• Title/Summary/Keyword: 비소세포 폐암

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The Change of Cell-cycle Related Proteins and Tumor Suppressive Effect in Non-small Cell Lung Cancer Cell Line after Transfection of p16(MTS1) Gene (폐암세포에 p16 (MTS1) 유전자 주입후 암생성능의 변화 및 세포주기관련 단백질의 변동에 관한 연구)

  • Kim, Young-Whan;Kim, Jae-Yeol;Yoo, Chul-Gyu;Han, Sung-Koo;Shim, Young-Soo;Lee, Kye-Young
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.4
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    • pp.796-805
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    • 1997
  • Background : It is clear that deregulation of cell cycle progression is a hallmark of neoplastic transformation and genes involved in the $G_1$/S transition of the cell cycle are especially frequent targets for mutations in human cancers, including lung cancer. p16 gene product, one of the G1 cell-cycle related proteins, that is recently identified plays an important role in the negative regulation of the the kinase activity of the cyclin dependent kinase (cdk) enzymes. Therefore p16 gene is known to be an important tumor suppressor gene and is also called MTS1 (multiple tumor suppressor 1). No more oncogenes have been reported to be frequently related to multiple different malignancies than the alterations of p16 gene. Especially when it comes to non-small cell lung cancer, there was no expression of p16 in more than 70% of cell lines examined. And also it is speculated that p16 gene could exert a key role in the development of non-small cell lung cancer. This study was designed to evaluate whether p16 gene could be used as a candidate for gene therapy of non-small cell lung cancer. Methods : After the extraction of total RNA from normal fibroblast cell line and subsequent reverse transcriptase reaction and polymerase chain reaction, the amplified p16 cDNA was subcloned into eukaryotic expression plasmid vector, pRC-CMV. The constructed pRC-CMV-p16 was transfected into the NCI-H441 NSCLC cell line using lipofectin. The changes of G1 cell-cycle related proteins were investigated with Western blot analysis and immunoprecipitation after extraction of proteins from cell lysates and tumor suppressive effect was observed by clonogenic assay. Results : (1) p16(-) NCI-H441 cell line transfected with pRC-CMV-p16 showed the formation of p16 : cdk 4 complex and decreased phosphorylated Rb protein, while control cell line did not. (2) Clonogenic assay demonstrated that the number of colony formation was markedly decreased in p16(-) NCI-H441 cell line transfected with pRC-CMV-p16 than the control cell line. Conclusion : It is confirmed that the expression of p16 protein in p16 absent NSCLC cell line with the gene transfection leads to p16 : cdk4 complex formation, subsequent decrease of phosphorylated pRb protein and ultimately tumor suppressive effects. And also it provides the foundation for the application of p16 gene as a important candidate for the gene therapy of NSCLC.

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Detection of Apoptosis by M30 Monoclonal Antibody in Non-small Cell Lung Carcinomas (비소세포 폐암에서 단클론항체 M30를 이용한 세포자멸사 측정)

  • Kim, Gwang-Il;Lee, Gun;Lim, Chang-Young;Lee, Hyeon-Jae
    • Journal of Chest Surgery
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    • v.40 no.2 s.271
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    • pp.114-121
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    • 2007
  • Background: Apoptosis plays a crucial role in carcinogenesis, as well as in development and tissue homeostasis. Terminal deoxyribonucleotidyl transferase mediated neck end labelling (TUNEL) and in situ nick end labelling (ISEL) have been used to investigate the apoptosis in tissues. Since the introduction of the M30 monoclonal antibody to overcome drawbacks of TUNEL and ISEL, the apoptosis in various tumors, with the exception of pulmonary carcinomas, has been studied. In this study, attempts were made to examine the correlation of apoptosis in non-small cell carcinomas, using both M30 and the expression of p53 protein, with the clinicopathological factors. Material and Method: Forty five patients with surgically resected non-small cell carcinomas were included. Immunohistochemical staining with M30 and p53 monoclonal antibody were peformed, and their expressions compared with the clinicopathological features. The overall survival time and recurrence-free survival time were calculated, and the factors influencing the survival time analyzed using a univariate analysis. The effects of the expression stati of M30 and p53 on the risks of cancer related to both death and recurrence were evaluated using a multivariate analysis. Result: The p53 positive group had many more M30 positive cells than the p53 negative group (p53 positive group; $61.7{\pm}26.8$ cells vs. p53 negative group; $45.6{\pm}29.6$ cells, p=0.005) and significantly more p53 positive patients showing at least 10 positive cells (apoptotic index, $Al{\ge}1$) on M30 staining (p53 positive group; 52.4% (11/21) vs. p53 negative group 16,7% (4/24), p=0.025). In the univariate analysis, the survival times in relation to smoking (pack-year), performance status (PS) and Al showed significant differences. The multivariate analysis demonstrated the relative risk (R.R) of cancer death increased almost 7.5-fold (R.R 7.482; 95% Cl $1.886{\sim}29.678$; p=0.004) and the risk of recurrence almost 3,8-fold (R.R 3.795; 95% Cl: $1.184{\sim}12.158$; p=0.025) in the high Al (${\ge}1$) compared to the low Al (<1) group. There was no prognostic effect of p53 expression on the survival time or risk of cancer death and recurrence. Conclusion: In non-small cell lung carcinomas, M30 immunohistochemistry was an excellent method for analyzing apoptosis; the high apoptotic index could be an adverse prognostic predictive factor.

Clinical Application of Serum CEA, SCC, Cyfra21-1, and TPA in Lung Cancer (폐암환자에서 혈청 CEA, SCC, Cyfra21-1, TPA-M 측정의 의의)

  • Lee, Jun-Ho;Kim, Kyung-Chan;Lee, Sang-Jun;Lee, Jong-Kook;Jo, Sung-Jae;Kwon, Kun-Young;Han, Sung-Beom;Jeon, Young-June
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.4
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    • pp.785-795
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    • 1997
  • Background : Tumor markers have been used in diagnosis, predicting the extent of disease, monitoring recurrence after therapy and prediction of prognosis. But the utility of markers in lung cancer has been limited by low sensitivity and specificity. TPA-M is recently developed marker using combined monoclonal antibody of Cytokeratin 8, 18, and 19. This study was conducted to evaluate the efficacy of new tumor marker, TPA-M by comparing the estabilished markers SCC, CEA, Cyfra21-1 in lung cancer. Method : An immunoradiometric assay of serum CEA, sec, Cyfra21-1, and TPA-M was performed in 49 pathologically confirmed lung cancer patients who visited Keimyung University Hospital from April 1996 to August 1996, and 29 benign lung diseases. Commercially available kits, Ab bead CEA (Eiken) to CEA, SCC RIA BEAD (DAINABOT) to SCC, CA2H (TFB) to Cyfra2H. and TPA-M (DAIICHI) to TPA-M were used for this study. Results : The mean serum values of lung cancer group and control group were $10.05{\pm}38.39{\mu}/L$, $1.59{\pm}0.94{\mu}/L$ in CEA, $3.04{\pm}5.79{\mu}/L$, $1.58{\pm}2.85{\mu}/L$ in SCC, $8.27{\pm}11.96{\mu}/L$, $1.77{\pm}2.72{\mu}/L$ in Cyfra21-1, and $132.02{\pm}209.35\;U/L$, $45.86{\pm}75.86\;U/L$ in TPA-M respectively. Serum values of Cyfra21-1 and TPA-M in lung cancer group were higher than control group (p<0.05). Using cutoff value recommended by the manufactures, that is $2.5{\mu}/L$ in CEA, $3.0{\mu}/L$ in Cyfra21-1, 70.0 U/L in TPA-M, and $2.0{\mu}/L$ in SCC, sensitivity and specificity of lung cancer were 33.3%, 78.6% in CEA, 50.0%, 89.7% in Cyfra21-1, 52.3%, 89.7% in TPA-M, 23.8%, 89.3% in SCC. Sensitivity and specificity of nonsmall cell lung cancer were 36.1%, 78.1% in CEA, 50.1%, 89.7% in Cyfra21-1, 53.1%, 89.7% in TPA-M, 33.8%, 89.3% in SCC. Sensitivity and specificity of small cell lung cancer were 25.0%, 78.5% in CEA, 50.0%, 89.6% in Cyfra21-1, 50.0%, 89.6% in TPA-M, 0%, 89.2% in SCC. Cutoff value according to ROC(Receiver operating characteristics) curve was $1.25{\mu}/L$ in CEA, $1.5{\mu}/L$ in Cyfra2-1, 35 U/L in TPA-M, $0.6{\mu}/L$ in SCC. With this cutoff value, sensitivity, specificity, accuracy and kappa index of Cyfra21-1 and TPA-M were better than CEA and SCC. SCC only was related with statistic significance to TNM stages, dividing to operable stages(TNM stage I to IIIA) and inoperable stages (IIIB and IV) (p<0.05). But no tumor markers showed any correlation with significance with tumor size(p>0.05). Conclusion : Serum TPA-M and Cyfra21-1 shows higher sensitivity and specificity than CEA and SCC in overall lung cancer and nonsmall cell lung cancer those were confirmed pathologically. SCC has higher specificity in nonsmall cell lung cancer. And the level of serum sec are signiticantly related with TNM staging.

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The Relationship Between Loss of Blood Group Antigen A in Cancer Tissue and Survival Time in the Antigen A Positive Non-Small Cell Lung Cancer (A 항원 양성 원발성 비소세포폐암 조직에서의 A 항원 소실과 생존기간과의 관계)

  • Yang, Sei-Hoon;Jeong, Eun-Taik
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.3
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    • pp.339-346
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    • 2000
  • Background : The moot important prognostic factor in non-small cell lung cancer is the TNM stage. Even after complete resection in early non-small cell lung cancer, the five-year survival rate is still low. However, new prognostic factors, including molecular biologic factors, have recently been found to guide the treatment of patients with non-small cell lung cancer. We evaluated the prognostic value of the loss of blood-group antigen A in tumor tissue, which has been implicated as an important prognostic factor for overall survival and the timing of the disease progression. Methods : The loss of blood-group antigen A was assessed immunohistochemically in paraffin-embedded tumor samples from 26 patients with blood types A or AB, who had undergone curative surgery. Monoclonal antibody was used to detect the blood group antigen A expression. Results : Fifteen patients (58%) expressed antigen A in their tumor tissue, whereas 11 patients (42%) did not show antigen A. The median survival time of the blood A antigen positive group was 11 months, while the median survival time of the blood A antigen negative group was 18 months. The difference in survival between the two groups was not statistically significant. Conclusion : The loss of blood-group antigen A in tumor tissue was not found to be a significant prognostic factor in patients with non-small cell lung cancer. This study needs to be extended for further evaluation.

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The Role of Bone Scans in Routine Preoperative Evaluations of Non-Small Cell Lung Cancer Patients. (비소세포 폐암의 병기에 있어 통상적인 골 스캔의 역할)

  • 김영태;홍장미;이재익;이정상;성숙환;김주현
    • Journal of Chest Surgery
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    • v.35 no.9
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    • pp.659-663
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    • 2002
  • The objective of this study was to assess the usefulness of bone scans in routine preoperative examinations of patients with newly diagnosed non-small cell lung carcinoma. Material and Method: We reviewed the medical records of 258 patients who were newly diagnosed with non-small cell lung cancer in our hospital between January 2000 and December 2000. More than half of the patients (132) were deemed to be inoperable due to their advanced stage based on the CT scans. The remaining 126 patients were considered potentially operable. For these patients, clinical evaluation including the presence of bone pain, serum alkaline phosphatase, and calcium levels was used as clinical predictors of bone metastasis. All patients received bone scans. Bone X-rays, MRI or bone biopsy were performed to confirm the presence of bone metastasis. The usefulness of the bone scan was evaluated by comparing its power of predicting bone metastasis to that of the clinical information. Result: In all patients, the positive and negative predictive values of bone scans for the bone metastasis were 44%, and 99%, respectively. Those of the clinical information were 38% , and 94%. However, in potentially operable patients, the negative predictive value of the clinical information was as high as 99%. Conclusion: If newly diagnosed non-small cell lung cancer patients are presented as potentially operable on the basis of CT scan with no clinical evidence of distant metastases, curative resection could be considered without performing routine bone scans because of the low probability of bone metastasis. However, if there are positive clinical findings, further evaluations, including bone scan should be followed as metastasis will be documented in more than 30% of patients.

Correlation between Cyclin D1, p53, Bcl-2 Protein Expression and Prognosis in Primary, Resected Stage IIIA Non-Small Cell Lung Cancer (NSCLC) (완전 절제된 제IIIA기 비소세포폐암에서 Cyclin D1, p53, Bcl-2 단백질 발현의 의의)

  • 정경영;양우익
    • Journal of Chest Surgery
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    • v.31 no.12
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    • pp.1200-1205
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    • 1998
  • Background: Lung cancer formation is a multistage process involving activation of protooncogene and inactivation of tumor suppressor genes. We evaluate the significance of cyclin D1, p53, bcl-2 gene mutations in patients with curatively resected stage IIIA non-small cell lung cancer(NSCLC). Material and Method: One hundred consecutive cases of stage IIIA lung cancers from patients operated on curatvely between 1990 and 1995 for which adequate paraffin blocks and clinical history were available. Immunohistochemical studies were performed on the representative tissue sections from each case by the labelled streptovidin- biotin method. Sections for cyclin D1, p53, Bcl-2 immunostaining were pretreated in a microwave oven for 10 to 20 minutes in citrate buffer before immunostaining. The overnight incubation with NCL-cyclin D1-GM for cyclin D1, with clone DO-7 for p53, with clone 124 for bcl-2 was done. Mean follow-up was 24.1 months (range 2-84 months) after operation. Result: One hundred cases of lung cancers were composed of 56 cases of squamous cell carcinoma, 37 cases of adenocarcinoma, 5 cases of adenosquamous cell carcinoma, and 2 cases of large cell carcinoma. The 5-year survival was 32.1%. The positive expression rate of cyclin D1 was 35%, p53 was 56%, and bcl-2 was 17%. But there were no correlation between cyclin D1, p53, Bcl-2 protein expression and survival. Conclusion: These observation indicate that cyclin D1, p53, bcl-2 protein overexpression might be implicated in the oncogenesis of non-small cell lung carcinomas but they have no usefulness as a prognostic marker.

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Chest CT Image Patch-Based CNN Classification and Visualization for Predicting Recurrence of Non-Small Cell Lung Cancer Patients (비소세포폐암 환자의 재발 예측을 위한 흉부 CT 영상 패치 기반 CNN 분류 및 시각화)

  • Ma, Serie;Ahn, Gahee;Hong, Helen
    • Journal of the Korea Computer Graphics Society
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    • v.28 no.1
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    • pp.1-9
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    • 2022
  • Non-small cell lung cancer (NSCLC) accounts for a high proportion of 85% among all lung cancer and has a significantly higher mortality rate (22.7%) compared to other cancers. Therefore, it is very important to predict the prognosis after surgery in patients with non-small cell lung cancer. In this study, the types of preoperative chest CT image patches for non-small cell lung cancer patients with tumor as a region of interest are diversified into five types according to tumor-related information, and performance of single classifier model, ensemble classifier model with soft-voting method, and ensemble classifier model using 3 input channels for combination of three different patches using pre-trained ResNet and EfficientNet CNN networks are analyzed through misclassification cases and Grad-CAM visualization. As a result of the experiment, the ResNet152 single model and the EfficientNet-b7 single model trained on the peritumoral patch showed accuracy of 87.93% and 81.03%, respectively. In addition, ResNet152 ensemble model using the image, peritumoral, and shape-focused intratumoral patches which were placed in each input channels showed stable performance with an accuracy of 87.93%. Also, EfficientNet-b7 ensemble classifier model with soft-voting method using the image and peritumoral patches showed accuracy of 84.48%.

Microsatellite Instability in Non-Small Cell Lung Cancer (비소세포폐암에서 Microsatellite Instability)

  • Jeon, Hyo-Sung;Kim, Jeong-Ran;Son, Ji-Woong;Park, Sun-Ha;Park, Tae-In;Kim, Chang-Ho;Kim, In-San;Jung, Tae-Hoon;Park, Jae-Yong
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.1
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    • pp.24-32
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    • 2000
  • Purpose: Microsatellite instability(MSI) is frequently used as an indicator of microsatellite mutator phenotype(MMP) tumors. MSI has been observed in a percentage of non-small cell lung cancer(NSCLC). However, its role in tumorigenesis of NSCLC remains unknown. The frequency and pattern of MSI in NSCLC were evaluated and clinical parameters of MSI-positive tumors with those of MSS(microsatellite stable) tumors were compared. Materials and Methods: Twenty surgically resected NSCLCs were analyzed for 15 microsatellite markers located at chromosomes 3p and 9p. The peripheral blood lymphocytes of patients were used as the source of the normal DNA. Results: 1) Of 20 cases, 8(40%) demonstrated MSI. 2) Instability was observed more frequently in tri- and tetra-nucleotide repeats than in dinucleotide repeats. In all cases, instability appeared as a shift of individual allelic bands. 3) LDH was observed in 10(50%) of 20 tumors analyzed. 4) Of 20 cases, MSI-H tumor(showing MSI in the majority of markers) was absent. There were 5 MSI-L tumors(showing MSI in a greater than 10% of markers). 5) No significant difference was observed between MSI-L tumors and MSI-negative tumors in terms of clinicopathologic features such as pack-year history of smoking, histologic subtype, and(delete) stage of disease. There was also no significant difference in the incidence of LDH in relation to the status of MSI. Conclusion: These data strongly suggest that MSI plays different roles in lung and colon cancer. MMP pathway appears to be far less important in the tumorigenesis of NSCLC, caused mainly by cigarette smoke, with little familial tendency.

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