• Tuberculosis and Respiratory Diseases
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• v.47 no.4
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• pp.471-477
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• 1999

Background : Smoking and high-risk occupation have been known to be the risk factors of lung cancer. The carcinogen-metabolizing enzymes in human body such as glutathione S-transferase M1, T1 and N-acetyltransferase 1 have also been regarded as risk factors in many cancers, because the activities of those enzymes play a role in metabolizing the carcinogen. A case-control study was conducted to evaluate the genetic polymorphism of GSTM1, T1 and NAT1 in lung carcinogenesis in Korean men. Methods : The histologically proven lung cancer cases were recruited from Seoul National University Hospital. The patients of more than 40-year-old with the nonmalignant urinary tract diseases were recruited as controls from the same hospitals. The informations of demographical characteristics and smoking were obtained by interview or chart review and the genetic polymorphisms of GSTM1, T1 and NAT1 were determined by PCR-based assay. The statistical analyses were performed by linear logistic regression. Results : The number of case-control was 118 and 150, respectively. The smoking history was significantly higher in the lung cancer patients than the controls. The prevalence of GSTM1 null-type was statistically higher(OR=2.25 ; 95% CI=1.12-4.51) in squamous cell carcinoma than other genotypes, but other histologic types were not The prevalence of GSTT1 null-type were not statistically higher than other genotypes in all histologic types. The fast acetylator of NAT1 was more prevalent than normal(OR=2.13 ; 95% CI=1.04-4.40) in all lung cancer patients. Conclusion : The null-type of GSTM1 and fast acetylator of NAT1 are associated with development of lung cancer in Korean men.

• Tuberculosis and Respiratory Diseases
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• v.47 no.4
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• pp.478-487
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• 1999

Background : Differential diagnosis of pleural malignant mesothelioma from secondary metastatic adenocarcinoma is often difficult. A variety of pathologic techniques have been developed to make a differential diagnosis of carcinoma from mesothelioma. Immunohistochemistry detecting diverse antigenic substances such as CEA, Leu-M1, Bn-3, S-100 protein, vimentin, CK and EMA has been claimed to be of value as a panel in the differential diagnosis of adenocarcinoma from mesothelioma. The aim of this study was to investigate the suitable antibodies to distinguish mesothelioma from metastatic adenocarcinoma and establish candidate markers in a panel. Methods : Complete, one-hour immunohistochemical staining using antibodies against cytokeratin (CK), epithelial membrane antigen(EMA), S-100 protein, vimentin, B72-3, Leu-M1, and carcino-embryonic antigen(CEA) was applied to cell blocks from 7 mesotheliomas and 7 adenocarcinomas which were confirmed by electron microscopic and histpathologic methods. Results : All adenocarcinomas and 71.4% of mesotheliomas expressed the cytokeratin and EMA. S-100 protein and vimentin were expressed in 57.1% and 42.9% of mesotheliomas and 14.3% and 28.5% of adenocarcinomas, respectively. B72-3 was expressed in all adenocarcinomas, but in none of mesotheliomas. Leu-M1 was positive in 71.4% of the adenocarcinoma and 14.3% of the mesotheliomas. CEA was positive in all adenocarcinomas and 42.9% of mesotheliomas. Leu-M1 and B72-3 were coexpressed in 71.4% of adenocarcinomas but in none of mesothelioma. B72-3 and CEA were coexpressed in all adenocarcinomas, but in none of mesotheliomas. Conclusion : We concluded that B72-3 immunohistochemistry or panel staining of B72-3 and CEA could be recommanded for the differential diagnosis of pleural mesothelioma from metastatic adenocarcinoma.

• Tuberculosis and Respiratory Diseases
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• v.64 no.5
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• pp.362-368
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• 2008

Background: LKB1(STK11) is a serine/threonine kinase that functions as a tumor growth suppressor. The functions of LKB1 in lung cancer are not completely understood. This study evaluated the relationship between LKB1 protein expression and the clinicopathological features in lung cancer tissues. Methods: The expression of LKB1 was studied in paraffin-embedded tumor blocks, which were obtained from 77 patients who had undergone surgery at Wonkwang University Hospital. The expression of the LKB1 protein was considered positive if the staining intensity in the tumor tissue adjacent to the normal airway epithelium was >30%. Results: The LKB1 expression was positive in 31 (40%) of samples. Loss of LKB1 expression was significantly associated with being male, smoking history, and squamous cell carcinoma. In the peripheral sites, the loss of LKB1 expression was strongly associated with a smoking history. A loss of LKB1 expression was more frequently associated with progression according to TNM staging, particularly more than T2, N progression. Conclusion: There was a significant relationship between the loss of the LKB1 protein and gender, smoking history, and histological type in primary lung cancer. Although LKB1 expression was not found to be a significant prognostic factor, further studies with a larger cohort of patient's lung cancer tissue samples will be needed to confirm this.

• Tuberculosis and Respiratory Diseases
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• v.64 no.5
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• pp.347-355
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• 2008

Background: IPF is characterized by chronic, fibrosing inflammatory lung disease of unknown etiology. Typical symptoms of IPF are exertional dyspnea with nonproductive cough. Why patients with typical IPF have dry cough rather than productive cough, is unknown. IP-10 plays an important regulatory role in leukocyte trafficking into the lung. The present study investigated the effect of IP-10 in the pathogenesis of dry cough rather than productive cough in IPF patients. Methods: IP-10 concentration was measured by ELISA from BALF of IPF patients. To evaluate the role of IP-10 in mucin expression, the expression of the MUC5AC mucin gene was measured in NCI-H292 cells, a human pulmonary mucoepidermoid carcinoma cell line, after stimulation by TNF-${\alpha}$ with or without IP-10 pretreatment. EGFR-MAPK expression was also examined as a possible mechanism. Results: IP-10 levels were significantly higher in the BALF of IPF patients compared to healthy controls. IP-10 pretreatment reduced TNF-${\alpha}$ induced MUC5AC mucin expression by inhibiting the EGFR-MAPK signal transduction pathway in NCI-H292 cells. Conclusion: These findings suggest that little mucus production in IPF patients might be attributable to IP-10 overproduction, which inhibits the EGFR-MAPK signal transduction pathway required for MUC5AC mucin gene expression.

• Tuberculosis and Respiratory Diseases
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• v.40 no.2
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• pp.177-184
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• 1993

Background: Accurate staging of bronchogenic carcinoma is important in determining resectability and metastasis of tumor to the subcarinal nodes is generally believed to indicate poor prognosis. The technique of Transbronchial needle aspiration (TBNA) has offered a safe & effective way to asscess mediastinal lymph node involvement in the staging of lung cancer. We performed TBNA in patients who were suspected lung cancer to evaluate the clinical usefulness of the TBNA. Method: TBNA of the subcarinal lymph node was performed at the time of initial diagnostic bronchoscopy in 60 patients with suspected lung cancer, and 42 cases of histologically proved bronchogenic cancer were analized. Results: The frequency of adequate samples by transbronchial needle aspiration (TBNA) was 81% and the positive rate of malignant cells by TBNA was 14.7%. There were no differences in positive rates by tumor cell types. In patients with thickened carina on bronchoscopy, the TBNA was positive in 33.3% as compared to 5.3% of normal carina on bronchoscopy, and the difference was statistically significant (p<0.05). In patients with enlarged subcarinal lymph node on chest CT, the positive rate of malignant cells (50.0%) was higher than that of normal sized subcarinal lymph node on chest CT (4.8%) (p<0.01). There were no specific complications in the TBNA procedure. Conclusion: TBNA is a relatively safe procedure and it offers the possibility of avoiding the cost and morbidity of surgical staging in patients especially whose carina is thickened on bronchoscopy and whose subcarinal LN was enlarged on chest CT.

• Archives of Pharmacal Research
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• v.21 no.4
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• pp.458-464
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• 1998

Search for a new $\alpha$-methylene-$\gamma$-butyrolactone-bearing 6-substituted purine as a potental antitumor agent has led to synthesize seven, hitherto unreported, $5^1$-Methyl-$5^1$-[(6-substituted-9H-purin-9-yl)methyl]-$2^1$-oxo-$3^1$- methylenetetrahydrofurans (H, Cl, l, $CH_3$, $NH_2$, SH, >C=O) (6a-g). These include $5^1$-Methyl-$5^1$-[(9H-purin-9-yl)methyll-$2^1$-oxo-$3^1$ -methylenetetrahydrofurans (6a), $5^1$-Methyl-$5^1$-[(6-chloro-9H-purin-9-yl)methyl]-$2^1$-oxo-$3^1$-methylenetetrahydr ofurans (6b), $5^1$-Methyl-$5^1$-[(6-chloro-9H-purin-9-yl) methyl]-$2^1$-oxo-$3^1$-methylenetetrahydrofurans (6c), $5^1$-Methyl-$5^1$-[(6-methyl-9H-purin-9-yl) methyl]-$2^1$-oxo-$3^1$-methylenetetrahydrofurans (6d), $5^1$-Methyl-$5^1$-[(9H-adenin-9-yl)methyll-$2^1$-oxo-$3^1$-methylenetetrahydrofurans (6e), $5^1$-Methyl-$5^1$-[(6-mercapto-9H-purin-9-yl) methyl]-$2^1$-oxo-$3^1$-methylenetetrahydrofurans (6f) and $5^1$-Methyl-$5^1$-[(9H-hypoxanthin-9-yl)methyll-$2^1$-oxo-$3^1$-methylenetetrahydrof urans (6g) which were made by the Reformatsky-type reaction of ethyl $\alpha$-(bromomethyl) acrylate with the corresponding (6-substituted-9H-purin-9-yl)-2-propanone intermediates (5a-g). These ketone intermediates 5a-g, 1-(9H-purin-9-yl)-2-propanone (5a), 1-(6-chloro-9H-purin-9-yl)-2-propanone (5b), 1-(6-iodo-9H-purin-9-yi)-2-propanone (5c), 1-(6-methyl-9H-purin-9-yl)-2-propanone (5d), 1-(9H-adenin-9-yl)-2-propanone (Se), 1-(6-mercapto-9H-purin-9-yl)-2-propanone (5f), and 1-(9H-hypoxanthin-9-yl)-2-propanone (5g) were directly obtained by the alkylation of the 6-substituted purine bases with the chloroacetone in the presence of $K_2$$CO_3$ (or NaH) under DMF (or DMSO). The preliminary in vitro cytotoxcity assay for the synthetic .alpha.-methylene-y-butyro-lactone compounds (6a-g) were determined against three cell lines (PM-3A, P-388, and K-562) and showed the moderate antitumor activity ($IC_50$ ranged from 1.4 to 4.3 $\mu\textrm{g}$/ml) with the compound $5^1$-methyl-$5^1$ -[(9H-hypoxanthin-9-yl)methyl]-$2^1$-oxo-$3^1$-methylenetetrahydrofuran (6g) showing the least antitumor activity.

• Journal of Chest Surgery
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• v.31 no.9
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• pp.877-883
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• 1998

Background: Cardiopulmonary bypass(CPB), a standard adjunct for open heart surgery, can also play an important role in treating patients with noncardiac diseases. Material and Method: We report a collective analysis of noncardiac applications of cardiopulmonary bypass experienced at Seoul National University Hospital from 1969 to 1996. Out of a total of 20 patients, 8 were treated for membranous obstruction of inferior vena cava(MOVC), 5 for malignant melanoma, 3 for pulmonary embolism, 1 for double lung transplantation, 1 for intracranial giant aneurysm(GA), 1 for renal cell carcinoma(RC), and 1 for liposarcoma. CPB was used to induce profound hypothermia with circulatory arrest in 6 patients(MOVC 4, GA 1, RC 1). Result: CPB time was 113 mins on average for MOVC, 161 mins for GA, and 156 mins for RC, while the lowest rectal temperature was 26$^{\circ}C$ on average in MOVC, and 19$^{\circ}C$ in GA and RC. Postoperative recovery was good in all MOVC patients. The patient with GA, who underwent reoperation for the removal of hematoma, died 14 days postoperatively. The patient with RC recovered from the operation in a good condition but died from metastatic spread 6 months later. CPB was instituted for pulmonary embolectomy in 3 patients, in whom postoperative courses were uneventful, except in 1 patient who showed transient neurologic symptoms. CPB was used in a patient with double-lung transplantation for hemodynamic and ventilatory support. The patient was weaned successfully from CPB but died from low output and septicemia 19 days postoperatively. CPB without circulatory arrest was used to treat in 4 patients with MOVC. These patients showed good postoperative courses. CPB was used to administer high concentrations of chemotherapeutic agents to the extremities in 6 patients(malignant melanoma 5, recurrent liposarcoma 1). CPB time was 153 mins on average. No complications such as edema and neurologic disability were found. Conclusion: Although CPB has a limited indication in noncardiac diseases, if properly applied, it can be a very useful adjunct in a variety of surgical cases.

• Journal of Chest Surgery
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• v.38 no.6 s.251
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• pp.428-433
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• 2005

Advanced age in Esophagectomy increases the risk of postoperative morbidity and mortality. However, the recent development of operative technique and perioperative care might have decreased the postoperative morbidity and mortality after esophagectomy. Material and Method: From March 2001 to July 2004, 174 patients underwent esophageal resection for esophageal cancer in the Center for Lung Cancer, National Cancer Center. The patients were divided into two groups : group 1 consisted of 27 patients aged 70 years or more, and group 2 consisted of 147 patients under 70 years of age. The two groups were compared according to preoperative risk factors, postoperative morbidity, operative mortality and survival. Result: The mean age was 63_4. There were 159 men. On histopathological examination, $93.1\%$ had squamous cell carcinoma. On the locations, $78.7\%$ were in mid and lower esophagus. Curative resections for esophageal cancer were possible in $162(93.1\%)$ patients. Mean hospital stay was 19.4 days with out difference between the groups. The overall postoperative morbidity were occurred in 61 patients $(35.1\%)$. The most frequent morbidity was pulmonary complication in $30(17.2\%)$. Preoperative incidence of hypertension, cardiac and pulmonary dysfunction were more common in Group I. However, there was no difference in overall postoperative morbidity, operative mortality and survival rate between the two groups. Conclusion: Esophagectomy for esophageal cancer could be carried out safely in patients over 70 years of age with satisfactory short-term results. Advanced age is no longer a risk factor for esophagectomy.

• Radiation Oncology Journal
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• v.16 no.1
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• pp.51-61
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• 1998

Purpose : Treatment of choice for uterine cervix cancer stage IIB is radiotherapy. We analyzed survivals, Prognostic factors, patterns of failure and complications. Materials and Methods : This is a retrospective analysis of 167 patients with stage IIB carcinoma of uterine cervix treated with curative external pelvic and high dose rate intracavitary radiotherapy at the Department of Therapeutic Radiology, Soonchunhyang University Hospital from August 1985 to August 1994. All the patients followed up from 3 to 141 months(mean 60 months) and age of patients ranged from 31 to 78 years at presentation(mean : 55 years). Results : Overall complete response rate was $84\%$. The response rate for squamous cell carcimoma and adenocarcinoma were $86\%$ and $60\%$, respectively. Overall 5-years survival rate and disease free survival rate was 62 and $59\%$, respectively Mass size and treatment response were significant Prognostic factors for survival Pathologic type and parametrial involvement were marginally significants Prognostic factors. Local failure was 43 cases, distant metastasis was 14 cases and local failure plus distant metastasis was 3 cases, and most of local failures occurred within 24 months, distant metastasis within 12 months after treatment Twenty eight($16.8\%$) patients developed late rectal and urinary complications There were tendency to increasing severity and frequency according to increased fractional dose and total(rectal and bladder) dose. Conclusions : Survival rate was significantly related to tumor size and radiotherapy response. Tumor size should be considered in the clinical s1aging. To increased survival and local control, clinical trials such as decreasing duration of radiotherapy or addition of chemotherapy is needed. To detect early recurrence, regular follow up after RT is important. Because total rectal and bladder dose affected late complications. meticulous vaginal packing is needed to optimize dose of normal tissues and to decrease late complications.

• Radiation Oncology Journal
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• v.22 no.4
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• pp.288-297
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• 2004

Puporse: The aims of this study were to evaluate the change of $[^18F]fluoromisonidazole$($[^18F]FMISO$) uptake in C3H mouse squamous cell carcinoma-VII (SCC-VII) treated with mild hyperthermia ($42^{circ}C$) and nicotinamide and to assess the biodistribution of the markers in normal tissues under similar conditions. Methods and Materials: $[^18F]FMISO$ was producedby our hospital. Female C3H mice with a C3H SCC-VII tumor grown on their extremities were used. Tumors were size matched. Non-anaesthetized, tumor-bearing mice underwent control or mild hyperthermia at $42^{circ}C$ for 60 min with nicotinamide (50 mg/kg i.p. injected) and were examined by gamma counter, autoradiography and animal PET scan 3 hours after tracer i.v. injected with breathing room air, The biodistribution of these agents were obtained at 3 h after $[^18F]FMISO$ injection. Blood, tumor, muscle, heart, lung, liver, kidney, brain, bone, spleen, and intestine were removed, counted for radioactivity and weighed. The tumor and liver were frozen and cut with a cryomicrotome into 10- um sections. The spatial distribution of radioactivity from the tissue sections was determined with digital autoradiography. Results: The mild hyperthermia with nicotinamide treatment had only slight effects on the biodistribution of either marker in normal tissues. We observed that the whole tumor radioactivity uptake ratios were higher in the control mice than in the mild hyperthermia with nicotinamide treated mice for $[^18F]FMISO$ ($1.56{\pm}1.03$ vs. $0.67{\pm}0.30$; p=0.063). In addition, autoradiography and animal PET scan demonstrated that the area and intensity of $[^18F]FMISO$ uptake was significantly decreased. Conclusion: Mild hyperthermla and nicotinamide significantly improved tumor hypoxia using $[^18F]FMISO$ and this uptake reflected tumor hypoxic status.