• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.5-19
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• 1998

Introduction: Direct histologic and bacteriologic examination of a representative specimen of lung tissue is the only certain method of providing an accurate diagnosis in various pulmonary diseases including diffuse pulmonary diseases. The purpose of national survey was to define the indication, incidence, effectiveness, safety and complication of open and thoracoscopic lung biopsy in korea. Methods: A multicenter registry of 37 university or general hospitals equipped more than 400 patient's bed were retrospectively collected and analyzed for 3 years from the January 1994 to December 1996 using the same registry protocol. Results: 1) There were 511 cases from the 37 hospitals during 3 years. The mean age was 50.2 years(${\pm}15.1$ years) and men was more prevalent than women(54.9% vs 45.9%). 2) The open lung biopsy was performed in 313 cases(62%) and thoracoscopic lung biopsy was performed in 192 cases(38%). The incidence of lung biopsy was more higher in diffuse lung disease(305 cases, 59.7%) than in localized lung disease(206 cases, 40.3%) 3) The duration after abnormalities was found in chest X-ray until lung biopsy was 82.4 days(open lung biopsy: 72.8 days, thoracoscopic lung biopsy: 99.4 days). The bronchoscopy was performed in 272 cases(53.2%), bronchoalveolar lavage was performed in 123 cases(24.1%) and percutaneous lung biopsy was performed in 72 cases(14.1%) before open or thoracoscopic lung biopsy. 4) There were 230 cases(45.0%) of interstitial lung disease, 133 cases(26.0%) of thoracic malignancies, 118 cases(23.1%) of infectious lung disease including tuberculosis and 30 cases (5.9 %) of other lung diseases including congenital anomalies. No significant differences were noted in diagnostic rate and disease characteristics between open lung biopsy and thoracoscopic lung biopsy. 5) The final diagnosis through an open or thoracoscopic lung biopsy was as same as the presumptive diagnosis before the biopsy in 302 cases(59.2%). The identical diagnostic rate was 66.5% in interstitial lung diseases, 58.7% in thoracic malignancies, 32.7% in lung infections, 55.1 % in pulmonary tuberculosis, 62.5% in other lung diseases including congenital anomalies. 6) One days after lung biopsy, $PaCO_2$ was increased from the prebiopsy level of $38.9{\pm}5.8mmHg$ to the $40.2{\pm}7.1mmHg$(P<0.05) and $PaO_2/FiO_2$ was decreased from the prebiopsy level of $380.3{\pm}109.3mmHg$ to the $339.2{\pm}138.2mmHg$(P=0.01). 7) There was a 10.1 % of complication after lung biopsy. The complication rate in open lung biopsy was much higher than in thoracoscopic lung biopsy(12.4% vs 5.8%, P<0.05). The incidence of complication was pneumothorax(23 cases, 4.6%), hemothorax(7 cases, 1.4%), death(6 cases, 1.2%) and others(15 cases, 2.9%). 8) The 5 cases of death due to lung biopsy were associated with open lung biopsy and one fatal case did not describe the method of lung biopsy. The underlying disease was 3 cases of thoracic malignancies(2 cases of bronchoalveolar cell cancer and one malignant mesothelioma), 2 cases of metastatic lung cancer, and one interstitial lung disease. The duration between open lung biopsy and death was $15.5{\pm}9.9$ days. 9) Despite the lung biopsy, 19 cases (3.7%) could not diagnosed. These findings were caused by biopsy was taken other than target lesion(5 cases), too small size to interpretate(3 cases), pathologic inability(11 cases). 10) The contribution of open or thoracoscopic lung biopsy to the final diagnosis was defininitely helpful(334 cases, 66.5%), moderately helpful(140 cases, 27.9%), not helpful or impossible to judge(28 cases, 5.6%). Overall, open or thoracoscopic lung biopsy were helpful to diagnose the lung lesion in 94.4 % of total cases. Conclusions: The open or thoracoscopic lung biopsy were relatively safe and reliable diagnostic method of lung lesion which could not diagnosed by other diagnostic approaches such as bronchoscopy. We recommend the thoracoscopic lung biopsy when the patients were in critical condition because the thoracoscopic biopsy was more safe and have equal diagnostic results compared with the open lung biopsy.

• Tuberculosis and Respiratory Diseases
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• v.56 no.6
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• pp.646-656
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• 2004

Background : The aim of this study was to elucidate the mediastinal lymphatic drainage of nonsmall- cell lung cancer (NSCLC). Methods : We retrospectively analyzed the frequency of enlarged mediastinal lymph node (LN) in 256 NSCLC patients with N2 or N3 diseases on CT scan, especially with respect to the location of primary tumor. Results : In 57 patients with right upper lobe (RUL) tumors, right lower paratracheal LN (89.5%) was the most commonly enlarged, followed by subcarinal LN (54.4%). In 61 patients with left upper lobe (LUL) tumors, left lower paratracheal (70.5%) and subaortic LNs (52.5%) were commonly enlarged. Subcarinal LN enlargement without ipsilateral superior mediastinal LN enlargement was rarely found in both upper lobe tumors; RUL 8.8%, LUL 6.6%. In patients with right or left lower lobe (RLL or LLL) tumors, the most commonly enlarged LN was subcarinal; 88.2%, 65.7%, respectively. In RLL tumors with both subcarinal and superior mediastinal LN enlargements, the frequency of ipsilateral superior mediastinal LN involvement was similar to that of bilateral superior mediastinal involvement. In LLL tumors with both subcarinal and superior mediastinal LN enlargements, bilateral superior mediastinal involvement was more frequent than ipsilateral superior mediastinal involvement. Conclusion : The results of this study suggest that both upper lobe tumors are mainly drained directly to ipsilateral superior mediastinal LNs, and that both lower lobe lesions are drained to superior mediastinal LN via subcarinal LNs.

• Journal of Chest Surgery
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• v.43 no.6
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• pp.700-704
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• 2010

Background: For staging primary lung cancer, integrated positron emission tomography/computed tomography (PET/CT) imaging is popular. The purpose of this study was to evaluate the accuracy of PET/CT scanning in lymph nodal staging of lung cancer. Material and Method: We studied 48 patients who had received CT, PET/CT and pulmonary resections due to primary non-small cell lung cancer in our hospital between January 2006 and August 2009. Mediastinal lymph nodes were classified as superior mediastinal nodes, aortic nodes, inferior mediastinal nodes, or N1 nodes. We compared the power of CT and PET/CT for diagnosing pulmonary lymph nodes for each of the four types of nodes. Result: PET/CT was more sensitive than CT for all groups except inferior mediastinal nodes. However, the differences were not significant (McNemar's test: superior mediastinal nodes, p=0.109; aortic nodes, p=1.000; inferior mediastinal nodes, p=0.625, N1 nodes, p=0.424). Conclusion: The accuracy of PET/CT is similar to that of CT alone for staging lymph nodes. The two imaging modalities might be used as complementary, cooperative tools. We expect that integrated PET/CT will be found to be significantly mmore sensitive after more trials are done and more data is accumulated.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.42 no.4
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• pp.359-366
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• 2016

Exosome, a small vesicle secreted from cells, has diverse functions depending on cell origins and tissue types and plays a important role in cell viability and intercellular communication. Recently, many researchers have demonstrated the use of exosomes for the treatment of cancers and immune diseases, and the development of diagnostic biomarker. However, the secretion mechanism of exosome from skin cell and its physiological functions in skin remain unclear. Thus, this study aimed to explore whether keratinocyte-derived exosome affects proliferation and migration in HaCaTs. Exosomes were isolated from HaCaTs by ExoQuick-TC and then boiled or unbolied. Boiled and unboiled exosome induced proliferation in HaCaTs in a dose-dependant manner ($0.1{\sim}20{\mu}g/mL$), respectively. Boiled and unboiled exosome at concentration of $20{\mu}g/mL$ increased proliferation level in HaCaTs by $186.96{\pm}3.87%$ and $193.48{\pm}10.48%$ compared with control group. Unboiled exosome stimulated migration in HaCaTs in a dose-dependent manner ($0.1{\sim}20{\mu}g/mL$), which reached a maxium at concentration of $20{\mu}g/mL$ ($179.39{\pm}4.89%$ of control), but boiled exosome did not affect HaCaT migration. In addition, unboiled exosome ($0.1{\sim}20{\mu}g/mL$) dose-dependently stimulated sprout outgrowth in HaCats. These results demonstrate that in exosome from HaCaTs, heat-stable components such as lipid may induce HaCaT proliferation and heat-unstable components such as protein may stimulate migration and sprout outgrowth in HaCaTs, thereby leading to reepithelialization and skin-wound healing activities. It is concluded that exosomes from HaCaTs may be used as cosmetic materials.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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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.

• Tuberculosis and Respiratory Diseases
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• v.60 no.2
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• pp.160-170
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• 2006

Background : The aberrant promoter hypermethylation of p16INK4a, as a tumor suppressor gene, is contributory factor to non-small cell lung cancer(NSCLC). However, its potential diagnostic impact of lung cancer is unclear. This study measured the level of $p16^{INK4a}$ promoter hypermethylation in the sputum and blood, and compared this with the level measured in the tissue obtained from NSCLC and pulmonary inflammation. Methods : Of the patients who visited the Our Lady of Mercy Hospital in Incheon, Korea for an evaluation of a lung mass and underwent blood, sputum, and tissue tests, 23patients (18 NSCLC, 5 pulmonary inflammation) were enrolled in this study. DNA was extracted from each sample and the level of p16INK4amethylation was determined using methylation-specific polymerase chain reaction. Results : $p16^{INK4a}$ methylation of the blood was observed in 88.9% (16 of 18) and 20.0% (1 of 5) of NSCLC and from pulmonary inflammation samples, respectively (P=0.008). Methylation of the sputum was observed in 83.3% (10 of 12) 80.0% (4 of 5) of NSCLC and pulmonary inflammation samples, respectively (P=1.00). Among the 8 NSCLC tissue samples, methylation changes were detected in 75.0% of samples (6 cases). Four out of seven tissue samples (57.1%) showed concordance, being methylated in both the blood and sputum. Conclusions : There was a higher level of $p16^{INK4a}$ methylation of the blood from NSCLC patients than from pulmonary inflammation. The tissue showed a high concordance with the blood in the NSCLC samples. These findings suggest that $p16^{INK4a}$ promoter hypermethylation of the blood can used to discriminate between NSCLC and pulmonary inflammation.

• Tuberculosis and Respiratory Diseases
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• v.52 no.5
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• pp.441-452
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• 2002

Background : Anti-apoptotic proteins may be involved in tumor development, progression and the response to treatment, Bcl-2 is by far the most studied anti-apoptotic protein. A novel inhibitor of apoptosis, designated survivin, and the heat shock proteins (HSPs) have recently been found in many human cancers. Immunohistochemical methods were used to determine the expression level of survivin, HSP70 and bcl-2 in non-small cell lung cancer (NSCLC) to evaluate their clinical significance. Materials and Methods : Tissue array slides were obtained from 99 surgically resected NSCLCs. Immunohistochemical staining was performed by an immuno-peroxidase technique using an avidin-biotinylated horseradish peroxidase complex. Anti-survivin rabbit polyclonal antibodies, anti-HSP70 mouse monoclonal antibodies and anti-bcl-2 mouse monoclonal antibodies were used as the primary antibodies. Results : Positive staining of survivin was detected in 33.3% of the cases. Survivin positivity is associated with to females and recurrence. A nonstatistically significant trend toward increased survivin expression was observed in non-smokers, and its expression inversely correlated with the number of cigarettes smoked in smokers. HSP70 was detected in 84.8% but this did not correlated with the clinicopathologic characteristics. Bcl-2 was detected in 18.2% and its expression correlated to tumor recurrence. No significant difference in the median survival time was noted in a comparison of all cases with survivin expression and those without. There was no association between HSP70 or bcl-2 expression and survival. Conclusion : Survivin expression was significantly associated with females and tumor recurrence. In addition its expression was inversely associated with the number of cigarettes smoked. However, HSP70 and bcl-2 expression were not associated with the clinical parameters or survival. This suggests that measuring the survivin levels may be useful in identifying patients at high risk for disease recurrence. Therefore, survivin might be a new diagnostic/therapeutic target in cancer.

• Radiation Oncology Journal
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• v.15 no.2
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• pp.79-95
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• 1997

Purpose : Phospholipase C(PLC) isozymes play significant roles in signal transduction mechanism. $PLC-\gamma$ 1 is one of the key regulatory enzymes in signal transduction for cellular proliferation and differentiation. Ras oncoprotein, EGFR, and PKC are also known to be involved in cell growth. The exact mechanisms of these signal transduction following irradiation, however, were not clearly documented Thus, this study was Planned to determine the biological significance of PLC, ras oncoprotein, EGFR, and PKC in damage and regeneration of rat intestinal mucosa following irradiation. Material and Method : Sixty Sprague-Dawley rats were irradiated to entire body with a single dose of 8Gy. The rats were divided into S groups according to the sacrifice days after irradiation. The expression of PLC, ras oncoprotein, EGFR and PKC in each group were examined by the immunoblotting and immunohistochemistry. The histopathologic findings were observed using H&I stain, and the mitoses for the evidence of regeneration were counted using the light microscopy & PCNA kit. The Phosphoinositide(PI) hydrolyzing activity assay was also done for the indirect evaluation of $PLC-\gamma$ 1 activity. Results: In the immunohistochemistry , the expression of $PLC-{\beta}$ was negative for all grøups. The expression of $PLC-{\gamma}1$ was highest in the group III followed by group II in the proliferative zone of mucosa. The expression of $PKC-{\delta}1$ was strongly positive in group 1 followed by group II in the damaged surface epithelium. The above findings were also confirttled in the immunoblotting study. In the immunoblotting study, the expressions of $PLC-{\beta}$, $PLC-{\gamma}1$, and $PKC-{\delta}1$ were the same as the results of immunohis-tochemistry. The expression of ras oncoprctein was weakly positive in groups II, III and IV. The of EGFR was the highest in the group II, III, follwed by group IV and the expression of PKC was weakly positive in the group II and III. Conclusion: $PLC-{\gamma}1$ mediated signal transduction including ras oncoprotein, EGFR, and PKC play a significant role in mucosal regeneration after irradiation. $PLC-{\delta}1$ mediated signal transduction might have an important role in mucosal damage after irradiation. Further studies will be necessary to confirm the signal transduction mediating the $PKC-{\delta}1$.

• The Korean Journal of Nuclear Medicine
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• v.8 no.1_2
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• pp.57-62
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• 1974

이 논문(論文)은 1973년(年) ICSH주최로 열린 panel에서 적혈구파괴(赤血球破壞) 장소(場所)를 결정(決定)하기 위한 생체(生體) 체표계측법(醫表計測法)의 표준화(標準化)에 관(關)한 토론(討論) 결과(結果)를 초록(抄錄)한 것이다. 체표계측(體表計測)은 체외(體外)에서 계측기(計測器)를 이용(利用)하여 각(各) 장기(臟器)에서의 방사표지물질(放射標識物質)의 분포(分布) 및 시간경과(時間經過)에 따른 변화(變化)를 측정(測定)하는 것으로서 $^{51}Cr$를 사용(使用)하여 적혈구수명(赤血球壽命)을 측정(測定)할 때 간(肝), 비(脾), 심장(心臟)의 방사능(放射能)을 계측(計測)한다. 이 방법(方法)은 각(各) 장기(臟器)에서의 적혈구파괴(赤血球破壞)의 정도(程度)를 예측할 수 있다. 특(特)히 용혈성(溶血性) 빈혈환자(貧血患者)에서 비장적출(脾臟摘出) 여부를 결정(決定)하는데 도움이 된다. 이 panel에서는 주(主)로 오차(誤差)의 원인(原因)이 되는 여러가지 요인(要因)에 대(對)하여 토론(討論)하였으며 일반적으로 다음과 같은 것에 의견(意見)의 일치(一致)를 보았다. 즉(卽) 비장(脾臟)의 위치(位置)는 $^{99m}Tc$로 비주사(脾走査)를 실시하여 결정(決定)하는것이 좋고, $^{51}Cr$은 체중(體重) 1kg당 $1.5{\mu}Ci$를 사용하여, 계측기(計測器)는 NaI crystal(직경이 5cm이상, 두께가 3.75cm이상)의 scintillation doctor를 사용하고, 계측(計測)은 $^{51}Cr$로 표지(標識)된 적혈구(赤血球) 주입후(注入後) 15분(分) 이후(以後)에 하고 다음날 계측(計測)한 후(後) 2주(週) 동안에 적어도 6번 계측(計測)한다. Data 처리는 excess count법(法)과 비(脾)와 간(肝)의 비(比)로서하는 것이 좋다.定値)에 차이(差異)가 있어 그 결과(結果)의 해석(解釋) 및 비교(比較) 검토(檢討)에 적지않은 난점(難點)이 생겨 표준화(標準化)된 공통적(共通的)인 방법(方法)의 사용(使用)이 중요(重要)하다는 사실(事實)이 인식(認識)되게 되었다. 1966년(年) 호주(濠洲)의 Sydney에서 개최(開催)되었든 제11차(第11次) 국제혈액학회(國際血學會)때 열린 제4차(第4次) International Committee for Standardization in Haematology(ICSH)에서 Diagnostic Applications of Radioisotopes in Haematology에 관(關)한 expert panel을 갖을것을 의결(議決)하여 다음과 같은 12명(名)의 위원(委員)이 결정(決定)되었으며 위원회(委員會)의 의장(議長)에 Dr. Szur, 총무(總務)에 Dr. Glass가 각각(各各) 선임(選任)되었다. 그간(間) 1967년(年) 영경(英京) London에서 첫 회합(會合)이 있은후(後) New York, Vienna(IAEA후원(後援)) Brthesda(NIH후원(後援))에서 전문위원회(專門委員會)를 갖고 적혈구수명측정법(赤血球壽命測定法)에 관(關)한 의견(意見)의 일치(一致)를 보았다. ICSH와 국제혈액학회(國際血學會)에서는 이번에 결정(決定)된 적혈구수명측정법(赤血球壽命測定法)을 널리 소개(紹介)하며, 측정법(測定法)과 얻어진 결과(結果)의 해석(解釋)에 표준화(標準化)를 기(期)할 목적(目的)으로 이에 연관성(聯關性)있는 전문지(專門誌)에 게재(揭載)할 것을 요청(要請) 받었기에 이에 전문(全文)을 소개(紹介)하는 바이다. 이들은 방사성(放射性) chromium 법(法)의 모든 세부적(細部的)인 면(面)을 표준화(標準化)하고 있으며 그간(間) 가장 논란(論難)의 대상(對象)이 되었던, $^{51}Cr$-표지방법(標識方法)에 있어서의 세가지 변법(變法),

• Radiation Oncology Journal
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• v.21 no.1
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• pp.66-74
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• 2003

Purpose : The matrix metalloprotelnases (MMPs) are a family of enzymes whose main function is the degradation of the extracellular matrix. Several studies have revealed that MMPs and TIMPS are related to the wound heating process and in photoaging caused by ultraviolet Irradiation. However, the expressions of MMP and TIMP after irradiation have not, to the best of our knowledge, been studied. This study investigates the expressions of MMP-2 and TIMP-2 in rat Intestinal mucosa following irradiation. Materials and Methods : The entire abdomen of Sprague-Dawley rats was irradiated using a single dose method. The rats were sacrificed on day 1, 2, 3, 5, 7 and 14 following irradiation. Histopathological observations were made using hematoxilin & eosin staining. The expressions of MMP-2 and TIMP-2 were examined using immunohistochemistry, Irnrnunoblotting and ELISA. Results : Radiation induced damage associated with atrophic villi, and infiltration of inflammatory cell was observed from the first postirradiation day, and severe tissue damage was observed on the second and the third postirradiation days. An increase in mitosis and the number of regenerating crypts, as evidence of regeneration, were most noticeable on the fifth postirradiation day. From the immunohistochemlstry, the MMP-2 expression was observed from the first postirradiation day, but was most conspicuous on the third and the fifth postirradiation days. The TIMP-2 expression was most conspicuous on the fifth postirradiation day. From the irnrnunoblotting, the MMP-2 expression was strongly positive on the third postirradlatlon day, and that of TIMP-2 showed a strong positive response on the fifth postirradiation day. In ELISA tests, the expressions of MMP-2 and TIMP-2 were increased in the postirradiation groups compared to those of the normal controls, and showed a maximum increase on the fifth postirradiatlon day. These results were statistically significant. Conclusion : The expressions of MMP-2 and TIMP-2 were increased in the intestinal mucosa of the rats following irradiation, and these results correlated with the histopathological findings, such as tissue damage and regeneration. Therefore, this study suggests that MMP-2 and TIMP-2 play roles in the mechanisms of radiation-induced damage and regeneration of intestinal mucosa of rats.