• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4765-4768
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• 2013

Aims: This study was conducted to evaluate the levels of TNF-${\alpha}$, IL-6, IL-8 and VEGF in serum of patients with non- small cell lung cancer, for assessing their possible diagnostic and prognostic roles. Methods: We enrolled 48 patients newly diagnosed with non-small cell lung cancer and 40 healthy controls. TNF- ${\alpha}$, IL-6 and IL-8 levels were measured in the serum of all the subjects with specific radioimmunoassay kits, while EGF was analyzed by sandwich enzyme immunoassay techniques. Results: A statistically significant difference was observed between lung cancer patients and the control group regarding the values of TNF-${\alpha}$, IL-6, IL-8 and VEGF in serum. Moreover, TNF-${\alpha}$, IL-8 and VEGF levels were higher in patients with advanced stages compared to early stages. In addition, higher serum levels of TNF-${\alpha}$, IL-6, IL-8 and VEGF were found in smokers than in non-smokers, both in patients and controls. Conclusion: Serum levels of TNF-${\alpha}$, IL-6, IL-8 and VEGF were all elevated in lung cancer patients, suggesting that inflammatory cytokines could be jointly used as a screening tool. Though TNF-${\alpha}$, IL-8 and VEGF levels were related to advanced disease, long-term survival studies of NSCLC patients should be performed to confirm whether they can act as biomarkers of advanced disease. In addition, smoking would be an important contributor to the processes of inflammation and lung cancer.

• 대한수의학회지
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• 제45권4호
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• pp.495-500
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• 2005

The nucleoside analogue gemcitabine (2', 2-difluorideoxycytide) is potential against a wide variety of solid tumors and considered to be one of the most active drugs in the treatment of non-small cell lung cancer (NSCLC). In this study, we investigated the signals of gemcitabine-induced apoptosis, especially in point of caspase pathway in A549. We exposed A549 cells to gemcitabine for dose/time dependent manner and the results showed that gemcitabine induced apoptotic cell death in a time/dose-dependent manner. We also treated to gemcitabine and Z-VAD-fmk as a pan-caspase inhibitor for 24 hours. Gemcitabine alone induced 35.3% cell death, and co-treatment with gemcitabine and Z-VAD-fmk induced 15.1% apoptotic cell death. Our results demonstrated that Z-VAD-fmk as a pan-caspase did not completely block the gemcitabine-induced apoptosis. Western blotting analysis showed that gemcitabine increased caspase-3, active caspase-8, p21 and p53 protein expressions in A549. Co-treatment with Z-VAD-fmk completely blocked caspase-3 and active caspase-8 protein expressions, but did not change the level of p21 and p53 protein expressions. Our data indicate that gemcitabine induced apoptosis through caspase-dependent and -independent pathways in A549.

• Journal of Chest Surgery
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• 제40권11호
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• pp.745-751
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• 2007

배경: 폐암환자에서 수술 전에 종격동 림프절의 전이 여부를 확인하기 위해 종격동경이 많이 이용되고 있으나 수술의 적응이 되는 모든 환자에서 종격동경을 시행할 것인지에 대해서는 논란의 여지가 있다. 이에 본 연구에서는 모든 비소세포성폐암 환자에서 통상적으로 종격동경을 시행하는 것이 임상적으로 의미가 있는지 살펴보고자 하였다. 대상 및 방법: 2002년 3월부터 2004년 12월까지 비소세포성폐암으로 진단받고 수술을 시행한 90명의 환자를 대상으로 방사선학적 검사와 종격동 검사를 시행하여 각 검사의 민감도, 특이도, 양성예측치, 음성예측치, 정확도를 비교하였고 방사선학적 N0/1기군과 N2/3기군에서 이들 수치를 분석하여 각 군에서 종격동경 검사가 임상적으로 의미를 가지는가를 후향적으로 분석하였다. 결과: 방사선학적 검사와 종격동경의 민감도, 특이도, 정확도를 비교하였을 때 민감도에는 차이가 없었으나 특이도, 정확도는 종격동경 검사가 우수하였다. 방사선학적 N0/1기군은 62명으로 이 군에서 시행한 종격동경의 민감도는 28.6%였고 방사선학적 N2/3기군은 28명으로 이 군에서의 종격동경의 민감도는 72.7%로 방사선학적 N0/1기군에서의 민감도가 N2/3군에 비해 아주 낮았다. 종격동경으로 진단이 되지 못한 N2/3 양성인 환자 8명 중 7명의 환자에서 수술 시 용골하 림프절의 전이가 확인되었다. 결론: 술 전 병기결정에 종격동경이 종격동 림프절의 전이를 진단하는 가장 정확한 방법이지만 침습적 방법이라는 점과 일부 림프절만이 검사가 가능하다는 점, 방사선학적 N0/1기군에서 특히 낮은 민감도를 고려할 때 모든 군에서 종격동경을 시행하는 것은 임상적 의미를 찾기 어려웠으며 방사선학적 병기 N2/3군에서 선택적으로 종격동경 검사를 시행하는 것이 유용할 것으로 생각한다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2465-2472
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• 2014

Background: The American Joint Committee on Cancer (AJCC) published a new staging system ($7^{th}$ edition) in 2009. In our study, we evaluated the survival results and prognostic factors among T4 local advanced non-small cell lung cancer (LA-NSCLC) patients in a large heterogeneous group, in accordance with this new system. Materials and Methods: We retrospectively evaluated the files of 122 T4 N0-3 M0 LA-NSCLC patients, identified according to the new staging system, treated at two centers between November 2003 and June 2012. Variables correlating with univariate survival at p<0.20 were later included in multivariate Cox regression analysis. Here, selection of relevant predictors of survival was carried out in accordance with the likelihood ratio formula with p<0.05 regarded as significant. Results: The median age was 60 and the median follow-up period was 17.4 months. Median overall survival (OS) was 18.3 months, the 1 year overall survival (OS) rate was 72%, and the 5 year OS rate was 28%. Statistically significant predictors of survival were (p<0.20) ECOG-PS (Eastern Cooperative Oncology Group Performance Status), age, T4 factor subgroup, stage and primary treatment in OS univariate analysis. On multivariate analysis for OS ECOG-PS (p=0.001), diagnostic stage (p=0.021), and primary treatment (p=0.004) were significant. In the group receiving non-curative treatment, the median OS was 11.0 months, while it was 19.0 months in the definitive RT group and 26.6 months in the curative treatment group. There was a significant difference between the non-curative group and the groups which had definitive RT and curative operations (respectively p<0.001 and p=0.001) in terms of OS, but not between the groups which had definitive RT and curative operations. The median event free survival (EFS) rate was 9.9 months, with rates of 46% and 19% at 3 and 5 years, respectively. On univariate analysis of EFS rate with ECOG-PS, weight loss and staging, statistical significance was found only for thorax computerized tomography (CT)+18F-fluorodeoxy-glucose positron emission tomography-CT (PET-CT) use, stage and primary treatment (p<0.20). In multivariate analysis with EFS, only the primary treatment was statistically significant (p=0.001). In the group receiving non-curative treatment, the median EFS was 10.5 months while in the curative operation group it was 14.7 months. When all the primary treatment groups were taken into consideration, grade III/IV side effect swas observed in 57 patients (46.6%). Esophagitis was most prominent among those that received definitive radiotherapy. Conclusions: Independent prognostic factors among these 122 heterogeneous LA-NSCLC T4 N0-3 M0 patients were age at diagnosis, ECOG-PS, stage and primary treatment, the last also being a significant prognostic indicator of EFS. Our findings point to the importance of appropriate staging and a multidisciplinary approach with modern imaging methods in this patient group. In those with T4 lesions, treatment selection and the effective use of curative potential should be the most important goal of clinical care.

• Radiation Oncology Journal
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• 제15권3호
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• pp.233-241
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• 1997

목적 : 비소세포폐암으로 근치적 방사선치료를 시행받은 환자의 생존율 및 예후인자를 알아보기 위하여 본 연구를 시행하였다. 방법 : 1992년 1월부터 1993년 12월까지 수술이 불가능한 비소세포폐암으로 원자력병원 치료방사선과에서 40Gy 이상의 근치적 방사선치료를 시행받은 62명의 환자에 대해 후향적으로 치료 결과를 분석하였다. 병기별 분포는 병기 IIIA 14예, 병기 IIIB 48예였다. 방사선치료는 일일 선량 1.8-2.0Gy씩 주 5회로 원발병소에 총 40.0-70.2Gy의 방사선을 조사하였다. 환자중 37예에서 유도 학학요법을 시행하였다. 결과 : 방사선 치료 후 반응은 완전 관해가 3예, 부분관해가 34예였다 그외는 무반응이였다. 전체환자의 중앙 생존기간은 11개월이었으며 1년 생존율은 45.0%, 2년 생존율은 14.3%였고 5년 생존율은 6.0%였다. 병기에 따른 1년 생존율 및 중간 생존기간은 각각 병기 IlIA에서 28.6%, 6.5개월, 병기 lIIB에서 50.3%, 13개월이였다. 단변수 분석에서 생존율에 영향을 미치는 예후인자로는 T 병기, 병기, 방사선 치료 직후의 반응이 통계학적으로 의미가 있었고(P<0.05) 연령, 성별, 병리p적 소견, N 병기, 쇄골상 림프절 전이 유무, 화학 요법 시행유무 등은 통계학적으로 의미가 없었다(P>0.1). 그외 치료전 전신상태는 통계학적 의미는 없었지만 생존율에 영향을 주는 경향을 보여주었다(0.05

• Tuberculosis and Respiratory Diseases
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• 제66권4호
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• pp.280-287
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• 2009

연구배경: 표피성장인자수용체(epidermal growth factor receptor, EGFR) 티로신 활성효소 억제제(tyrosine kinase inhibitor, TKI)는 진행성 비소세포폐암의 새로운 치료제이다. 몇몇 연구 결과 gefitinib와 erlotinib에 대한 반응률과 반응 예측인자에 차이가 있을 가능성을 제시하였다. 저자들은 한국인 진행성 비소세포폐암에서 gefitinib와 erlotinib의 효과 및 독성을 비교하고 각 약제에 대해 서로 다른 반응 예측인자가 있는지 평가하였다. 방 법: 2003년 7월부터 2009년 2월까지 이화여자대학 교부속병원에서 진행성 비소세포폐암으로 gefitinib 또는 erlotinib로 치료 받은 환자들의 임상정보를 수집하였다. 중앙 생존기간은 Kaplan-Meier법으로 계산하였다. 결 과: 대상 환자는 총 86명이었다(gefitinib군 52명 대 erlotinib군 34명). 나이의 중앙값은 64세였고 53명(62%)이 남자였다. 86명 중 83명에서 반응평가가 가능했으며, 83명 중 35명이 반응을 보였고 12명이 안정성 질환이었으며 36명이 진행성 질환으로, 치료 반응률이 42%였고 질병 조절률이 57%였다. 중앙 추적관찰기간 502일 동안, 진행까지의 중앙기간은 129일이었으며 중앙 생존기간은 259일이었다. 치료 반응률(gefitinib 44% 대 erlotinib 39%, p=0.678), 중앙 생존기간(gefitinib 301일 대 erlotinib 202일, p=0.151) 및 병의 진행까지 기간의 중앙값(gefitinib 136일 대 erlotinib 92일, p=0.672)은 두 군 사이에 차이가 없었다. 두 약제는 비슷한 독성을 보였다. Cox 회귀모형을 이용한 다변수분석에서 선암이 생존과 관련된 독립적인 예후인자였다(상대위험도: 0.487, 95% 신뢰구간: 0.292~0.811, p=0.006). 아집단 분석 결과 두 약제에 대한 서로 다른 반응 예측인자는 없었다. 결 론: Gefitinib와 erlotinib 사이에 반응률, 생존기간, 진행까지의 기간 및 독성에 차이는 없었다. 각 약제에 대한 특이적인 반응 예측인자도 없었다.

• Journal of Chest Surgery
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• 제40권2호
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• pp.109-113
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• 2007

배경: 비소세포폐암에 흔히 발생하는 악성 흉수는 환자의 예후에 나쁜 인자로 작용하여, 원격전이가 발생한 환자들과 비슷한 생존기간을 보인다. 비소세포폐암에 발생하는 악성 흉수의 진단과 치료에 대한 연구는 많이 이루어졌으나, 환자의 예후에 영향을 미치는 인자에 대한 연구는 많지 않다. 저자들은 악성 흉수가 발생한 비소세포폐암 환자들의 예후에 영향을 미치는 예후 인자들을 알아보고자 연구를 시행하였다. 대상 및 방법: 2002년 1월부터 2003년 12월까지 악성 흉수를 동반한 비소세포폐암으로 치료를 받은 환자 33명을 대상으로 하였다. 환자의 예후에 영향을 미칠 가능성이 있는 환자의 특성(성별, 연령), 폐암 조직형 및 병기, 흉수 천자액 검사(pH, CEA, LDH, glucose, albumin), 흉수 발견 후 치료 방법을 인자로 설정하여 조사하였다. 각 인자의 생존기간을 Kaplan-Meier법으로 구한 후, log-rank test를 통한 단변량분석으로 인자 각 군의 생존기간 차이를 비교하였고, 환자의 예후에 영향을 미치는 독립적 예후 인자를 찾기 위해 다변량분석으로 Cox Regression을 실시하였다. 결과: 대상환자 33명의 폐암 조직형은 선암이 23명으로 가장 많았다. 폐암과 악성 흉수가 동시에 진단된 경우를 제외하면 폐암 진단 후 악성 흉수가 진단되기까지의 중앙값 기간은 7.3개월($25^{th}{\sim}75^{th}:\;3.9{\sim}11.8$)이었다. 환자의 중앙값 생존기간은 3.6개월(95% Confidence Interval: $1.14{\sim}5.99$)이었다. 단변량분석에선 폐암 조직형이 유의성은 떨어지나 생존기간에 차이를 보였다(선암 4.067 vs. 비선암 1.867 개월, p=0.067). 교란변수의 영향을 제거한 다변량분석에서 통계적 유의성은 없으나 비선암이 선암보다 사망위험도가 높아지는 경향을 보였다(R.R 2.754, 95% Cl $0.988{\sim}7.672$, p=0.053). 결론: 본 연구에서 저자들은 악성흉수가 발생한 비소세포폐암 환자들의 예후에 영향을 미치는 예후 인자를 확인할 수 없었다. 그러나 조직형에 따라 암사망 위험도에 차이를 보이는 경향이 관찰되어 향후 이에 대한 연구가 필요할 것이다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6779-6782
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• 2015

Background: Chemoradiotherapy is an important treatment modality for lung cancers. The aim of this study was to investigate alterations in, as well as the interrelationship between, lung function and quality of life of patients receiving chemoradiotherapy due to locally advanced non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) limited to the thorax. Materials and Methods: The study included patients receiving definitive chemoradiotherapy for lung carcinoma. The respiratory function of the patients was assessed by measuring forced expiratory volume in 1 s per unit (FEV1) and forced expiratory volume in 1s per unit of vital capacity (FEV1/VC) before, in the middle of and after treatment. During the study, EORTC QLQ C30 and LC13 questionnaires developed by the Committee of the European Organization for Research and Treatment of Cancer (EORTC) were employed to evaluate the quality of life on the same day as respiratory function tests (RFT). Findings: The study included 23 patients in total: 19 (82.6%) diagnosed with NSCLC and 4 (17.4%) with SCLC. The average percentage FEV1 was $55.6{\pm}21.8%$ in the pre-treatment period, $56.2{\pm}19.2%$ in the middle of treatment and $60.4{\pm}22%$ at the end of treatment. The improvement in functional scores, symptom scores and general health scores during treatment was not statistically significant (P= 0.568, P= 0.734, P= 0.680, P=0.757 respectively). Conclusions: Although this study showed an improvement in respiratory function and quality of life of patients during treatment with thoracic chemoradiotherapy, no statistically significant results were obtained. While evaluating the effectiveness of treatments for lung carcinoma, the effects of treatment on respiratory function and quality of life should be considered.

• Asian Pacific Journal of Cancer Prevention
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• 제16권1호
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• pp.77-81
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• 2015

Background: The aim of the study was to determine whether the expression of baseline phosphorus (P) and magnesium (Mg) levels were prognostic in terms of stage and overall survival (OS) in newly diagnosed non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients. Materials and Methods: Retrospectively, 130 patients were selected at the time of diagnosis oflung cancer (100 with NSCLC and 30 with SCLC), before the initialization of any chemo-radiotherapy. The median age was 67 (range 29-92). IA, IB, IIA, IIB, IIIA, IIIB and IV stages were present in 3, 4, 19, 6, 25, 8, and 65 patients, respectively. After centrifugation, the levels of serum P and Mg were measured using the nephelometric method/ photometry and evaluated before any type of treatment. Results: Higher than normal levels of P were found in 127/130 patients, while only four patients had elevated Mg serum values. In terms of Spearman test, higher P serum values correlated with either stage (rho=- 0.334, p<0.001) or OS (rho=-0.212, p=0.016). Additionally, a significant negative correlation of Mg serum levels was found with stage of disease (rho=-0.135, P=0.042). On multivariate cox-regression survival analysis, only stage (p<0.01), performance status (p<0.01) and P serum (p=0.045) showed a significant prognostic value. Conclusions: Our study indicated that pre-treatment P serum levels in lung cancer patients are higher than the normal range. Moreover, P and Mg serum levels are predictive of stage of disease. Along with stage and performance status, the P serum levels had also a significant impact on survival. This information may be important for stratifying patients to specific treatment protocols or intensifying their therapies. However, larger series are now needed to confirm our results.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3057-3063
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• 2014

Background: Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC) has been intensively studied. The gold standard for ALK detection is FISH, but this is not routinely conducted in clinical practice, so that the IHC method has a role. The aim of this study was to identify the incidence of ALK rearrangement and risk or prognostic factors for ALK positivity using both of IHC and FISH methods. Materials and Methods: From January 2008 to December 2012, 267 completely resected NSCLC patients in Chiang Mai University Hospital were enrolled in this study. Clinical and pathological variables and outcomes of treatment were retrospectively reviewed. IHC and FISH were used to evaluate ALK rearrangement. Sensitivity and specificity of IHC were analyzed. Multivariable analysis was used to identify clinico-pathological correlations with positive results of IHC and clinical outcomes. Results: Twenty-two (8.2%) of 267 specimens were IHC-positive for ALK with intense cytoplasmic staining, whereas only 10 (3.8%) were FISH-positive. Sensitivity, specificity and the positive likelihood ratio with IHC were 80.0%, 94.9%, and 15.8 respectively. Age less than 55 years (RR 4.4, 95%CI 1.78-10.73, p value=0.001) and presence of visceral pleural invasion (VPI) (RR 2.9, 95%CI 1.21-6.78, p value =0.017) were identified as risk factors for ALK rearrangement with FISH. There were no statistically significant differences in other clinical and pathological variables. ALK rearrangement was not a prognostic factor for tumor recurrence or overall survival. Conclusions: The incidences of ALK positivity in completely resected NSCLCs in northern Thailand were 8.2% by IHC and 3.8% by FISH. IHC with mouse monoclonal, Ventana D5F3 antibody can be used as a screening tool before FISH method because of high specificity and high positive likelihood ratio. Age less than 55 years and VPI are risk factors for ALK positivity.