• Tuberculosis and Respiratory Diseases
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• v.61 no.3
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• pp.248-255
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• 2006

Background: LOH11A is a region with frequent allele loss (>75%) in lung cancer that is located on the centromeric part of chromosome 11p15.5. Clinical and cell biological studies suggest that this region contains a gene associated with metastatic tumor spread. RRM1 encoding the M1 subunit of ribonucleotide reductase, which is an enzyme that catalyses the rate-limiting step in deoxyribonucleotide synthesis, is located in the LOH11A region. Methods: Polymorphisms were found at nucleotide position (-)37 (C/A) and (-)524 (C/T) from the beginning of exon 1 of the RRM1 gene that might regulate the expression of RRM1. We studied the polymorphisms in 127 Korean individuals (66 lung cancer and 61 normal controls) and compared with those of 140 American patients with lung cancer. Results: CC, AC and AA were found at the (-)37 position in 64(50.4%), 55(43.3%), and 8(6.3%) out of 127 Korean individuals (66 cancer, 61 non-cancer patients), respectively. There was a similar frequency of allele A at (-)37 in the American(27.9%) and Korean population(28.0%). CC, CT and TT was found at the (-)524 position in 24(18.9%), 44(34.6%), and 59(46.5%) out of the 127 Korean individuals, respectively. There was a similar frequency of allele C at (-)524 in the American(34.6%) and Korean population(36.2%). There was no difference in the frequency of the (-)37 and (-)524 genotypes between the cancer and non-cancer group. However there was a significant correlation of the genotypes between (-)37 and (-)524 (p<0.001), which suggests the possible coordination of these polymorphisms in the regulation of the promoter activity of the RRM1 gene. Conclusion: RRM1 promoter polymorphisms were not found to be significant risk factors for lung cancer. However, a further study of the promoter activity and expression of the RRM1 gene according to the pattern of the polymorphism will be needed.

• Tuberculosis and Respiratory Diseases
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• v.42 no.6
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• pp.855-861
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• 1995

Background: Parathyroid hormone-related protein(PTHrp) was first identified as the cause of hypercalcemia in malignancy. Hypercalcemia can be found in malignancy, especially in the epidermoid carcinoma of the lung, even without extensive metastases to the bones. The application of sensitive assays for PTHrp may help in the early diagnosis of lung cancer, in the monitoring of treatment and in the detection of recurrence. Method: Serum PTHrp was measured by radioimmunoassay detecting the N-terminal 1~34 peptide of human PTHrp(PTHrp 1-34) in 63 histologically confirmed lung cancer patients and 22 healthy controls. Result: Serum PTHrp(mean$\pm$S.E.) was $312{\pm}68.9pg/ml$ in 63 lung cancer patients and $158{\pm}38.2pg/ml$ in 22 controls(p>0.05). PTHrp was $356{\pm}103.9pg/ml$ in 34 epidermoid carcinoma patients, $281{\pm}148.7pg/ml$ in 15 adenocarcinoma patients and $316{\pm}140.8pg/ml$ in 9 small cell carcinoma patients. In epidermoid carcinoma patients, PTHrp was $570{\pm}472.3pg/ml$ in stage II(n=3; p<0.05 vs controls), $166{\pm}22.4pg/ml$ in stage IIIa(n=9), $282{\pm}113.3pg/ml$ in stage IIIb(n=12) and $668{\pm}367.9pg/ml$ in stage IV(n=9; p<0.05 vs controls). PTHrp was significantly increased in 8 epidermoid carcinoma patients with bone metastases($1526{\pm}811.2\;pg/ml$; p<0.0005 vs controls). Hypercalcemia was observed in an epidermoid carcinoma patient whose PTHrp value was 244 pg/ml. Conclusion: The serum PTHrp was increased in advanced epidermoid carcinoma patients even without hypercalcemia. The measurement of PTHrp may be not helpful in the early diagnosis of lung cancer. But the lung cancer should be suspected in the marked elevation of PTHrp. It may be of value in detecting patients of advanced diseases with bone metastases or patients who might develop the malignancy associated hypercalcemia.

• Tuberculosis and Respiratory Diseases
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• v.59 no.2
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• pp.142-150
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• 2005

Background : Continuous growth stimulation by various factors, as well as chronic oxidative stress, may co-exist in many solid tumors, such as lung cancer. A new family of antioxidant proteins, the peroxiredoxins (Prxs), have been implicated in the regulation of many cellular processes, including cell proliferation, differentiation and apoptosis. However, a real pathophysiological significance of Prx proteins, especially in lung disease, has not been sufficiently defined. Therefore, this study was conducted to investigate the distribution and expression of various Prx isoforms in lung cancer and other pulmonary conditions. Method : Patients diagnosed with lung cancer, and who underwent surgery at the Ajou Medical Center, were enrolled. The expressions of Prxs, Thioredoxin (Trx) and Thioredoxin reductase (TR) were analyzed using proteomic techniques and the subcellular localization of Prx proteins was studied using immunohistochemistry on normal mouse lung tissue. Result : Immunohistochemical staining has shown the isoforms of Prx I, II, III and V are predominantly expressed in bronchial and alveolar lining epithelia, as well as in the alveolar macrophages of the normal mouse lung. The isoforms of Prx I and III, and thioredoxin were also found to be over-expressed in the lung cancer tissues compared to their paired normal lung controls. There was also an increased amount of the oxidized form of Prx I, as well as a putative truncated form of Prx III, in the lung cancer samples when analyzed using 2-dimensional electrophoresis. In addition, a 43 kDa intermediate molecular weight protein band, and other high molecular weight bands of over 20 kDa, recognized by the anti-Prx I antibody, were present in the tissue extracts of lung cancer patients on 1-Dimensional electrophoresis, which require further investigation. Conclusion : The over-expressions of Prx I and III, and Trx in human lung cancer tissue, as well as their possible chaperoning function, may represent an attempt by tumor cells to adjust to their microenvironment in a manner advantageous to their survival and proliferation, while maintaining their malignant potential.

• Tuberculosis and Respiratory Diseases
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• v.39 no.5
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• pp.400-406
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• 1992

Background: It has been known that see antigen was used in diagnosis of uterine cervical cancer and also known to be higher in squamous cell lung cancer. There has been no report about see antigen in squamous cell lung cancer in Korea. This study was designed to evaluate the usefulness of see antigen as a diagnostic tool and index for follow up after treatment. Method: The serum level of see antigen was measured in 12 cases with squamous cell lung carcinoma, 9 patients with other types of lung cancer, 7 patients with benign lung disease and 7 normal subjects by radioimmunoassay with Abott see Riabeap radioimmunoassay kit. We also measured see antigen after treatment in 6 patients who had received chemotherapy or sugery. Result: 1) The level of see antigen ($mean{\pm}1$ SD) was $2.27{\pm}1.53$, $0.67{\pm}0.38$, $0.62{\pm}0.53$, $0.53{\pm}0.36\;ng/ml$ respectively. 2) The see antigen activity in squamous cell lung carcinoma according to stage were as gollows. I; $2.07{\pm}1.56$, $III_a$; $5.04{\pm}0.53$ $III_b$; $1.94{\pm}0.7$ IV; $1.07{\pm}0.64$ (ng/ml). 3) In squamous cell lung cancer, 5 of 12 (42%) cases was shown more than 2.0 ng/ml see antigen. (sensitivity; 42%), but there was no case in any other type of lung cancer, benign lung disease, and in control groups (specificity; 100%). 4) The serum sec antigen level after treatment was significantly decreased in patients with partial or complete remission (p<0.01). Conclusion; It was suggested that see antigen might be used as a useful tumor marker for the response of treatment and assessment of prognosis in squamous cell lung cancer, but further study should be performed for the clinical use of see antigen.

• Tuberculosis and Respiratory Diseases
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• v.48 no.5
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• pp.748-756
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• 2000

Background : Bronchogenic carcinoma is generally considered as a disease that predominantly affects middleaged and elderly men. A small percentage of patients with lung cancer are diagnosed in the third or fourth decade of life or earlier. The current study was performed to review the clinical characteristics of bronchogenic carcinoma in patients younger than 40 years of age at Chungnam National University Hospital. Method : To determine the clinicopathologic characteristics including survival rates of lung cancer patients younger than 40 years of age and to compare them with those of patients 이der than 40 years of age at diagnosis, data of 905 patients diagnosed as lung cancer from January. 1990 to Marm 1997 were analyzed. Result : Twenty-three of 905 patients(2.5%) belonged to the young age group (less than 40 years). Male to female ratios of young age group and control group were 2.8 : 1 and 5.3 : 1, respectively. The mean duration of symptoms from onset to the definite diagnosis was 3.2 months in the young age group. The most common initial symptoms in the young age group were cough(52.2%) and dyspnea(43.5%). Adenocarcinoma (43.5%) was more frequent in the young age group than in the control group(20.1%). Stage III and IV(70%) tumors were more frequent in the young age group than in the control group(52.3%). Distant metastasis rate of the young age group(56.5%) was higher than that of the control group(22.3%). Conclusion : The predominance of adenocarcinoma, the lower male-female ratio, and the high incidence of advanced stage tumor at diagnosis are the characteristics of lung cancer in patients younger than 40 years of age.

• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.195-203
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• 1999

Background: Telomerase enzyme activity is not detected in most normal cells, a phonomenon believed to be associated with limitations on cellular proliferation. Since this activity is detected in nearly all human tumor, including lung cancers, it has been suggested that telomerase activation may be coupled to acquisition of malignant phenotype. In this study, we determined whether telomerase activity was associated with tumor pathologic stage. Methods: Primary tumor specimens obtained by bronchoscopic biopsies from 33 patients were analyzed. Telomerase activity was measured by means of a modified Telomeric Repeat Amplication Protocol(TRAP) assay. Results: Telomerase activity was detected in 23 of the 27 non-small-cell lung cancer and 5 of 6 small-cell lung cancer. A few primary tumors did not appear to have detectable telomerase activity. Positive associations were found between the telomerase-positive rate and tumor stage(p<0.05). Conclusion: High telomerase activity is detected frequently in primary lung cancers that exhibit high tumor cell proliferation rates and advanced pathologic stage.

• The Korean Journal of Nuclear Medicine
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• v.28 no.2
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• pp.186-191
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• 1994

Tc-99m MIBI, a lipophilic cation, was reported as a useful agent for localization of lung cancer. The effect of radiation therapy on the uptake of Tc-99m MIBI in lung cancer, however, was not well evaluated. The aim of the present study was to elucidate the usefulness of Tc-99m MIBI SPECT in the localization and the assessment of radiotherapy in non-small cell lung cancer. Twenty patients(19 males and 1 female, mean age 59, 16 squamous cell ca and 4 adenoca) were studied with Tc-99m MIBI SPECT before radiation therapy. Eleven patients(10 males and 1 female, mean age 59, 8 squamous cell ca and 3 adenoca) were repeated the study 1 month after the completion of radiation therapy(mean dose 6453cGy). All patients showed positive uptakes of Tc-99m MIBI in their tumors. One patient showed a hot uptake in atelectatic area. There was no difference of Tc-99m MIBI uptakes between squamous cell ca and adenoca either on planar or tomographic images. Tc-99m MIBI uptake ratios of squamous cell ca and adenoca were $1.50{\pm}0.16$ and $1.45{\pm}0.15$ on planar images, and $2.73{\pm}0.46$ and $2.54{\pm}0.37$ on tomographic images, respectively. The concordance between radiological change(chest x-ray and CT) and change of Tc-99m MIBI uptakes was 9/11 (81.8% ). In conclusion, Tc-99m MIBI SPECT was useful in the localization of tumor and the assessment of radiation therapy in non-small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.50 no.5
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• pp.568-578
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• 2001

Background : Lung cancer is frequently cited as an example of a disease caused solely by exposure to environmental carcinogens. However, there is a growing realization that the genetic constitution is also important in determining individual's susceptibility to lung cancer. This genetic susceptibility may result from functional polymorphims of the genes involved in carcinogen metabolism. In this study, the association between GSTM1 and CYP1A1 polymorphisms and the lung cancer risk in Korean males was investigated. Materials and Method : The study population consisted of 153 male lung cancer patients and 143 healthy male controls. The GSTM1 and CYP1A1 genotypes were determined by multiplex PCR and PCR-RFLP analysis. Result : There were no significant differences in the frequency of the GSTM1 null genotype between the cases and the controls. When the cases were categorized by their histologic type, the frequency of the GSTM1 null genotype in the small cell carcinoma group was higher than those of the controls(67.2% vs 55.9%), but the difference was not statistically significant(OR=1.772 ; 95% CI=0.723-4.340). The distribution of the CYP1A1 MspI genotypes among the cases were similar to those among the controls. When the cases were grouped by their histologic type, the ml/m1, ml/m2, m2/m2 genotypes frequencies among the small cell carcinomas(23.0%, 38.5%, and 38.5%, respectively) were significantly different from those of the controls(36.4%, 46.2%, and 7.4%, respectively, p<0.05). When the m1/m1 genotype was used as a reference, the ml/m2 and m2/m2 genotypes were associated with an increased risk for small cell lung cancer(ml/m2 genotype : OR=1.337, 95% CI=0.453-3.947 ; m2/m2 genotype : OR=3.374, 95% CI=1.092-10.421). Conclusion : These results suggest that the GSTM1 and CYP1A1 genotypes may be a genetic determinant of the risk for lung cancer, particlulary small cell carcinoma. Further investigation is needed to confirm these results.

• 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.

• The Journal of Korean Medicine
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• v.16 no.2 s.30
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• pp.177-194
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• 1995

The following conclusions were obtained after bibliographic investigation on the therapy of lung cancer by western, oriental, and integrated oriental and western medicine. 1. Lung cancer is classified into small cell lung cancer(SCLC) or non small cell lung cancer(NSCLC) in the treatment by western medicine, and applied with the means of surgery, radiotherapy and chemotherapy alone or combined, depending on the stage and the symptom. 2. Treatment by oriental medicine includes the means of strengthening body resistance to dispel pathogenic factors(扶正祛邪), combined approach of reinforcement and expulsion(攻補兼施), and reinforcing both qi and blood(氣血雙補), depending on the initial, middle, and terminal stage. And also treatment based on differentiation of symptom(辨證施治) is applied according to the type of symptom; deficiency of qi of both lung and spleen(肺脾氣虛), heat symptom of lung by deficiency of yin(肺熱陰虛), stagnation of damp-phlegm and blood(濕痰瘀阻), stagnation of qi and blood(氣血瘀滯), deficiency of both qi and yin(氣陰兩虛). Single or combined herb drug is used according to the symptom. 3. Treatment by integrated oriental and western medicine improved survival rate and quality of life. It promoted recovery and improved survival rate in the patients receiving surgery. Integrated radiotherapy and oriental medicine treatment reduced adverse effect by radiotherapy and improved therapeutic effect and survival rate. Integrated chemotherapy with oriental medicine treatment reduced side effect by chemotherapy and improved quality of life and survival rate. These results suggest that therapy of lung cancer should be applied with integrated oriental and western medicine from diagnosis to treatment for promoting therapeutic effect. And further study on this therapy should be ensued.