• Korean Journal of Clinical Laboratory Science
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• v.49 no.4
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• pp.460-469
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• 2017

Heat shock proteins (HSPs) are induced as a self-defense mechanism of cells when exposed to various external stresses, such as high fever, infection, free radicals, and heavy metals. They affect the prognosis in the process of tumor formation. HSP is classified into four families: HSP27, HSP60, HSP90, and HSP100, depending on molecular weight. Heat shock protein 90 (HSP90), a molecular chaperone, plays an important role in the cellular protection against various stressful stimuli and in the regulation of cell cycle progression and apoptosis. In the present study, we assessed the differential expression of HSP90 family proteins in non-small cell lung cancer (NSCLC), and the correlation of their expression levels with clinicopathologic factors and patient survival rates. The result of this study can be summarized as follows; $HSP90{\alpha}$ showed higher expression in patients with no lymphovascular invasion (p=0.014). $HSP90{\beta}$ showed a higher expression of squamous cell carcinoma (p=0.003), and an over expression of glucose-related protein (GRP94) was significantly associated with poor differentiation (p=0.048). However, none of the HSP90 proteins showed a significant association with the survival status in patients with NSCLC. This study also indicates that $HSP90{\alpha}$ might contribute more to the carcinogenesis of NSCLC than $HSP90{\beta}$, and GRP94 and isoform selectivity should be considered when HSP90 inhibitors are studied or utilized in the treatment of NSCLC.

• Journal of Chest Surgery
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• v.34 no.5
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• pp.418-421
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• 2001

53세 남자 환자가 객혈을 주소로 입워하여 우축 상엽 편평상피세로 폐암으로 진단 받았다. 캄퓨터 단층촬영상 하부 기관에 종양의 침윤이 의심되었다. 우측 하엽과 중엽을 보존하기 위해서 우측상엽과 하부 기관외측을 포함하여 절제하는 기관기관지 성형술 시행하였고, 수술후 우측 폐의 팽창은 완전하였다. 수술 후 1주일째 시행한 기관지 내시경 검사상 우측 중엽과 하엽의 기관지는 뒤틀림 없이 잘 유지되어 있었다. 수술 후 항암치료와 방사선 치료를 받고 현재 환자는 수술 후 1년 7개월 동안 외래 추적관찰 중이다. 저자들은 우측 상엽의 폐암이 기관 하부를 침범한 경우에 우측 기관 소매 전폐절제술의 합병증을 피하고 환자의 폐기능을 보조하면서 침윤된 우측상엽을 포함하여 절제하는 기관기관지 성형술을 시행하여 이에 보고하는 바이다.

• Journal of radiological science and technology
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• v.6 no.1
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• pp.91-102
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• 1983

The study was carried out on 468 cases among total 4,347 cancer cases which was confirmly diagnosed as malignant neoplasms at Yonsei Center Hospital, appended to Yonsei University, during 10 years from January 1, 1971 to December 31, 1980. The results of this study are as follows: 1. Total malignant neoplasm cases treated with radiation were 4,347, 1,685 of whom were males, and 2,662 females(male to female ratio was 1:1.58). 2. Lung cancer were 10.8% of total malignant neoplasm cases(468 cases), 391 cases for the male and 77 cases for the female. So, average the male to female ratio was 8:1 and cases of the male were much more. 3. The age distribution of lung cancer cases was from 27 to 82 years old. The highest age distribution was $50{\sim}59$ for males(37.9%) and $60{\sim}69$ for females(41.6%) ; 77.1% of total lung cancer cases were over 50 years old. 4. In regard to stages, the distribution of the third stage was highest(49.3%). That of the first stage was much higher during the last period(11.8%) than the first period(2.7%), and that of the fourth stage was much lower during the last period (7.8%) than the first period(21.1%). 5. In regard to pathological type, the distribution was 51.3% for squamous cell carcinoma, 29.3% for undifferentiated cell cercinoma, 12.2% for adenocarcinoma, and 7.2% for bronchoalveolar cell carcinoma in order of frequency. In regard to adenocarcinoma, the male to female ratio was 1:3.7 and cases of the female were much more. 6. In regard to tumor location, the distribution of tumor location in the right-left lobe was 59.1% in the right lobe, 33.6% in the left lobe, and 7.3% in the both lobes in order of frequency. And that of tumor location in the upper and lower lobes was all higher in the upper lobe ; especially, that of the right upper lobe was highest(31.2% of total cases). 7. For the main symptom, coughing was highest(64%), 50% for hemoptysis, and 41% for dyspnea.

• Tuberculosis and Respiratory Diseases
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• v.47 no.1
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• pp.35-41
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• 1999

Background: Sleeve lobectomy of the main bronchus has been proposed to spare lung tissue in patients who cannot tolerate pneumonectomy because of impaired lung function. The purpose of this study was to evaluate whether sleeve lobectomy can preserve lung function as expected from preoperative evaluation of lung function in patients with non-small cell lung cancer. Method: Between January 1995 and March 1998, 15 patients with non-small cell lung cancer who underwent sleeve resection were evaluated. Preoperative evaluations included spirometry and quantitative lung perfusion scan, from which predicted postoperative $FEV_1$ was calculated. At least 3 months after operation follow up spirometry and bronchoscopy were performed. Predicted FEVj was compared with measured postoperative $FEV_1$. Result: Fourteen men and one woman, with median age of 58 years, were reviewed. The diagnosis was squamous cell carcinoma in 13 patients and adenocarcinoma of lung in 2 patients. Our results showed a excellent preservation of pulmonary function after sleeve lobectomy. Correlation between the predicted (mean, $2180{\pm}570mL$) and measured $FEV_1$ (mean, $2293{\pm}499mL$) was good(r=0.67, P<0.05). Furthermore, patient with low $FEV_1$ (<2L) showed improved lung function after sleeve lobectomy. Conclusion: These findings indicated a complete recovery of the reimplanted lung lobes after sleeve lobectomy. Therefore, this technique could be safely used in lung cancer patients with impaired lung function.

• The Korean Journal of Cytopathology
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• v.7 no.2
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• pp.163-168
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• 1996

Abnormalities of p53 gene are common in lung cancers and are associated with immunologically detectable p53 protein. p53 immunoreactivity is uncommon in normal cells but is frequently seen in neoplasia. Therefore, assessment of p53 expression may assist in the cytological diagnosis of malignancy. The usefulness of p53 immunostaining as a marker of malignancy in the cytological analysis of bronchial brush specimens from the patients with lung cancers was investigated in this study. A total of 71 bronchial brush samples submitted for cytologic diagnosis were immunostained with D07, a monoclonal antibody to recombinant p53 protein. Resultant p53 data were correlated with cytologic diagnosis and clinical information. Of the 17 smears with a benign cytodiagnosis, all were p53 negative. Of the 40 cases with a malignant cytodiagnosis (histologically confirmed), 35 were p53 positive and 5 were negative. Of the 14 cases that were cytologically suspicious but nondiagnostic for malignancy, 11 were p53 positive, 9 of which were subsequently proved to be malignant by histologic examination, and the remaining 2 cases were tuberculosis clinically. Forty four of 51 histologically confirmed lung carcinomas were p53 positive, including 25 of 28 squamous cell carcinomas, 13 of 17 small cell carcinomas, 3 of 3 adenocarcinomas, and 3 of 3 large cell undifferentiated carcinomas. These results suggest that p53 immunostaining could be of value as a marker of malignancy in the cytologic examination of bronchial brush specimens. Furthermore, we have shown the possible clinical utility of p53 immunostaining in cytopathological diagnosis, that is, as a valuable adjunct to morphological assessment in the analysis of cytopathologically suspicious cases.

• Tuberculosis and Respiratory Diseases
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• v.46 no.1
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• pp.36-43
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• 1999

Background : Tumor growth is the net result of intrinsic proliferation and escape from active cell death. bcl-2 is a member of a new category of oncogenes that is not involved in influencing cell proliferation but is involved in regulating cell death(apoptosis). Based on this information, it seems to be reasonable to expect that there may be clinical prognostic significance of bcl-2 expression in non-small cell lung cancer. But its prognostic significance is not established. Methods: To investigate the role of bcl-2 in lung cancer, we performed immunohistochemical stain of bcl-2 on 57 biopsy specimens from resected primary non-small cell lung cancer. Thereafter, flow cytometric cell cycle analysis was done. And we analyzed the correlation between bcl-2 expression, clinical parameters, S-, $G_1$-phase fraction and survival. Results: bcl-2 were detected in 43.8% of total 57 patients(according to histology, squamous cancer 47%, adenocarcinoma 32%, according to TNM stage, I 28.6%, II 52.3%, III 45.5%. both differences were insignificant). By using the flow cytometric analysis, mean S-phase fraction of bcl-2(+) and (-) group were 14.1($\pm7.8$)%, 24.7($\pm10.5$)% (p<0.005), mean $G_1$-phase fraction of bcl-2(+) and bcl-2(-) group were 75.5($\pm10.8$)%, 65.5($\pm11.4$)%(p<0.05). 2yr, 3yr and 5yr survival and median survival time of bcl-2(+) group were 65%, 54%, 41%, 53 months, and those of bcl-2(-) group were 71%, 52%, 46%, 37 months. (p>0.05, Kaplan-Meier, log rank) Conclusion: bcl-2 was detected in 43.8% of primary non-small cell lung cancer. The S-phase fraction of bcl-2(+) group was less than bcl-2(-) group, and G1-phase fraction of bcl-2(+) group was more than bcl-2(-) group. But, expression of bcl-2 could not be a prognostic factor.

• Radiation Oncology Journal
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• v.38 no.2
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• pp.99-108
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• 2020

Purpose: The probability of recurrence of cancer after adjuvant or definitive radiotherapy in patients with human papillomavirus-negative (HPV(-)) head and neck squamous cell carcinoma (HNSCC) varies for each patient. This study aimed to identify and validate radiation sensitivity signature (RSS) of patients with HPV(-) HNSCC to predict the recurrence of cancer after radiotherapy. Materials and Methods: Clonogenic survival assays were performed to assess radiosensitivity in 14 HNSCC cell lines. We identified genes closely correlated with radiosensitivity and validated them in The Cancer Genome Atlas (TCGA) cohort. The validated RSS were analyzed by ingenuity pathway analysis (IPA) to identify canonical pathways, upstream regulators, diseases and functions, and gene networks related to radiosensitive genes in HPV(-) HNSCC. Results: The survival fraction of 14 HNSCC cell lines after exposure to 2 Gy of radiation ranged from 48% to 72%. Six genes were positively correlated and 35 genes were negatively correlated with radioresistance, respectively. RSS was validated in the HPV(-) TCGA HNSCC cohort (n = 203), and recurrence-free survival (RFS) rate was found to be significantly lower in the radioresistant group than in the radiosensitive group (p = 0.035). Cell death and survival, cell-to-cell signaling, and cellular movement were significantly enriched in RSS, and RSSs were highly correlated with each other. Conclusion: We derived a HPV(-) HNSCC-specific RSS and validated it in an independent cohort. The outcome of adjuvant or definitive radiotherapy in HPV(-) patients with HNSCC can be predicted by analyzing their RSS, which might help in establishing a personalized therapeutic plan.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.516-524
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• 1997

Background : Cancer invasion and metastasis require the dissolution of the extracellular matrix in which several proteolytic enzymes are involved. One of these enzymes is the urokinase-type plasminogen activator(u-PA), and plasminogen activator inhibitors(PAI-1, PAI-2) also 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 levels of u-PA and plasminogen activator inhibitors in various cancer tissues are significantly higher than those in normal tissues and have significant correlations with tumor size and lymph node involvement. Here, we measured the concentration of plasma u-PA and PAI-1 antigens in the patients with lung cancer and compared the concentration of them with histologic types and staging parameters. Methods : We measured the concentration of plasma u-PA and PAI-1 antigens using commercial ELISA kit in 37 lung cancer patients, 21 benign lung disease patients and 24 age-matched healthy controls, and we compared the concentration of them with histologic types and staging parameters in lung cancer patients. Results : The concentration of u-PA was $1.0{\pm}0.3ng/mL$ in controls, $1.0{\pm}0.3ng/mL$ in benign lung disease patients and $0.9{\pm}0.3ng/mL$ in lung cancer patients. The concentration of PAI-1 was $14.2{\pm}6.7ng/mL$ in controls, $14.9{\pm}6.3ng/mL$ in benign lung disease patients, and $22.1{\pm}9.8ng/mL$ in lung cancer patients. The concentration of PAI-1 in lung cancer patients was higher than those of benign lung disease patients and controls. The concentration of u-PA was $0.7{\pm}0.4ng/mL$ in squamous cell carcinoma, $0.8{\pm}0.3ng/mL$ in adenocarcinoma, 0.9ng/mL in large cell carcinoma, and $1.1{\pm}0.7ng/mL$ in small cell carcinoma. The concentration of PAI-1 was $22.3{\pm}7.2ng/mL$ in squamous cell carcinoma, $22.6{\pm}9.9ng/mL$ in adenocarcinoma, 42 ng/mL in large cell carcinoma, and $16.0{\pm}14.2ng/mL$ in small cell carcinoma. The concentration of u-PA was 0.74ng/mL in stage I, $1.2{\pm}0.6ng/mL$ in stage II, $0.7{\pm}0.4ng/mL$ in stage IIIA, $0.7{\pm}0.4ng/mL$ in stage IIIB, and $0.7{\pm}0.3ng/mL$ in stage IV. The concentration of PAI-1 was 21.8ng/mL in stage I, $22.7{\pm}8.7ng/mL$ in stage II, $18.4{\pm}4.9ng/mL$ in stage IIIA, $25.3{\pm}9.0ng/mL$ in stage IIIB, and $21.5{\pm}10.8ng/mL$ in stage IV. When we divided T stage into T1-3 and T4, the concentration of u-PA was $0.8{\pm}0.4ng/mL$ in T1-3 and $0.7{\pm}0.4ng/mL$ in T4, and the concentration of PAI-1 was $17.9{\pm}5.6ng/mL$ in T1-3 and $26.1{\pm}9.1ng/mL$ in T4. The concentration of PAI-1 in T4 was significantly higher than that in T1-3. The concentration of u-PA was $0.8{\pm}0.4ng/mL$ in M0 and $0.7{\pm}0.3ng/mL$ in M1, and the concentration of PAI-1 was $23.6{\pm}8.3ng/mL$ in M0 and $21.5{\pm}10.8ng/mL$ in M1. Conclusions : The plasma levels of PAI-1 in lung cancer were higher than benign lung disease and controls, and the plasma levels of PAI-1 in T4 were significantly higher than T1-3. These findings suggest involvement of PAI-1 with local invasion of lung cancer, but it should be confirmed by the data on comparison with pathological staging and tissue level in lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.45 no.5
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• pp.962-974
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• 1998

Background: Alteration of p53 tumor suppressor genes is most frequently identified in human neoplasms, including lung carcinoma. It is well known that bcl-2 oncoprotein protects cells from apoptosis. Recent studies have demonstrated that bcl-2 expression is associated with favorable prognosis for patients with non-small cell lung carcinoma. However, the precise biologic role of bcl-2 in the development of these tumors is still obscure. p53 and bcl-2 have important regulatory influence in the apoptotic pathway and thus their relationship is of interest in tumorigenesis, especially lung cancer. Purpose: The author investigated to know the prognostic significance of the expression of p53 and bcl-2 in radically resected non-small cell lung cancer. Method: 84 cases of formalin-fixed paraffin-embedded blocks from resected primary non-small cell lung cancer from 1980 to 1994 at Hanyang University Hospital were available for both clinical follow-up and immunohistochemical staining using monoclonal antibodies for p53 and bcl-2. Results : The histologic classification of the tumor was based on WHO criteria., and the specimens included 45 squamous cell carcinomas(53.6%), 28 adeonocarcinomas(33.3%) and 11 large cell carcinomas(13.1 %). p53 immunoreactivity was noted in 47 cases of 84 cases(56.0%). bcl-2 immunoreactivity was noted in 15 cases of 84 cases(17.9%). The mean survival duration was $64.23{\pm}10.73$ months in bcl-2 positive group and $35.28{\pm}4$. 39 months in bcl-2 negative group. The bcl-2 expression was significantly correlated with survival in radically resected non-small cell lung cancer patients(p=0.03). The mean survival duration was $34.71{\pm}6.12$ months in p53 positive group and $45.35{\pm}6.30$ months in p53 negative group(p=0.21). The p53 expression was not predictive for survival. There was no correlation between combination of the different status of p53 and bcl-2 expression in our study. Conclusions : The interaction and the regulation of new biologic markers, such as those involved in the apoptotic pathway, are complex. bcl-2 overexpression is a good prognostic factor in non-small cell lung cancer and p53 expression is not significantly associated with the prognostic factor in non-small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.43 no.1
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• pp.54-62
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• 1996

Background: $^{99m}Tc$ MIBI(Methoxyisobutylisonitrile complex), a member of the isonitrile class of coordination compounds, is a lipophilic cation presently under investigation for clinical use as myocardial perfusion imaging agent and is widely used to detect myocardial infarction. Preliminary reports indicate that $T_1$-201 accumulate in human neoplasm and several authors reported $^{99m}Tc$ MIBI may also localized in primary malignant tumor and metastatic deposits from lung cancer. We evaluated the uptake of $^{99m}Tc$ MIBI in lung cancer and localization of mediastinal and other site metastasis, and compared the benign lesion of the lung. Method: Thirty four patients of lung cancer and ten patients of benign lung lesion were studied with chest CT and $^{99m}Tc$ MIBI Lung SPECT. $^{99m}Tc$ MIBI uptake ratio was assessed by TR/NL(Lung lesion/ Normal area), HT/NL (Heart/Normal area) and HT/TR(Heart/Lung lesion). Results: 1) All lung cancer patients showed increased uptakes of $^{99m}Tc$ MIBI in malignant lung lesion and Tc-99m MIBI uptake was also increased in mediastinal and lymph node metastasis except two cases. 2) There was significant different ratio of TR/NL between malignant and benign lesion, $3.79{\pm}1.82$ and $1.67{\pm}0.63$ on planar images, respectively(p<0.001). 3) There was no significant difference of $^{99m}Tc$ MIBI uptake ratio between squamous cell carcinoma, small cell carcinoma and adeno carcinoma($3.64{\pm}1.66$, $3.57{\pm}0.72$, $4.31{\pm}2.28$ respectively). Conclusion: $^{99m}Tc$ MIBI lung SPECT was useful in the localization of tumor and mediastinal or other site metastatic lesion in lung cancer and also in the differential diagnosis between benign and malignant lesion.