• 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.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.113-117
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• 2001

Purpose : To evaluate effect of postoperative radiotherapy on survival and local control for patients with non-small cell lung cancer (NSCLC). Materials and Methods : Ninety two NSCLC patients with N1or N2 involvement who were treated with postoperative radiotherapy following surgery with curative intent from May 1987 to October 1999 were retrospectively analyzed. Age of the patients was ranged from 32 to 78 years. According to TNM Stage, 35 patients had Stage II and 57 had Stage III disease. There were 49 patients with N1 involvement and 43 patients with N2 involvement. Fifty six patients were noted to have $T1\~2$ tumors and 36 patients to have $T3\~4$ tumors. Delivered total dose was ranged from 40 to 60 Gy. Majority of patients received 50 Gy or 50.4 Gy. Follow-up period was ranged from 9 month to 7 years with median follow-up of 26 months. Results : Overall survival rates at 3 and 5 years for entire group of patients were $46\%\;and\;38\%$, respectively. Corresponding disease free survival rates were $44\%\;and\;36\%$. There was significant difference in survival between patients with Stage II and Stage III disease ($50\%\;vs\;28\%$ at 5-year). Five year survival rates for N1 and N2 patients were $52\%\;and\;20\%$, respectively (p<0.05). These were $40\%\;and\;34\%$ for patients with $T1\~2$ tumors and $T3\~4$ tumors. There were documented local relapses in $13\%$ of the patients. For patients with N1 and N2 Stage, local relapse rates were $8\%\;and\;18\%$, respectively. Conclusion : Our study confirms that postoperative radiotherapy for patients with non-small cell lung cancer improves local control. However, influence of postoperative radiotherapy on long-term survival is less clear. More effective systemic treatment to prevent distant metastasis should be investigated in future study to improve long-term survival.

• Radiation Oncology Journal
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• v.24 no.4
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• pp.237-242
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• 2006

$\underline{Purpose}$: We evaluated retrospectively the outcome of locally advanced non-small cell lung cancer patients treated with definitive radiotherapy to find out prognostic factros affecting survival. $\underline{Materials\;and\;Methods}$: 216 cases of stage IIIB non-small cell lung cancer were with treated radiotherapy at our Hospital between 1991 to 2002 and reviewed retrospectively. Cases were classified by mode of treatment and response to treatment. Patients showing complete response or partial response to treatment were included in the "response group", while those showing stable or progressive cancer were included in the "non-response group". $\underline{Results}$: 30 patients completed the planned radiotherapy treatments and 39 patients completed combined treatments or chemoradiotherapy. Median survival was 4.6 months for patients treated with radiotherapy and 9.9 months for those undergoing combined radiotherapy and chemotherapy. Survival rates for the first year were 13.3% with radiotherapy and 35.9% with chemoradiotherapy. In the second year, 3.3% of the radiotherapy patients survived and 20.5% of the patients receiving chemoradiotherapy survived. By the third year, 15.4% of the patients receiving the combined treatments survived. None of the patients treated with radiotherapy alone lived to the third year, however. Overall survival was significantly different between the radiotherapy patients and the combined chemoradiotherapy patients (p<0.001). In the response group, median survival was 7.2 months with radiotherapy and 16.5 months with combined therapy. In the non-response group, median survival was 4.4 months with radiotherapy and 6.7 months with combined treatments. Severe acute complications (grade 3) occurred in 2 cases using radiotherapy, and in 7 cases using combined therapy. $\underline{Conclusion}$: When the patients with stage IIIB non-small cell lung cancer received chemoradiotherapy, treatment response rate and overall survival was greater than with radiation alone.

• Tuberculosis and Respiratory Diseases
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• v.58 no.5
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• pp.465-472
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• 2005

Background : The survival benefit associated with first-line chemotherapy in lung cancer has led to the need for second-line chemotherapy, for which Docetaxel ($Taxotere^{(R)}$) has proven efficacy in both settings. This study evaluated the safety and efficacy of docetaxel in patients with non-small cell lung cancer who had failed first-line platinum-based chemotherapy. Methods : Thirty one patients with non-small-cell lung cancer, who had failed first-line platinum-based chemotherapy, between March 1999 and August 2003, were enrolled in this study. Patients received intravenous docetaxel, either $75mg/m^2$ or $100mg/m^2$, with routine premedication every three weeks. Results : Fourteen patients (45.2%) had a partial response. The median survival and progression-free survival times were 12.5 months (95% CI 7.3-17.6) and 3.0 months (95% CI 1.6-4.5), respectively. This study showed 2 factors gave different survival benefits; the age (< 60 years: 20.1 months vs. ${\geq}60years$: 6.6 months, p = 0.0105) and the histological type (adenocarcinoma: 25.6 months vs. others: 7.9 months, p=0.0055). The predominant toxicity was neutropenia, which occurred as WHO grade 3 or 4 in 38.7 % of patients. One treatment-related death was also reported. Non-hematological toxicity was minor and easily controlled. There were no significant statistical differences in the survival benefit and toxicity between the two doses. Conclusion : Docetaxel, as second-line monotherapy, was well tolerated and effective in patients with non-small-cell lung cancer who failed first-line platinum-based chemotherapy.

• Journal of Life Science
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• v.26 no.9
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• pp.1056-1062
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• 2016

Lung cancer is currently the most common malignant disease and the leading cause of mortality in the world and non-small cell lung cancer (NSCLC) accounts for 75-80% of lung cancer cases. miR-155 gene was found to be over expressed in several solid tumors, such as thyroid carcinoma, breast cancer, colon cancer, cervical cancer, pancreatic ductal adenocarcinoma (PDAC) and lung cancer. The aims of this study were to define the expression of miR-155 in lung cancer and its associated clinic-pathologic characteristics. Total RNA was purified from formalin-fixed, paraffin-embedded NSCLC tissues and benign lung tissues. Expression of miR-155 in human lung cancer tissues were evaluated as mean fold changes of miR-155 in cancer tissues compared to benign lung tissues by quantitative real-time reverse transcriptase polymerase chain reaction (real-time qRT-PCR) and associations of miR-155 expression with clinic-pathologic findings of cancer. Compared with the benign control group, miR-155 expression was significantly overexpressed in NSCLCs (p=<0.001). miR-155 was more overexpressed in squamous cell carcinoma than in adenocarcinoma. Poorly differentiated tumors showed significantly overexpression of miR-155 than well-differentiated tumors (p=<0.001). Overexpression of miR-155 was significantly associated with lymph node metastasis (p=<0.05). In survival analysis for all NSCLC patients, high miR-155 expression was significantly correlated with worse overall survival (p=<0.05). These results suggested that miR-155 might play an important role in lung cancer progression and metastasis.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.536-546
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• 1996

Background : The survival benefit of combination chemotherapy comparing supportive care to patients with advanced non-small cell lung cancel, especially stage IV non-small cell lung cancer patients with metastatic disease, is controversial. The main goal of this study was to evaluate the difference in survival between patients treated with chemotherapy and those who were not and to identify prognostic factors in the patients with stage IV non-small cell lung cancer. Methods : From January 1989 to December 1994, total 67 patients including 20 patients treated with combination chemotherapy and 47 patients treated with only supportive care in stage IV non-small cell lung cancer patients with metastatic disease were enrolled in this study. Combination chemotherapy consisted of etoposide $120mg/m^2$ iv for 3 days and cis-platin iv day 1 every 4 weeks. The treatment groups were retrospectively analyzed by age, sex, histologic cell type, weight loss, serum LDH level, ECOG performance status and major organ metastasis. Results : The significant prognostic factors influencing survival on this study were ECOG performance status and histologic subtype. Overall response rate by combination chemotherapy was 30%(complete response 0%, partial response 30%). Median survival of overall patients was 13.6 weeks and median survival of Chemotherapy group, 20 weeks, was significantly longer than that of supportive care group, 11.7 week(p<0.01). Median survival of responded in patients receiving chemotherapy, 45.5 weeks, was significantly longer than that of non-responder, 17.3 weeks(p<0.05). 1 year-survival rate of chemotherapy group and supportive care group was 15N and 8%, respectively. Nausea or vomiting, alopecia and anemia were seen in nearly most cases after this combination chemotherapy. Toxicities above grade 3 included neutropenia, anemia, thrombocytopenia, infection, fever, nausea, vomiting and alopecia. But this combination chemotherapy was relatively well tolerated except one treatment-related death from sepsis associated with severe granulocytopenia. Conclusion : These results suggest that systemic chemotherapy might be helpful to the stage IV non-small cell lung cancer patients with good performance status and large scale randomized prospective trials should be performed.

• Radiation Oncology Journal
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• v.24 no.4
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• pp.223-229
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• 2006

$\underline{Purpose}$: Combined modality therapy including chemotherapy, surgery and radiotherapy is considered the standard of care for the treatment of stage III non-small cell lung cancer (NSCLC). This study was conducted to evaluate the efficacy of paclitaxel and cisplatin with induction chemotherapy followed by concurrent chemoradiotherapy for stage IIIB NSCLC. $\underline{Materials\;and\;Methods}$: Between July 2000 and October 2005, thirty-nine patients with stage IIIB NSCLC were treated with two cycles of induction chemotherapy followed by concurrent chemoradiotherapy. The induction chemotherapy included the administration of paclitaxel ($175\;mg/m^2$) by intravenous infusion on day 1 and treatment with cisplatin ($75\;mg/m^2$) by intravenous infusion on day 1 every 3 weeks. Concurrent chemoradiotherapy included the use of paclitaxel ($60\;mg/m^2$) plus cisplatin ($25\;mg/m^2$) given intravenously for 6 weeks on day 43, 50, 57, 71, 78 and 85. Thoracic radiotherapy was delivered with 1.8 Gy daily fractions to a total dose of $54{\sim}59.4\;Gy$ in $6{\sim}7$ weeks (median: 59.4 Gy). $\underline{Results}$: The follow up period was $6{\sim}63$ months (median: 21 months). After the induction of chemotherapy, 41.0% (16 patients) showed a partial response and 59.0% (23 patients) had stable disease. After concurrent chemoradiotherapy, 10.3% (4 patients) had a complete response, 41.0% (16 patients) had a partial response, and the overall response rate was 51.3% (20 patients). The 1-, 2-, 3-year overall survival rates were 66.7%, 40.6%, and 27.4% respectively, with a median survival time of 20 months. The 1-, 2-, 3-year progression free survival rates were 43.6%, 24.6%, and 24.6%, respectively, with median progression free survival time of 10.7 months. Induction chemotherapy was well tolerated. Among 39 patients who completed the entire treatment including chemoradiotherapy, 46.3% (18 patients) had esophagitis greater than grade 3 and 28.2% (11 patients) had radiation pneumonitis greater than grade 3. $\underline{Conclusion}$: Paclitaxel and cisplatin with induction chemotherapy followed by concurrent chemoradiotherapy for stage IIIB NSCLC seems to be an effective treatment. Occurrence of esophagitis and pneumonitis represents a significant morbidity and suggests a modification of the treatment regimen, either with the chemotherapy schedule or with radiotherapy treatment planning.

• Tuberculosis and Respiratory Diseases
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• v.53 no.4
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• pp.379-388
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• 2002

Background : Although patients with stage IV non-small cell lung cancer are known to have a poor prognosis, the prognostic factors for survival have not been well evaluated. Such factors may be different from those for overall survival. This study was performed to analyze the prognostic factors for survuval and the variation of survival according to metastatic organ, in patients with stage IV non-small cell lung cancer. Materials and Methods : From January 1997 to December 2000, 151 patients with confirmed stage IV non-small cell lung cancer were enrolled into this study retrospectively. The clinical and laboratory data were analyzed using univareate Kaplan-Meied and Multivariate Cox regression models. Results : On univariate analysis, age, performance status, serum albumin level, weight loss, forced expiratory volume in one second (FEV1), systemic chemotherapy, the number of metastatic organs and serum lactate dehydrogenase (LDH) level were significant factors (p<0.05). In multivariate analysis, important factors for survival were ECOG performance (relative risk of death [RR]: 2.709), systemic chemotherapy (RR: 1.944), serum LDH level (RR: 1.819) and FEV1 (RR: 1.774) (p<0.05), Metastasis to the brain and liver was also a significant factor on univariate analysis). The presence of single lung metastasis was associated with better survival than that of other metastatic organs (p=0.000). Conclusion : We confirmed that performance status and systemic chemotherapy were independent prognostic factors, as has been recognized. The survival of stage IV non-small cell lung cancer patients was different according to the metastatic organs. Among the metastatic sites, only patients with metastasis to the lung showed bettrer survival than that of other sites, while metastasis of the brain or liver was associated with worse survival than that of other sites.

• Tuberculosis and Respiratory Diseases
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• v.50 no.6
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• pp.668-675
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• 2001

Background : Non-smalll lung cancer(NSCLC) develops as a result of the accumulation of multiple genetic abnormalities. Loss of heterozygosity(LOH) is one of the most frequent genetic alterations that is found in NSCLC, and the chromosomal regions that display a high rate of LOH are thought to harbor tumor suppressor genes(TSGs). This study was done to determine the frequency of LOH in 21q with the aim of identifying potential TSG loci. Method : Thirty-nine surgically resected NSCLCs were analysed. Patients peripheral lymphocytes were used as the source of the normal DNA. Five microsatellite Inarkers of 21q were used to study LOH : 21q21.1(D21S1432, and D21S1994); 21q21.2-21.3(D21S1442) ; 21q22.1(21S1445) ; and 21q22.2-22.3(D21S266). The fractional allelic loss(FAL) in a tumor was calculated as the ratio of the number of markers showing LOH to the number of informative markers. Result : LOH for at least one locus was detected in 21 of 39 tumors(53.8%). Among the 21 tumors with LOH, 5(21.8%) showed LOH at almost all informative loci. Although statistically not significant, LOH was found more frequently in squamous cell carcinomas(15 of 23, 65.2%) than in adenocarcinomas(6 of 16, 37.5%). In the squamous cell carcinomas the frequency of LOH was higher in stage II-III (80.0%) than in stage I (53.8%). The FAL value in squamous cell carcinomas($0.431{\pm}0.375$) was significantly higher than that found in adenocarcinomas($0.l92{\pm}0.276$). Conclusion : These results suggest that LOH on 21q may be involved in the development of NSCLC, and that TSG(s) that contribute to the pathogenesis of NSCLC may exist on 21q.

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