 month were $36\%,\;43\%,\;and\;59\%$, respectively. No significant increase of acute or late complications including radiation pneumonitis was noted with maximum follow up of 24 month. Although the longer follow up is needed, it is worthwhile to try the prospective randomized study to evaluate the efficacy of hyperfractionated radiotherapy with concomitant boost technique for unresectable non-small cell lung cancers in view of excellent tolerance of this treatment. In the future, further increase of total radiation dose might be necessary to improve local control for non-small cell lung cancer.

• Journal of Chest Surgery
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• v.39 no.11 s.268
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• pp.828-837
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• 2006

Background: Tissue hypoxia is characteristic of many human malignant neoplasm, and hypoxia inducible factor-1(HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increasing $O_2$ delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-$1{\alpha}$ has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-$1{\alpha}$ on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-$1{\alpha}$ expression on angiogenetic factors, relationship between the tumor proliferation and HIF-$1{\alpha}$ expression, interaction of HIF-$1{\alpha}$ expression and p53, and relationship between HIF-$1{\alpha}$ expression and clinico-pathological prognostic parameters were investigated. Material and Method: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex(ABC) immunohistochemistry. Relationship between the HIF-$1{\alpha}$ expression and VEGF, p53 overexpression and correlation between the HIF-$1{\alpha}$ expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. Result: HIF-$1{\alpha}$ expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma(40.7%). High HIF-$1{\alpha}$ expression was significantly associated with several pathological parameters, such as pathological TMN stage(p=0.004), pT stage(p=0.020), pN stage (p=0.029), and lymphovascular invasion(p=0.019). High HIF-$1{\alpha}$ expression was also significantly associated with VEGF immunoreactivity(p<0.001), and aberrant p53 expression(p=0.040). but was marginally associated with Ki-67 labeling index(p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-$1{\alpha}$ expression was worse than that of patients with low-expression(p=0.002). High HIF-$1{\alpha}$ expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. Conclusion: It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-$1{\alpha}$ expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung carcinoma.