• Journal of Chest Surgery
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• v.34 no.5
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• pp.377-385
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• 2001

배경: Cisplain과 같은 세포돗성 약제에 대한 내성은 폐암 치료 실패의 중요한 원인이다. 이러한 항암제에 대한 내성의 발생기전은 복잡하고 아직 완전히 알려져 있지 않지만 불량한 예후의 원인으로 생각된다. 특히 약제 내성이 발생한 환자의 경우 기존의 종양의 급속한 성장뿐 아니라 새로운 전이 병소가 급속히 발생 및 진단됨은 약제 내성을 가진 종양이 전이에의 용이성을 획득하는게 아닌가 의심케한다. 이를 규명하기 위해 Cisplatin에 내성을 지닌 비소세포폐암 세포주 H460/CISm이 전이 능력을 Cisplatin에 민감한 비소세포폐암 세로주 H460과 비교하고자 한다. 대상 및 방법: 약제 내성 세포주를 확보하기 위하여 H460세포에 cisplatin을 점차적으로 증가시켜 처리한 후 배양하였다. H460 세포와 H460/CIS 세로에서의 혈관신생인자와 성장관련인 자의 발현양상, gelatin zymography 분석 그리고 in vivo 실험으로 nude 마우스에서의 자발적 전이 능력의 차이를 비교하였다. 결과: H460 세포를 이식한 마우스에 폐에서는 종양이 형성되지 않았으나 H460/CIS세포를 이식한 마우스 10마리중 8마리에서 종양이 형성되었다. 또한 H460/CIS 세포주에서 전이 관련 유전자로 알려진 angiopoietin-1, vascular endothelial growth factor, basic fibroblast growth factor, matrix metalloproteinase 2 등이 더 발현되었고, 전이의 침습성을 유발하는 gelatinase의 활성이 증가된 것을 확인할 수 있었다. 결론: 본 여구 결과를 통해 cisplatin에 내성을 가진 비소세포폐암세포에서 전이 능력이 증가될 수 있다고 여겨지며 이러한 사실을 토대로 초기 비소세포폐암 환자의 수술 전 항암약물요법의 타당성에 대해서 이야기 하기 위해서는 많은 임상적 연구가 필요하리라 생각된다.

• Proceedings of the KAIS Fall Conference
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• 2009.05a
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• pp.227-230
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• 2009

목적 : 비소세포 폐암에서 HIF-$1{\alpha}$, VEGF의 발현과 예후와 관련된 여러 임상적 표지자 및 병리학적 표지자와의 상관관계를 조사하고자 하였다. 방법 : 이들의 예후인자로서의 의미를 알아보고자 외과적으로 절제한 44예의 비소세포 폐암종을 대상으로 VEGF, HIF-$1{\alpha}$에 대한 면역조직화학염색을 시행하였다. 결과 : WHO 분류에 의한 조직학적인 형태인 편평세포암종 28예, 선암종 16예의 비세포성 폐암이 이 연구에 포함되었다. 비소세포성 폐암 24예와 16예에서 VEGF 및 HIF-$1\alpha$이 발현되었다. 결론 : 이 연구에서 VEGF 발현과 병기와의 상관관계, HIF-$1{\alpha}$의 과발현과 병기 사이에서 통계적으로 유의한 상관관계를 볼 수 없었다. 또한 HIF-$1{\alpha}$의 과발현과 VEGF의 발현 사이에 통계학적으로 유의한 관련성이 없었다.

• Journal of Chest Surgery
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• v.30 no.6
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• pp.566-572
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• 1997

A major obstacles to evaluation of newly-developed treatment strategy for human lung cancer has been the lack of appropriate experimental animal models. We describe a new experimental model of orthotopically-developed non-small cell lung cancer in nude rat, involving inoculation of tumor cell suspension by thoracotomy. Over 40 direct implantation to the periphery of the lung has been performed to date, each requiring less than'1 hour for completion. This model has been used to perform a series of experiments to investigate whether the rat lung and surrounding structures trapped tumor cells with 2 different non-small cell lung cancer cell lines(NCI-H46O and NCI-H1299). Every animal showed development of tumor masses, which were loculated at the periphery of the lung karenchyma and identified also by radiography. After 3 weetu of the inoculation, tumor develop meat at the mediastinal strutures were identified. The life expectancies of the victims were different between the cell lines, but were approximately 5 weeks when NCI-H46O cell line was used. This new orthotopic lung cancer model may be facilitate future studies of the new therapeutics of localized non-small cell lung cancer .

• The Korean Journal of Nuclear Medicine Technology
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• v.13 no.3
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• pp.171-174
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• 2009

Purpose: Cancerous death rate 1 place from 2008 year domestic is the lung cancer. The body count which is caused by in the lung cancer every year is increasing. At this lung cancer is the most non small cell lung cancer. $Monototal^{TM}$ test is short reaction time. it is known as the experiment where the example standard of living is high about non small cell lung cancer. This is the study evaluate usefulness of $Monototal^{TM}$ kit. Materials and Methods: $Monototal^{TM}$ were measured using IRMA kit, using 40 CEA positive patients sample which are diagnosed NSCLC, 15 SCC positive patients sample which are diagnosed NSCLC, 40 Cyfra 21-1 positive sample, 20 negative sample in Seoul national university from March to April, 2009. Results: According to result of the $Monototal^{TM}$ test, which is benignancy rate 87.5% in CEA positive patients sample, 93.3% SCC positive patients sample and 100% Cyfra 21-1 positive sample Conclusions: We recommend that using of $Monototal^{TM}$ parallel with different tumor markers. It was useful that diagnosis and convalescence presumption of Non small cell lung cancer.

• Journal of Chest Surgery
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• v.38 no.4 s.249
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• pp.263-270
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• 2005

In recent years, a combination of two demographic phenomena, an increased number of older people in the population and an increase in the incidence of lung cancer with age, has made it mandatory to develop therapeutic modalities with less toxicity for the treatment of inoperable elderly patients with lung cancer. Therefore, we investigated the correlation between COX-2 expression and cytotoxicity of Nimesulide, a specific COX-2 inhibitor. Material and Method: Immunohistochemical staining of COX-2 was performed. After exposure of Nimesulide, XTT analysis, FACS analysis and Hoechst staining were carried out. Result: COX-2 protein was expressed in non-treated A549 cells strongly, but not in H1299. Cytotoxicity of Nimesulide against A549 cell and H1299 cell were similar and $IC_{50}$ of Nimesulide in both cell lines were $70.9{\mu}M$ in A549 cell line and $56.5{\mu}M$ in H1299 cell line respectively. FACS analysis showed $G_0/G_1$ arrest in both cell lines and the S phase cell fraction was decreased. Morphologic assessment of apoptosis by Hoechst 33258 staining, many apoptotic cells were detected in both cell lines. Conclusion: Selective COX-2 inhibitor, Nimesulide, can inhibit the proliferation of non-small cell lung cancer cell lines in vitro. Inhibitory effect of Nimesulide are induction of apoptosis and $G_0/G_1$ arrest. There is no correlation between COX-2 expression and cytotoxicity of Nimesulide, a specific COX-2 inhibitor. Therefore, highly selective COX-2 inhibitors such as Nimesulide can be expected to lead to even greater efficacy of their use as adjuncts to various anticancer angents and radiation therapy for the treatment of high-risk patients.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.39 no.6
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• pp.502-510
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• 1992

Background: Neuron specific enolase (NSE) is a neuronal form of the glycolytic enzyme enolase which was first found in extracts of brain tissue, and later in a variety of APUD cells and neurons of the diffuse endocrine system. SCLC shares many APUD properties with normal neuroendocrine cells. NSE immunostaining and serum NSE measurement may be a useful marker of neuroendocrine differentiation in lung tumors and diagnosis of small cell carcinoma. Methods: NSE immunohistochemical staining was done and at the same time serum NSE levels were measured in 22 small cell lung cancer and 21 non small cell lung cancer which were confirmed histologically. Results: 1) NSE immunoreactivity was detected in 9 of the 18 (50%) small cell lung cancer, in 5 of the 16 non small cell lung cancer. 2) Whereas the mean value in non-small cell lung cancer group was $11.79{\pm}4.47\;ng/ml$, the mean level of serum NSE in small cell lung cancer increased up to $59.3{\pm}77.8\;ng/ml$. In small cell lung cancer patients, mean value of limited disease group was $20.19{\pm}12.91\;ng/ml$, while mean value of extended disease group was $91.9{\pm}94.2\;ng/ml$ showing statistically significant difference. If serum levels above 20 ng/ml were tentatively defined as positive, 16 of 22 (73%) patients with SCLC had positive serum NSE level, but only one patient with NSCLC did. There was no correlation between serum NSE level and immunoreactivity of NSE. Conclusion: These studies indicate that serum NSE measurement may be a useful marker for the diagnosis and disease extent and NSE immunostaining can be used to demonstrate the neuroendocrine components of lung tumor.

• Journal of Chest Surgery
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• v.32 no.2
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• pp.151-157
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• 1999

Background: Increasing evidences from experimental studies indicate that apoptosis may be inversely related to angiogenesis in tumor progression. Material and Method: To explore how apoptosis correlates with tumor angiogenesis, we measured the apoptotic index(AI) using the terminal deoxynucleotidyl transferase method(Apop Tag In Situ Apoptosis Detection Kit, ONCOR) and the intratumoral microvessel density using the anti-CD31 monoclonal antibody in non-small cell lung cancer. Result: Statistical analysis revealed an inverse correlation between AIs and intratumoral microvessel densities in squamous cell lung carcinoma(Spearman rank correlation coefficient r=- 0.229, p=0.047). Conclusion: The results of this study demonstrated that the amount of apoptosis in squamous cell lung carcinoma may be influenced by the extent of neovascularization. This suggests that tumor angiogenesis may contribute to a reduction of apoptosis in tumor cells.

• Tuberculosis and Respiratory Diseases
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• v.58 no.1
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• pp.54-58
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• 2005

Background : To evaluate the role of estrogen and progesterone in the carcinogenesis of NSCLC, IHC studies for the expression of the receptors of estrogen and progesterone have been performed with inconsistent results. Recently the TMA method has been developed and has become recognized as a useful and rapid method for extensively analysing molecular markers at the gene and protein level. We have investigated their expressions in the tissue from NSCLC using the microarray method. Methods : The TMA construction was made with 70 formalinfixed, paraffin-embedded tissues of NSCLC. After heat-induced epitope retrieval, IHC staining on primary tissues of NSCLC was performed with the monoclonal antibodies, ER1D5 and PR1A6. Results : Our sample of 70 consisted of 74% men and 26% women. Of the patients, 49% were current smokers, 27% were non-smokers and 24% were former smokers. By histologic classification, 34 patients had squamous cell carcinoma, 24 had adenocarcinoma, 9 had adenosquamous cell carcinoma, and 3 had other carcinomas. No cancer cells were immunostained with these monoclonal antibodies in any primary tissues of NSCLC. Conclusions : No expression of neither of the two receptors was found in any of the lung cancer tissues. This suggests that adequate genetic variants for IHC staining need to be developed for NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.776-784
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• 1998

Background: The cyclin D1 gene is one of the most frequently amplified chromosomal regions(11q13) in human carcinomas. In laryngeal and head and neck carcinomas, its overexpression has been shown to be associated with advanced local invasion and presence of lymph node metastases. Cyclin D1 may therefore playa key role in cell growth regulation and tumorigenesis. Lung cancer is a worldwide problem and in many contries it is the most lethal malignancy. As relapse is frequent after resection of early stage non-small cell lung cancer, there is an urgent need to define prognostic factors. Purpose: This study was undertaken to evaluate the prognostic value of the cyclin D1, that is one the G1 cyclins which control cell cycle progression by allowing G1 to S phase transition, on the patients in radically resected non-small cell lung cancer. Method: Total 81 cases of formalin-fixed paraffin-embedded blocks from resected primary non-small cell lung cancer from January 1, 1983 to July 31, 1995 at Hanyang University Hospital were available for both clinical follow-up and immunohistochemical staining using monoclonal antibodies for cyclin D1. Results : The histologic classification of the tumor was based on WHO criteria, and the specimens included 45 squamous cell carcinomas, 25 adenocarcinomas and 11 large cell carcinomas. Cyclin D1 overexpression was noted in 26 cases of 81 cases tested (30.9%). Cyclin D1 expression was not significantly associated with cell types of the tumor, pathological staging and the size of the tumor. But cyclin D1 overexpression was significantly correlated with positive lymph node metastasis(p=0.035). The mean survival duration was $22.76{\pm}3.50$ months in cyclin D1 positive group and $45.38{\pm}5.64$ months in eyclin D1 negative group. There was a nearly significant difference in overall survival between cyclin D1 positive and negative groups(p=0.0515) in radically resected non-small cell lung cancer. Conclusion: Based on this study, cyelin D1 overexpression appears an important poor prognostic indicator in non-small cell lung cancer and may have diagnostic and prognostic importance in the treatment of resectable non-small cell lung cancer.