폐암 환자에서 Urokinase Type Plasminogen Activator 및 Plasminogen Activator Inhibitor Type 1의 임상적 의의

권순대,최원일,한승범,권건영,전영준 계명대학교 의과학연구소 2000 계명의대학술지 Vol.19 No.2

Cancer invasion and metastasis require the dissolution of extracellular matrix in which several proteolytic enzyme are involved. One of these enzyme the urokinase-type plasminogen activator(u-PA), and plasminogen activator inhibitor type 1(PAI-1) have a possible role in cancer invasion and metastasis by protection of cancer itself from proteolysis by u-PA. It has been reported that the level of u-PA and PAI-1 in various cancer tissues are significantly higher than those in normal tissue and significant correlation with tumor size and lymph node involvement. We measured the concentration of plasma u-PA and PAI-1 antigens in patients with lung cancer and compared the concentration of them with histologic types and staging parameters, and also compared those concentrations in pre-treatment and post-treatment. In this study we measured the concentration of plasma u-PA and PAI-1 antigens using commercial ELISA kit in 40 lung cancer patients and 22 patient with benign lung diseases. The concentration of u-PA was 1.37±0.7 ng/mL in a group of benign lung disease patients and 1.75±0.75 ng/mL in lung cancer patients. The concentration of PAI-1 was 20.86±13.2 ng/mL in benign lung disease and 20.09 ng/mL in lung cancer. The concentration of u-PA in lung cancer patients was higher than those of benign lung disease patients. The concentration of u-PA was 2.42±2.69 ng/mL in lung cancer patients who were not treated, 1.78 ng±0,79 ng/mL in patients who were treated. The concentration of PAI-1 was 19.53±11.75 ng/mL in not-treated lung cancer patients, 10.71±6.26 ng/mL in treated patient group. The concentration of PAI-1 in treated lung cancer patients was lower than those of not-treated lung cancer patients. The concentration of u-PA was 1.82 ng/mL in stage I & Ⅱ, 1.93±0.11 ng/mL in stage Ⅲ, 1.65±0.17 ng/mL in stage Ⅳ. The concentration of PAI-1 was 15.92±5.57 ng/mL in stage I & Ⅱ, 20.95±0.54 ng/mL in stage Ⅲ, 23.99±2.5 ng/mL in stage Ⅳ. The concentration of u-PA was 1.28±0.45 ng/mL in small cell carcinoma, 1.86±0.12 ng/mL in nonsmall cell carcinoma 1.76±0.0 ng/mL in squamous cell carcinoma 1.93±0.2 ng/mL in adenocarcinoma. The concentration of PAI-1 was 18.74±3.83 ng/mL in small cell carcinoma 23.13±3.95 ng/mL in nonsmall cell carcinoma 25.39±2.81 ng/mL in squamous cell carcinoma 20.96±1.62 ng/mL in adenocarcinoma. The plasma levels of u-PA in lung cancer patients were higher than those benign lung disease and plasma level of PAI- 1 in who were treated (surgery, chemotherapy and/or radiotherapy) were lower than those who were not treated. These findings suggest involvement of U-PA with local invasion of lung cancer and possible roles in predicting the prognosis and survival of lung cancer patients.

폐암의 해부학적 부위와 정량적 폐관류 주사와의 관계

이민수,박상선,고영일,장안수,임성철,양주열,김영철,최인석,박경옥 全南大醫大 1993 전남의대학술지 Vol.30 No.1

Risk factors associated with EGFR mutated advanced lung cancer

( Won-il Choi ),( Jihyeon Jeong ),( Choong Won Lee ) 대한결핵 및 호흡기학회 2019 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.127 No.-

Background: Epidermal growth factor receptor (EGFR) mutation is the most frequently encountered oncogenic driver in lung cancer. Risk factors for EGFR mutation may help prevention, surveillance, and diagnosis strategies of EGFR mutated lung cancer. Methods: A nationwide, retrospective, longitudinal, cohort study was performed between January 2002 and December 2015. Patient data were collected from the Korean National Health Insurance Database. The lung cancer group included EGFR tyrosine kinase inhibitor (TKI) treated patients. Controls were randomly selected from people without a history of lung cancer and determined to be four times the number of patients with EGFR mutated advanced lung cancer. The risk model of developing EGFR mutated lung cancer was constructed by multiple logistic regression analysis with age, sex, smoking status, body mass index, comorbidities, residential area, and income. Results: Among the 2010 new cases of lung cancer treated in 2010-2015, 214 cases were classified as EGFR mutated advanced lung cancer. The risk of developing EGFR mutated advanced lung cancer was higher in patients in their 50s (odds ratio [OR]: 3.42; 95% confidence interval [CI]: 1.68-6.93), 60s (OR: 7.04; 95% CI: 3.35-14.77), 70s (OR: 10.27; 95% CI: 4.73-22.30), and >80 years (OR: 5.98; 95% CI: 2.25-15.92) compared to those in their 40s. The risk of developing EGFR mutated lung cancer was also higher in hospitalized patients with a history of pneumonia (OR: 5.22; 95% CI: 1.88-14.46) and those with gastroesophageal reflux disease (OR: 2.02; 95% CI: 1.32-3.07). The risk was not associated with cigarette smoking, sex, and body mass index. Conclusions: In this observational study of patients with EGFR mutated advanced lung cancer, compared with those who did not have lung cancer, it was associated with age, history of being hospitalized for pneumonia, and gastroesophageal reflux disease.

Analysis of volatile organic compounds in exhaled breath for lung cancer diagnosis using a sensor system

Chang, Ji-Eun,Lee, Dae-Sik,Ban, Sang-Woo,Oh, Jaeho,Jung, Moon Youn,Kim, Seung-Hwan,Park, SungJoon,Persaud, Krishna,Jheon, Sanghoon Elsevier 2018 Sensors and actuators. B Chemical Vol.255 No.1

<P><B>Abstract</B></P> <P>Lung cancer is the leading cause of cancer deaths in worldwide. There are many challenges to detect early stage lung cancer in accurate, inexpensive, and non-invasive ways. In this study, we have designed, fabricated, and characterized a sensor system as a novel lung cancer diagnosis tool. In order to investigate the clinical feasibility of the system to detect early stage lung cancer, exhaled breath was collected from 37 patients with non-small cell lung cancer (81.1% of stage I and II) and 48 healthy controls. Three types of samples were collected from each patient; 1) before lung cancer surgery, 2) the first outpatient clinic visit after surgery, and 3) the second outpatient clinic visit after surgery. The sampling schedule from the healthy controls matched that of the lung cancer patients. The volatile organic compounds (VOCs) in the exhaled breath were analyzed by the sensor system. The sensor system consisted of an array of seven metal oxide gas sensors, a gas flow controlling module, heating module, gas adsorption-desorption module and classifiers for data analysis. The result obtained for the first set of samples, using a multilayer perceptron (MLP) for classification indicated a total accuracy of 75.0% with 79.0% of sensitivity and 72.0% of specificity. 93.5% of healthy controls showed nearly unchanged data from the first to the third samples, while 45.2% of lung cancer patients showed definitely changed data from the first to the third samples when analyzed the projection results of original data onto the selected principal components (PCs) obtained from principal component analysis (PCA). The study showed that VOCs in exhaled breath potentially discriminated mostly early stage lung cancer patients before the surgery from healthy volunteers with our sensor system. Furthermore, the prognosis of the lung cancer patients after surgery would be predicted by this system. These results suggest that breath analysis may develop as a novel diagnostic tool for early lung cancer.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We have designed and fabricated a sensor system for early lung cancer diagnosis. </LI> <LI> Breath gas was collected from lung cancer patients before and after the surgery. </LI> <LI> Volatile organic compounds in the breath gas were analyzed by the sensor system. </LI> <LI> Lung cancer patients were distinguished from healthy controls with 75.0% accuracy. </LI> <LI> Breath analysis may develop as a novel diagnostic tool for early lung cancer. </LI> </UL> </P>

The Incidence Rate and Severity of Orthotopic Lung Cancer in an Animal Model Depends on the Number of A549 Cells and Transplantation Period

Jinsoo Lee,Young-Ah Han,Hyo-Seon Yang,Jeong-Ah Song,Young-Su Yang,Soonjin Kwon,Min-Sung Kang,Kyuhong Lee,Jeong-Doo Heo,Kyu-Hyuk Cho,Chang Woo Song 한국실험동물학회 2010 Laboratory Animal Research Vol.26 No.4

The incidence rate of lung cancer is continually increasing, and lung cancer is the leading cause of cancer-related death worldwide. Nevertheless, few therapeutic methods are available for lung cancer. Therefore, establishing appropriate lung cancer animal models is important to investigate mechanismsand to evaluate new drugs for lung cancer. In the present study, we transplanted non-small cell lung cancer A549 human adenocarcinoma cells (2×10⁴, 2.0×10?, and 2.0×10? cells) into the right lobe of BALB/c nude mice via the intercostal space to develop an orthotopic lung cancer animal model that is minimally invasive and similar to human lung cancer. We then investigated the incidence rate and severity of lung cancer according to the A549 cell number (2×10⁴, 2.0×10?, and 2.0×10? cells) and transplantation periods (4~23 days). Lung cancer development was confirmed with gross examination, which was supported by histopathological examination. These results indicate that the incidence rate and severity of lung cancer was increased depending on the number of transplanted cells and transplantation period which the cell number and duration are increasing risk of lung cancer. Thus, this study can provide appropriate reference data to develop an orthotopic lung cancer animal model using the nonsmall cell lung cancer A549 cell line for researching mechanisms and evaluating candidate drugs, including various approaches for treating lung cancer.

Determinants of Willingness to Undergo Lung Cancer Screening among High-Risk Current and Ex-smokers in Sabah, Malaysia: A Cross-Sectional Pilot Study

Nyanti Larry Ellee,Chua Chia Zhen,Loo Han Chuan,Khor Cheng Zhi,Toh Emilia Sheau Yuin,Gill Rasvinder Singh,Chan Eng Tat,Tan Ker Yin,Rosli Taufiq,Rahim Muhammad Aklil Abd,Ibrahim Arfian,Huan Nai Chien,R 대한결핵및호흡기학회 2023 Tuberculosis and Respiratory Diseases Vol.86 No.4

Background: Attitudes towards smoking, lung cancer screening, and perceived risk of lung cancer have not been widely studied in Malaysia. The primary objective of this study was to describe the factors affecting the willingness of high-risk current smokers and ex-smokers to undergo low-dose computed tomography (LDCT) screening for lung cancer.Methods: A prospective, cross-sectional questionnaire study was conducted in current smokers or ex-smokers aged between 55 and 80 years at three hospitals in Kota Kinabalu, Sabah, Malaysia. The questionnaire recorded the following parameters: perceived lung cancer risk; Prostate Lung Colon Ovarian Cancer 2012 risk prediction model excluding race and ethnicity predictor (PLCOm2012norace); demographic characteristics; psychosocial characteristics; and attitudes towards lung cancer and lung cancer screening.Results: A vast majority of the 95 respondents (94.7%) indicated their willingness to undergo screening. Stigma of lung cancer, low levels of knowledge about lung cancer symptoms, concerns about financial constraints, and a preference for traditional medication were still prevalent among the respondents, and they may represent potential barriers to lung cancer screening uptake. A desire to have an early diagnosis (odds ratio [OR], 11.33; 95% confidence interval [CI], 1.53 to 84.05; p=0.02), perceived time constraints (OR, 3.94; 95% CI, 1.32 to 11.73; p=0.01), and proximity of LDCT screening facilities (OR, 14.33; 95% CI, 1.84 to 111.4; p=0.01) had significantly higher odds of willingness to undergo screening.Conclusion: Although high-risk current smokers and ex-smokers are likely to undergo screening for lung cancer, several psychosocial barriers persist. The results of this study may guide the policymakers and clinicians regarding the need to improve lung cancer awareness in our population.

폐암 환자의 혈청 Angiotensin Converting Enzyme 활성도의 변화

정기호,최형석,유철규,이계영,김영환,한성구,심영수,김건열,한용철,Jeong, Ki-Ho,Choi, Hyung-Seok,Yoo, Chul-Gyu,Lee, Kye-Young,Kim, Young-Whan,Han, Sung-Koo,Shim, Young-Soo,Kim, Keun-Youl,Han, Yong-Chol 대한결핵및호흡기학회 1992 Tuberculosis and Respiratory Diseases Vol.39 No.4

연구배경 : Angiotensin-converting enzyme (ACE)은 인체의 여러 조직 또는 혈청내에 존재하는 glycoprotein peptidyldipeptide hydrolase로써 여러 종류의 peptides에서 dipeptides를 떼어내는 역할을 담당한다. 이러한 ACE는 주로는 혈관 내피 세포에서 형성되며 인체에서는 폐에 가장 많은 모세혈관들이 존재하므로 ACE가 혈중에 존재하는 기질과 작용하는 곳 또한 폐의 모세 혈관내이다. 임상적으로 ACE는 유육종증의 진단 및 경과 관찰에 이용되며 기타 급성 또는 만성 폐질환에서 혈청 ACE 활성도가 감소된다는 사실이 보고되고 있다. 그러나 한 시점에서의 혈청 ACE 활성도는 폐손상의 유무 및 그 정도를 잘 반영한다고 볼 수는 없으나 시간 간격을 두고 차례대로 측정한 값은 예후와 관련이 있다고 알려져 있다. 이에 저자는 폐암환자를 대상으로 혈청내의 ACE 활성도를 측정하여 이들 환자에 있어서 향후 예후 예측의 지표로써의 가능성을 알아보고자 하였다. 방법 : 연구대상은 새로 진단된 폐암 환자로 하였고 대조군으로는 연구 대상군과 비슷한 연령군으로 하되 두군 모두에서 고혈압, 심장질환, 간질환, 신장 질환 그리고 폐암 이외의 기타 폐질환이 있는 사람은 제외시켰다. 연구대상군은 편평상피세포 폐암환자 19명, 선암폐암환자 13명, 소세포 폐암환자 9명 이었다. 결과 : 1) 편평상피세포 폐암환자의 혈청내 ACE 활성도는 $36.2{\pm}14.2$ U/L 이었고 선암 폐암환자는 $46.0{\pm}18.7$ U/L, 소세포 폐암환자는 $45.7{\pm}14.1$ U/L, 대조군은 $41.4{\pm}18.7$ U/L로 폐암환자의 ACE 활성도는 대조군과 차이가 없었으며 폐암의 세포형에 따라서도 차이가 없었고 폐암의 병기에 따라서도 ACE 활성도는 차이가 없었다. 2) 편평상피세포 폐암환자 4명과 선암 폐암환자 4명은 폐암의 치료로써 폐절제술을 받았으며 수술 전후 ACE 활성도는 편평세포 폐암환자가 수술전 $35.8{\pm}13.9$ U/L, 수술후 $12.5{\pm}3.9$ U/L로 의미있게 감소하였으며 선암 폐암환자에서는 각각 $47.1{\pm}5.9$ U/L, $15.0{\pm}3.9$ U/L로 수술후 의미있게 감소하였다. 3) 편평상피 세포 폐암환자중 3명과 선암 폐암환자 4명에 대하여 항암제를 투여받은 3개월에 걸쳐 측정한 ACE 활성도는 유의한 변화가 없었으며 임상적으로도 폐암의 호전은 없었다. 4) 소세포 폐암환자 9명은 3개월동안의 항암제 투여 중 임상적으로는 호전이 있었으나 혈청내 ACE 활성도는 의미있는 변화가 없었다. 결론 : 이상에서 폐정제술후 혈청내 ACE 활성도는 감소됨을 알 수 있었으나 폐암의 세포형, 병기, 임상적 호전과 혈청내 ACE 활성도는 연관이 없어 혈청 ACE 활성도는 폐암환자의 질병 경과 판정의 지표로써 부적합함을 알 수 있었다. Background: Angiotensin converting enzyme is a glycoprotein peptidyldipeptide hydrolase which cleaves the c-terminal dipeptides of several oligopeptides. It is a menbrane-bound protein mainly synthesized by the endothelial cells. Since the lung has the largest capillary bed of any organ in the body, it is here that ACE acts on circulating substrates like angiotensin I and bradykinin. It is well known that ACE correlates with disease activity in sarcoidosis and also there are reports that changes in serum ACE activity are found in many acute and chronic lung diseases. So we planned this study to see if serum ACE activity can act as a prognostic factor in lung cancer. Methods: Forty-one newly diagnosed lung cancer patients were included in the study group. There were 19 patients with squamous cell lung cancer, 13 with adenocarcinoma, and 9 with small cell carcinoma. Patients were excluded from the study if they had high blood pressure, heart disease, liver disease, renal disease, or other lung disease. Serum ACE activity was analyzed according to cell type, staging, mode of treatment, and clinical response to treatment. Results: 1) There was no difference in serum ACE activity between lung cancer patients and the control group. Also no difference in serum ACE activity was found according to cancer cell type or staging. 2) In patients who underwent curative resection of lung cancer, serum ACE activity was decreased significantly after the operation. 3) In patients who were diagnosed as non-small cell lung cancer and were treated with 4 cycles of anti-cancer chemotherapy without clinical improvement, changes in serum ACE activity were not seen after the treatment. 4) In patients diagnosed as small cell lung cancer treated with 4 cycles of anti-cancer chemotherapy with clinical improvement, changes in serum ACE activity were also not observed. Conclusion: Serum ACE activity was decreased after lung resection but had no relation to cell type, staging, or clinical response to treatment in lung cancer patients. Therefore, serum ACE activity is not suitable in predicting clinical outcome of lung cancer patients.

Aberrant Expression of E-cadherin in Lung Tissues of Patients with Probable Lung Cancer

Yuan, Yu-Lin,Wang, Yu-Ming,Liu, Hua,Qin, Gui-Fang,Tang, Ai-Guo,Duan, Yong Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.10

Introduction: This study assessed the relationship of E-cadherin mRNA and protein expression with the diagnosis of lung cancer with the aim of providing an auxiliary diagnostic method. Methods: Semi-quantitative nested RT-PCR and western blotting were applied to detect E-cadherin mRNA transcripts and protein, respectively, in 30 cases of diagnostic lung cancer, 30 cases of clinically suspected patients with lung cancer and 30 cases of other disease. Immunohistochemical staining was also used to detect E-cadherin. Results: Remarkably decreased levels of relative E-cadherin mRNA value and increased E-cadherin protein negativity were observed in probable lung cancer, when compared with possible lung cancer and others. With a threshold of 1.45, relative E-cadherin mRNA value showed a sensitivity of 90% and a specifity of 83% for the diagnosis of lung cancer. The combination of decreased relative E-cadherin mRNA value and negative E-cadherin protein increased the specificity and sensitivity. Conclusion: These data suggest that Chinese patients with diagnostic lung cancer have similar decreased levels of relative E-cadherin mRNA and E-cadherin protein value in the lung cancer tissues as in lung cancer patients in other countries. Measurement of relative E-cadherin mRNA and protein values in lung cancer tissues has potential for lung cancer diagnosis.

The Impact of Lung Cancer on Combined Pulmonary Fibrosis and Emphysema

오지연,최주환,이영석,민경훈,허규영,이승룡,강경호,심재정 대한결핵 및 호흡기학회 2018 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.126 No.0

Background: Combined pulmonary fibrosis and emphysema (CPFE) patients are frequently associated with lung cancer. However, the impact and outcomes of lung cancer in patients with CPFE are not clear. Thus, we investigated the impact of lung cancer regarding acute exacerbation (AE), rapid deterioration (RD) and mortality in patients with CPFE. Methods: We retrospectively reviewed medical records from Korea University Guro Hospital for 12 years. We selected CPFE patients by computed tomography findings. We evaluated the following variables in CPFE patients with and without lung cancer: age, sex, smoking history and amount, body mass index, past medical history, pulmonary function test, the gender, age and physiology (GAP) score, AE, RD and mortality. Results: Among 227 CPFE patients, 61 patients were diagnosed lung cancer. Among 61 lung cancer patients, 10 patients experienced AE, 48 experienced RD, and 41 patients died during observation period. Lung cancer was the significant predictor of AE (HR 3.274, 95% CI 1.444-7.425, P<0.01), RD (HR, 2.347; 95% CI 1.554-3.546, P<0.01) and mortality (HR 4.738, 95% CI 2.548-8.813, P<0.01). AE rather than age, GAP score or lung cancer stage was the most significant factors associated with mortality in CPFE lung cancer patients (AE vs non RD: HR 9.198, 95% CI 1.133-74.704, P=0.38). Conclusion: Lung cancer has a significant impact on outcomes of CPFE. Diagnosis and treatment of lung cancer in CPFE are at risk of severe complicating events, and diagnostic and treatment plan of lung cancer should be carefully in patients with CPFE.

Increased risk of lung cancer in individuals with a family history of the disease: A pooled analysis from the International Lung Cancer Consortium

Cote, M.L.,Liu, M.,Bonassi, S.,Neri, M.,Schwartz, A.G.,Christiani, D.C.,Spitz, M.R.,Muscat, J.E.,Rennert, G.,Aben, K.K.,Andrew, A.S.,Bencko, V.,Bickeboller, H.,Boffetta, P.,Brennan, P.,Brenner, H.,Due Pergamon Press 2012 European journal of cancer Vol.48 No.13

Background and methods: Familial aggregation of lung cancer exists after accounting for cigarette smoking. However, the extent to which family history affects risk by smoking status, histology, relative type and ethnicity is not well described. This pooled analysis included 24 case-control studies in the International Lung Cancer Consortium. Each study collected age of onset/interview, gender, race/ethnicity, cigarette smoking, histology and first-degree family history of lung cancer. Data from 24,380 lung cancer cases and 23,305 healthy controls were analysed. Unconditional logistic regression models and generalised estimating equations were used to estimate odds ratios and 95% confidence intervals. Results: Individuals with a first-degree relative with lung cancer had a 1.51-fold increase in the risk of lung cancer, after adjustment for smoking and other potential confounders (95% CI: 1.39, 1.63). The association was strongest for those with a family history in a sibling, after adjustment (odds ratios (OR)=1.82, 95% CI: 1.62, 2.05). No modifying effect by histologic type was found. Never smokers showed a lower association with positive familial history of lung cancer (OR=1.25, 95% CI: 1.03, 1.52), slightly stronger for those with an affected sibling (OR=1.44, 95% CI: 1.07, 1.93), after adjustment. Conclusions: The occurrence of lung cancer among never smokers and similar magnitudes of the effect of family history on lung cancer risk across histological types suggests familial aggregation of lung cancer is independent of those risks associated with cigarette smoking. While the role of genetic variation in the aetiology of lung cancer remains to be fully characterised, family history assessment is immediately available and those with a positive history represent a higher risk group.