• Tuberculosis and Respiratory Diseases
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• v.75 no.2
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• pp.59-66
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• 2013

Background: This study was conducted in order to elucidate the effects of docetaxel on the growth of peroxiredoxin 1 (Prx1) knockdown A549 xenograft tumors and further tested the role of Prx1 as a predictor for how a patient would respond to docetaxel treatment. Methods: Effects of docetaxel on the growth of scrambled- and shPrx1-infected A549 xenograft tumors in nude mice were measured. Moreover, immunohistochemical expression of Prx1 was evaluated in paraffin-embedded tissues from 24 non-small cell lung cancer patients who had received docetaxel-cisplatin regimens as a first-line treatment. Results: Docetaxel treatment in Prx1 knockdown xenograft tumor resulted in reduced tumors growth compared with other groups. Prx1 knockdown increased the production of cleaved caspases-8 and -9 in the control itself compared to scramble tumors. Moreover, docetaxel treatment in Prx1 knockdown tissue led to an increased protein band. Phosphorylated Akt was found in Prx1 scramble tissues. Phosphorylated FOXO1 was detected in the docetaxel treatment group. On the other hand, Prx1 knockdown completely suppressed the Akt-FOXO1 axis. The median progression-free survival (PFS) of patients with low Prx1 expression was 7 months (95% confidence interval [CI], 6.0-7.7), whereas the median progression-free survival of patients with high Prx1 expression was 4 months (95% CI, 4.0-5.0). However, high Prx1 expression was not associated with decreased PFS (p=0.114). Conclusion: Our findings suggest that elevated Prx1 provides resistance to docetaxel treatment through suppression of FOXO1-induced apoptosis in A549 xenograft tumors, but may not be related with the predictive significance for response to docetaxel treatment.

• Journal of Korean Neurosurgical Society
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• v.44 no.6
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• pp.358-363
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• 2008

Objective : This study was performed to assess the efficacy of GKS in patients with ten or more brain metastases. Methods : From Aug 2002 to Dec 2007, twenty-six patients (13 men and 13 women) with ten or more cerebral metastatic lesions underwent GKS. The mean age was 55 years (32-80). All patients had Karnofsky performance status (KPS) score of 70 or better. According to recursive partitioning analysis (RPA) classification, 3 patients belonged to class I and 23 to class II. The location of primary tumor was lung (21), breast (3) and unknown (2). The mean number of the lesions per patient was 16.6 (10-37). The mean cumulated volume was 10.9 cc (1.0-42.2). The median marginal dose was 15 Gy (9-23). Overall survival and the prognostic factors for the survival were retrospectively analyzed by using Kaplan Meier method and univariate analysis. Results : Overall median survival from GKS was 34 weeks (8-199). Local control was possible for 79.5% of the lesions and control of all the lesions was possible in at least 14 patients (53.8%) until 6 months after GKS. New lesions appeared in 7 (26.9%) patients during the same period. At the last follow-up, 18 patients died; 6 (33.3%) from systemic causes, 10 (55.6%) from neurological causes, and 2 (11.1 %) from unknown causes. Synchronous onset in non-small cell lung cancer (p=0.007), high KPS score (${\geq}80$, p=0.029), and controlled primary disease (p=0.020) were favorable prognostic factors in univariate analysis. Conclusion : In carefully selected patients, GKS may be a treatment option for ten or more brain metastases.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1803-1811
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• 2015

Hepatoma-derived growth factor (HDGF) is a novel jack-of-all-trades in cancer. Here we quantify the prognostic impact of this biomarker and assess how consistent is its expression in solid tumors. A comprehensive search strategy was used to search relevant literature updated on October 3, 2014 in PubMed, EMBASE and WEB of Science. Correlations between HDGF expression and clinicopathological features or cancer prognosis was analyzed. All pooled HRs or ORs were derived from random-effects models. Twenty-six studies, primarily in Eastern Asia, covering 2,803 patients were included in the analysis, all of them published during the past decade. We found that HDGF overexpression was significantly associated with overall survival (OS) ($HR_{OS}=2.35$, 95%CI=2.04-2.71, p<0.001) and disease free survival (DFS) ($HR_{DFS}=2.25$, 95%CI =1.81-2.79, p<0.001) in solid tumors, especially in non-small cell lung cancer, hepatocellular carcinoma and cholangiocarcinoma (CCA). Moreover, multivariate survival analysis showed that HDGF overexpression was an independent predictor of poor prognosis ($HR_{OS}=2.41$, 95%CI: 2.02-2.81, p<0.001; $HR_{DFS}=2.39$, 95%CI: 1.77-3.24, p<0.001). In addition, HDGF overexpression was significantly associated with tumor category (T3-4 versus T1-2, OR=2.12, 95%CI: 1.17-3.83, p=0.013) and lymph node status (N+ versus N-, OR=2.37, 95%CI: 1.31-4.29, p=0.03) in CCA. This study provides a comprehensive examination of the literature available on the association of HDGF overexpression with OS, DFS and some clinicopathological features in solid tumors. Meta-analysis results provide evidence that HDGF may be a new indicator of poor cancer prognosis. Considering the limitations of the eligible studies, other large-scale prospective trials must be conducted to clarify the prognostic value of HDGF in predicting cancer survival.

• Tuberculosis and Respiratory Diseases
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• v.75 no.4
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• pp.140-149
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• 2013

Background: Plasminogen activator inhibitor type 1 (PAI-1), an important regulator of plasminogen activator system which controls degradation of extracellular membrane and progression of tumor cells, and PAI-1 gene polymorphic variants have been known as the prognostic biomarkers of non-small cell lung cancer patients. Recently, experimental in vitro study revealed that transforming growth factor-${\beta}1$ initiated PAI-1 transcription through epithelial growth factor receptor (EGFR) signaling pathway. However, there is little clinical evidence on the association between PAI-1 A15T gene polymorphism and prognosis of Korean population with pulmonary adenocarcinoma and the influence of activating mutation of EGFR kinase domain. Methods: We retrospectively reviewed the medical records of 171 patients who were diagnosed with pulmonary adenocarcinoma and undergone EGFR mutation analysis from 1995 through 2009. Results: In all patients with pulmonary adenocarcinoma, there was no significant association between PAI-1 A15T polymorphic variants and prognosis for overall survival. However, further subgroup analysis showed that the group with AG/AA genotype had a shorter 3-year survival time than the group with GG genotype in patients with EGFR mutant-type pulmonary adenocarcinoma (mean survival time, 24.9 months vs. 32.5 months, respectively; p=0.015). In multivariate analysis of 3-year survival for patients with pulmonary adenocarcinoma harboring mutant-type EGFR, the AG/AA genotype carriers had poorer prognosis than the GG genotype carriers (hazard ratio, 7.729; 95% confidence interval, 1.414-42.250; p=0.018). Conclusion: According to our study of Korean population with pulmonary adenocarcinoma, AG/AA genotype of PAI-1 A15T would be a significant predictor of poor short-term survival in patients with pulmonary adenocarcinoma harboring mutant-type EGFR.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.2
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• pp.208-215
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• 2015

The aim of the study was to investigate the antioxidant activities of ethanol extract of perilla seed (PSE) and its inhibitory effects against major characteristics of cancer cells, such as unrestricted growth and activated metastasis in vitro. The total polyphenol and flavonoid levels of PSE were 222.6 mg gallic acid equivalent/100 g and 285.7 mg quercetin equivalent/100 g, respectively. The radical scavenging activity and ferric reducing antioxidant power of PSE at concentration of 87.5 to $350{\mu}g/mL$ were 24~45% and 28~62%, respectively. Treatment of HCT116 colorectal carcinoma cells and H1299 non-small cell lung carcinoma cells with PSE dose-dependently inhibited growth by 18~94% (at concentration range of 87.5 to $350{\mu}g/mL$) and completely abolished colony formation (at concentration of $175{\mu}g/mL$). PSE was also effective in inhibiting migration of H1299 cells (by 30~37% at concentration range of 87.5 to $350{\mu}g/mL$) and adhesion of both HCT116 and H1299 cells (by 14~16% at concentration of $350{\mu}g/mL$). These results indicate that PSE exerts antioxidant and anti-cancer activities in vitro. It needs to be determined whether or not similar effects can be reproduced in vivo.

• Radiation Oncology Journal
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• v.15 no.3
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• pp.243-249
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• 1997

Purpose : In radiation therapy, NTCF is very importart indicator of selecting the optimal treatment plan. In our study, we tried to find out usefullness of NTCP in lung cancer by comparng the incidence of radiation pneumonitis with NTCP. Materials and Methods : From August 1993 to December 1994, thirty six patients with locally advanced non=small cell lung cancer were treated by concurrent chemoradiation therapy. Total dose of radiation therapy was 6480cGy (120cGy, bid) and chemotherapeutlc agents were mitomycin C. vinblastion, cisplatin (2 cycles, 4 weeks interval). We evaluated the development of raniation pneumonitis by CT scan, chest x-rar and clinical symptoms. We used grading system of South Western Oncology Group (SWOG) for radiation pneumanitis. Dose Volume Histograms (DVH) were analyzed for ipsilateral and whole lung, Non uniform DVH was translated to uniform DVH by effective volume method. With these data, we calculated NTCP for ipsilateral and whole lung. Finally we compared the clinical results to NTCP. Results : Eight of thrity six patients developed radiation pneumonitis. Of these 8 patients , 6 had grade I severity and 2 had grade II. The average NTCP value cf the patients who showed radiation pneumonitis was significantly higher than that uf the patients without pneumonitis $(66\%\;vs.\;26.4\%)$. But the results of pulmonary function test was not correlated with NTCP. Conclusion : NTCP of lung is very good indicator for selecting rival treatment planning in lung cancer. According to the results of NTCP, it may be possible to adjust target volume and optimize target dose. In the near future, we are going to anaiyze the effect of hyperfractionation and concurrent chemotherapy in addition to NTCP.

• Tuberculosis and Respiratory Diseases
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• v.42 no.5
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• pp.685-694
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• 1995

Introduction: Transthoracic fine needle aspiration biopsy(TNAB) has shown to be a resonably safe, simple, and accurate procedure in diagnosis of intrathoracic lung lesions. We reviewed the results of 1,005 TNAB of chest lesions performed on 930 patients with 20 or 22-gauze needles over a period of 10 years. Methods: From November 1983 to June 1995, 1,005 cases in 930 patients with an undiagnosed lung lesion underwent TNAB at the Hanyang University Hospital: 66% were men and 34% were women. Most of the patients were 40~60 years old and the youngest patient was 3 years of age. Result: 540 patients had various malignant chest lesions and 322 patients had benign pulmonary lesions. The diagnostic accuracy of TNAB was 96.1 percent in malignant diseases with one false positive result and 90.1% in benign diseases. A definitive diagnosis was not obtained in the remaining 68 patients. The most common diagnoses among 519 malignancy chest lesions with TNAB were the following: squamous cell lung carcinoma, 31.7%; adenocarcinoma, 24.7%; small cell lung carcinoma, 16.7%; metastatic cancer, 14.2%; large cell lung carcinoma, 6.2% and so on. Complications included pneumothorax in 12.3% necessitating chest tube drainage in 0.6%. Minor hemoptysis occurred in 3.6%. There was no death directly attributable to the procedure. Conclusion: We concluded that TNAB permits a direct approach to all kinds of localized lung lesions with a high degree of accuracy and without major complications.

• Tuberculosis and Respiratory Diseases
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• v.43 no.1
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• pp.75-87
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• 1996

Background: Lung cancer is the second most frequent malignancy in man in Korea. Surgery is the best treatment modality for non-small cell lung cancer, but most patients were presented in far advanced stage. So radiation therapy(RT) with or without chemotherapy is the next choice and radiation-induced pneumonitis and pulmonary fibrosis is the major limiting factor for the curative RT. Radiation pneumonitis is manifested with fever, cough and dyspnea, 2~3 months after the termination of radiotherpy. Chest X ray shows infiltration, typically limited to the radiation field, but occasionally bilateral infiltration was reported. Also Gibson et al reported that BAL lymphocytosis was found in both lungs, even though the radiation was confined to one lung. The aim of this study is to investigate the change of adhesion molecules expression on BAL cells and serum soluble ICAM-1(sICAM-1) level after the RT and its relationship to the development of radiation pneumonitis. The second aim is to confirm the bilaterality of change of BAL cell pattern and adhesion molecule expression. Subjects: BAL and the measurement of sICAM level in serum and BALF were done on 29 patients with lung cancer who received RT with curative intention. The BAL was done before the RT in 16 patients and 1~2 month after RT in 18 patients. 5 patients performed BAL before and after RT. Result: Clinically significant radiation pneumonitis developed in 7 patients. After RT, total cell count in BAL was significantly increased from $(20.2{\pm}10.2){\times}10^6\;cells/ml$ to $(35.3{\pm}21.6){\times}10^6\;cells/ml$ (p=0.0344) and %lymphocyte was also increased from $5.3{\pm}4.2%$ to $39.6{\pm}23.4%$ (p=0.0001) in all patient group. There was no difference between ipsilateral and contraleteral side to RT, and between the patients with and without radiation-pneumonitis. In whole patient group, the level of sICAM-1 showed no significant change after RT(in serum: $378{\pm}148$, $411{\pm}150\;ng/ml$, BALF: $20.2{\pm}12.2$, $45.1{\pm}34.8\;ng/ml$, respectively), but there was a significant difference between the patients with pneumonitis and without pneumonitis (serum: $505{\pm}164$ vs $345{\pm}102\;ng/ml$, p=0.0253, BALF: $67.9{\pm}36.3$ vs $25.2{\pm}17.9\;ng/ml$, p=0.0112). The expression of ICAM-1 on alveolar macrophages (AM) tends to increase after RT (RMFI: from $1.28{\pm}0.479$ to $1.63{\pm}0.539$, p=0.0605), but it was significantly high in patients with pneumonitis ($2.10{\pm}0.390$) compared to the patients without pneumonitis ($1.28{\pm}0.31$, p=0.0002). ICAM-1 expression on lymphocytes and CD 18 (${\beta}2$-integrin) expression tended to be high in the patients with pneumonitis but the difference was statiastically not significant. Conclusion: Subclinical alveolitis on the basis of BAL finding developed bilaterally in all patients after RT. But clinically significant pneumonitis occurred in much smaller fraction and the ICAM-1 expression on AM and the sICAM-1 level in serum were good indicator of it.

• Journal of Chest Surgery
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• v.36 no.6
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• pp.397-403
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• 2003

Background: The research sought to identify the clinical features of pleomorphic carcinoma of the lung generally known as a rare subtype in accordance with the lung cancer classification done in 1999 by WHO. Material and Method: 250 cases of surgically resected lung cancers were collected in this hospital from January 1992 to December 2001. This study included 42 cases of pleomorphic carcinoma diagnosed through light microscope and immunohistochemistry. Result: Out of 42 cases, males represented 31, and females 11, the age ranged from 26 to 77. Main clinical symptoms included coughing, hemoptysis, sputum. Diagnoses disclosed the stage as stage la in 3 cases (7%), Ib in 16 (38%), IIa in 1 (2%), IIb in 8 (19%), IIIa in 15 (35%), and IIIb in 1 (2%). Out of these, no lymph node metastasis was represented in 23 cases (54%), while N1 and N2 involving lymph node metastasis was shown 19 cases (46%). A total of 19 patients developed metastasis, comprising the brain in 5 cases (26%), bone in 4 (21%), muscle in 4 (21%), Lymph node in 2 (10%), and 1 liver, ovary, contralateral lung, and adrenal gland, respectively. The size of the tumor ranged from 1 cm to 11 cm, averaging 5.85 cm. Out of the 42 patients, the total two-year and five-year survival rates in accordance with the Kaplan-Meier method represented 26% and 13%, respectively, These figures compared to the corresponding 44% and 34% in cases other than pleomorphic carcinoma from the survey target of 256 cases, proved to be significantly low (p<0.002). No significant difference was found in the survival rates compared between age and tumor size, between stage I and above stage II, and between N0 and above N1. Patients who developed postoperative metastasis all died, and showed significantly low survival rates (p<0.002) compared to those patients without metastasis. Conclusion: With the new diagnosis method of f999 WHO's lung cancer classification applied, pleomorphic carcinoma showed a higher prevalence rate than under previous classifications, their postoperative survival rate was significantly low compared to histologic type of non small cell lung carcinomas.

• Journal of Applied Biological Chemistry
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• v.57 no.3
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• pp.247-250
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• 2014

A lipid-soluble extract in ginseng marc was prepared by n-hexane extraction to evaluate its antioxidant and anticancer potential. A hexane extract of ginseng marc (HEGM) possessed a 2,2-diphenyl-1-picryl-hydrazyl free radical scavenging activity which was related to the amount of total phenolics. Also, HEGM showed a potent inhibitory activity on human non-small cell lung cancer (A549, $GI_{50}=34.0{\mu}g/mL$) and colon cancer (SNU-C4, $GI_{50}=45.2{\mu}g/mL$) cells proliferation in vitro in a concentration-dependent manner as did the hexane extract of ginseng with $GI_{50}$ values of $20.0{\mu}g/mL$ in A549 and $37.0{\mu}g/mL$ in SNU-C4. These results imply that HEGM can be utilized as an antioxidant and anticancer substance.